Cardiovascular disease

system involvement

From Wikipedia, the free encyclopedia

Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood
vessels.[1] Common CVDs include: ischemic heart disease (IHD), stroke, hypertensive
heart disease, rheumatic heart disease (RHD), aortic aneurysms, cardiomyopathy, atrial
fibrillation, congenital heart disease, endocarditis, and peripheral artery disease (PAD),
among others.[1][2]

Cardiac dysrhythmias abnormalities of heart rhythm

Inflammatory heart disease

The underlying mechanisms varies depending on the disease in question. IHD, stroke,
and PAD involve atherosclerosis. This may be caused by high blood
pressure, smoking, diabetes, lack of exercise, obesity, high blood cholesterol, poor diet,
and excessive alcohol, among others. High blood pressure results in 13% of CVD
deaths, while tobacco results in 9%, diabetes 6%, lack of exercise 6% and obesity 5%.
Others such as RHD may follow untreated streptococcal infections of the throat.[1]
It is estimated that 90% of CVD is preventable.[3] Prevention of atherosclerosis is by
decreasing risk factors through: healthy eating, exercise, avoidance of tobacco smoke
and limiting alcohol intake.[1] Treating high blood pressure and diabetes is also beneficial.
[1]
Treating people who have strep throat with antibiotics can decrease the risk of RHD.
[4]
The effect of the use of aspirin in people who are otherwise healthy is of unclear
benefit.[5][6] The USPSTF recommends against its use for prevention in women less than
55 and men less than 45 years old; however, in those who are older it is recommends in
some individuals.[7] Treatment of those who have CVD improves outcomes.[1]
Cardiovascular diseases are the leading cause of death globally.[1] This is true in all areas
of the world except Africa.[1] Together they resulted in 17.3 million deaths (31.5%) in 2013
up from 12.3 million (25.8%) in 1990.[2] Deaths, at a given age, from CVD are more
common and have been increasing in much of the developing world, while rates have
declined in most of the developed world since the 1970s.[8][9] IHD and stroke account for
80% of CVD deaths in males and 75% of CVD deaths in females.[1] Most cardiovascular
disease affects older adults. In the United States 11% of people between 20 and 40 have
CVD, while 37% between 40 and 60, 71% of people between 60 and 80, and 85% of
people over 80 have CVD.[10] The average age of death from IHD in the developed world
is around 80 while it is around 68 in the developing world. [8] Disease onset is typically
seven to ten years earlier in men as compared to women.

Endocarditis inflammation of the inner layer of the heart,

the endocardium. The structures most commonly involved are the heart valves.

Inflammatory cardiomegaly

Myocarditis inflammation of the myocardium, the muscular part of the

heart.

Valvular heart disease

Cerebrovascular disease disease of blood vessels that supply blood to the

brain (includes stroke)

Peripheral arterial disease disease of blood vessels that supply blood to the
arms and legs

Congenital heart disease heart structure malformations existing at birth

Rheumatic heart disease heart muscles and valves damage due to rheumatic
fever caused by Streptococcus pyogenes a group A streptococcal infection.

Types

Pulmonary heart disease a failure at the right side of the heart with respiratory

Risk factors
Cardiomyopathy diseases of cardiac muscle
There are several risk factors for heart diseases: age, gender, tobacco use, physical

Hypertensive heart disease diseases of the heart secondary to high blood

pressure or hypertension

inactivity, excessive alcohol consumption, unhealthy diet, obesity, family history of

cardiovascular disease, raised blood pressure (hypertension), raised blood sugar
(diabetes mellitus), raised blood cholesterol (hyperlipidemia), psychosocial factors,

Heart failure

poverty and low educational status, and air pollution.[13][14][15][16][17] While the individual
contribution of each risk factor varies between different communities or ethnic groups the

overall contribution of these risk factors is very consistent. [18] Some of these risk factors,

women, estrogen is the predominant sex hormone. Estrogen may have protective effects

such as age, gender or family history, are immutable; however, many important

through glucose metabolism and hemostatic system, and may have direct effect in

cardiovascular risk factors are modifiable by lifestyle change, social change, drug

improvingendothelial cell function.[22] The production of estrogen decreases after

treatment and prevention of hypertension, hyperlipidemia, and diabetes.

menopause, and this may change the female lipid metabolism toward a more
atherogenic form by decreasing the HDL cholesterol level while increasing LDL and total
cholesterol levels.[22]

Age
Among men and women, there are notable differences in body weight, height, body fat
Age is by far the most important risk factor in developing cardiovascular or heart

distribution, heart rate, stroke volume, and arterial compliance. [23] In the very elderly

diseases, with approximately a tripling of risk with each decade of life. [19] It is estimated

people, age-related large artery pulsatility and stiffness is more pronounced among

that 82 percent of people who die of coronary heart disease are 65 and older.

women than men.[23] This may be caused by the women's smaller body size and arterial

[20]

At the

same time, the risk of stroke doubles every decade after age 55. [21]

dimensions which are independent of menopause. [23]

Multiple explanations have been proposed to explain why age increases the risk of
cardiovascular/heart diseases. One of them is related to serum cholesterol level. [22] In

Tobacco

most populations, the serum total cholesterol level increases as age increases. In men,
this increase levels off around age 45 to 50 years. In women, the increase continues

Cigarettes are the major form of smoked tobacco.[27] Risks to health from tobacco use

sharply until age 60 to 65 years.[22]

result not only from direct consumption of tobacco, but also from exposure to secondhand smoke.[27] Approximately 10% of cardiovascular disease is attributed to smoking;

Aging is also associated with changes in the mechanical and structural properties of the
vascular wall, which leads to the loss of arterial elasticity and reduced arterial compliance
and may subsequently lead to coronary artery disease.

[27]

however, people who quit smoking by age 30 have almost as low a risk of death as

never smokers.[28]

[23]

Sex

Physical inactivity
Insufficient physical activity (defined as less than 5 x 30 minutes of moderate activity per

Men are at greater risk of heart disease than pre-menopausal women. [19][24] Once

week, or less than 3 x 20 minutes of vigorous activity per week) is currently the fourth

past menopause, it has been argued that a woman's risk is similar to a man's [24] although

leading risk factor for mortality worldwide.[27] In 2008, 31.3% of adults aged 15 or older

more recent data from the WHO and UN disputes this.[19] If a female has diabetes, she is

(28.2% men and 34.4% women) were insufficiently physically active.[27] The risk of

more likely to develop heart disease than a male with diabetes.[25]

ischemic heart disease and diabetes mellitus is reduced by almost a third in adults who

Coronary heart diseases are 2 to 5 times more common among middle-aged men than
women.[22] In a study done by the World Health Organization, sex contributes to
approximately 40% of the variation in sex ratios of coronary heart disease mortality.
[26]

Another study reports similar results finding that gender differences explains nearly

half the risk associated with cardiovascular diseases[22] One of the proposed explanations
for gender differences in cardiovascular diseases is hormonal difference. [22] Among

participate in 150 minutes of moderate physical activity each week (or equivalent). [29] In
addition, physical activity assists weight loss and improves blood glucose control, blood
pressure, lipid profile and insulin sensitivity. These effects may, at least in part, explain its
cardiovascular benefits.[27]

Diet

equal distributions of power, wealth, education, housing, environmental factors, nutrition,

and health care were needed to address inequalities in cardiovascular disease and non-

High dietary intakes of saturated fat, trans-fats and salt, and low intake of fruits,

communicable diseases.[40]

vegetables and fish are linked to cardiovascular risk, although whether all these
associations are causal is disputed. The World Health Organization attributes
approximately 1.7 million deaths worldwide to low fruit and vegetable consumption. [27] The

Air pollution

amount of dietary salt consumed is also an important determinant of blood pressure

levels and overall cardiovascular risk.[27] Frequent consumption of high-energy foods,

Particulate matter has been studied for its short- and long-term exposure effects on

such as processed foods that are high in fats and sugars, promotes obesity and may

cardiovascular disease. Currently, PM2.5 is the major focus, in which gradients are used to

increase cardiovascular risk.

determine CVD risk. For every 10 g/m3 of PM2.5 long-term exposure, there was an

[27]

High trans-fat intake has adverse effects on blood lipids

and circulating inflammatory markers,[30] and elimination of trans-fat from diets has been

estimated 818% CVD mortality risk.[41] Women had a higher relative risk (RR) (1.42) for

widely advocated.[31] There is evidence that higher consumption of sugar is associated

PM2.5induced coronary artery disease than men (0.90) did. [41] Overall, long-term PM

with higher blood pressure and unfavorable blood lipids, [32] and sugar intake also

exposure increased rate of atherosclerosis and inflammation. In regards to short-term

increases the risk of diabetes mellitus.

exposure (2 hours), every 25 g/m3 of PM2.5 resulted in a 48% increase of CVD mortality

[33]

High consumption of processed meats is

associated with an increased risk of cardiovascular disease, possibly in part due to

risk.[42] In addition, after only 5 days of exposure, a rise in systolic (2.8 mmHg) and

increased dietary salt intake.[34]

diastolic (2.7 mmHg) blood pressure occurred for every 10.5 g/m 3 of PM2.5.[42] Other
research has implicated PM2.5 in irregular heart rhythm, reduced heart rate variability

The relationship between alcohol consumption and cardiovascular disease is complex,

(decreased vagal tone), and most notably heart failure.[42][43] PM2.5 is also linked to carotid

and may depend on the amount of alcohol consumed. There is a direct relationship

artery thickening and increased risk of acute myocardial infarction. [42][43]

between high levels of alcohol consumption and risk of cardiovascular disease.

[27]

Drinking at low levels without episodes of heavy drinking may be associated with a

reduced risk of cardiovascular disease.[35] Overall alcohol consumption at the population

level is associated with multiple health risks that exceed any potential benefits.

Socioeconomic disadvantage
Cardiovascular disease affects low- and middle-income countries even more than highincome countries.[37] There is relatively little information regarding social patterns of
cardiovascular disease within low- and middle-income countries,

[37]

Tests

[27][36]

but within high-

income countries low income and low educational status are consistently associated with
greater risk of cardiovascular disease.[38] Policies that have resulted in increased socio-

Coronary artery calcification[44]

Carotid total plaque area[45]

Elevated Low-density lipoprotein-p[46]

Elevated blood levels of brain natriuretic peptide (also known as B-type) (BNP)[47]

economic inequalities have been associated with greater subsequent socio-economic

differences in cardiovascular disease [37] implying a cause and effect relationship.
Psychosocial factors, environmental exposures, health behaviours, and health-care
access and quality contribute to socio-economic differentials in cardiovascular
disease. [39] The Commission on Social Determinants of Health recommended that more

Pathophysiology
Population-based studies show that atherosclerosis, the major precursor of
cardiovascular disease, begins in childhood. The Pathobiological Determinants of

Atherosclerosis in Youth Study demonstrated that intimal lesions appear in all the aortas

and more than half of the right coronary arteries of youths aged 79 years. [48]

standard alcoholic drinks per day may reduce risk by 30%.[62][63] However, excessive
alcohol intake increases the risk of cardiovascular disease.[64]

This is extremely important considering that 1 in 3 people die from complications

attributable to atherosclerosis. In order to stem the tide, education and awareness that

Limit alcohol consumption to the recommended daily limits;[59] consumption of 12

Lower blood pressures, if elevated

this disease must be taken.

Decrease body fat if overweight or obese[65]

Obesity and diabetes mellitus are often linked to cardiovascular disease,[49] as are a

Increase daily activity to 30 minutes of vigorous exercise per day at least five

cardiovascular disease poses the greatest threat, and measures to prevent or reverse

history of chronic kidney disease andhypercholesterolaemia.[50] In fact, cardiovascular

times per week (multiply by three if horizontal);[59]

disease is the most life-threatening of the diabetic complications and diabetics are twoto four-fold more likely to die of cardiovascular-related causes than nondiabetics. [51][52][53]

Screening

Reduce sugar consumptions

Decrease psychosocial stress.[66] This measure may be complicated by imprecise

Screening ECGs (either at rest or with exercise) are not recommended in those without

definitions of what constitute psychosocial interventions.[67] Mental stress

symptoms who are at low risk.[54] This includes those who are young without risk factors.

inducedmyocardial ischemia is associated with an increased risk of heart problems

[55]

In those at higher risk the evidence for screening with ECGs is inconclusive. [54]

in those with previous heart disease.[68] Severe emotional and physical stress leads to
a form of heart dysfunction known as Takotsubo syndrome in some people.[69] Stress,

Additionally echocardiography, myocardial perfusion imaging, and cardiac stress

testing is not recommended in those at low risk who do not have symptoms. [56]
Some biomarkers may add to conventional cardiovascular risk factors in predicting the
risk of future cardiovascular disease; however, the clinical value of some biomarkers is
questionable.

however, plays a relatively minor role in hypertension.[70] Specific relaxation therapies

are of unclear benefit.[71][72]
For adults without a known diagnosis of hypertension, diabetes, hyperlipidemia, or
cardiovascular disease, routine counseling to advise them to improve their diet and
increase their physical activity has not been found to significantly alter behavior, and thus

Prevention

is not recommended.[73] It is unclear whether or not dental care in those

Currently practiced measures to prevent cardiovascular disease include:

at high risk of heart disease has not been well studied as of 2014. [75]

A low-fat, high-fiber diet including whole grains and fruit and vegetables.[59][60] Five
portions a day reduces risk by about 25%.[61]

Tobacco cessation and avoidance of second-hand smoke[59]

with periodontitis affects the risk of cardiovascular disease.[74] Exercise in those who are

Diet
See also: Saturated fat and cardiovascular disease controversy and Salt and
cardiovascular disease
A diet high in fruits and vegetables decreases the risk of cardiovascular disease
and death.[61] Evidence suggests that the Mediterranean diet may improve cardiovascular
outcomes.[76] There is also evidence that a Mediterranean diet may be more effective than

a low-fat diet in bringing about long-term changes to cardiovascular risk factors (e.g.,

Supplements

lower cholesterol level and blood pressure).[77] The DASH diet (high in nuts, fish, fruits
and vegetables, and low in sweets, red meat and fat) has been shown to reduce blood

While a healthy diet is beneficial, in general the effect of antioxidant supplementation

pressure,[78] lower total and low density lipoprotein cholesterol[79] and improve metabolic

(vitamin E, vitamin C, etc.) or vitamins has not been shown to protection against

syndrome;[80] but the long-term benefits outside the context of a clinical trial have been

cardiovascular disease and in some cases may possibly result in harm. [99][100] Mineral

questioned.[81] A high fiber diet appears to lower the risk.[82]

supplements have also not been found to be useful.[101] Niacin, a type of vitamin B3, may
be an exception with a modest decrease in the risk of cardiovascular events in those at

Total fat intake does not appear to be an important risk factor.[83][84] A diet high in trans fatty

high risk.[102][103] Magnesium supplementation lowers high blood pressure in a dose

acids, however, does appear to increase rates of cardiovascular disease.[84][85]Worldwide,

dependent manner.[104] Magnesium therapy is recommended for patients with

dietary guidelines recommend a reduction in saturated fat.[86] However, there are

ventricular arrhythmia associated with torsades de pointes who present with long QT

some questions around the effect of saturated fat on cardiovascular disease in the

syndrome as well as for the treatment of patients with digoxin intoxication-induced

medical literature.

arrhythmias.[105] Evidence to support omega-3 fatty acid supplementation is lacking.[106]

[85]

[87][88]

A 2014 review did not find evidence of harm from saturated fats.

A 2012 Cochrane review found suggestive evidence of a small benefit from replacing

dietary saturated fat by unsaturated fat.[89] A 2013 meta analysis concludes that
substitution with omega 6 linoleic acid (a type of unsaturated fat) may increase
cardiovascular risk.[86] Replacement of saturated fats with carbohydrates does not change
or may increase risk.[90][91] Benefits from replacement with polyunsaturated fat appears
greatest;[84][92]however, supplementation with omega-3 fatty acids (a type of polysaturated
fat) does not appear to have an effect.[93]
The effect of a low-salt diet is unclear. A Cochrane review concluded that any benefit in
either hypertensive or normal-tensive people is small if present. [94] In addition, the review
suggested that a low-salt diet may be harmful in those with congestive heart failure.
[94]

However, the review was criticized in particular for not excluding a trial in heart failure

where people had low-salt and -water levels due to diuretics.[95] When this study is left
out, the rest of the trials show a trend to benefit. [95][96] Another review of dietary salt
concluded that there is strong evidence that high dietary salt intake increases blood
pressure and worsens hypertension, and that it increases the number of cardiovascular
disease events; the latter happen both through the increased blood pressure and, quite
likely, through other mechanisms.[97][98] Moderate evidence was found that high salt intake
increases cardiovascular mortality; and some evidence was found for an increase in
overall mortality, strokes, and left ventricular hypertrophy.[97]

Medication
Aspirin has been found to be of only modest benefit in those at low risk of heart disease
as the risk of serious bleeding is almost equal to the benefit with respect to
cardiovascular problems.[107] In those at really low risk it is not recommended.[108]
Statins are effective in preventing further cardiovascular disease in people with a history
of cardiovascular disease.[109] As the event rate is higher in men than in women, the
decrease in events is more easily seen in men than women.[109] In those without
cardiovascular disease but risk factors statins appear to also be beneficial with a
decrease in mortality and further heart disease. [110] The time course over which statins
provide preventation against death appears to be long, of the order of one year, which is
much longer than the duration of their effect on lipids.[111] The
medications niacin, fibrates and CETP Inhibitors, while they may increase HDL
cholesterol do not affect the risk of cardiovascular disease in those who are already on
statins.[112]
The use of vasoactive agents for people with pulmonary hypertension with left heart
disease or hypoxemic lung diseases may cause harm and unnecessary expense. [113]

Management
Cardiovascular disease is treatable with initial treatment primarily focused on diet and
lifestyle interventions.[1]

Epidemiology

the blood plasma of rats. Reduction of blood pressure is also observed when
pharmacological doses are applied. Thus, it is deemed to be a plausible treatment for

Cardiovascular diseases are the leading cause of death. In 2008, 30% of all global death

hypertension. However, further research needs to be conducted to investigate the side-

is attributed to cardiovascular diseases. Death caused by cardiovascular diseases are

effects, optimal dosage, etc. before it can be licensed for use.

also higher in low- and middle-income countries as over 80% of all global death caused
by cardiovascular diseases occurred in those countries. It is also estimated that by 2030,
over 23 million people will die from cardiovascular diseases each year.

Rheumatic fever
From Wikipedia, the free encyclopedia

It is estimated that 60% of the world's cardiovascular disease burden will occur in the
South Asian subcontinent despite only accounting for 20% of the world's population. This
may be secondary to a combination of genetic predisposition and environmental factors.
Organizations such as the Indian Heart Association are working with the World Heart
Federation to raise awareness about this issue.[115]

Research
The first studies on cardiovascular health were performed in year 1949 by Jerry
Morris using occupational health data and were published in year 1958.[116] The causes,
prevention, and/or treatment of all forms of cardiovascular disease remain active fields
ofbiomedical research, with hundreds of scientific studies being published on a weekly
basis.
A fairly recent emphasis is on the link between low-grade inflammation that hallmarks
atherosclerosis and its possible interventions. C-reactive protein (CRP) is a common
inflammatory marker that has been found to be present in increased levels in patients
who are at risk for cardiovascular disease.[117] Also osteoprotegerin, which is involved with
regulation of a key inflammatory transcription factor called NF-B, has been found to be
a risk factor of cardiovascular disease and mortality.[118][119]
Some areas currently being researched include the possible links
between infection with Chlamydophila pneumoniae (a major cause of pneumonia) and
coronary artery disease. The Chlamydia link has become less plausible with the absence
of improvement after antibiotic use.[120]
Several research also investigated the benefits of melatonin on cardiovascular diseases
prevention and cure. Melatonin is a pineal gland secretion and it is shown to be able to
lower total cholesterol, very-low-density and low-density lipoprotein cholesterol levels in

Rheumatic fever, also known as acute rheumatic fever (ARF), is

an inflammatory disease that can involve the heart, joints, skin, and brain.[1] The disease
typically develops two to four weeks after a throat infection.[2] Signs and symptoms
include fever, multiple painful joints, involuntary muscle movements, and a characteristic
but uncommon non itchy rash known as erythema marginatum. The heart is involved in
about half of cases. Permanent damage to the heart valves, known as rheumatic heart
disease (RHD), usually only occurs after multiple attacks but may occasionally occur
after a single case of ARF. The damaged valves may result in heart failure. The abnormal
valves also increase the risk of the person developing atrial fibrillation and infection of the
valves.[1]
Acute rheumatic fever may occur following an infection of the throat by the
bacteria Streptococcus pyogenes.[1] If it is untreated ARF occurs in up to three percent of
people.[3] The underlying mechanism is believed to involve the production
of antibodies against a person's own tissues. Some people due to their genetics are
more likely to get the disease when exposed to the bacteria than others. Other risk
factors include malnutrition and poverty.[1] Diagnosis of ARF is often based on the
presence of signs and symptoms in combination with evidence of a recent streptococcal
infection.[4]
Treating people who have strep throat with antibiotics, such as penicillin, decreases their
risk of getting ARF.[5] This often involves testing people with sore throats for the infection,
which may not be available in the developing world. Other preventative measures include
improved sanitation. In those with ARF and RHD prolonged periods of antibiotics are
sometimes recommended. Gradual return to normal activities may occur following an
attack. Once RHD develops, treatment is more difficult. Occasionally valve
replacement surgery or repair is required. Otherwise complications are treated as per
normal.[1]
Acute rheumatic fever occurs in about 325,000 children each year and about 18 million
people currently have rheumatic heart disease. Those who get ARF are most often
between the ages of 5 and 14,[1] with 20% of first-time attacks occurring in adults.[6] The
disease is most common in the developing world and among indigenous peoples in
the developed world.[1] In 2013 it resulted in 275,000 deaths down from 374,000 deaths in
1990.[7] Most deaths occur in the developing world where as many as 12.5% of people
affected may die each year.[1] Descriptions of the condition are believed to date back to at

least the 5th century BCE in the writings of Hippocrates.[8] The disease is so named
because its symptoms are similar to those of some rheumatic disorders.

Group A Streptococcus pyogenes has a cell wall composed of branched polymers which
sometimes contain M protein that are highly antigenic. The antibodies which the immune
system generates against the M protein may cross react with cardiac myofiber
protein myosin,[11] heart muscle glycogen and smooth muscle cells of arteries,
inducing cytokinerelease and tissue destruction. However, the only proven cross reaction
is with perivascular connective tissue.[citation needed] This inflammation occurs through direct
attachment of complement and Fc receptor-mediated recruitment of neutrophils and

Signs and symptoms

macrophages. Characteristic Aschoff bodies, composed of swollen eosinophilic collagen

surrounded by lymphocytes and macrophages can be seen on light microscopy. The

The disease typically develops two to four weeks after a throat infection. Symptoms

larger macrophages may become Anitschkow cells or Aschoff giant cells. Acute

include: fever, multiple painful joints with the joints affected changing with

rheumatic valvular lesions may also involve a cell-mediated immunity reaction as these

time, involuntary muscle movements, and a characteristic but uncommon non itchy rash

lesions predominantly contain T-helper cells and macrophages.[12]

[2]

known as erythema marginatum. The heart is involved in about half of cases. Permanent
damage to the heart valves usually only occurs after multiple attacks but may

In acute rheumatic fever, these lesions can be found in any layer of the heart and is

occasionally occur after a single case of ARF. The damaged valves may result in heart

hence called pancarditis. The inflammation may cause a serofibrinous pericardial

failure. The abnormal valves also increase the risk of the person developing atrial

exudate described as "bread-and-butter" pericarditis, which usually resolves without

fibrillation and infection of the valves.

sequelae. Involvement of the endocardium typically results in fibrinoid necrosis and

[1]

Other

verrucae formation along the lines of closure of the left-sided heart valves. Warty
projections arise from the deposition, while subendocardial lesions may induce irregular
thickenings called MacCallum plaques.

Abdominal pain

Rheumatic heart disease

Nose bleeds

Pathophysiology
Rheumatic fever is a systemic disease affecting the peri-arteriolar connective tissue and
can occur after an untreated Group A Beta hemolytic streptococcal pharyngeal infection.
It is believed to be caused by antibody cross-reactivity. This cross-reactivity is a Type II
hypersensitivity reaction and is termed molecular mimicry. Usually, self reactive B cells
remain anergic in the periphery without T cell co-stimulation. During a Streptococcus
infection, mature antigen presenting cells such as B cells present the bacterial antigen to
CD4-T cells which differentiate into helper T2 cells. Helper T2 cells subsequently activate
the B cells to become plasma cells and induce the production of antibodies against the
cell wall of Streptococcus. However the antibodies may also react against the
myocardium and joints,[10] producing the symptoms of rheumatic fever.

Chronic rheumatic heart disease (RHD) is characterized by repeated inflammation with

fibrinous repair. The cardinal anatomic changes of the valve include leaflet thickening,
commissural fusion, and shortening and thickening of the tendinous cords. [12] It is caused
by an autoimmune reaction to Group A -hemolytic streptococci (GAS) that results in
valvular damage.[13] Fibrosis and scarring of valve leaflets,commissures and cusps leads
to abnormalities that can result in valve stenosis or regurgitation.[14] The inflammation
caused by rheumatic fever, usually during childhood, is referred to as rheumatic
valvulitis. About half of patients with acute rheumatic fever develop inflammation
involving valvular endothelium.[15] The majority of morbidity and mortality associated with
rheumatic fever is caused by its destructive effects on cardiac valve tissue. [14] The
pathogenesis of RHD is complex and not fully understood, but it is known to
involve molecular mimicry and genetic predisposition that lead to autoimmune reactions.

Molecular mimicry occurs when epitopes are shared between host antigens and GAS

Diagnosis

antigens.[16] This causes an autoimmune reaction against native tissues in the heart that
are incorrectly recognized as "foreign" due to the cross-reactivity of antibodies generated

Modified Jones criteria were first published in 1944 by T. Duckett Jones, MD. [22] They

as a result of epitope sharing. The valvular endothelium is a prominent site of

have been periodically revised by the American Heart Association in collaboration with

lymphocyte-induced damage. CD4+ T cells are the major effectors of heart tissue

other groups.[23] According to revised Jones criteria, the diagnosis of rheumatic fever can

autoimmune reactions in RHD.[17] Normally, T cell activation is triggered by the

be made when two of the major criteria, or one major criterion plus two minor criteria, are

presentation of GAS antigens. In RHD, molecular mimicry results in incorrect T cell

present along with evidence of streptococcal infection: elevated or rising antistreptolysin

activation, and these T lymphocytes can go on to activate B cells, which will begin to

O titre or DNAase.[6] Exceptions are chorea and indolent carditis, each of which by itself

produce self-antigen-specific antibodies. This leads to an immune response attack

can indicate rheumatic fever.[24][25][26] An April 2013 review article in the Indian Journal of

mounted against tissues in the heart that have been misidentified as pathogens.

Medical Research stated that echocardiographic and Doppler (E & D) studies, despite

Rheumatic valves display increased expression of VCAM-1, a protein that mediates the

some reservations about their utility, have identified a massive burden of rheumatic heart

adhesion of lymphocytes.[18] Self-antigen-specific antibodies generated via molecular

disease, which suggests the inadequacy of the 1992 Jones' criteria. E & D studies have

mimicry between human proteins and GAS antigens up-regulate VCAM-1 after binding to

identified subclinical carditis in patients with acute rheumatic fever, as well as in follow-

the valvular endothelium. This leads to the inflammation and valve scarring observed in

ups of rheumatic heart disease patients who initially presented as having isolated cases

rheumatic valvulitis, mainly due to CD4+ T cell infiltration.[18]

of Sydenham's chorea.[27] Signs of a preceding streptococcal infection include:

recent scarlet fever, raised antistreptolysin O or other streptococcal antibody titre, or

While the mechanisms of genetic predisposition remain unclear, a few genetic factors
have been found to increase susceptibility to autoimmune reactions in RHD. The
dominant contributors are a component of MHC class II molecules, found on
lymphocytes and antigen-presenting cells, specifically the DR andDQ alleles on human
chromosome 6.[19] Certain allele combinations appear to increase RHD autoimmune
susceptibility. Human leukocyte antigen (HLA) class II allele DR7 (HLA-DR7) is most
often associated with RHD, and its combination with certain DQ alleles is seemingly

positive throat culture.

Major criteria
Polyarthritis: A temporary migrating inflammation of the large joints, usually starting in the
legs and migrating upwards.

as congestive heart failure with shortness of breath, pericarditis with a rub, or a

associated with the development of valvular lesions.[19] The mechanism by which MHC

new heart murmur.

class II molecules increase a host's susceptibility to autoimmune reactions in RHD is

unknown, but it is likely related to the role HLA molecules play in presenting antigens to T
cell receptors, thus triggering an immune response. Also found on human chromosome 6

the front of the knees.

TNF- may exacerbate valvular tissue inflammation, contributing to RHD

pathogen recognition. Different variants of MBL2 gene regions are associated in RHD.

Subcutaneous nodules: Painless, firm collections of collagen fibers over bones

or tendons. They commonly appear on the back of the wrist, the outside elbow, and

is the cytokine TNF- which is also associated with RHD.[19] High expression levels of
pathogenesis. Mannose-binding lectin (MBL) is an inflammatory protein involved in

Carditis: Inflammation of the heart muscle (myocarditis) which can manifest

Erythema marginatum: A long-lasting reddish rash that begins on the trunk or

RHD-induced mitral valve stenosis has been associated with MBL2 alleles encoding for

arms as macules, which spread outward and clear in the middle to form rings, which

high production of MBL.[20]Aortic valve regurgitation in RHD patients has been associated

continue to spread and coalesce with other rings, ultimately taking on a snake-like

with different MBL2 alleles that encode for low production of MBL.[21] Other genes are

appearance. This rash typically spares the face and is made worse with heat.

also being investigated to better understand the complexity of autoimmune reactions that
occur in RHD.

Sydenham's chorea (St. Vitus' dance): A characteristic series of rapid movements

alternative treatments must always be considered when administering aspirin and

without purpose of the face and arms. This can occur very late in the disease for at

aspirin-containing products in children and teenagers. Ibuprofen for pain and discomfort

least three months from onset of infection.

and corticosteroids for moderate to severe inflammatory reactions manifested by

Minor criteria

rheumatic fever should be considered in children and teenagers. Steroids are reserved

Fever of 38.238.9 C (100.8102.0 F)

prevent further scarring of tissue and may prevent development of sequelae such as

Arthralgia: Joint pain without swelling (Cannot be included if polyarthritis is

present as a major symptom)

Raised erythrocyte sedimentation rate or C reactive protein

Leukocytosis

ECG showing features of heart block, such as a prolonged PR interval[28]

[29]

(Cannot be included if carditis is present as a major symptom)

Previous episode of rheumatic fever or inactive heart disease

Prevention
Prevention of recurrence is achieved by eradicating the acute infection
and prophylaxis with antibiotics. The American Heart Association suggests that dental
health be maintained, and that people with a history of bacterial endocarditis, a heart
transplant, artificial heart valves, or "some types of congenital heart defects" may wish to
consider long-term antibiotic prophylaxis.[30]

Treatment
The management of acute rheumatic fever is geared toward the reduction of
inflammation with anti-inflammatory medications such as aspirin or corticosteroids.
Individuals with positive cultures for strep throat should also be treated with antibiotics.
Aspirin is the drug of choice and should be given at high doses of 100 mg/kg/day. One
should watch for side effects like gastritis and salicylate poisoning. In children and
teenagers, the use of aspirin and aspirin-containing products can be associated
with Reye's syndrome, a serious and potentially deadly condition. The risks, benefits and

for cases where there is evidence of involvement of heart. The use of steroids may
mitral stenosis. Monthly injections of longacting penicillin must be given for a period of
five years in patients having one attack of rheumatic fever. If there is evidence of carditis,
the length of therapy may be up to 40 years. Another important cornerstone in treating
rheumatic fever includes the continual use of low-dose antibiotics (such
as penicillin, sulfadiazine, or erythromycin) to prevent recurrence.

Vaccine
No vaccines are currently available to protect against S. pyogenes infection, although
there has been research into the development of one. Difficulties in developing a vaccine
include the wide variety of strains of S. pyogenes present in the environment and the
large amount of time and people that will be needed for appropriate trials for safety and
efficacy of the vaccine.[31]

Infection
People with positive cultures for Streptococcus pyogenes should be treated with
penicillin as long as allergy is not present. This treatment will not alter the course of the
acute disease.
The most appropriate treatment stated in the Oxford Handbook of Clinical Medicine for
rheumatic fever is benzathine benzylpenicillin.

Inflammation
While corticosteroids are often used, evidence to support this is poor.[1] Salicylates are
useful for pain.

Heart failure
Some patients develop significant carditis which manifests as congestive heart failure.
This requires the usual treatment for heart failure: ACE inhibitors, diuretics, beta
blockers, and digoxin. Unlike normal heart failure, rheumatic heart failure responds well
to corticosteroids.

Epidemiology
Rheumatic fever is common worldwide and responsible for many cases of
damaged heart valves. As of 2010 globally it resulted in 345,000 deaths, down from
463,000 in 1990.[33]
In Western countries, it became fairly rare since the 1960s, probably due to widespread
use of antibiotics to treat streptococcusinfections. While it has been far less common in
the United States since the beginning of the 20th century, there have been a few
outbreaks since the 1980s. Although the disease seldom occurs, it is serious and has a
case-fatality rate of 25%.[34]
Rheumatic fever primarily affects children between ages 5 and 17 years and occurs
approximately 20 days after strep throat. In up to a third of cases, the underlying strep
infection may not have caused any symptoms.
The rate of development of rheumatic fever in individuals with untreated strep infection is
estimated to be 3%. The incidence of recurrence with a subsequent untreated infection is
substantially greater (about 50%).[35] The rate of development is far lower in individuals
who have received antibiotic treatment. Persons who have suffered a case of rheumatic
fever have a tendency to develop flare-ups with repeated strep infections.
The recurrence of rheumatic fever is relatively common in the absence of maintenance of
low dose antibiotics, especially during the first three to five years after the first episode.
Heart complications may be long-term and severe, particularly if valves are involved.
Survivors of rheumatic fever often have to take penicillin to prevent streptococcal
infection which could possibly lead to another case of rheumatic fever that could prove
fatal.

form of which is constrictive pericarditis. The following is the clinical classification of

acute vs. chronic:

Pericarditis

Clinically: Acute (<6 weeks), Subacute (6 weeks to 6 months) and Chronic (>6
months)

From Wikipedia, the free encyclopedia

Pericarditis is an inflammation of the pericardium (the fibrous sac surrounding

the heart). A characteristic chest pain is often present.
The causes of pericarditis are varied, including infections of the pericardium by viruses or
bacteria (e.g., Mycobacterium tuberculosis), idiopathic causes, uremic pericarditis, postinfarct pericarditis (within 24 hours of a heart attack), or Dressler's syndrome (weeks to
months after a heart attack).

Classification
Pericarditis can be classified according to the composition of the fluid that accumulates
around the heart.[1]
Types of pericarditis include the following:

serous

purulent

fibrinous

caseous

hemorrhagic

Acute vs. chronic

Depending on the time of presentation and duration, pericarditis is divided into "acute"
and "chronic" forms. Acute pericarditis is more common than chronic pericarditis, and
can occur as a complication of infections, immunologic conditions, or even as a result of
a heart attack (myocardial infarction). Chronic pericarditis however is less common, a

Signs and symptoms

Substernal or left precordial pleuritic chest pain with radiation to the trapezius ridge (the
bottom portion of scapula on the back), which is relieved by sitting up and bending
forward and worsened by lying down (recumbent or supine position) or inspiration (taking
a breath in), is the characteristic pain of pericarditis.[3] The pain may resemble the pain
of angina pectoris or heart attack, but differs in that pain changes with body position, as
opposed to heart attack pain that is pressure-like, and constant with radiation to the left
arm and/or the jaw. Other symptoms of pericarditis may include dry cough, fever, fatigue,
and anxiety. Due to similarity to myocardial infarction (heart attack) pain, pericarditis can
be misdiagnosed as an acute myocardial infarction (a heart attack) solely based on the
clinical data and so extreme suspicion on the part of the diagnostician is required.
Acute myocardial infarction (heart attack) can also cause pericarditis, but the presenting
symptoms often differ enough to warrant diagnosis. The following table organizes the
clinical presentation of pericarditis:

upon inspiration
(breathing in)

Sudden or chronically

Onset/duration

Sudden pain, that lasts

worsening pain that can come

for hours or sometimes

and go in paroxysms or it can

days before a patient

last for hours before the

comes to the ER

patient decides to come to the

ER

Characteristic/Paramete

Pericarditis

Myocardial infarction

Physical examinations
Sharp, pleuritic, retroPain description

The classic sign of pericarditis is a friction rub heard with a stethoscope on the

sternal (under the

Crushing, pressure-like, heavy

cardiovascular examination usually on the lower left sternal border.[3] Other physical signs

sternum) or left

pain. Described as "elephant

include a patient in distress, positional chest pain, diaphoresis (excessive sweating), and

precordial (left chest)

on the chest."

possibility of heart failure in form of pericardial tamponade causing pulsus paradoxus,

pain

and theBeck's triad of low blood pressure (due to decreased cardiac output), distant
(muffled) heart sounds, and distension of the jugular vein (JVD).

Pain radiates to the

trapezius ridge (to the
Radiation

lowest portion of the

scapula on the back) or

Acute complications
Pain radiates to the jaw, or the
left or arm, or does not radiate.

no radiation.

Pericarditis can progress to pericardial effusion and eventually cardiac tamponade. This
can be seen in patients who are experiencing the classic signs of pericarditis but then
show signs of relief, and progress to show signs of cardiac tamponade which include
decreased alertness and lethargy, pulsus paradoxus (decrease of at least 10 mmHg of

Exertion

Does not change the

pain

the systolic blood pressure upon inspiration),low blood pressure (due to

Can increase the pain

decreased cardiac index), (jugular vein distention from right sided heart failure and fluid
overload), distant heart sounds on auscultation, and equilibration of all the diastolic blood
pressures on cardiac catheterization due to the constriction of the pericardium by the

Position

Pain is worse in
the supine position or

Not positional

fluid.

In such cases of cardiac tamponade, EKG or Holter monitor will then depict electrical

Trauma to the heart, e.g. puncture, resulting in infection or inflammation

Uremia (uremic pericarditis)

Malignancy (as a paraneoplastic phenomenon)

Side effect of some medications,

alternans indicating wobbling of the heart in the fluid filled pericardium, and the capillary
refillmight decrease, as well as severe vascular collapse and altered mental status due to
hypoperfusion of body organs by a heart that can not pump out blood effectively.
The diagnostic test for cardiac tamponade, is trans-esophageal echocardiography (TEE)
although trans-thoracic echocardiography (TTE) can also be utilized in cases where
there is a high suspicion of aortic dissection and high blood pressure, or in patients

e.g. isoniazid, cyclosporine, hydralazine, warfarin, and heparin

where esophageal probing is not feasible. Chest X-ray can depict a "water bottle"
appearance of the heart in tamponade, although chest X-ray is neither specific enough

Radiation induced

Aortic dissection

Tetracyclines

Postpericardiotomy syndrome: Usually after CABG surgery

nor accurate enough in the acute setting. Of note is the fact that chest x-ray can be
entirely normal in acute pericardial effusion/tamponade and therefore should not be
relied upon as the sole diagnostic tool.

Diagnosis

Infectious
Laboratory values can show increased urea (BUN), or increased blood creatinine in
Pericarditis may be caused by viral, bacterial, or fungal infection. The most common viral

cases of uremic pericarditis. Generally however, laboratory values are normal, but if

pathogen has traditionally been considered to be coxsackievirus based on studies in

there is a concurrent myocardial infarction (heart attack) or great stress to the heart,

children from the 1960s, but recent data suggest that adults are most commonly affected

laboratory values may show increased cardiac markers like Troponin (I, T), CK-

with cytomegalovirus, herpesvirus, and HIV.

MB, Myoglobin, and LDH1 (Lactase Dehydrogenase isotype 1). The preferred initial

[4][5]

Pneumococcus or tuberculous

pericarditis are the most common bacterial forms. Anaerobic bacteria can also be a rare

diagnostic testing is the EKG which will show a 12-lead electrocardiogram with diffuse,

cause. Fungal pericarditis is usually due to histoplasmosis, or

non-specific, concave ("saddle-shaped"), ST segment-elevations all leads except aVR

in immunocompromisedhosts Aspergillus, Candida, and Coccidioides. The most

and V1[3] and PR segment-depression possible in any lead except aVR; [3] sinus

common cause of pericarditis worldwide is infectious pericarditis with Tuberculosis. [citation

tachycardia, and low-voltage QRS complexes can also be seen if there is

needed]

subsymptomatic levels of pericardial effusion. The PR depression is often seen early in

[6]

the process as the thin atria are affected more easily than the ventricles by the

Other

inflammatory process of the pericardium.

Idiopathic: No identifiable etiology found after routine testing.

Since the mid-19th Century, retrospective diagnosis of pericarditis has been made upon
Immunologic conditions including systemic lupus erythematosus (more common
among women) or rheumatic fever

the finding of adhesions of the pericardium.[7]When pericarditis is diagnosed clinically, the

underlying cause is often never known; it may be discovered in only 16-22 percent of
patients with acute pericarditis.

Myocardial infarction (Dressler's syndrome)

Treatment
The treatment in viral or idiopathic pericarditis is with aspirin,[3] or non-steroidal antiinflammatory drugs (NSAIDs such as ibuprofen).[8] Colchicine may be added to the
above as it decreases the risk of further episodes of pericarditis.
[8]

[9]

Severe cases may require one or more of the following:

pericardiocentesis to treat pericardial effusion/tamponade

antibiotics to treat tuberculosis or other bacterial causes.

steroids are used in acute pericarditis but are not favored because they increase
the chance of recurrent pericarditis.

in rare cases, surgery

in cases of constrictive pericarditis, pericardiectomy

as vegetations, which is a mass of platelets, fibrin, microcolonies of microorganisms, and

scant inammatory cells.[1] In the subacute form of infective endocarditis, the vegetation
may also include a center of granulomatous tissue, which may fibrose or calcify.[2]
There are several ways to classify endocarditis. The simplest classification is based on
cause: either infective or non-infective, depending on whether a microorganism is the
source of the inflammation or not. Regardless, the diagnosis of endocarditis is based on
clinical features, investigations such as an echocardiogram, and blood
cultures demonstrating the presence of endocarditis-causing microorganisms. Signs and
symptoms include: fever, chills, sweating, malaise, weakness, anorexia, weight
loss,splenomegaly, flu like feeling, cardiac murmur, heart failure, patechia of anterior
trunk, Janeway's lesions, etc.

Cause

Infective
Main article: Infective endocarditis
Since the valves of the heart do not receive any dedicated blood supply, defensive
immune mechanisms (such as white blood cells) cannot directly reach the valves via the
bloodstream. If an organism (such as bacteria) attaches to a valve surface and forms a
vegetation, the host immune response is blunted. The lack of blood supply to the valves
also has implications on treatment, since drugs also have difficulty reaching the infected
valve.
Normally, blood flows smoothly past these valves. If they have been damaged
(from rheumatic fever, for example) the risk of bacteria attachment is increased.[2]
Rheumatic fever is common worldwide and responsible for many cases of
damaged heart valves. Chronic rheumatic heart disease is characterized by repeated
inflammation with fibrinous resolution. The cardinal anatomic changes of the valve
include leaflet thickening, commissural fusion, and shortening and thickening of the
tendinous cords.[3] The recurrence of rheumatic fever is relatively common in the absence
of maintenance of low dose antibiotics, especially during the first three to five years after

Endocarditis
Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It
usually involves the heart valves. Other structures that may be involved include
the interventricular septum, the chordae tendineae, the mural endocardium, or the
surfaces of intracardiac devices. Endocarditis is characterized by lesions, known

the first episode. Heart complications may be long-term and severe, particularly if valves
are involved. While rheumatic fever since the advent of routine penicillin administration
for Strep throat has become less common in developed countries, in the older generation
and in much of the less-developed world, valvular disease (including mitral valve
prolapse, reinfection in the form of valvular endocarditis, and valve rupture) from
undertreated rheumatic fever continues to be a problem.[4]

In an Indian hospital between 2004 and 2005, 4 of 24 endocarditis patients failed to

specific pathogen (this requires two samples of blood). Negative blood cultures, however,

demonstrate classic vegetation. All had rheumatic heart disease and presented with

does not exclude the diagnosis of infective endocarditis. The decisive role played by

prolonged fever. All had severe eccentric mitral regurgitation. (One had severe aortic

echocardiography in the diagnosis (through the anterior chest wall or transesophageal),

regurgitation also.) One had flail posterior mitral leaflet.

with which you can reliably establish the presence of microbial vegetation, the degree of

[5]

Non-infective
Nonbacterial thrombotic endocarditis (NBTE), also called marantic endocarditis is most
commonly found on previously undamaged valves. [2] As opposed to infective

valvular and violations of the pumping function of the heart.

Myocarditis
From Wikipedia, the free encyclopedia

endocarditis, the vegetations in NBTE are small, sterile, and tend to aggregate along the
edges of the valve or the cusps.[2] Also unlike infective endocarditis, NBTE does not
cause an inflammation response from the body.[2] NBTE usually occurs during a
hypercoagulable state such as system wide bacterial infection, or pregnancy, though it is
also sometimes seen in patients with venous catheters.[2] NBTE may also occur in
patients with cancers, particularly mucinous adenocarcinoma [2] where Trousseau

Myocarditis or inflammatory cardiomyopathy is inflammation of heart muscle. The

consequences of myocarditis vary widely. It can cause a mild disease without any
symptoms that resolves itself, or it may cause chest pain, heart failure, or sudden death.
An acutemyocardial infarction-like syndrome with normal coronary arteries has a good
prognosis. Heart failure, even with a dilated left ventricle, may have a good
prognosis. Ventricular arrhythmias and high-degree heart block have a poor prognosis.
Loss of right ventricular function is a strong predictor of death. [1]

syndrome can be encountered. Typically NBTE does not cause many problems on its
own, but parts of the vegetations may break off and embolize to the heart or brain, or
they may serve as a focus where bacteria can lodge, thus causing infective endocarditis.
[2]

Another form of sterile endocarditis, is termed Libman-Sacks endocarditis; this form

occurs more often in patients with lupus erythematosus and is thought to be due to the
deposition of immune complexes.[2] Like NBTE, Libman-Sacks endocarditis involves
small vegetations, while infective endocarditis is composed of large vegetations. [2] These
immune complexes precipitate an inflammation reaction, which helps to differentiate it
from NBTE. Also unlike NBTE, Libman-Sacks endocarditis does not seem to have a

Myocarditis is most often due to infection by common viruses, such as parvovirus B19,
less commonly nonviral pathogens such asBorrelia burgdorferi (Lyme disease)
or Trypanosoma cruzi, or as a hypersensitivity response to drugs.[1] Myocarditis is often
an autoimmune reaction. Streptococcal M protein and coxsackievirus B have regions that
are similar to the myosin protein found in the heart muscle. During and after the infection,
the immune system may attack cardiac myosin.[1] Myocarditis may or may not include
death (necrosis) of heart tissue. It may include dilated cardiomyopathy.[1] A definitive
diagnosis requires a heart biopsy.[1]
Cardiomyopathy, including myocarditis, resulted in 443,000 deaths in 2013 up from
294,000 in 1990.

Definition

preferred location of deposition and may form on the undersurfaces of the valves or even
on the endocardium.[2]

Diagnostics
Examination of suspected infective endocarditis includes a detailed examination of the
patient, complete history taking, and especially careful cardiac auscultation, various

The definition of myocarditis varies, but the central feature is an infection of the heart,
with an inflammatory infiltrate, and damage to the heart muscle, without the blockage of
coronary arteries that define a heart attack (myocardial infarction) or other common
noninfectious causes.[3]

Signs and symptoms

blood tests, ECG, cardiac ultrasound (echocardiography). In the overall analysis of blood
revealed the typical signs of inflammation (increased erythrocyte sedimentation rate,

The signs and symptoms associated with myocarditis are varied, and relate either to the

leukocytosis). It is also necessary to sow twice venous blood in order to identify the

actual inflammation of the myocardium or to the weakness of the heart muscle that is

secondary to the inflammation. Signs and symptoms of myocarditis include the following:

[4]

Viral (adenovirus, parvovirus B19, coxsackie virus, HIV, enterovirus, rubella

virus, polio virus, cytomegalovirus, human herpesvirus 6 and possibly hepatitis C)

Chest pain (often described as "stabbing" in character)

Protozoan (Trypanosoma cruzi causing Chagas disease and Toxoplasma gondii)

Congestive heart failure (leading to swelling, shortness of

Bacterial (Brucella, Corynebacterium diphtheriae, gonococcus, Haemophilus

breath and liver congestion)

Palpitations (due to abnormal heart rhythms)

Sudden death (in young adults, myocarditis causes up to 20% of all cases of
sudden death)[5]

Fever (especially when infectious, e.g. in rheumatic fever)

Symptoms in infants and toddlers tend to be more nonspecific, with

influenzae, Actinomyces, Tropheryma whipplei, Vibrio cholerae, Borrelia

burgdorferi, leptospirosis, and Rickettsia, Mycoplasma pneumoniae)

Fungal (Aspergillus)

Parasitic (ascaris, Echinococcus granulosus, Paragonimus

westermani, schistosoma, Taenia solium, Trichinella spiralis, visceral larva migrans,
and Wuchereria bancrofti)

Bacterial myocarditis is rare in patients without immunodeficiency.

generalized malaise, poor appetite, abdominal pain, and/or chronic cough. Later
stages of the illness will present with respiratory symptoms with increased work of
breathing, and is often mistaken for asthma.

Toxins

Since myocarditis is often due to a viral illness, many patients give a history of symptoms
consistent with a recent viral infection, including fever, rash, diarrhea, joint pains, and

Drugs, including ethanol, anthracyclines and some other forms of chemotherapy,

and antipsychotics, e.g. clozapine, also some designer drugs such as mephedrone[6]

Immunologic

easily becoming tired.

Myocarditis is often associated with pericarditis, and many people with myocarditis
present with signs and symptoms that suggest myocarditis and pericarditis at the same

Allergic (acetazolamide, amitriptyline)

Rejection after a heart transplant

Autoantigens (scleroderma, systemic lupus erythematosus, sarcoidosis, systemic

time.

Causes

vasculitis such as Churg-Strauss syndrome, and granulomatosis with

polyangiitis, Kawasaki disease)

A large number of causes of myocarditis have been identified, but often a cause cannot
be found. In Europe and North America, viruses are common culprits. Worldwide,
however, the most common cause is Chagas' disease, an illness endemic to Central and
South America that is due to infection by the protozoan Trypanosoma cruzi.[4]

Infections

Toxins (arsenic, toxic shock syndrome toxin, carbon monoxide, or snake venom)

Heavy metals (copper or iron)

Physical agents

Treatment

As most viral infections cannot be treated with directed therapy, symptomatic treatment is

Electric shock, hyperpyrexia, and radiation

Diagnosis
Myocarditis refers to an underlying process that causes inflammation and injury of the
heart. It does not refer to inflammation of the heart as a consequence of some other
insult. Many secondary causes, such as a heart attack, can lead to inflammation of the
myocardium and therefore the diagnosis of myocarditis cannot be made by evidence of
inflammation of the myocardium alone.[7]
Myocardial inflammation can be suspected on the basis of electrocardiographic (ECG)
results, elevated C-reactive protein (CRP) and/orErythrocyte sedimentation rate (ESR),
and increased IgM (serology) against viruses known to affect the myocardium. Markers
of myocardial damage (troponin or creatine kinase cardiac isoenzymes) are elevated.[4]

the only form of therapy for those forms of myocarditis.[10] In the acute phase, supportive
therapy, including bed rest, is indicated. For symptomatic
patients, digoxin and diuretics provide clinical improvement. For patients with moderate
to severe dysfunction, cardiac function can be supported by use of inotropes such as
Milrinone in the acute phase, followed by oral therapy with ACE inhibitors (Captopril,
Lisinopril) when tolerated. People who do not respond to conventional therapy are
candidates for bridge therapy with left ventricular assist devices. Heart transplantation is
reserved for patients who fail to improve with conventional therapy.[11]
In several small case series and randomized control trials, systemic corticosteroids have
shown to have beneficial effects in patients with proven myocarditis.[11] However, data on
the usefulness of corticosteroids should be interpreted with caution, since 58% of adults
recover spontaneously, while most studies on children and infants lack control groups.
[10]

The ECG findings most commonly seen in myocarditis are diffuse T wave inversions;
saddle-shaped ST-segment elevations may be present (these are also seen in

Studies have shown no benefit for the use of herbal medicine on all cause mortality in

viral myocarditis.

pericarditis).[4]
The gold standard is still biopsy of the myocardium, in general done in the setting
of angiography. A small tissue sample of theendocardium and myocardium is taken, and
investigated by a pathologist by light microscopy andif necessary

Epidemiology

immunochemistry and special staining methods. Histopathological features are

myocardial interstitium with abundant edema and inflammatory infiltrate, rich

The exact incidence of myocarditis is unknown. However, in series of routine autopsies,

inlymphocytes and macrophages. Focal destruction of myocytes explains the myocardial

19% of all patients had evidence of myocardial inflammation. In young adults, up to

pump failure.[4]

20% of all cases of sudden death are due to myocarditis.[4]

Cardiac magnetic resonance imaging (cMRI or CMR) has been shown to be very useful

Among patients with HIV, myocarditis is the most common cardiac pathological finding

in diagnosing myocarditis by visualizing markers forinflammation of the myocardium.

at autopsy, with a prevalence of 50% or more.

[8]

Recently, consensus criteria for the diagnosis of myocarditis by CMR have been

published.[9]

Sydenham's chorea
From Wikipedia, the free encyclopedia

(Redirected from Rheumatic chorea)

"Saint Vitus' dance" redirects here. For other uses, see Saint Vitus' dance
(disambiguation).
Sydenham's chorea or chorea minor (historically referred to as Saint Vitus Dance) is
a disorder characterized by rapid, uncoordinated jerking movements primarily affecting
the face, hands and feet.[1] Sydenham's chorea (SC) results from childhood infection with
Group A beta-haemolytic Streptococcus[2] and is reported to occur in 2030% of patients
with acute rheumatic fever(ARF). The disease is usually latent, occurring up to 6 months
after the acute infection, but may occasionally be the presenting symptom of rheumatic
fever. Sydenham's chorea is more common in females than males and most patients are
children, below 18 years of age. Adult onset of Sydenham's chorea is comparatively rare
and the majority of the adult cases are associated with exacerbation of chorea following
childhood Sydenham's chorea.

Presentation
Sydenham's chorea is characterized by the abrupt onset (sometimes within a few hours)
of neurologic symptoms, classically chorea, usually affecting all four limbs. Other
neurologic symptoms include behavior change, dysarthria, gait disturbance, loss of fine
and gross motor control with resultant deterioration of handwriting, headache, slowed
cognition, facial grimacing, fidgetiness and hypotonia.[3][4] Also, there may be tongue
fasciculations ("bag of worms") and a "milk sign", which is a relapsing grip demonstrated
by alternate increases and decreases in tension, as if hand milking.[5]
Non-neurologic manifestations of acute rheumatic fever are carditis, arthritis, erythema
marginatum, and subcutaneous nodules.[3]
The PANDAS (pediatric autoimmune neuropsychiatric disorders associated with
streptococcal infections) syndrome is similar, but is not characterized by Sydenham's
motor dysfunction. PANDAS presents with tics and/or a psychological component (e.g.,
OCD) and occurs much earlier, days to weeks after GABHS infection rather than 69
months later.[6] It may be confused with other conditions such as lupus and Tourette
syndrome.

that may be accompanied by chorea include abetalipoproteinemia, ataxiatelangiectasia, Fahr disease, glutaric aciduria, Wilson disease, Lesch-Nyhan
syndrome, hyperthyroidism,lupus erythematosus, pregnancy (Chorea gravidarum), and
certain anticonvulsants or psychotropic agents.

History
Sydenhams chorea became a well defined nosological entity only during the second half
of the nineteenth century. Such progress was promoted by the availability of large clinical
series provided by newly founded paediatric hospitals. A 2005 study examined the
demographic and clinical features of patients with chorea admitted to the first British
paediatric hospital (the Hospital for Sick Children, Great Ormond Street, London)
(GOSH) between 1852 and 1936. The seasonal and demographic characteristics of
Sydenhams chorea during this time appear strikingly similar to those observed today,
and witness the introduction of modern statistically averaging techniques in the
approach to complex paediatric syndromes. Great Ormond Street hospital case notes
provide detailed descriptions of the typical cases of SC, and show that British
physicians working in the early age of paediatric hospitals recognized the most distinctive
clinical features of this condition.[7]
Throughout the nineteenth century the term chorea referred to an ill-defined spectrum
of hyperkinesias, including those recognised today as chorea, tics, dystonia,
ormyoclonus. William Osler started his monography on chorea stating that in the whole
range of medical terminology there is no such olla podrida as Chorea, which for a
century has served as a sort of nosological pot into which authors have cast
indiscriminately affections characterised by irregular, purposeless movements. [7]
Sydenhams chorea (SC), a frequent cause of paediatric acute chorea, is a major
manifestation of rheumatic fever (RF) The association of chorea with rheumatism was
first reported in 1802, and confirmed in the following decades by several French and
English authors.[7] The inclusion of chorea under the rheumatic umbrella helped
discriminate SC from other choreic syndromes.The incidence of Acute Rheumatic
Fever and rheumatic heart disease (RHD) is not declining. Recent figures quote the
incidence of Acute Rheumatic Fever as 0.60.7/1,000 population in the United States
and Japan compared with 1521/1,000 population in Asia and Africa.[8] The prevalence of

Movements cease during sleep, and the disease usually resolves after several months.

Acute Rheumatic Fever and Sydenham's Chorea has declined progressively in

Unlike in Huntington disease, which is generally of adult onset and associated with an

developed countries over the last decades.[9][10] Physicians working in early childrens

unremitting autosomal dominant movement disorder and dementia, neuroimaging in

hospitals recognised new clinical syndromes through the definition of typical clinical

Sydenham's chorea is normal and other family members are unaffected. Other disorders

cases. Complex multi-systemic diseases, such as RF, were categorised only after the

observation of large, hospital based series. Therefore, paediatric hospitals gradually

SC expression. Supporting this view, oral contraceptives and pregnancy can cause

became an important setting for the application of a modern statistical averaging

relapses of disease.[7]

technique to paediatric syndromes. Historical authorities in paediatrics, such as Walter

Butler Cheadle and Octavius Sturges, worked at the Hospital for Sick Children, Great

Ten percent of the 1,548 patients whose records were researched for the British study

Ormond Street, London (the first British paediatric hospital), and their clinical notes help

were subsequently admitted with a relapse of chorea. Given that relapse admissions had

to understand how the typical case of SC was defined.[7]

a negative impact on the hospital cure rate, this rate might underestimate the actual
relapse incidence in the general population of patients.[7]

Between 1860 and 1900 the proportion of choreic patients ranged between 5% and 7%
of the total number of patients admitted (mean per year, 1003), whereas from 1900 to
1936 it was constantly below 4% (mean per year). Chorea was the fourth most frequent
cause of admission between 1860 and 1900, and in the 1880s temporarily became the
second most frequent diagnosis among inpatients. Contemporary articles report a
homogeneous distribution of paediatric chorea all over England However, since many
choreic children were cured at home, the hospital based rates probably underestimate
the incidence of chorea in the general paediatric population. [7]
A higher number of cases were admitted during the colder months, consistent with the
reference epidemiological report on chorea at the end of the century. In the 1950s and
1960s the highest frequency of chorea was recorded during the winter months in several
Northern and Central European countries. Interestingly, the incidence of rheumatism
among GOS inpatients peaked in October, preceding chorea by approximately two
months. This is consistent with the current knowledge that most of the RF symptoms
appear about 10 days after the streptococcal infection, whereas SC occurs typically 23
months after infection.
More than 80% of choreic patients were aged between 7 and 11 years (mean 9.2). Due
to a referral bias, this age may be falsely low. Indeed, the British Medical Association
(1887) reported the peak age between 11 and 15 years. In the present series, the
female:male ratio was 2.7, in accordance with the general choreic population of Britain
towards the end of the 1800s. Interestingly, in children below age 7, the female
preponderance is less manifest. This was observed also by Charles West (founder
physician of GOS), and subsequently by Osler, who stated that the second hemi-decade
contains the greatest number of cases in males, and the third the greatest number in

Prognosis
Fifty percent of patients with acute Sydenham's Chorea spontaneously recover after 2 to
6 months whilst mild or moderate chorea or other motor symptoms can persist for up to
and over two years in some cases. Sydenham's is also associated with psychiatric
symptoms with obsessive compulsive disorder being the most frequent manifestation.

Causes
A major manifestation of acute rheumatic fever, Sydenham's chorea is a result of an
autoimmune response that occurs following infection by group A -hemolytic
streptococci[11]that destroys cells in the corpus striatum of the basal ganglia.[4][11]
[12]

Molecular mimicry to streptococcal antigens leading to an autoantibody production

against the basal ganglia has long been thought to be the main mechanism by which
chorea occurs in this condition. In 2012, antibodies in serum to the cell surface antigen;
dopamine 2 receptor were shown in up to a third of patients in a cohort of Sydenham's
chorea. Whether these antibodies represent an epi-phenomenon or are they pathogenic,
remains to be proven.[13]
There are many causes of childhood chorea, including cerebrovascular accidents,
collagen vascular diseases, drug intoxication, hyperthyroidism, Wilson's
disease, Huntington's disease, abetalipoproteinemia, Fahr disease, biotin-thiamineresponsive basal ganglia disease due to mutations in the SLC19A3 gene, Lesch-Nyhan
syndrome, and infectious agents.[3]

Treatment and management

females. In the majority of the 20th century studies, female preponderance is evident
only in children over 10 years of age. These observations suggest a role for oestrogen in

Treatment of Sydenham's Chorea is based on the following three principles:

1. The first tenet of treatment is to eliminate the streptococcus at a primary,

secondary and tertiary level. Strategies involve the adequate treatment of throat
and skin infections, with a 10-day course of penicillin when Sydenham's Chorea
is newly diagnosed, followed by long-term penicillin prophylaxis. Behavioural and
emotional changes may precede the movement disorders in a previously well
child.
2. Treatment of movement disorders. Therapeutic efforts are limited to palliation of
the movement disorders. Haloperidol is frequently used because of its antidopaminergic effect. It has serious potential side-effects, e.g., tardive dyskinesia.

Mitral valve
From Wikipedia, the free encyclopedia

The mitral valve (also known as the bicuspid valve or left atrioventricular valve) is a
dual-flap (bi- from the Latin, meaningdouble, and mitral- from the Latin,
meaning shaped like a mitre) valve in the heart that lies between the left atrium (LA) and
the left ventricle (LV). The mitral valve (not to be confused with the congenital bicuspid
aortic valve) and the tricuspid valve are known collectively as the atrioventricular valves
because they lie between the atria and the ventricles of the heart and control the flow of
blood.

In a study conducted at the RFC, 25 out of 39 patients on haloperidol reported

side-effects severe enough to cause the physician or parent to discontinue
treatment or reduce the dose. Other medications which have been used to
control the movements include pimozide,clonidine, valproic
acid, carbamazepine and phenobarbitone.
3. Immunomodulatory interventions include steroids, intravenous immunoglobulins,
and plasma exchange. Patients may benefit from treatment with steroids;
controlled clinical trials are indicated to explore this further.

During diastole, a normally-functioning mitral valve opens as a result of increased

pressure from the left atrium as it fills with blood (preloading). As atrial pressure
increases above that of the left ventricle, the mitral valve opens. Opening facilitates the
passive flow of blood into the left ventricle. Diastole ends with atrial contraction, which
ejects the final 20% of blood that is transferred from the left atrium to the left ventricle.
This amount of blood is known as end-diastolic volume (EDV), and the mitral valve
closes at the end of atrial contraction to prevent a reversal of blood flow.

Structure
The mitral valve is typically 46 cm in area. It has two cusps, or leaflets,

Etymology

(the anteromedial leaflet and the posterolateral leaflet) that guard the opening. The

It is named after British physician Thomas Sydenham (16241689).[8][14] The alternate

orientation of the two leaflets resemble a bishop's mitre, whence the valve receives its

eponym, "Saint Vitus Dance", is in reference to Saint Vitus, a Christian saint who was

name.[1]) The anterior cusp protects approximately two-thirds of the valve (imagine a

persecuted by Roman emperors and died as a martyr in AD 303. Saint Vitus is

crescent moon within the circle, where the crescent represents the posterior cusp). Note

considered to be the patron saint of dancers, with the eponym given as homage to the

that although the anterior leaflet takes up a larger part of the ring and rises higher, the

manic dancing that historically took place in front of his statue during the feast of Saint

posterior leaflet has a larger surface area. These valve leaflets are prevented

Vitus in Germanic and Latvian cultures.

from prolapsing into the left atrium by the action of tendons attached to the posterior

opening is surrounded by a fibrous ring known as the mitral valve annulus. (The

surface of the valve, chordae tendineae.

The inelastic chordae tendineae are attached at one end to the papillary muscles and the
other to the valve cusps. Papillary muscles are fingerlike projections from the wall of the
left ventricle. Chordae tendineae from each muscle are attached to both leaflets of the
mitral valve. Thus, when the left ventricle contracts, the intraventricular pressure forces
the valve to close, while the tendons keep the leaflets coapting together and prevent the

valve from opening in the wrong direction (thus preventing blood to flow back to the left

Clinical significance

atrium). Each chord has a different thickness. The thinnest ones are attached to the free
leaflet margin, whereas thickest ones (strut chords) are attached quite away from the

The closing of the mitral valve and the tricuspid valve constitutes the first heart

free margin. This disposition has important effects on systolic stress distribution

sound (S1). It is not the valve closure itself which produces the sound but the sudden

physiology[2]

cessation of blood flow, when the mitral and tricuspid valves close.

Function

There are some valvular heart diseases that affect the mitral valve. Mitral stenosis is a

See also: Heart valves

During left ventricular diastole, after the pressure drops in the left ventricle due to
relaxation of the ventricular myocardium, the mitral valve opens, and blood travels from
the left atrium to the left ventricle. About 70 to 80% of the blood that travels across the
mitral valve occurs during the early filling phase of the left ventricle. This early filling
phase is due to active relaxation of the ventricular myocardium, causing a pressure
gradient that allows a rapid flow of blood from the left atrium, across the mitral valve. This
early filling across the mitral valve is seen on doppler echocardiography of the mitral
valve as the E wave.
After the E wave, there is a period of slow filling of the ventricle.

narrowing of the valve. This can be heard as an opening snap in a heart sound which is
not normally present.
Classic mitral valve prolapse is caused by an excess of connective tissue that thickens
the spongiosa layer of the cusp and separates collagen bundles in the fibrosa. This
weakens the cusps and adjacent tissue, resulting in an increased cuspal area and
lengthening of the chordae tendineae. Elongation of the chordae tendineae often causes
rupture, commonly to the chordae attached to the posterior cusp. Advanced lesions
also commonly involving the posterior leafletlead to leaflet folding, inversion, and
displacement toward the left atrium.[4]
A valve prolapse can result in mitral insufficiency which is a regurgitation or backflow of
blood due to the incomplete closure of the valve. Surgery can be performed

Left atrial contraction (left atrial systole) (during left ventricular diastole) causes added

to replace orrepair a damaged valve. A less invasive method is that of mitral

blood to flow across the mitral valve immediately before left ventricular systole. This late

valvuloplasty which uses a balloon catheter to open up a stenotic valve.

flow across the open mitral valve is seen on doppler echocardiography of the mitral valve
as the A wave. The late filling of the LV contributes about 20% to the volume in the left
ventricle prior to ventricular systole, and is known as theatrial kick.
The mitral annulus changes in shape and size during the cardiac cycle. It is smaller at
the end of atrial systole due to the contraction of the left atrium around it, like a sphincter.
This reduction in annulus size at the end of atrial systole may be important for the proper
coapting of the leaflets of the mitral valve when the left ventricle contracts and pumps
blood.[3] Leaking valves can be corrected by mitral valve annuloplasty, a common surgical
procedure that aims at restoring proper leaflet coaptation.

Rheumatologist
A rheumatologist is a physician specialized in the field of medical sub-specialty called
rheumatology, and holds either a board certification after specialized training after
attaining a medical degree (M.D. or D.O.) through fellowship programs in the United
States, or specialist registrar positions in the United Kingdom, or DM in India or
equivalent programs elsewhere in the world. In the United States, training in this field
requires four years undergraduate school, four years of medical school, and then three
years of residency, followed by two or three years additional Fellowship training. The
requirements may vary in other countries. Rheumatologists
are internists or pediatricians who are qualified by additional postgraduate training and
experience in the diagnosis and treatment of arthritis and other diseases of the joints,
muscles and bones. Many rheumatologists also conduct research to determine the
cause and better treatments for these disabling and sometimes fatal diseases. Treatment
modalities are based on scientific research, currently, practice of rheumatology is largely
evidence based.[2]
Rheumatologists treat arthritis, autoimmune diseases, pain disorders affecting joints,
and osteoporosis. There are more than 200 types of these diseases,
including rheumatoid arthritis, osteoarthritis, gout, lupus, back pain, osteoporosis,
and tendinitis. Some of these are very serious diseases that can be difficult to diagnose
and treat. They treat soft tissue problems related to musculoskeletal system sports
related soft tissue disorders and the specialty is also interrelated with physiotherapy,
physical medicine and rehabilitation of disabled patients. Patient education programs and

Rheumatology
From Wikipedia, the free encyclopedia

occupational therapy also go hand in hand with this specialty.

Diseases
Main article: Rheumatism

(Redirected from Rheumatic)

Diseases diagnosed or managed by the rheumatologist include:

Rheumatology (Greek , rheuma, river) is a sub-specialty in internal
medicine and pediatrics, devoted to diagnosis and therapyof rheumatic diseases.
Clinicians who specialize in rheumatology are called rheumatologists. Rheumatologists
deal mainly with clinical problems involving joints, soft tissues, autoimmune
diseases, vasculitis, and heritable connective tissue disorders.
Many of these diseases are now known to be disorders of the immune system, and
rheumatology is increasingly the study ofimmunology.
One of the major changes in modern rheumatology is the development of new drugs
called biologics, or disease modifying agents, which can control severe disease more
effectively.

Degenerative arthropathies

Osteoarthritis

Inflammatory arthropathies

Rheumatoid arthritis

Spondyloarthropathies

Ankylosing spondylitis

Reactive arthritis (reactive arthropathy)

Psoriatic arthropathy

Enteropathic spondylitis

Polyarteritis nodosa

Juvenile Idiopathic Arthritis (JIA)

Henoch-Schnlein purpura

Crystal arthropathies: gout, pseudogout

Serum sickness

Septic arthritis

Giant cell arteritis, Temporal arteritis

Takayasu's arteritis

Behet's syndrome

Kawasaki's disease (mucocutaneous lymph node syndrome)

Buerger's disease (thromboangiitis obliterans)

eosinophilic granulomatosis with polyangiitis (formerly known as ChurgStrauss Syndrome)

granulomatosis with polyangiitis (formerly known as Wegener's

granulomatosis)

Systemic conditions and connective tissue diseases

Lupus

Sjgren's syndrome

Scleroderma (systemic sclerosis)

Polymyositis

Soft Tissue Rheumatism

Dermatomyositis

Local diseases and lesions affecting the joints and structures around the joints including

Polymyalgia rheumatica

vascular lesions, and ganglia. For example:

Mixed connective tissue disease

Low back pain

Relapsing Polychondritis

Tennis elbow

Sarcoidosis

Golfer's elbow

Vasculitis

Olecranon bursitis

tendons, ligaments capsules, bursae, stress fractures, muscles, nerve entrapment,

Microscopic Polyangiitis

Diagnosis

Treatment

Apart from an extensive medical history, there are useful methods of diagnosis both

Most rheumatic diseases are treated with analgesics, NSAIDs (Non-Steroid Anti-

performed easy enough in a physical examination and, on the other hand, more

Inflammatory Drugs), steroids (in serious cases), DMARDs (Disease-Modifying Anti-

complicated ones, often requiring a rheumatologist or other specialized physicians.

Rheumatic Drugs), monoclonal antibodies, such as infliximab and adalimumab, and the

Physical examination
Following are examples of methods of diagnosis able to be performed in a normal
physical examination.

Schober's test tests the flexion of the lower back.

Multiple joint inspection

Musculoskeletal Examination

Screening Musculoskeletal Exam (SMSE) - a rapid assessment of

structure and function

soluble TNF receptor etanercept and Methotrexate for moderate to severe Rheumatoid
arthritis.[3]Biologic agent Rituximab (Anti-B-Cell Therapy) is now licensed for use in
refractory Rheumatoid Arthritis.[4] Physiotherapy is vital in the treatment of many
rheumatological disorders. Occupational therapy can help patients finding alternative
ways for common movements which would otherwise be restricted by their disease.
Patients with rheumatoid arthritis often need a long term, coordinated and a
multidisciplinary team approach towards management of individual patients, treatment is
often tailored according the individual needs of the individual patient which is also
dependent on the response and the tolerability of medications.

Scientific research
Recently, a large body of scientific research deals with the background of autoimmune
disease, the cause of many rheumatic disorders. Also, the field of osteoimmunology has
emerged to further examine the interactions between the immune system, joints and

General Musculoskeletal Exam (GMSE) - a comprehensive assessment

of joint inflammation

bones. Epidemiological studies and medication trials are also being conducted. Scientific
research on biologics and clinical trials on monoclonal antibody therapies have added a
new dimension to the medical treatment of arthritic disorders.

Regional Musculoskeletal Exam (RMSE) - focused assessments of

structure, function and inflammation combined with special testing

Specialized

Laboratory tests (e.g. Erythrocyte Sedimentation Rate, Rheumatoid Factor, AntiCCP (Anti-citrullinated protein antibody), ANA (Anti-Nuclear Antibody) )

X-rays, Ultrasounds, and other imaging methods of affected joints

Cytopathology and chemical pathology of fluid aspirated from affected joints (e.g.
to differentiate between septic arthritis and gout)

Mitral valve stenosis

Mitral stenosis is a valvular heart disease characterized by the narrowing of the orifice of
the mitral valve of the heart

Signs and symptoms

Signs and symptoms of mitral stenosis include the following:

Heart failure symptoms, such as dyspnea on exertion, orthopnea and paroxysmal

pressures in the left atrium and the left ventricle during ventricular diastole will be equal.
The result is that the left ventricle gets filled with blood during early ventricular diastole,

nocturnal dyspnea (PND)[2]

with only a small portion of extra blood contributed by contraction of the left atrium (the

Palpitations

"atrial kick") during late ventricular diastole. When the mitral valve area goes below

[2]

2 cm2, the valve causes an impediment to the flow of blood into the left ventricle, creating

Chest pain[2]

Hemoptysis

Thromboembolism in later stages when the left atrial volume is increased (i.e.,

a pressure gradient across the mitral valve. This gradient may be increased by increases
in the heart rate or cardiac output. As the gradient across the mitral valve increases, the
amount of time necessary to fill the left ventricle with blood increases. Eventually, the left

[2]

ventricle requires the atrial kick to fill with blood. As the heart rate increases, the amount
[2]

of time that the ventricle is in diastole and can fill up with blood (called the diastolic filling

dilation). The latter leads to increase risk of atrial fibrillation, which increases the risk

period) decreases. When the heart rate goes above a certain point, the diastolic filling

of blood stasis (motionless). This increases the risk of coagulation.

period is insufficient to fill the ventricle with blood and pressure builds up in the left
atrium, leading to pulmonary congestion.

Ascites and edema and hepatomegaly (if right-side heart failure develops)

[2]

When the mitral valve area goes less than 1 cm2, there will be an increase in the left
Fatigue and weakness increase with exercise and pregnancy.[2]

Cause
Almost all cases of mitral stenosis are due to disease in the heart secondary
to rheumatic fever and the consequent rheumatic heart disease.[2][3] Uncommon causes of
mitral stenosis are calcification[4][5] of the mitral valve leaflets, and as a form of congenital
heart disease. However, there are primary causes of mitral stenosis that emanate from a
cleft mitral valve.[citation needed] It is the most common valvular heart disease in pregnancy.[6]
Other causes include infective endocarditis where the vegetations may favor increase
risk of stenosis. Other rare causes are include mitral annular calcification,
endomyocardial fibroelastosis, malignant carcinoid syndrome, systemic lupus
erythematosus, whipple disease, fabry disease, and rheumatoid arthritis. [7]

Pathophysiology
The normal area of the mitral valve orifice is about 4 to 6 cm2. In normal cardiac
physiology, the mitral valve opens during left ventriculardiastole, to allow blood to flow
from the left atrium to the left ventricle. A normal mitral valve will not impede the flow of
blood from the left atrium to the left ventricle during (ventricular) diastole, and the

atrial pressures (required to push blood through the stenotic valve). Since the normal left
ventricular diastolic pressures is about 5 mmHg, a pressure gradient across the mitral
valve of 20 mmHg due to severe mitral stenosis will cause a left atrial pressure of about
25 mmHg. This left atrial pressure is transmitted to the pulmonary vasculature and
causes pulmonary hypertension. Pulmonary capillary pressures in this level cause an
imbalance between thehydrostatic pressure and the oncotic pressure, leading to
extravasation of fluid from the vascular tree and pooling of fluid in the lungs (congestive
heart failure causing pulmonary edema).
The constant pressure overload of the left atrium will cause the left atrium to increase in
size. As the left atrium increases in size, it becomes more prone to develop atrial
fibrillation (AF). When atrial fibrillation develops, the atrial kick is lost (since it is due to
the normal atrial contraction).
In individuals with severe mitral stenosis, the left ventricular filling is dependent on the
atrial kick. The loss of the atrial kick due to atrial fibrillation can cause a precipitous
decrease in cardiac output and sudden congestive heart failure.
Patients with mitral stenosis prompts a series of hemodynamic changes that frequently
cause deterioration of the patient's clinical status. A reduction in cardiac output,
associated with acceleration of heart rate and shortening of the diastolic time, frequently

leads to congestive heart failure. In addition, when AF sets in,

Advanced disease may present with signs of right-sided heart failure such as parasternal

systemic embolization becomes a real danger.[8]

heave, jugular venous distension, hepatomegaly, ascites and/or pulmonary hypertension,

the latter often presenting with a loud P2.[2]

Mitral stenosis typically progresses slowly (over decades) from the initial signs of mitral
stenosis to NYHA functional class II symptoms to the development of atrial fibrillation to

Almost all signs increase with exercise and pregnancy.[2]

the development of NYHA functional class III or IV symptoms. Once an individual

develops NYHA class III or IV symptoms, the progression of the disease accelerates and
the patient's condition deteriorates.[citation needed]

Other peripheral signs include:

Diagnosis

Malar flush - due to back pressure and buildup of carbon dioxide (CO2). CO2 is a
natural vasodilator.[10]

Physical examination

Atrial fibrillation - irregular pulse and loss of 'a' wave in jugular venous pressure

Left parasternal heave - presence of right ventricular hypertrophy due to

Upon auscultation of an individual with mitral stenosis, the first heart sound is usually
loud and may be palpable (tapping apex beat) because of increased force in closing the
mitral valve. The first heart sound is made by the mitral and tricuspid heart valves

pulmonary hypertension

closing. These are normally synchronous, and the sounds are termed M1 and T1,
respectively. M1 becomes louder in mitral stenosis. It may be the most prominent sign. [2]

If pulmonary hypertension secondary to mitral stenosis is severe, the P2 (pulmonic)

Medical signs of atrial fibrillation include:[citation needed]

Tapping apex beat that is not displaced

component of the second heart sound (S2) will become loud.

Heart rate is about 100-150/min. Irregularly irregular pulse with a pulse deficit>10.
An opening snap that is a high-pitch additional sound may be heard after the A2 (aortic)

Varying first heart sound intensity. Opening snap is not heard sometimes. Absent a

component of the second heart sound (S2), which correlates to the forceful opening of the

waves in the neck veins. Presystolic accentuation of diastolic murmur disappears.

mitral valve. The mitral valve opens when the pressure in the left atrium is greater than

Embolic manifestations may appear.

the pressure in the left ventricle. This happens in ventricular diastole (after closure of
the aortic valve), when the pressure in the ventricle precipitously drops. In individuals
with mitral stenosis, the pressure in the left atrium correlates with the severity of the
mitral stenosis. As the severity of the mitral stenosis increases, the pressure in the left
atrium increases, and the mitral valve opens earlier in ventricular diastole. [2]
A mid-diastolic rumbling murmur with presystolic accentuation will be heard after the
opening snap.[2][9] The murmur is best heard at the apical region and is not radiated. Since
it is a low-pitch sound, it is heard best with the bell of the stethoscope.[2] Its duration

Echocardiography
In most cases, the diagnosis of mitral stenosis is most easily made by echocardiography,
which shows left atrial enlargement, thick and calcified mitral valve with narrow and "fishmouth"-shaped orifice and signs ofright ventricular failure in advanced disease.[2] It can
also show decreased opening of the mitral valve leaflets, and increased blood flow
velocity during diastole. The trans-mitral gradient as measured by Doppler
echocardiography is the gold standard in the evaluation of the severity of mitral stenosis.

Cardiac chamber catheterization

increases with worsening disease. Rolling the patient toward left as well as isometric
[2]

exercise will accentuate the murmur. A thrill might be present when palpating at the

Another method of measuring the severity of mitral stenosis is the simultaneous left and

apical region of the precordium.[citation needed]

right heart chamber catheterization. The right heart catheterization (commonly known

asSwan-Ganz catheterization) gives the physician the mean pulmonary capillary wedge

The indication for invasive treatment with either a mitral valve replacement or

pressure, which is a reflection of the left atrial pressure. The left heart catheterization, on

valvuloplasty is NYHA functional class III or IV symptoms.

the other hand, gives the pressure in the left ventricle. By simultaneously taking these
pressures, it is possible to determine the gradient between the left atrium and left

Another option is balloon dilatation.[12] To determine which patients would benefit from

ventricle during ventricular diastole, which is a marker for the severity of mitral stenosis.

percutaneous balloon mitral valvuloplasty, a scoring system has been developed.

This method of evaluating mitral stenosis tends to overestimate the degree of mitral

Scoring is based on 4 echocardiographic criteria: leaflet mobility, leaflet thickening,

stenosis, however, because of the time lag in the pressure tracings seen on the right-

subvalvar thickening, and calcification. Individuals with a score of 8 tended to have

heart catheterization and the slow Y descent seen on the wedge tracings. If a trans-

suboptimal results.[13] Superb results with valvotomy are seen in individuals with a crisp

septal puncture is made during right heart catheterization, however, the pressure

opening snap, score < 8, and no calcium in the commissures.

gradient can accurately quantify the severity of mitral stenosis.[citation needed]

Other assisting diagnostic techniques

Treatment also focuses on concomitant conditions often seen in mitral stenosis:

Chest X-ray may also assist in diagnosis, showing left atrial enlargement.[2]
Electrocardiography may show P mitrale, that is, broad, notched P waves in several or

Any angina is treated with short-acting nitrovasodilators, betablockers and/or calcium blockers[9]

many leads with a prominent late negative component to the P wave in lead V 1, and may

Any hypertension is treated aggressively, but caution must be taken in

administering beta-blockers[9]

also be seen in mitral regurgitation, and, potentially, any cause of overload of the left
atrium.[11] Thus, P-sinistrocardiale may be a more appropriate term.[11]

Natural history
The natural history of mitral stenosis secondary to rheumatic fever (the most common

Any heart failure is treated with digoxin, diuretics, nitrovasodilators and, if not
contraindicated, cautious inpatient administration of ACE inhibitors[9]

Mitral valvuloplasty

cause) is an asymptomatic latent phase following the initial episode of rheumatic fever.
This latent period lasts an average of 16.3 5.2 years. Once symptoms of mitral stenosis

Mitral valvuloplasty is a minimally invasive therapeutic procedure to correct an

begin to develop, progression to severe disability takes 9.2 4.3 years. [citation needed]

uncomplicated mitral stenosis by dilating the valve using a balloon. Under local
anaesthetic, a catheter with a special balloon is passed from the right femoral vein, up

In individuals having been offered mitral valve surgery but refused, survival with medical

the inferior vena cava and into the right atrium. The interatrial septum is punctured and

therapy alone was 44 6% at 5 years, and 32 8% at 10 years after they were offered

the catheter passed into the left atrium using a "trans-septal technique." The balloon is

correction.

sub-divided into 3 segments and is dilated in 3 stages. First, the distal portion (lying in

Treatment
Treatment is not necessary in asymptomatic patients.[2]
The treatment options for mitral stenosis include medical management, mitral valve
replacement by surgery, and percutaneous mitral valvuloplasty by balloon catheter.]

the left ventricle) is inflated and pulled against the valve cusps. Second, the proximal
portion is dilated, in order to fix the centre segment at the valve orifice. Finally, the central
section is inflated, this should take no longer than 30 seconds, since full inflation
obstructs the valve and causes congestion, leading to circulatory arrest and
flash pulmonary edema.

With careful patient pre-selection, percutaneous balloon mitral valvuloplasty (PBMV) is

acute MI due topapillary muscle rupture, rupture of a chorda tendinea or bacterial

associated with good success rates and a low rate of complications. By far the most

endocarditis of the mitral valve.

serious adverse event is the occurrence of acute severe mitral regurgitation. Severe
mitral regurgitation usually results from a tear in one of the valve leaflets or the

Individuals with chronic compensated MI may be asymptomatic for long periods of time,

subvalvular apparatus. It can lead to pulmonary oedema and hemodynamic compromise,

with a normal exercise tolerance and no evidence of heart failure. Over time, however,

necessitating urgent surgical mitral valve replacement.

there may be decompensation and patients can develop volume overload (congestive
heart failure). Symptoms of entry into a decompensated phase may include fatigue,

Other serious complications with PBMV usually relate to the technique of trans-septal

shortness of breath particularly on exertion, and leg swelling. Also there may be

puncture (TSP). The ideal site for TSP is the region of the fossa ovalis in the inter-atrial

development of an irregular heart rhythm known as atrial fibrillation.[3]

septum. Occasionally, however, the sharp needle used for TSP may inadvertently
traumatize other cardiac structures, leading to cardiac tamponade or serious blood loss. [

Findings on clinical examination depend on the severity and duration of MI. The mitral
component of the first heart sound is usually soft and with a laterally displaced apex

Although the immediate results of PBMV are often quite gratifying, the procedure does

beat,[3] often with heave.[4] The first heart sound is followed by a high-pitched holosystolic

not provide permanent relief from mitral stenosis. Regular follow-up is mandatory, to

murmur at the apex, radiating to the back or clavicular area.[3] Its duration is, as the name

detect restenosis. Long-term follow-up data from patients undergoing PBMV indicates

suggests, the whole of systole. The loudness of the murmur does not correlate well with

that up to 70-75% individuals can be free of restenosis 10 years following the procedure.

the severity of regurgitation. It may be followed by a loud, palpable P2,[3] heard best when

The number falls to about 40% 15 years post-PBMV.

lying on the left side.[4] A third heart sound is commonly heard.[3]

Mitral insufficiency

In acute cases, the murmur and tachycardia may be the only distinctive signs.[4]

From Wikipedia, the free encyclopedia

Patients with mitral valve prolapse may have a holosystolic murmur or often a mid-to-late

See also: aortic insufficiency and tricuspid insufficiency

Mitral insufficiency (MI), mitral regurgitation or mitral incompetence is a disorder of
the heart in which the mitral valve does not close properly when the heart pumps
out blood. It is the abnormal leaking of blood backwards from the left ventricle, through
the mitral valve, into the left atrium, when the left ventricle contracts, i.e. there
is regurgitation of blood back into the left atrium.[1] MI is the most common form
of valvular heart disease.

systolic click and a late systolic murmur. Cases with a late systolic regurgitant murmur
may still be associated with significant hemodynamic consequences. [5]

Cause
The mitral valve apparatus comprises two valve leaflets, the mitral valve annulus, which
forms a ring around the valve leaflets, and thepapillary muscles, which tether the valve
leaflets to the left ventricle and prevent them from prolapsing into the left atrium.

Symptoms and signs

The chordae tendineae are also present and connect the valve leaflets to the papillary
muscles. Dysfunction of any of these portions of the mitral valve apparatus can cause

The symptoms associated with MI are dependent on which phase of the disease process

regurgitation.

the individual is in. Individuals with acute MI are typically severely symptomatic and will
have the signs and symptoms of acute decompensated congestive heart

The most common cause of MI in developing countries is mitral valve prolapse (MVP).

failure (i.e.shortness of breath, pulmonary edema, orthopnea, and paroxysmal nocturnal

Mitral valve prolapse is in turn is caused bymyxomatous degeneration,[6] and is the most

dyspnea[3]), as well as symptoms of cardiogenic shock (i.e., shortness of breath at rest).

common cause of primary mitral regurgitation in the United States, causing about 50% of

Cardiovascular collapse with shock (cardiogenic shock) may be seen in individuals with

cases. Myxomatous degeneration of the mitral valve is more common in women as well

as with advancing age, which causes a stretching of the leaflets of the valve and the

(the regurgitant volume). The combination of the forward stroke volume and the

chordae tendineae. Such elongation prevent the valve leaflets from fully coming together

regurgitant volume is known as the total stroke volume of the left ventricle.

when the valve closes, causing the valve leaflets to prolapse into the left atrium, thereby
In the acute setting, the stroke volume of the left ventricle is increased

causing MI.

(increased ejection fraction); this happens because of more complete emptying of the
Ischemic heart disease causes MI by the combination of ischemic dysfunction of the

heart. However, as it progresses the LV volume increases and the contractile function

papillary muscles, and the dilatation of the left ventricle. This can lead to the subsequent

deteriorates, thus leading to dysfunctional LV and a decrease in ejection fraction. [10] The

displacement of the papillary muscles and the dilatation of the mitral valve annulus.

increase in stroke volume is explained by the FrankStarling mechanism, in which

increased ventricular pre-load stretches the myocardium such that contractions are more

Rheumatic fever and Marfan's syndrome are other typical causes.[3] MI and mitral valve

forceful.

prolapse are also common in Ehlers Danlos Syndrome.[7]

The regurgitant volume causes a volume overload and a pressure overload of the left
Secondary mitral insufficiency is due to the dilatation of the left ventricle that causes

atrium and the left ventricle. The increased pressures in the left side of the heart may

stretching of the mitral valve annulus and displacement of the papillary muscles. This

inhibit drainage of blood from the lungs via the pulmonary veins and lead to pulmonary

dilatation of the left ventricle can be due to any cause of dilated

congestion.

cardiomyopathy including aortic insufficiency, nonischemic dilated cardiomyopathy,

and Noncompaction Cardiomyopathy. Because the papillary muscles, chordae, and

Chronic phase

valve leaflets are usually normal in such conditions, it is also called functional mitral

Compensated

insufficiency.

[8]

If the MI develops slowly over months to years or if the acute phase cannot be managed
Acute MI is most often caused by endocarditis, mainly S. aureus.[3] Rupture or

with medical therapy, the individual will enter the chronic compensated phase of the

dysfunction of the papillary muscle are also common causes in acute cases,

disease. In this phase, the left ventricle develops eccentric hypertrophy in order to better

[3]

dysfunction, which can include mitral valve prolapse.

[4]

Pathophysiology
The pathophysiology of MI can be broken into three phases of the disease process: the
acute phase, the chronic compensated phase, and the chronic decompensated phase. [9]

Acute phase
Acute MI (as may occur due to the sudden rupture of a chorda tendinae or papillary
muscle) causes a sudden volume overload of both the left atrium and the left ventricle.
The left ventricle develops volume overload because with every contraction it now has to
pump out not only the volume of blood that goes into the aorta (the forward cardiac
output or forward stroke volume) but also the blood that regurgitates into the left atrium

manage the larger than normal stroke volume. The eccentric hypertrophy and the
increased diastolic volume combine to increase the stroke volume (to levels well above
normal) so that the forward stroke volume (forward cardiac output) approaches the
normal levels.
In the left atrium, the volume overload causes enlargement of the left atrium, allowing the
filling pressure in the left atrium to decrease. This improves the drainage from the
pulmonary veins, and signs and symptoms of pulmonary congestion will decrease.
These changes in the left ventricle and left atrium improve the low forward cardiac output
state and the pulmonary congestion that occur in the acute phase of the disease.
Individuals in the chronic compensated phase may be asymptomatic and have normal
exercise tolerances.

Decompensated

Treatment

An individual may be in the compensated phase of MI for years, but will eventually

The treatment of mitral insufficiency depends on the acuteness of the disease and

develop left ventricular dysfunction, the hallmark for the chronic decompensated phase

whether there are associated signs of hemodynamic compromise.

of mitral insufficiency. It is currently unclear what causes an individual to enter the

decompensated phase of this disease. However, the decompensated phase is

In acute MI secondary to a mechanical defect in the heart (i.e., rupture of a papillary

characterized by calcium overload within the cardiac myocytes.

muscle or chordae tendineae), the treatment of choice is mitral valve surgery. If the
patient is hypotensive prior to the surgical procedure, an intra-aortic balloon pump may

In this phase, the ventricular myocardium is no longer able to contract adequately to

be placed in order to improve perfusion of the organs and to decrease the degree of MI. [3]

compensate for the volume overload of mitral regurgitation, and the stroke volume of the
left ventricle will decrease. The decreased stroke volume causes a decreased forward

If the individual with acute MI is normotensive, vasodilators may be of use to decrease

cardiac output and an increase in the end-systolic volume. The increased end-systolic

the afterload seen by the left ventricle and thereby decrease the regurgitant fraction. The

volume translates to increased filling pressures of the left ventricle and increased

vasodilator most commonly used is nitroprusside.

pulmonary venous congestion. The individual may again have symptoms of congestive
heart failure.

Individuals with chronic MI can be treated with vasodilators as well to decrease afterload.
[3]

In the chronic state, the most commonly used agents are ACE

The left ventricle begins to dilate during this phase. This causes a dilatation of the mitral

inhibitors andhydralazine. Studies have shown that the use of ACE inhibitors and

valve annulus, which may worsen the degree of MI. The dilated left ventricle causes an

hydralazine can delay surgical treatment of mitral insufficiency.[12][13] The current guidelines

increase in the wall stress of the cardiac chamber as well.

for treatment of MI limit the use of vasodilators to individuals with hypertension, however.
Any hypertension is treated aggressively,[4] e.g. by diuretics and a low-sodium diet.[3] In

While the ejection fraction is less in the chronic decompensated phase than in the acute

both hypertensive and normotensive cases, digoxin and antiarrhythmics are also

phase or the chronic compensated phase, it may still be in the normal range (i.e.: > 50

indicated.[3][4] Also, chronic anticoagulation is given where there is concomitant mitral

percent), and may not decrease until late in the disease course. A decreased ejection

valve prolapse[4] or atrial fibrillation.[3] In general, medical therapy is non-curative and is

fraction in an individual with mitral insufficiency and no other cardiac abnormality should

used for mild-to-moderate regurgitation or in patients unable to tolerate surgery.

alert the physician that the disease may be in its decompensated phase.
Surgery is curative of mitral valve regurgitation. There are two surgical options for the

Diagnosis

treatment of MI: mitral valve replacement and mitral valve repair.[3] Mitral valve repair is
preferred to mitral valve replacement where a repair is feasible as bioprosthetic

There are many diagnostic tests that have abnormal results in the presence of MI. These

replacement valves have a limited lifespan of 10 to 15 years, whereas synthetic

tests suggest the diagnosis of MI and may indicate to the physician that further testing is

replacement valves require ongoing use of blood thinners to reduce the risk of stroke.

warranted. For instance, the electrocardiogram (ECG) in long-standing MI may show

There are two general categories of approaches to mitral valve repair: Resection of the

evidence of left atrial enlargement and left ventricular hypertrophy. Atrial fibrillation may

prolapsed valvular segment (sometimes referred to as the 'Carpentier' approach), and

also be noted on the ECG in individuals with chronic mitral regurgitation. The ECG may

installation of artificial chordae to "anchor" the prolapsed segment to the papillary muscle

not show any of these findings in the setting of acute MI.

(sometimes referred to as the 'David' approach). With the resection approach, any
prolapsing tissue is resected, in effect removing the hole through which the blood is
leaking. In the artificial chordae approach, ePTFE (expanded polytetrafluoroethylene, or

Gore-Tex sutures are used to replace the broken or stretched chordae tendonae,
bringing the natural tissue back into the physiological position, thus restoring the natural
anatomy of the valve. With both techniques, an annuloplasty ring is typically secured to
the annulus, or opening of the mitral valve, to provide additional structural support. In
some cases, the "double orifice" (or 'Alfieri') technique for mitral valve repair, the opening
of the mitral valve is sewn closed in the middle, leaving the two ends still able to open.
This ensures that the mitral valve closes when the left ventricle pumps blood, yet allows
the mitral valve to open at the two ends to fill the left ventricle with blood before it pumps.
In general, mitral valve surgery requires "open-heart" surgery in which the heart is
arrested and the patient is placed on a heart-lung machine (cardiopulmonary bypass).
This allows the complex surgery to proceed in a still environment.

Aortic valve
The aortic valve is one of the two semilunar valves of the heart, the other being
the pulmonary valve. The heart has four valves and the other two are the mitral and
the tricuspid valves. The aortic valve normally has three cusps or leaflets, although in 12% of the population it is found to congenitally have two leaflets.[1] It lies between the left
ventricle and the aorta.

Function
During ventricular systole, pressure rises in the left ventricle. When the pressure in the
left ventricle rises above the pressure in the aorta, the aortic valve opens,
allowing blood to exit the left ventricle into the aorta. When ventricular systole ends,

Due to the physiological stress associated with open-heart surgery, elderly and very sick

pressure in the left ventricle rapidly drops. When the pressure in the left ventricle

patients may be subject to increased risk, and may not be candidates for this type of

decreases, the aortic pressure forces the aortic valve to close. The closure of the aortic

surgery. As a consequence, there are attempts to identify means of correcting MI on a

valve contributes the A2 component of the second heart sound (S2).

beating heart. The Alfieri technique for instance, has been replicated using a
percutaneous catheter technique, which installs a clip to hold the middle of the mitral
valve closed.

Clinical significance
There are two prototypical processes that can affect the aortic valve - aortic stenosis in

Surgery

which the valve fails to open fully, thereby obstructing blood flow out from the heart,

Indications for surgery for chronic MI include signs of left ventricular dysfunction with

incompetent and blood flows passively back to the heart in the wrong direction. These

ejection fraction less than 60%, severe pulmonary hypertension with pulmonary artery

two conditions frequently co-exist. Common causes of aortic

systolic pressure greater than 50 mmHg at rest or 60 mmHg during activity, and new

regurgitation include vasodilation of the aorta, previous rheumatic fever, infection,

onset atrial fibrillation.

i.e. infective endocarditis, degeneration of the aortic valve, and Marfan's syndrome.

and aortic insufficiency, also called aortic regurgitation, in which the aortic valve is

The most common congenital abnormality of the heart is the bicuspid aortic valve. In
this condition, instead of three cusps, the aortic valve has two cusps. This condition is
often undiagnosed until later in life when the person develops symptomatic aortic
stenosis. Aortic stenosis occurs in this condition usually in patients in their 40s or 50s, an
average of 10 years earlier than can occur in people with normal aortic valves. Aortic
stenosis can also be caused by rheumatic fever and degenerative calcification.[3]
Turner syndrome a congenital condition that affects females, can often have a bicuspid
aortic valve as one of its symptoms.

Aortic valve replacement

Aortic valve replacement is a surgical procedure in which a patient's aortic valve is
replaced by a different valve. The aortic valve can be affected by a range of diseases
and require aortic valve replacement. The valve can become either leaky (regurgitant or
insufficient) or stuck partially shut (stenotic). Aortic valve replacement currently requires
open heart surgery. Research is being done now to develop valves that can be implanted
using a catheter without open heart surgery. There are two basic types of artificial heart
valve, mechanical valves and tissue valves. Tissue heart valves are usually made from
animal tissues, either animal heart valve tissue or animal pericardial tissue. The tissue is
treated to prevent rejection and to prevent calcification.
There are alternatives to animal tissue valves. In some cases, a human aortic valve can
be implanted. These are called homografts. Homograft valves are donated by patients
and recovered after the patient expires. The durability of homograft valves is probably
the same as for porcine tissue valves. Another procedure for aortic valve replacement is
the Ross procedure (after Donald Ross) or pulmonary autograft. The Ross procedure
involves going to surgery to have the aortic valve removed and replacing it with the
patient's own pulmonary valve. A pulmonary homograft (a pulmonary valve taken from a
cadaver) or a valvular prothesis is then used to replace the patient's own pulmonary
valve.
The first minimally invasive aortic valve surgery took place at the Cleveland Clinic in
1996.
Another option for aortic valve replacement is transcatheter aortic valve
replacement (TAVR). This procedure is for patients who are not candidates for surgery or
who have high risk for surgery. This procedure can be done through the femoral artery,
via direct aortic access, or via left ventricular apical access.

Aortic stenosis
From Wikipedia, the free encyclopedia

Aortic stenosis (AS) is the narrowing of the exit of the left ventricle of the heart such
that problems result. It may occur at the aortic valve as well as above and below this
level. It typically gets worse over time. Symptoms often come on gradually with a
decreased ability to exercise often occurring first. If heart failure, loss of consciousness,
or heart related chest pain occurs due to AS the outcomes are worse. Loss of
consciousness typically occurs with standing or exercise. Signs of heart failure
include shortness of breath especially with lying down, at night, and with exercise as well
as swelling of the legs. Thickening of the valve without narrowing is known as aortic
sclerosis.[1]
Causes include being born with a bicuspid aortic valve and rheumatic fever. A bicuspid
aortic valve affects about one to two percent of the population while rheumatic heart
disease mostly occurring in the developing world. A normal valve, however, may also
harden over the decades. Risk factors are similar to those of coronary artery disease and
include smoking, high blood pressure, high cholesterol, diabetes, and male sex. The
aortic valve usually has three leaflets and is located between the left ventricle of
the heartand the aorta. AS typically results in a heart murmur. Its severity can be divided
into mild, moderate, severe, and very severe based on ultrasound of the heart findings.[1]
Aortic stenosis is typically followed using repeated ultrasounds. Once it has become
severe treatment primarily involves valve replacement surgery with transcatheter aortic
valve replacement (TAVR) being an option in some who are at high risk from surgery.
Valves may either be mechanical or bioprosthetic with each having risks and benefits.
Another less invasive procedure, balloon aortic valvuloplasty (BAV) may result in benefit
but this is for only for a few months. Complications like heart failure may be treated as
per normal in those with mild to moderate AS. In those with severe disease a number of
medications should be avoided including ACE inhibitors, nitroglycerin, and some beta
blockers.[1] Nitroprusside or phenylephrine may be used in those with decompensated
heart failure depending on the blood pressure.[1][2]

Aortic stenosis is the most common valvular heart disease in the developed world.[3] It
affects about 2% of people who are over 65 years of age. [1] Estimated rates are not
known in most of the developing world as of 2014. [4] In those who have symptoms,
without repair, the chance of death at five years is about 50% and at 10 years is about
90%.[1] Aortic stenosis was first described by French physician Lazare Rivire in 1663.

Signs and symptoms

Symptoms related to aortic stenosis depend on the degree of stenosis. Most people with
mild to moderate aortic stenosis do not have symptoms. Symptoms usually present in
individuals with severe aortic stenosis, though they may occur in those with mild to
moderate aortic stenosis as well. The three main symptoms of aortic stenosis are loss of
consciousness, anginal chest pain and shortness of breath with activity or other
symptoms of heart failure such as shortness of breath while lying flat, episodes of
shortness of breath at night, or swollen legs and feet.[3][6]

Angina
Angina in setting of heart failure also increases the risk of death. In patients with angina,
the 5 year mortality rate is 50% if the aortic valve is not replaced.
Angina in the setting of AS occurs due to left ventricular hypertrophy (LVH) that is caused
by the constant production of increased pressure required to overcome the pressure
gradient caused by the AS. While the muscular layer of the left ventricle thickens, the
arteries that supply the muscle do not get significantly longer or bigger, so the muscle
may not receive enough blood supply to meet its oxygen requirement. This ischemia may
first be evident during exercise, when the heart muscle requires increased blood supply
to compensate for the increased workload. The individual may complain of anginal chest
pain with exertion. At this stage, a cardiac stress test with imaging may be suggestive of
ischemia.
Eventually, however, the heart muscle will require more blood supply at rest than can be
supplied by the coronary artery branches. At this point there may be signs of ventricular
strain pattern (ST segment depression and T wave inversion) on the EKG, suggesting
subendocardial ischemia. The subendocardium is the region that is most susceptible to
ischemia because it is the most distant from the epicardial coronary arteries.

Syncope
Syncope (fainting spells) from aortic valve stenosis is usually exertional. In the setting of
heart failure it increases the risk of death. In patients with syncope, the 3 year mortality
rate is 50%, if the aortic valve is not replaced.
It is unclear why aortic stenosis causes syncope. One popular theory is that severe AS
produces a nearly fixed cardiac output. When a person with aortic stenosis exercises,
their peripheral vascular resistance will decrease as the blood vessels of the skeletal
muscles dilate to allow the muscles to receive more blood to allow them to do more work.
This decrease in peripheral vascular resistance is normally compensated for by an
increase in the cardiac output. Since patients with severe AS cannot increase their
cardiac output, the blood pressure falls and the patient will faint due to decreased blood
perfusion to the brain.
A second theory as to why syncope may occur in AS is that during exercise, the high
pressures generated in the hypertrophied left ventricle cause a vasodepressor response,
which causes a secondary peripheral vasodilation that, in turn, causes decreased blood
flow to the brain resulting in loss of consciousness. Indeed, in aortic stenosis, because of
the fixed obstruction to bloodflow out from the heart, it may be impossible for the heart to
increase its output to offset peripheral vasodilation.
A third mechanism may sometimes be operative. Due to the hypertrophy of the left
ventricle in aortic stenosis, including the consequent inability of the coronary arteries to
adequately supply blood to the myocardium (see "Angina" below), abnormal heart
rhythms may develop. These can lead to syncope.
Finally, in calcific aortic stenosis[8][9] at least, the calcification in and around the aortic
valve can progress and extend to involve the electrical conduction system of the heart. If
that occurs, the result may be heart block - a potentially lethal condition of which syncope
may be a symptom.

Congestive heart failure

Congestive heart failure (CHF) carries a grave prognosis in patients with AS. Patients
with CHF attributable to AS have a 2-year mortality rate of 50% if the aortic valve is not
replaced. CHF in the setting of AS is due to a combination of left ventricular

hypertrophywith fibrosis, systolic dysfunction (a decrease in the ejection fraction)

Acute rheumatic fever post-inflammatory is the cause of less than 10% of cases.[12] Rare

and diastolic dysfunction (elevated filling pressure of the LV).[3]

causes of aortic stenosis include Fabry disease,systemic lupus erythematosus, Paget

disease, high blood uric acid levels, and infection.[13]

Associated symptoms

Pathophysiology
In Heyde's syndrome, aortic stenosis is associated with gastrointestinal bleeding due
to angiodysplasia of the colon.[10] Recent research has shown that the stenosis causes a

The human aortic valve normally consists of three cusps or leaflets and has an opening

form of von Willebrand disease by breaking down its associated coagulation factor

of 3.0-4.0 square centimeters.[5][13] When the left ventricle contracts, it forces blood

(factor VIII-associated antigen, also called von Willebrand factor), due to increased

through the valve into the aorta and subsequently to the rest of the body. When the left

turbulence around the stenosed valve.

ventricle expands again, the aortic valve closes and prevents the blood in the aorta from
flowing backward (regurgitation) into the left ventricle. In aortic stenosis, the opening of

Complications

the aortic valve becomes narrowed or constricted (stenotic) (i.e., due to calcification).

Notwithstanding the foregoing, the American Heart Association has recently changed its
recommendations regarding antibiotic prophylaxis for endocarditis. Specifically, as of
2007, it is recommended that such prophylaxis be limited only to those with prosthetic
heart valves, those with previous episode(s) of endocarditis, and those with certain types
of congenital heart disease.

Degenerative aortic stenosis, the most common variety, and bicuspid aortic stenosis both
begin with damage to endothelial cells from increased mechanical stress.[6]
[13]

Inflammation is thought to be involved in the earlier stages of the pathogenesis of AS

and its associated risk factors are known to promote the deposition of LDL
cholesterol and a highly damaging substance known as Lipoprotein(a) into the aortic
valve resulting in significant damage and stenosis over time. [6][13]

Since the stenosed aortic valve may limit the heart's output, people with aortic stenosis
are at risk of syncope and dangerously low blood pressure should they use any of a
number of medications for cardiovascular diseases that often coexist with aortic stenosis.
Examples include nitroglycerin, nitrates, ACE inhibitors, terazosin (Hytrin),
andhydralazine. Note that all of these substances lead to peripheral vasodilation. Under
normal circumstances, in the absence of aortic stenosis, the heart is able to increase its

As a consequence of this stenosis, the left ventricle must generate a higher pressure
with each contraction to effectively move blood forward into the aorta. [3][14] Initially, the LV
generates this increased pressure by thickening its muscular walls (myocardial
hypertrophy). The type of hypertrophy most commonly seen in AS is known as concentric
hypertrophy,[3] in which the walls of the LV are (approximately) equally thickened.

output and thereby offset the effect of the dilated blood vessels. In some cases of aortic

In the later stages, the left ventricle dilates, the wall thins, and the systolic function

stenosis, however, due to the obstruction of blood flow out of the heart caused by the

deteriorates (resulting in impaired ability to pump blood forward). Morris and Innasimuthu

stenosed aortic valve, cardiac output cannot be increased. Low blood pressure

et al. showed that different coronary anatomy is associated with different valve diseases.

or syncope may ensue.

Research is ongoing to see if different coronary anatomy might lead to turbulent flow at
the level of valves leading to inflammation and degeneration.

Causes

Diagnosis
Aortic stenosis is most commonly caused by age-related progressive calcification (>50%
of cases) with a mean age of 65 to 70 years. Another major cause of aortic stenosis is

Aortic stenosis is most often diagnosed when it is asymptomatic and can sometimes be

the calcification of a congenital bicuspid aortic valve

detected during routine examination of the heart and circulatory system. Good evidence

presenting earlier, in those aged 40+ to 50+.

[6]

[11]

(30-40% of cases) typically

exists to demonstrate that certain characteristics of the peripheral pulse can rule in the
diagnosis.[18] In particular, there may be a slow and/or sustained upstroke of the arterial

pulse, and the pulse may be of low volume. This is sometimes referred to as pulsus

even be present. Rather, new signs that reflect the presence of simultaneous aortic

parvus et tardus.[7][12] There may also be a noticeable delay between the first heart

stenosis and insufficiency, e.g., pulsus bisferiens, emerge.

sound (onauscultation) and the corresponding pulse in the carotid artery (so-called
'apical-carotid delay'). In similar manner, there may be a delay between the appearance

According to a meta analysis, the most useful findings for ruling in aortic stenosis in the

of each pulse in the brachial artery (in the arm) and the radial artery (in the wrist).

clinical setting were slow rate of rise of the carotid pulse (positive likelihood ratio ranged
2.8130 across studies), mid to late peak intensity of the murmur (positive likelihood

The first heart sound may be followed by a sharp ejection sound ("ejection click") best

ratio, 8.0101), and decreased intensity of the second heart sound (positive likelihood

heard at the lower left sternal border and the apex, and, thus, appear to be "split". The

ratio, 3.150).[18]

ejection sound, caused by the impact of left ventricular outflow against the partially fused
aortic valve leaflets, is more commonly associated with a mobile bicuspid aortic
valve than an immobile calcified aortic valve. The intensity of this sound does not vary
with respiration, which helps distinguish it from the ejection click produced by a stenotic

Other peripheral signs include:

dysfunction of the left ventricle has developed

pulmonary valve, which will diminish slightly in intensity during inspiration. [19]
An easily heard systolic, crescendo-decrescendo (i.e., 'ejection') murmur is heard loudest

sustained, heaving apex beat,[7] which is not displaced unless systolic

A precordial thrill

narrowed pulse pressure

at the upper right sternal border, at the 2nd right intercostal space,[12] and radiates to
the carotid arteries bilaterally.[3][7] The murmur increases with squatting and decreases
with standing and isometric muscular contraction such as the Valsalva maneuver, which
helps distinguish it from hypertrophic obstructive cardiomyopathy (HOCM). The murmur
is louder during expiration, but is also easily heard during inspiration. The more severe
the degree of the stenosis, the later the peak occurs in the crescendo-decrescendo of
the murmur.
The second heart sound (A2) tends to become decreased and softer as the aortic
stenosis becomes more severe.[12] This is a result of the increasing calcification of the
valve preventing it from "snapping" shut and producing a sharp, loud sound. Due to
increases in left ventricular pressure from the stenotic aortic valve, over time the ventricle
may hypertrophy, resulting in a diastolic dysfunction. As a result, one may hear a fourth

Electrocardiogram

heart sound due to the stiff ventricle.[7] With continued increases in ventricular pressure,
dilatation of the ventricle will occur, and a third heart sound may be manifest.

Although aortic stenosis does not lead to any specific findings on

the electrocardiogram (ECG), it still often leads to a number of electrocardiographic

Finally, aortic stenosis often co-exists with some degree of aortic insufficiency (aortic

abnormalities. ECG manifestations of left ventricular hypertrophy (LVH) are common in

regurgitation). Hence, the physical exam in aortic stenosis may also reveal signs of the

aortic stenosis[6][7] and arise as a result of the stenosis having placed a chronically high

latter, for example an early diastolic decrescendo murmur. Indeed, when both valve

pressure load on theleft ventricle (with LVH being the expected response to chronic

abnormalities are present, the expected findings of either may be modified or may not

pressure loads on the left ventricle no matter what the cause).

As noted above, the calcification process that occurs in aortic stenosis can progress to

The aortic valve area can be calculated non-invasively using echocardiographic flow

extend beyond the aortic valve and into the electrical conduction system of the heart.

velocities. Using the velocity of the blood through the valve, the pressure gradient across

Evidence of this phenomenon may rarely include ECG patterns characteristic of certain

the valve can be calculated by the continuity equation or using the modifiedBernoulli's

types of heart block such as Left bundle branch block.

equation:

Heart catheterization

Gradient = 4(velocity) mmHg

[6]

Cardiac chamber catheterization provides a definitive diagnosis, indicating severe

A normal aortic valve has a gradient of only a few mmHg. A decreased valvular area

stenosis in valve area of <1.0 cm (normally about 3 cm ).

causes increased pressure gradient, and these parameters are used to classify and

[20]

It can directly measure the

pressure on both sides of the aortic valve. The pressure gradient may be used as a

grade the aortic stenosis as mild, moderate or severe. The pressure gradient can be

decision point for treatment. It is useful in symptomatic patients before surgery. The

abnormally low in the presence of mitral stenosis, heart failure, co-existent aortic

[7]

regurgitation and also ischaemic heart disease (disease related to decreased blood
supply and oxygen causing ischaemia).

Severity of aortic stenosis[12]

Degree

Mean gradient

Aortic valve area

(mmHg)

(cm2)

Echocardiogram may also show left ventricular hyperthrophy, thickened and immobile
aortic valve and dilated aortic root.[7] However, it may appear deceptively normal in acute
cases.[12]

Mild

<25

>1.5

Moderate

25 - 40

1.0 - 1.5

Severe

>40

< 1.0

disease, showing the degree of calcification of the valve, and in a chronic condition, an

Very severe

>70

< 0.6

Management

Chest X-ray
A chest X-ray can also assist in the diagnosis and provide clues as to the severity of the
enlarged left ventricle[7][12] and atrium.[7]

standard for diagnosis of aortic stenosis is non invasive testing with echocardiography.

Treatment is generally not necessary in people without symptoms.[7] In moderate cases,

Cardiac catheterization is reserved for cases in which there is discrepancy between the

echocardiography is performed every 12 years to monitor the progression, possibly

clinical picture and non-invasive testing, due to risks inherent to crossing the aortic valve

complemented with a cardiac stress test.[12] In severe cases, echocardiography is

such as stroke.[6]

performed every 36 months.[12] In both moderate and mild cases, the patient should

Echocardiogram
Echocardiogram (heart ultrasound) is the best non-invasive tool / test to evaluate the
aortic valve anatomy and function.

immediately make a revisit or be admitted for inpatient care if any new related symptoms
appear.[12] There are no therapeutic options currently available to treat patients with aortic
valve stenosis; however, studies have indicated that the disease occurs as a result of
active cellular processes, suggesting that targeting these processes may lead to viable
therapeutic approaches.[21]

Medication

several decades, currently aortic valve replacement approaches include open heart
surgery, minimally invasive cardiac surgery (MICS) and minimally invasive catheter-

The effect of statins on the progression of AS is still unclear. The latest trials do not show

based (percutaneous) aortic valve replacement.

any benefit in slowing AS progression,[6] but did demonstrate a decrease in ischemic

cardiovascular events.[3] Angiotensin-converting enzyme (ACE) and angiotensin

A diseased aortic valve is most commonly replaced using a surgical procedure with

II receptors have been found in stenotic aortic valves. This leads to the hypothesis that

either a mechanical or a tissue valve. The procedure is done either in an open-heart

the renin-angiotensin system may play a role in the progression of the disease. To date,

surgical procedure or, in a smaller but growing number of cases, a minimally invasive

there is no randomized trial examining the impact of ACE inhibitors in AS. Innasimuthu et

cardiac surgery (MICS) procedure.

al. showed that patients on bisphosphonates have less progression of aortic stenosis
and some regressed. This finding led to multiple trials which are ongoing. Subsequent
research has failed to confirm the initial positive result.[24]

Transcatheter aortic valve replacement

In general, medical therapy has relatively poor efficacy in treating aortic stenosis.

Globally more than 40,000 people have received transcatheter aortic valve

[7]

However, it may be useful to manage commonly coexisting conditions that correlate

with aortic stenosis:

replacement (TAVR). For people who are not candidates for surgical valve replacement,
transcatheter valve replacement may be a suitable alternative. When selecting the
optimal therapy for individual patients, the percutaneous (transcatheter) approach must

Any angina is generally treated with beta-blockers and/or calcium blockers.

[12]

Nitrates are contraindicated due to their potential to cause

profound hypotension in aortic stenosis.[25]

Any hypertension is treated aggressively, but caution must be taken in

administering beta-blockers.[12]

Any heart failure is generally treated with digoxin and diuretics, and, if not
contraindicated, cautious inpatient administration of ACE inhibitors.[12]

While observational studies demonstrated an association between lowered cholesterol

with statins and decreased progression, a randomized clinical trial published in 2005
failed to find any effect on calcific aortic stenosis. A 2007 study did demonstrate a
slowing of aortic stenosis with the statin rosuvastatin.[6][26]

Aortic valve replacement

Main article: aortic valve replacement
In adults, symptomatic severe aortic stenosis usually requires aortic valve
replacement (AVR).[3] While AVR has been the standard of care for aortic stenosis for

be carefully weighed against the excellent results achieved with conventional surgery.

Balloon valvuloplasty
For infants and children, balloon valvuloplasty, where a balloon is inflated to stretch the
valve and allow greater flow, may also be effective. In adults, however, it is generally
ineffective, as the valve tends to return to a stenosed state. The surgeon will make a
small incision at the top of the patient's leg and proceed to insert the balloon into the
artery. The balloon is then advanced up to the valve and is inflated to stretch the valve
open.[27]

Heart failure
Acute decompensated heart failure due to AS may be temporarily managed by an intra
aortic balloon pump while pending surgery.[28] In those with high blood
pressurenitroprusside may be carefully used.[1] Phenylephrine may be used in those with
very low blood pressure.[2]

Prognosis

various collagen vascular diseases. Rheumatic heart disease is the most common cause
of aortic insufficiency in developing nations. Additionally, aortic insufficiency has been

If untreated, severe symptomatic aortic stenosis carries a poor prognosis with a 2-year

linked to the use of some medications, specifically medications

mortality rate of 50-60% and a 3-year survival rate of less than 30%. [29]

containing fenfluramineor dexfenfluramine isomers[3][4] and dopamine agonists.[5][6] Other

Epidemiology
Approximately 2% of people over the age of 65, 3% of people over age 75, [3] and 4%
percent of people over age 85 have aortic valve stenosis.[30] The prevalence is increasing
with the aging population in North America and Europe.[31]
Risk factors known to influence disease progression of AS include lifestyle habits similar
to those of coronary artery disease such as hypertension, advanced age, being
male,hyperlipidemia, diabetes mellitus, cigarette smoking, metabolic syndrome, and endstage kidney disease.

potential causes that affects the valve directly include the following: Marfan's
syndrome, EhlersDanlos syndrome, ankylosing spondylitis, and systemic lupus
erythematosus.[2] In acute cases of aortic insufficiency, the main causes are infective
endocarditis,[2][7] aortic dissection ortrauma.[2]

Physiology
In individuals with a normally functioning aortic valve, the valve is only open when the
pressure in the left ventricle is higher than the pressure in the aorta. This allows the
blood to be ejected from the left ventricle into the aorta during ventricular systole. The
amount of blood that is ejected by the heart is known as the stroke volume. Under
normal conditions, 5070% of the blood in a filled left ventricle is ejected into the aorta to
be used by the body (called the 'ejection fraction'). After ventricular systole, the pressure

Aortic insufficiency
From Wikipedia, the free encyclopedia

Aortic insufficiency (AI), also known as aortic regurgitation (AR), is the leaking of
the aortic valve of the heart that causes blood to flow in the reverse direction during
ventricular diastole, from the aorta into the left ventricle.[1]
Aortic insufficiency can be due to abnormalities of either the aortic valve or the aortic root
(the beginning of the aorta).

Causes

in the left ventricle decreases as it relaxes and begins to fill up with blood from the left
atrium. This relaxation of the left ventricle (early ventricular diastole) causes a fall in its
pressure. When the pressure in the left ventricle falls below the pressure in the aorta,
the aortic valve will close, preventing blood in the aorta from going back into the left
ventricle.

Pathophysiology
In aortic insufficiency (AI), when the pressure in the left ventricle falls below the pressure
in the aorta, the aortic valve is not able to completely close. This causes a leaking of
blood from the aorta into the left ventricle. This means that some of the blood that was
already ejected from the heart is regurgitating back into the heart. The percentage of

About half of the cases of aortic insufficiency are due to the aortic root dilation

blood that regurgitates back through the aortic valve due to AI is known as

(annuloaortic ectasia), which is idiopathic in over 80% of cases, but otherwise may result

the regurgitant fraction. For instance, if an individual with AI has a stroke volume of

fromaging, syphilitic aortitis, osteogenesis imperfecta, aortic dissection, Behet's

100 ml and during ventricular diastole 25ml regurgitates back through the aortic valve,

disease, reactive arthritis and systemic hypertension.[2] Aortic root dilation is the most

the regurgitant fraction is 25%. This regurgitant flow causes a decrease in

common cause of aortic insufficiency in developed countries. In about 15% the cause is

the diastolic blood pressure in the aorta, and therefore an increase in the pulse

innate bicuspidal aortic valve, while another 15% cases are due to retraction of the cusps

pressure (systolic pressure diastolic pressure). Thus, physical examination will reveal

as part of postinflammatory processes of endocarditis in rheumatic fever and

a bounding pulse, especially in the radial artery.

Since some of the blood that is ejected during systole regurgitates back into the left

This causes pressure in the left atrium to rise, and the individual will develop pulmonary

ventricle during diastole, there is decreased effective forward flow in AI.

edema.

Note that while diastolic blood pressure is diminished and the pulse pressure widens,

Severe acute aortic insufficiency is considered a medical emergency. There is a

systolic blood pressure generally remains normal or can even be slightly elevated. This is

high mortality rate if the individual does not undergo immediate surgery for aortic valve

because sympathetic nervous system and the renin-angiotensin-aldosterone axis of the

replacement. If the acute AI is due to aortic valve endocarditis, there is a risk that the

kidneys compensate for the decreased cardiac output. Catecholamines will increase the

new valve may become seeded with bacteria. However, this risk is small.[8]

heart rate and increase the strength of ventricular contraction, directly increasing cardiac
output. Catecholamines will also cause peripheral vasoconstriction, which causes

Acute AI usually presents as florid congestive heart failure, and will not have any of the

increased systemic vascular resistance and ensures that core organs are adequately

signs associated with chronic AI since the left ventricle had not yet developed the

perfused. Renin, a proteolytic enzyme, cleavesangiotensinogen to angiotensin I, which is

eccentric hypertrophy and dilatation that allow an increased stroke volume, which in turn

converted to angiotensin II, which is also a potent vasoconstrictor. In the case of chronic

cause bounding peripheral pulses. On auscultation, there may be a

aortic insufficiency with resultant cardiac remodeling, heart failure will develop, and it is

short diastolic murmur and a soft S1. S1 is soft because the elevated filling pressures

possible to see systolic pressures diminish.

close the mitral valve in diastole (rather than the mitral valve being closed at the
beginning of systole).

Aortic insufficiency causes both volume overload (elevated preload) and pressure
overload (elevated afterload due to increased stroke volume) of the heart.

Chronic aortic insufficiency

The volume overload (due to elevated pulse pressure and the systemic effects of

If the individual survives the initial hemodynamic derailment that acute AI presents as,

neuroendocrine hormones) causes left ventricular hypertrophy (LVH). There is

the left ventricle adapts by eccentric hypertrophy and dilatation of the left ventricle, and

both concentric hypertrophy and eccentric hypertrophy in AI. The concentric hypertrophy

the volume overload is compensated for. The left ventricular filling pressures will revert to

is due to the increased left ventricular pressure overload associated with AI, while the

normal and the individual will no longer have overt heart failure.

eccentric hypertrophy is due to volume overload caused by the regurgitant fraction.

In this compensated phase, the individual may be totally asymptomatic and may have

Hemodynamics

normal exercise tolerance.

The hemodynamic sequelae of AI are dependent on the rate of onset of AI. Acute AI and

Eventually (typically after a latency period) the left ventricle will become decompensated,

chronic AI will have different hemodynamics and individuals will have different signs and

and filling pressures will increase. While most individuals would complain of symptoms of

symptoms.

congestive heart failure to their physicians, some enter this decompensated phase

Acute aortic insufficiency

In acute AI, as may be seen with acute perforation of the aortic valve due to endocarditis,

asymptomatically. Proper treatment for AI involves aortic valve replacement prior to this
decompensation phase.

Symptoms

there will be a sudden increase in the volume of blood in the left ventricle. The ventricle
is unable to deal with the sudden change in volume. In terms of the Frank-Starling curve,

Symptoms of aortic insufficiency are similar to those of heart failure and include dyspnea

the end-diastolic volume will be very high, such that further increases in volume result in

on exertion, orthopnea and paroxysmal nocturnal dyspnea.[2] Palpitations and angina

less and less efficient contraction. The filling pressure of the left ventricle will increase.

pectoris may also be felt.[2] In acute cases there may be cyanosis and circulatory shock.[2]

Physical examination

for Ludwig Traube)

The physical examination of an individual with aortic insufficiency involves auscultation of

the heart to listen for the murmur of aortic insufficiency and the S3 heart sound (S3
gallop correlates with development of LV dysfunction). [2] The murmur of chronic aortic

Traube's sign (a 'pistol shot' systolic sound heard over the femoral artery; named

Duroziez's sign (systolic and diastolic murmurs heard over the femoral artery
when it is gradually compressed with the stethoscope)

insufficiency is typically described as early diastolic and decrescendo, which is best

heard in the third left intercostal space and may radiate along the left sternal border.

Also, these are usually less detectable in acute cases.[7]

If there is increased stroke volume of the left ventricle due to volume overload, an

Less used signs include:[10]

ejection systolic 'flow' murmur may also be present when auscultating the same aortic
area. Unless there is concomitant aortic valve stenosis, the murmur should not start with

Lighthouse sign (blanching and flushing of forehead)

Landolfi's sign (alternating constriction and dilatation of pupil)

Becker's sign (pulsations of retinal vessels)

Mller's sign (pulsations of uvula)

Mayne's sign (diastolic drop of BP>15 mm Hg with arm raised)

usefulness of some of the eponymous signs has been questioned:[9]

Rosenbach's sign (pulsatile liver)

large-volume, 'collapsing' pulse also known as:

Gerhardt's sign (also known as Sailer's sign) (enlarged spleen)

Watson's water hammer pulse

Hill's sign - a 60 mmHg difference in popliteal and brachial systolic cuff

Corrigan's pulse (rapid upstroke and collapse of the carotid artery pulse)

an ejection click.
There may also be an Austin Flint murmur,[2] a soft mid-diastolic rumble heard at the
apical area. It appears when regurgitant jet from the severe aortic insufficiency renders
partial closure of the anterior mitral leaflet.
Peripheral physical signs of aortic insufficiency are related to the high pulse pressure and
the rapid decrease in blood pressure during diastole due to blood returning to the heart
(the wrong way) from the aorta through the incompetent aortic valve, although the

low diastolic and increased pulse pressure

de Musset's sign (head nodding in time with the heart beat)

Quincke's sign (pulsation of the capillary bed in the nail; named for Heinrich
Quincke)

pressures, seen in chronic severe aortic insufficiency. Considered to be an artefact

of sphygmomanometric lower limb pressure measurement. [11]

Lincoln sign (pulsatile popliteal)

Sherman sign (dorsalis pedis pulse is quickly located and unexpectedly

prominent in age>75 yr)

Ashrafian sign (Pulsatile pseudo-proptosis)[10]

Unfortunately, none of the above putative signs of aortic insufficiency is of utility in

echocardiography with cardiac stress test and/or isotope perfusion imaging should be

making the diagnosis,[12] but they may help as pointers. What is of value is hearing a

performed every 36 months.[7]

diastolic murmur itself, whether or not the above signs are present.

Surgical treatment
The surgical treatment of choice at this time is an aortic valve replacement. This is
currently an open-heart procedure, requiring the individual to be placed
on cardiopulmonary bypass.
In the case of severe acute aortic insufficiency, all individuals should undergo surgery if
there are no absolute contraindications for surgery. Individuals with bacteremia with
aortic valve endocarditis should not wait for treatment with antibiotics to take effect, given
the high mortality associated with the acute AI. Instead, replacement with an aortic
valvehomograft should be performed if feasible.

Medical treatment
Medical therapy of chronic aortic insufficiency that is stable and asymptomatic involves
the use of vasodilators.[2] Small trials have shown a short term benefit in the use of ACE

A percutaneous approach to aortic valve replacement is now feasible, but the main
experience has been in the treatment of aortic stenosis.

inhibitors or angiotensin II receptor antagonists, nifedipine, and hydralazine in improving

left ventricular wall stress, ejection fraction, and mass. The use of these vasodilators is
only indicated in individuals who suffer from hypertension in addition to AI. The goal in
using these pharmacologic agents is to decrease the afterload so that the left ventricle is
somewhat spared. The regurgitant fraction may not change significantly, since the
gradient between the aortic and left ventricular pressures is usually fairly low at the
initiation of treatment.

include low sodium diet,[2] diuretics,[2] digoxin,[2] calcium blockers[7] and avoiding very
strenuous activity.[2][7]

mammalian heart, between the right atriumand the right ventricle. The function of the

Structure
The normal tricuspid valve usually has three leaflets and three papillary muscles. They

As of 2007, the American Heart Association no longer recommends antibiotics for

endocarditis prophylaxis before dental procedures in patients with aortic insufficiency.
Antibiotic prophylaxis to prevent endocarditis

before gastrointestinal or genitourinary procedures is no longer recommended for any

patient with valvular disease.

The tricuspid valve, or right atrioventricular valve, is on the right dorsal side of the
valve is to prevent back flow of blood into the right atrium.

Other rather conservative medical treatments for stable and asymptomatic cases

[14]

Tricuspid valve

[14]

In mild to moderate cases, echocardiography and cardiac

stress test should be followed up every 12 years. In severe moderate/severe cases,

are connected to the papillary muscles by thechordae tendineae, which lie in the right
ventricle. Tricuspid valves will not always consist of three leaflets and may also occur
with two or four leaflets; the number may change during one's lifetime. [1]

Function
See also: Heart valves

The tricuspid valve prevents back flow of blood into the right atrium. This valve is

Rare other causes include carcinoid syndrome, endocarditis, endomyocardial

weakened by drug abuse. The back flow of blood is also known as regression or

fibrosis, lupus erythematosus, right atrial myxoma and congenital tricuspid atresia.

tricuspid regurgitation.[2]

Diagnosis

Clinical significance
A mid diastolic murmur can be heard during auscultation caused by the blood flow
Tricuspid regurgitation is not uncommon in the tricuspid valve.

through the stenotic valve. It is best heard over the left sternal border with rumbling
character and tricuspid opening snap with wide splitting S1. May increase in intensity

It is common for a valve to be infected resulting in endocarditis, in intravenous

with inspiration (Carvallo's sign). The diagnosis and the severity can be assessed

drug users.[3][4] Patients who inject narcotics or other drugs intravenously may introduce

by echocardiography.

infection, which will travel to the right side of the heart, most often caused by
the bacteria S. aureus.[5] In other patients without a history of intravenous exposure,

Treatment

endocarditis is more frequently left-sided.[5]

Tricuspid valve stenosis itself usually doesn't require treatment. However, if there is
The tricuspid valve can be affected by rheumatic fever, which can cause tricuspid

damage to other valves in the heart as well, then surgical repair or replacement must be

stenosis or tricuspid insufficiency (also called tricuspid regurgitation).[6] Some patients are

considered.

born with congenital abnormalities of the tricuspid valve. Congenital apical displacement
of the tricuspid valve is called Ebstein's anomaly and typically causes significant tricuspid

The treatment is usually by surgery (tricuspid valve replacement) or percutaneous

regurgitation.

balloon valvuloplasty. The resultant tricuspid regurgitation from percutaneous treatment

is better tolerated than insufficiency occurring during mitral valvuloplasty

Certain carcinoid syndromes can affect the tricuspid valve by producing fibrosis due to
serotonin production by those tumors.
The first endovascular tricuspid valve implant was performed by surgeons at
the Cleveland Clinic.

Tricuspid valve stenosis

From Wikipedia, the free encyclopedia

Tricuspid valve stenosis is a valvular heart disease which results in the narrowing of
the orifice of the tricuspid valve of the heart. It is a relatively rare condition that
causes stenosis- increased resistance to blood flow through the valve.

Causes
It is almost always caused by rheumatic fever[1] and is generally accompanied by mitral
stenosis.

Tricuspid insufficiency

Tricuspid insufficiency (TI), a valvular heart disease also called tricuspid

dilation include right ventricular infarction,[1] inferior myocardial infarction[1] and cor

regurgitation (TR), refers to the failure of the heart'stricuspid valve to close properly

pulmonale.[1]

during systole. As a result, with each heart beat some blood passes from the right
ventricle to theright atrium, the opposite of the normal direction. Tricuspid regurgitation

Other diseases can directly affect the tricuspid valve. The most common of these

occurs in roughly less than 1% of people and is usually asymptomatic, but may also be a

is rheumatic fever, which is a complication of untreated strep throat infections. It is

feature of pulmonary hypertension and right-sided heart failure.

usually accompanied by mitral and aortic valvular disease.[1] Another condition directly
harming the valve is tricuspid endocarditis.[1]

Signs and symptoms

It may be found in those with a type of congenital heart disease called Ebstein's
Tricuspid insufficiency may be asymptomatic, especially if right ventricular function is well

anomaly.[1]

preserved. Signs and symptoms are generally those of right-sided heart failure, such
asascites, an enlarged liver, edema and jugular venous distension.[1] Vague upper

Other infrequent causes of tricuspid regurgitation include:

abdominal discomfort (from a congested liver), and fatigue (due to diminished cardiac
output) can all be present to some degree.

Carcinoid tumors, which release a hormone which damages the valve[1]

On examination, the jugular venous pressure is usually elevated, and 'CV' waves can be

Connective tissue diseases such as Marfan syndrome[1]

Systemic lupus erythematosus[1]

Myxomatous degeneration[1]

Injury

Rheumatoid arthritis

Radiation therapy

seen. It features prominent V waves and rapid y descents in jugular venous

pressure[1]Peripheral edema is often found. In severe cases, there may be ascites and
even cirrhosis (so-called 'cardiac cirrhosis').
Tricuspid insufficiency may lead to the presence of a pansystolic heart murmur.[1] Such a
murmur is usually of low frequency and best heard low on the lower left sternal border. It
tends to increase with inspiration, and decrease with expiration and Valsalva maneuver.
[1]

However, the murmur may be inaudible reflecting the relatively low pressures in the

right side of the heart. A third heart sound may also be present, also heard best with
inspiration at the left lower sternal border.[1] Parasternal heave may be felt along the left
lower sternal border as well.[1]

Another important risk factor for tricuspid regurgitation is use of the diet medications

Atrial fibrillation is usually present.[1]

called "Fen-Phen" (phentermine and fenfluramine) or dexfenfluramine

Causes

Diagnosis

Although congenital causes of tricuspid insufficiency exist, most cases are due to dilation

Diagnosis is usually made by echocardiography identifying tricuspid prolapse or flail.

of the right ventricle.[1] Such dilation leads to derangement of the normal anatomy and
mechanics of the tricuspid valve and the muscles governing its proper function. The
result is incompetence of the tricuspid valve. Left ventricular failure is, in turn, the most
common cause of right ventricular dilation.[1] Other common causes of right ventricular

[1]

The finding of a pulsatile liver and/or the presence of prominent CV waves in the

jugular pulse is also essentially diagnostic.

Electrocardiography assists in the diagnosis, indicating enlargement of right ventricle and

However, "non-articular rheumatism," also known as "regional pain syndrome" or "soft

atrium.[1]

tissue rheumatism," can cause significant discomfort and difficulty.[2] Furthermore, arthritis

Management

and rheumatism between them cover at least 200 different conditions.

The term "Rheumatic Diseases" is used in MeSH to refer to connective tissue disorders.[3]

Tricuspid insufficiency is managed with treatment of the underlying cause. [1] In most
cases, surgery is not indicated since the root problem lies with a dilated or damaged right
ventricle. Medical therapy with diuretics is the mainstay of treatment. Unfortunately, this
can lead to volume depletion and decreased cardiac output. Indeed, one must often
accept a certain degree of symptomatic tricuspid insufficiency in order to prevent a
decrease in cardiac output. Treatment with medicines to reduce cardiac afterload may
also be of benefit but a similar risk of depressed cardiac output applies.
Where surgery has to be performed, the following alternatives are available:

Palindromic rheumatism has been theorized to be a form of rheumatoid arthritis.[4]

Types
The major rheumatic disorders currently recognized include

Ankylosing spondylitis

Back pain

Bursitis/Tendinitis, Shoulder pain, wrist, biceps, leg, knee (patellar), ankle, hip,
and Achilles

Tricuspid valvular repair[1]

Valvuloplasty[1]

Capsulitis

Valve replacement

Neck pain

Rheumatism

Osteoarthritis

From Wikipedia, the free encyclopedia

Although these disorders probably have little in common in terms of their epidemiology,
they do share two characteristics: they cause chronic (though often intermittent) pain,

Rheumatism or rheumatic disorder is a non-specific term for medical problems

affecting the joints and/or connective tissue.[1] The study of, and therapeutic interventions
in, such disorders is called rheumatology.

Terminology
The term "rheumatism" is still used in colloquial speech and historical contexts, but is no
longer frequently used in medical or technical literature; there is no longer any
recognized disorder simply called "rheumatism." The traditional term covers such a
range of different problems that to ascribe symptoms to "rheumatism" is not to say very
much. Nevertheless, sources dealing with rheumatism tend to focus on arthritis.

and they are difficult to treat. They are also, collectively, very common.
Other rheumatic diseases which are caused by autoimmunity include:

Relapsing polychondritis

systemic lupus erythematosus

rheumatoid arthritis

juvenile arthritis

Essential hypertension

Sjgren syndrome

From Wikipedia, the free encyclopedia

scleroderma

Polymyositis

Dermatomyositis

Behet's disease

Reactive arthritis

Psoriatic arthritis[6]

Treatment
A vast number of traditional herbal remedies were recommended for "rheumatism".
[7]

Modern medicine, both conventional and alternative, recognises that the different

rheumatic disorders have different causes (and several of them have multiple causes)
and require different kinds of treatment.
Nevertheless, initial therapy of the major rheumatological diseases is with analgesics,
such as paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs), members of
which are ibuprofen and naproxen. Often, stronger analgesics are required.

(Redirected from Essential (primary) hypertension)

"Idiopathic hypertension" redirects here. For the condition of raised blood pressure within
the skull, see Idiopathic intracranial hypertension.
Essential hypertension (also called primary hypertension or idiopathic
hypertension) is the form of hypertension that by definition, has no identifiable cause. It
is the most common type of hypertension, affecting 95% of hypertensive patients, [1][2][3][4] it
tends to be familial and is likely to be the consequence of an interaction
between environmentaland genetic factors. Prevalence of essential hypertension
increases with age, and individuals with relatively high blood pressure at younger ages
are at increased risk for the subsequent development of hypertension. Hypertension can
increase the risk of cerebral, cardiac, and renal events.

History
Prior to Australian cardiovascular physiologist Paul Korner, in the 1940s, little was known
about essential hypertension.[6]

Classification
A recent classification recommends blood pressure criteria for defining normal blood
pressure,prehypertension, hypertension (stages I and II), and isolated systolic
hypertension, which is a common occurrence among the elderly. These readings are
based on the average of seated blood pressure readings that were properly measured
during 2 or more office visits. In individuals older than 50 years, hypertension is

The ancient Greeks recorded that bee venom had some beneficial effects on some types

considered to be present when a person's blood pressure is consistently at least

of rheumatism. Bee and ant stings were known as a folk remedy in the late 19th century,

140 mmHg systolic or 90 mmHg diastolic. Patients with blood pressures over

and at least one physician developed a treatment consisting of repeated formic

130/80 mmHg along with Type 1 or Type 2 diabetes, orkidney disease require further

acid injections.[8] Certain Amazonian tribes, including the Zo' use fire ant stings as a

treatment.[7]

remedy for aches and pains.[9]

Cod liver oil has also been used as a remedy.

Resistant hypertension is defined as the failure to reduce blood pressure to the

appropriate level after taking a three-drug regimen.[7] Guidelines for treating resistant
hypertension have been published in the UK, and US.[8]

Risk factors[edit]

and this results in decreasing efficiency of sodium excretion. The developing of certain
diseases such as renal microvascular disease and capillary rarefaction may relate to this

Hypertension is one of the most common complex disorders. The etiology of

decrease in efficiency of sodium excretion. There is experimental evidence that suggests

hypertension differs widely amongst individuals within a large population. [9] And by

that renal microvascular disease is an important mechanism for inducing salt-sensitive

definition, essential hypertension has no identifiable cause. However, several risk

hypertension.[16]

factors have been identified.

Obesity can increase the risk of hypertension to fivefold as compared with normal weight,
Hypertension may be secondary to other diseases but over 95% of patients have

and up to two-thirds of hypertension cases can be attributed to excess weight. [17] More

essential hypertension which is of unknown origin. It is observed though that:

than 85% of cases occur in those with a Body mass index greater than 25.[17] A definitive

Having a personal family history of hypertension increases the likelihood that an

individual develops HPT.[10]

link between obesity and hypertension has been found using animal and clinical studies;
from these it has been realized that many mechanisms are potential causes of obesityinduced hypertension. These mechanisms include the activation of the sympathetic

Essential hypertension is four times more common in black than white people,

nervous system as well as the activation of the reninangiotensin-aldosterone system. [18]

accelerates more rapidly and is often more severe with higher mortality in black

Another risk factor is salt (sodium) sensitivity which is an environmental factor that has

patients.[10][11][12][13]

received the greatest attention. Approximately one third of the essential hypertensive
population is responsive to sodium intake.[19] When sodium intake exceeds the capacity of

More than 50 genes have been examined in association studies with hypertension, and

the body to excrete it through the kidneys, vascular volume expands secondary to

the number is constantly growing. One of these genes is the angiotensinogen (AGT)

movement of fluids into the intra-vascular compartment. This causes the arterial pressure

gene, studied extensively by Kim et al. They showed that increasing the number of AGT

to rise as the cardiac output increases. Local autoregulatory mechanisms counteract this

increases the blood pressure and hence this may cause hypertension. [9] Twins have been

by increasing vascular resistance to maintain normotension in local vascular beds. As

included in studies measuring ambulatory blood pressure; from these studies it has been

arterial pressure increases in response to high sodium chloride intake, urinary sodium

suggested that essential hypertension contains a large genetic influence. Supporting

excretion increases and the excretion of salt is maintained at expense of increased

data has emerged from animal studies as well as clinical studies in human populations.

vascular pressures.[10] The increased sodium ion concentration stimulates ADH and thirst

The majority of these studies support the concept that the inheritance is probably

mechanisms, leading to increased reabsorption of water in the kidneys,

multifactorial or that a number of different genetic defects each has an elevated blood

concentrated urine, and thirst with higher intake of water. Also, the water movement

pressure as one of its phenotypic expressions. However, the genetic influence upon

between cells and the interstitium plays a minor role compared to this. The relationship

hypertension is not fully understood at the moment. It is believed that linking

between sodium intake and blood pressure is controversial. Reducing sodium intake

hypertension-related phenotypes with specific variations of the genome may yield

does reduce blood pressure, but the magnitude of the effect is insufficient to recommend

definitive evidence of heritability.[14] Another view is that hypertension can be caused by

a general reduction in salt intake.[20]

[9]

mutations in single genes, inherited on a Mendelian basis. [15]

Renin elevation is another risk factor. Renin is an enzyme secreted by
Hypertension can also be age related, and if this is the case, it is likely to be

the juxtaglomerular apparatus of the kidney and linked with aldosterone in a negative

multifactorial. One possible mechanism involves a reduction in vascular compliance due

feedback loop. In consequence, some hypertensive patients have been defined as

to the stiffening of the arteries. This can build up due to isolated systolic hypertension

having low-renin and others as having essential hypertension. Low-renin hypertension is

with a widened pulse pressure. A decrease in glomerular filtration rate is related to aging

more common in African Americans than white Americans, and may explain why African

Americans tend to respond better to diuretic therapy than drugs that interfere with

Pathophysiology

the Renin-angiotensin system. High renin levels predispose to hypertension by causing

Main article: Pathophysiology of hypertension

sodium retention through the following mechanism: Increased renin

Increased angiotensin II Increased vasoconstriction, thirst/ADH and aldosterone

Cardiac output and peripheral resistance are the two determinants of arterial

Increased sodium reabsorption in the kidneys (DCT and CD) Increased blood

pressure and soblood pressure is normally dependent on the balance between cardiac

pressure.

output and peripheral resistance.[28] Cardiac output is determined by stroke

volume and heart rate; stroke volume is related to myocardial contractility and to the size

Hypertension can also be caused by Insulin resistance and/or hyperinsulinemia, which

of the vascular compartment. Peripheral resistance is determined by functional and

are components of syndrome X, or the metabolic syndrome. Insulin is a

anatomic changes in small arteries and arterioles. The pathophysiology of essential

polypeptidehormone secreted by cells in the islets of Langerhans, which are contained

hypertension is an area of research, and until now remains not well understood, but

throughout the pancreas. Its main purpose is to regulate the levels of glucose in the

many theories have been proposed to explain this.

bodyantagonistically with glucagon through negative feedback loops. Insulin also exhibits
vasodilatory properties. In normotensive individuals, insulin may stimulate sympathetic

What is known is that cardiac output is raised early in the disease course, with total

activity without elevating mean arterial pressure. However, in more extreme conditions

peripheral resistance (TPR) normal; over time cardiac output drops to normal levels but

such as that of the metabolic syndrome, the increased sympathetic neural activity may

TPR is increased. Three theories have been proposed to explain this:

over-ride the vasodilatory effects of insulin.

It has been suggested that vitamin D deficiency is associated with cardiovascular risk

An overactive Renin-angiotensin system leads to vasoconstriction and retention

of sodium and water. The increase in blood volume leads to hypertension.

factors.[21] It has been observed that individuals with a vitamin D deficiency have higher

systolic and diastolic blood pressures than average. Vitamin D inhibits renin secretion
and its activity, it therefore acts as a "negative endocrine regulator of the renin-

An overactive sympathetic nervous system, leading to increased stress

responses.

angiotensin system". Hence a deficiency in vitamin D leads to an increase in renin

secretion. This is one possible mechanism of explaining the observed link between

It is also known that hypertension is highly heritable and polygenic (caused by more than

hypertension and vitamin D levels in the blood plasma.

one gene) and a few candidate genes have been postulated in the etiology of this

[22]

condition.
Also, some authorities claim that potassium might both prevent and treat hypertension.

[23]

Recent studies claims that obesity is a risk factor for hypertension because of activation
of the renin-angiotensin system (RAS) in adipose tissue,[24][25] and also linked reninangiotensin system with insulin resistance, and claims that any one can cause the other.
[26]

Cigarette smoking, a known risk factor for other cardiovascular disease, may also be a
risk factor for the development of hypertension.

Hypertension usually does not cause symptoms initially, but sustained hypertension over
time is a major risk factor for hypertensive heart disease, coronary artery disease,
[2]
stroke, aortic aneurysm, peripheral artery disease, and chronic kidney disease.
Hypertension is classified as either primary (essential) hypertension or secondary
hypertension. About 9095% of cases are categorized as primary hypertension, defined
as high blood pressure with no obvious underlying cause. [3] The remaining 510% of
cases are categorized as secondary hypertension, defined as hypertension due to an
identifiable cause, such as chronic kidney disease, narrowing of the aorta or kidney
arteries, or an endocrine disorder such as excess aldosterone, cortisol,
or catecholamines.
Dietary and lifestyle changes can improve blood pressure control and decrease the risk
of health complications, although treatment with medication is still often necessary in
people for whom lifestyle changes are not enough or not effective. The treatment of
moderately high arterial blood pressure (defined as >160/100 mmHg) with medications is
associated with an improved life expectancy. The benefits of treatment of blood pressure
that is between 140/90 mmHg and 160/100 mmHg are less clear, with some reviews
finding no benefit[4][5] and other reviews finding benefit.

Hypertension
From Wikipedia, the free encyclopedia
(Redirected from Arterial hypertension)

This article is about arterial hypertension. For other forms of hypertension,

see Hypertension (disambiguation).
Hypertension (HTN or HT), also known as high blood pressure or arterial
hypertension, is a chronic medical condition in which the blood pressure in
the arteries is elevated. Blood pressure is expressed by two measurements,
the systolic and diastolicpressures, which are the maximum and minimum pressures,
respectively, in the arterial system. The systolic pressure occurs when the left ventricle is
most contracted; the diastolic pressure occurs when the left ventricle is most relaxed
prior to the next contraction. Normal blood pressure at rest is within the range of 100
140 mmHg systolic and 6090 mmHg diastolic. Hypertension is present if the blood
pressure is persistently at or above 140/90 millimeters mercury (mmHg) for most adults;
different criteria apply to children.[1]

Signs and symptoms

Hypertension is rarely accompanied by any symptoms, and its identification is usually
through screening, or when seeking healthcare for an unrelated problem. Some with high
blood pressure report headaches (particularly at the back of the head and in the
morning), as well as lightheadedness, vertigo, tinnitus (buzzing or hissing in the ears),
altered vision or fainting episodes.[7] These symptoms, however, might be related to
associated anxiety rather than the high blood pressure itself.[8]

On physical examination, hypertension may be associated with the presence of changes

A "hypertensive emergency" is diagnosed when there is evidence of direct damage to

in the optic fundus seen by ophthalmoscopy.[9] The severity of the changes typical

one or more organs as a result of severely elevated blood pressure greater than 180

ofhypertensive retinopathy is graded from IIV; grades I and II may be difficult to

systolic or 120 diastolic.[13] This may include hypertensive encephalopathy, caused by

differentiate.[9] The severity of the retinopathy correlates roughly with the duration and/or

brain swelling and dysfunction, and characterized by headaches and an altered level of

the severity of the hypertension.

consciousness (confusion or drowsiness). Retinal papilledema and/or

[7]

Secondary hypertension
Main article: Secondary hypertension
Hypertension with certain specific additional signs and symptoms may suggest
secondary hypertension, i.e. hypertension due to an identifiable cause. For
example, Cushing's syndrome frequently causes truncal obesity, glucose
intolerance, moon face, a hump of fat behind the neck/shoulder, and purple
abdominal stretch marks.

[10]

Hyperthyroidismfrequently causes weight loss with increased

appetite, fast heart rate, bulging eyes, and tremor. Renal artery stenosis (RAS) may be
associated with a localized abdominal bruit to the left or right of the midline (unilateral
RAS), or in both locations (bilateral RAS). Coarctation of the aorta frequently causes a
decreased blood pressure in the lower extremities relative to the arms, and/or delayed or
absent femoral arterial pulses. . Pheochromocytoma may cause abrupt ("paroxysmal")
episodes of hypertension accompanied by headache, palpitations, pale appearance,
and excessive sweating.[10]

Hypertensive crisis
Main article: Hypertensive emergency
Severely elevated blood pressure (equal to or greater than a systolic 180 or diastolic of
110sometimes termed malignant or accelerated hypertension) is referred to as a
"hypertensive crisis", as blood pressure at this level confers a high risk of complications.
People with blood pressures in this range may have no symptoms, but are more likely to
report headaches (22% of cases)[11] and dizziness than the general population.[7] Other
symptoms accompanying a hypertensive crisis may include visual deterioration due to
retinopathy, breathlessness due to heart failure, or a general feeling of malaise due to
kidney failure.

[10]

Most people with a hypertensive crisis are known to have elevated blood

pressure, but additional triggers may have led to a sudden rise.[12]

fundal bleeds and exudates are another sign of target organ damage. Chest pain may
indicate heart muscle damage (which may progress to myocardial infarction) or
sometimes aortic dissection, the tearing of the inner wall of the aorta. Breathlessness,
cough, and the coughing up of blood-stained sputum are characteristic signs
of pulmonary edema, the swelling of lung tissue due to left ventricular failure an inability
of the left ventricle of the heart to adequately pump blood from the lungs into the arterial
system.[12] Rapid deterioration of kidney function (acute kidney injury)
and microangiopathic hemolytic anemia (destruction of blood cells) may also occur.[12] In
these situations, rapid reduction of the blood pressure is mandated to stop ongoing
organ damage.[12] In contrast there is no evidence that blood pressure needs to be
lowered rapidly in hypertensive urgencies where there is no evidence of target organ
damage and over aggressive reduction of blood pressure is not without risks. [10] Use of
oral medications to lower the BP gradually over 24 to 48h is advocated in hypertensive
urgencies.[12]

Pregnancy
Main article: Gestational hypertension
Hypertension occurs in approximately 810% of pregnancies.[10] Two blood pressure
measurements six hours apart of greater than 140/90 mm Hg is considered diagnostic of
hypertension in pregnancy.[14] Most women with hypertension in pregnancy have preexisting primary hypertension, but high blood pressure in pregnancy may be the first sign
ofpre-eclampsia, a serious condition of the second half of pregnancy and puerperium.
[10]

Pre-eclampsia is characterised by increased blood pressure and the presence

of protein in the urine.[10] It occurs in about 5% of pregnancies and is responsible for

approximately 16% of all maternal deaths globally.[10] Pre-eclampsia also doubles the risk
of perinatal mortality.[10] Usually there are no symptoms in pre-eclampsia and it is
detected by routine screening. When symptoms of pre-eclampsia occur the most
common are headache, visual disturbance (often "flashing lights"),
vomiting, epigastric pain, and edema. Pre-eclampsia can occasionally progress to a lifethreatening condition called eclampsia, which is a hypertensive emergency and has

several serious complications including vision loss, brain

Secondary hypertension results from an identifiable cause. Kidney disease is the most

swelling, seizures or convulsions, kidney failure, pulmonary edema, and disseminated

common secondary cause of hypertension.[10] Hypertension can also be caused by

intravascular coagulation (a blood clotting disorder).[10][15]

endocrine conditions, such as Cushing's

syndrome, hyperthyroidism, hypothyroidism, acromegaly, Conn's

Children

syndrome or hyperaldosteronism, hyperparathyroidism andpheochromocytoma.[10][26] Othe

Failure to thrive, seizures, irritability, lack of energy, and difficulty breathing[16] can be
associated with hypertension in neonates and young infants. In older infants and
children, hypertension can cause headache, unexplained irritability, fatigue, failure to

r causes of secondary hypertension include obesity, sleep apnea, pregnancy, coarctation

of the aorta, excessive liquorice consumption and certain prescription medicines, herbal
remedies and illegal drugs.

thrive, blurred vision, nosebleeds, and facial paralysis.[16][17]

Pathophysiology

Cause

In most people with established essential hypertension, increased resistance to blood

Primary hypertension

flow (total peripheral resistance) accounts for the high pressure while cardiac

Main article: Essential hypertension

output remains normal.[28] There is evidence that some younger people

with prehypertension or 'borderline hypertension' have high cardiac output, an elevated

Hypertension results from a complex interaction of genes and environmental factors.

heart rate and normal peripheral resistance, termed hyperkinetic borderline hypertension.

Numerous common genetic variants with small effects on blood pressure have been

[29]

identified[18] as well as some rare genetic variants with large effects on blood pressure,

later life as their cardiac output falls and peripheral resistance rises with age. [29] Whether

[19]

but the genetic basis of hypertension is still poorly understood.

These individuals develop the typical features of established essential hypertension in

this pattern is typical of all people who ultimately develop hypertension is disputed. [30] The
increased peripheral resistance in established hypertension is mainly attributable to

Blood pressure rises with aging and the risk of becoming hypertensive in later life is

structural narrowing of small arteries and arterioles,[31] although a reduction in the number

considerable.[20] Several environmental factors influence blood pressure. High salt intake

or density of capillaries may also contribute.[32] Whether increased active

raises the blood pressure in salt sensitive individuals; lack of exercise, obesity, stress,

arteriolarvasoconstriction plays a role in established essential hypertension is unclear.

[8]

and depression[21] can play a role in individual cases. The possible role of other factors

such as caffeine consumption,

[22]

and vitamin D deficiency

[23]

are less clear. Insulin

resistance, which is common in obesity and is a component of syndrome X (or

[33]

Hypertension is also associated with decreased peripheral venous compliance [34] which

may increase venous return, increase cardiac preload and, ultimately, cause diastolic
dysfunction.

the metabolic syndrome), is also thought to contribute to hypertension.[24] Events in early

life, such as low birth weight, maternal smoking, and lack of breast feeding may be risk

Pulse pressure (the difference between systolic and diastolic blood pressure) is

factors for adult essential hypertension,[25] although the mechanisms linking these

frequently increased in older people with hypertension. This can mean that systolic

exposures to adult hypertension remain unclear.[25]

pressure is abnormally high, but diastolic pressure may be normal or low a condition
termed isolated systolic hypertension.[35] The high pulse pressure in elderly people with
hypertension or isolated systolic hypertension is explained by increasedarterial stiffness,
which typically accompanies aging and may be exacerbated by high blood pressure. [36]

Secondary hypertension
Main article: Secondary hypertension

Many mechanisms have been proposed to account for the rise in peripheral resistance in
hypertension. Most evidence implicates either disturbances in the kidneys' salt and water

handling (particularly abnormalities in the intrarenal renin-angiotensin system)[37] and/or

usually performed because these conditions are additional risk factors for the

abnormalities of the sympathetic nervous system.[38] These mechanisms are not mutually

development of heart disease and may require treatment.[3]

exclusive and it is likely that both contribute to some extent in most cases of essential
hypertension. It has also been suggested that endothelial dysfunction and

Serum creatinine is measured to assess for the presence of kidney disease, which can

vascular inflammation may also contribute to increased peripheral resistance and

be either the cause or the result of hypertension. Serum creatinine alone may

vascular damage in hypertension.[39][40] Interleukin 17 has garnered interest for its role in

overestimateglomerular filtration rate and recent guidelines advocate the use of

increasing the production of several other immune system chemical signals thought to be

predictive equations such as the Modification of Diet in Renal Disease (MDRD) formula

involved in hypertension such as tumor necrosis factor alpha, interleukin 1, interleukin 6,

to estimate glomerular filtration rate (eGFR).[54] eGFR can also provide a baseline

and interleukin 8.

measurement of kidney function that can be used to monitor for side effects of certain
antihypertensive drugs on kidney function. Additionally, testing of urine samples
for protein is used as a secondary indicator of kidney

Diagnosis
Hypertension is diagnosed on the basis of a persistently high blood pressure.
Traditionally, theNational Institute of Clinical Excellence recommends three separate
sphygmomanometer measurements at one monthly intervals.[48][49] The American Heart
Association recommends at least three measurements on at least two separate health
care visits.[50] An exception to this is those with very high blood pressure readings
especially when there is poororgan function.[49] Initial assessment of the hypertensive
people should include a complete history and physical examination. With the availability
of 24-hour ambulatory blood pressure monitors and home blood pressuremachines, the
importance of not wrongly diagnosing those who have white coat hypertension has led to
a change in protocols. In the United Kingdom, current best practice is to follow up a
single raised clinic reading with ambulatory measurement, or less ideally with home
blood pressure monitoring over the course of 7 days. [49] Pseudohypertension in the
elderly or noncompressibility artery syndrome may also require consideration. This
condition is believed to be due to calcification of the arteries resulting in abnormally high
blood pressure readings with a blood pressure cuff while intra arterial measurements of
blood pressure are normal.[51] Orthostatic hypertension is when blood pressure increases
upon standing.[52]
Once the diagnosis of hypertension has been made, physicians will attempt to identify
the underlying cause based on risk factors and other symptoms, if present. Secondary
hypertension is more common in preadolescent children, with most cases caused
by kidney disease. Primary or essential hypertension is more common in adolescents
and has multiple risk factors, including obesity and a family history of hypertension.
[53]

Laboratory tests can also be performed to identify possible causes of secondary

hypertension, and to determine whether hypertension has caused damage to

the heart, eyes, and kidneys. Additional tests for diabetes and high cholesterol levels are

disease. Electrocardiogram (EKG/ECG) testing is done to check for evidence that the
heart is under strain from high blood pressure. It may also show whether there is
thickening of the heart muscle (left ventricular hypertrophy) or whether the heart has
experienced a prior minor disturbance such as a silent heart attack. A chest X-ray or
an echocardiogram may also be performed to look for signs of heart enlargement or
damage to the heart.[10]

Adults

recommended that children aged 3 years and older have blood pressure measurement

In people aged 18 years or older hypertension is defined as a systolic and/or a diastolic

blood pressure measurement consistently higher than an accepted normal value
(currently 139 mmHg systolic, 89 mmHg diastolic: see table Classification (JNC7)).
Lower thresholds are used (135 mmHg systolic or 85 mmHg diastolic) if measurements
are derived from 24-hour ambulatory or home monitoring. [49] Recent international
hypertension guidelines have also created categories below the hypertensive range to
indicate a continuum of risk with higher blood pressures in the normal range. JNC7
(2003)[54] uses the term prehypertension for blood pressure in the range 120-139 mmHg
systolic and/or 80-89 mmHg diastolic, while ESH-ESC Guidelines (2007)[56] and BHS IV
(2004)[57] use optimal, normal and high normal categories to subdivide pressures below
140 mmHg systolic and 90 mmHg diastolic. Hypertension is also sub-classified: JNC7
distinguishes hypertension stage I, hypertension stage II, and isolated systolic
hypertension. Isolated systolic hypertension refers to elevated systolic pressure with
normal diastolic pressure and is common in the elderly.[54] The ESH-ESC Guidelines
(2007)[56] and BHS IV (2004)[57]additionally define a third stage (stage III hypertension) for
people with systolic blood pressure exceeding 179 mmHg or a diastolic pressure over
109 mmHg. Hypertension is classified as "resistant" if medications do not reduce blood
pressure to normal levels.[54]

at least once at every health care visit[58] and the National Heart, Lung, and Blood

Children

lifestyle changes consistent with those outlined by the US National High BP Education

Institute and American Academy of Pediatrics made a similar recommendation.

[61]

However, the American Academy of Family Physicians[62] support the view of the U.S.

preventive Services Task Forcethat evidence is insufficient to determine the balance of

benefits and harms of screening for hypertension in children and adolescents who do not
have symptoms.[63]

Prevention
Much of the disease burden of high blood pressure is experienced by people who are not
labelled as hypertensive.[57] Consequently, population strategies are required to reduce
the consequences of high blood pressure and reduce the need for antihypertensive drug
therapy. Lifestyle changes are recommended to lower blood pressure, before starting
drug therapy. The 2004 British Hypertension Society guidelines [57] proposed the following
Program in 2002[64] for the primary prevention of hypertension:

Hypertension occurs in around 0.2 to 3% of newborns; however, blood pressure is not

measured routinely in healthy newborns.[17] Hypertension is more common in high risk

maintain normal body weight for adults (e.g. body mass index 2025 kg/m2)

reduce dietary sodium intake to <100 mmol/ day (<6 g of sodium chloride or <2.4

newborns. A variety of factors, such as gestational age, postconceptional age and birth
weight needs to be taken into account when deciding if a blood pressure is normal in a
newborn.

[17]

Hypertension defined as elevated blood pressure over several visits affects 1% to 5% of

g of sodium per day)

children and adolescents and is associated with long term risks of ill-health. [58] Blood

day, most days of the week)

pressure rises with age in childhood and, in children, hypertension is defined as an

average systolic or diastolic blood pressure on three or more occasions equal or higher
than the 95th percentile appropriate for the sex, age and height of the child. High blood

or diastolic blood pressure that is greater than or equal to the 90th percentile, but less

limit alcohol consumption to no more than 3 units/day in men and no more than 2
units/day in women

pressure must be confirmed on repeated visits however before characterizing a child as

having hypertension.[58] Prehypertension in children has been defined as average systolic

engage in regular aerobic physical activity such as brisk walking (30 min per

consume a diet rich in fruit and vegetables (e.g. at least five portions per day);

than the 95th percentile.[58] In adolescents, it has been proposed that hypertension and

Effective lifestyle modification may lower blood pressure as much as an individual

pre-hypertension are diagnosed and classified using the same criteria as in adults. [58]

antihypertensive drug. Combinations of two or more lifestyle modifications can achieve

The value of routine screening for hypertension in children over the age of 3 years is
debated.[59][60] In 2004 the National High Blood Pressure Education Program

even better results.[57]

Management

Several classes of medications, collectively referred to as antihypertensive medications,

Lifestyle modifications

are available for treating hypertension. Use should take into account the person's
cardiovascular risk (including risk of myocardial infarction and stroke) as well as blood

The first line of treatment for hypertension is identical to the recommended preventive

pressure readings, in order to gain a more accurate picture of the person's risks.

lifestyle changes

[75]

[65]

and includes dietary changes,

[66]

physical exercise, and weight loss.

Benefit of medications is related to a person's cardiac disease risk.[76] Evidence for

These have all been shown to significantly reduce blood pressure in people with

medications in those with mild hypertension (between 140/90 mmHg and

hypertension.

160/100 mmHg) and no other health problems is less clear with some reviews finding no

medication.

[55]

[67]

Their potential effectiveness is similar to and at times exceeds a single

If hypertension is high enough to justify immediate use of medications,

benefit[4][5] and other reviews finding benefit.[6] Medications are not recommended for

lifestyle changes are still recommended in conjunction with medication.

people with prehypertension or high normal blood pressure. [55]

Dietary change, such as a low sodium diet and a vegetarian diet are beneficial. A long

If treatment with medication is initiated the Joint National Committee on High Blood

term (more than 4 weeks) low sodium diet is effective in reducing blood pressure, both in

Pressure (JNC-7)[54] recommended that the physician not only monitor for response to

people with hypertension and in people with normal blood pressure. [68] Also, the DASH

treatment but should also seek any side effects resulting from the medication. Reduction

diet, a diet rich in nuts, whole grains, fish, poultry, fruit and vegetables lowers blood

of the blood pressure by 5 mmHg can decrease the risk of stroke by 34%, of ischaemic

pressure. A major feature of the plan is limiting intake of sodium, although the diet is also

heart disease by 21%, and reduce the likelihood of dementia, heart failure,

rich in potassium, magnesium, calcium, as well as protein.[69] A vegetarian diet is

and mortality from cardiovascular disease.[77] For most people, recommendations are to

associated with a lower blood pressure and switching to such a diet may be useful for

reduce blood pressure to less than or equal to somewhere between 140/90 mmHg to

reducing high blood pressure.

160/100 mmHg.[75][78] Attempting to achieve lower levels have not been shown to improve

[70]

A diet high in potassium lowers blood pressure in those

with high blood pressure and may improve outcomes in those with normal kidney

outcomes[78]while there is evidence that it increases side effects.[79] In those with diabetes

function.[71]

or kidney disease some recommend levels below 120/80 mmHg;[75][80] however, evidence
does not support these lower levels.[78][81] If the blood pressure goal is not met, a change in

Some programs aimed to reduce psychological stress such

treatment should be made as therapeutic inertia is a clear impediment to blood pressure

as biofeedback or transcendental meditation may be reasonable add-ons to other

control.[82]

treatment to reduce hypertension.

[72]

However several techniques, namely yoga,

relaxation and other forms of meditation do not appear to reduce blood pressure, [73] and

The best first line medication is disputed.[83] The Cochrane collaboration, World Health

there are major methodological limitations with many studies of stress reduction

Organization and the United States guidelines support low dose thiazide-based

techniques.

diuretic as first line treatment.[ The UK guidelines emphasise calcium channel

[74]

There is no clear evidence that the modest reduction in blood pressure

with stress reduction techniques results in prevention of cardiovascular disease. [73][74]

blockers (CCB) in preference for people over the age of 55 years or if of African or
Caribbean family origin, with angiotensin converting enzyme inhibitors (ACE-I) used first

Several exercise regimesincluding isometric resistance exercise, aerobic

line for younger people.[85] In Japan starting with any one of six classes of medications

exercise, resistance exercise, and device-guided breathingmay be useful in reducing

including: CCB, ACEI/ARB, thiazide diuretics, beta-blockers, and alpha-blockers is

blood pressure.[73]

deemed reasonable, while in Canada and Europe all of these but alpha-blockers are

Medications
See also: Comparison of international blood pressure guidelines

recommended as options.[55][83] When compared to placebo and other anti-hypertensive

medications as first-line therapy for hypertension, beta-blockers have greater benefit in
stroke reduction, but no difference on coronary heart disease or all-cause mortality.
[86]

However, three-quarters of active beta-blocker treatment in the randomised controlled

trials included in the review were with atenolol and none with the newer vasodilating

There are no randomized clinical trials addressing the goal blood pressure of

beta-blockers.

hypertensives over 79 years old. A recent review concluded that antihypertensive

treatment reduced cardiovascular deaths and disease, but did not significantly reduce

Medication combinations

total death rates.[91] Two professional organizations have published guidelines for the

The majority of people require more than one medication to control their hypertension. In
those with a systolic blood pressure greater than 160 mmHg or a diastolic blood pressure

management of hypertension in persons over 79 years old. [93][94]

Resistant hypertension

greater than 100 mmHg the American Heart Association recommends starting both a
thiazide and an ACEI, ARB or CCB.[67] An ACEI and CCB combination can be used as

Resistant hypertension is defined as hypertension that remains above goal blood

well.

pressure in spite of using, at once, three antihypertensive medications belonging to

[67]

different drug classes. Guidelines for treating resistant hypertension have been published
Unacceptable combinations are non-dihydropyridine calcium blockers (such as verapamil

in the UK[95] and US.[96] It has been proposed that a proportion of resistant hypertension

or diltiazem) and beta-blockers, dual reninangiotensin system blockade (e.g.

may be the result of chronic high activity of the autonomic nervous system; this concept

angiotensin converting enzyme inhibitor + angiotensin receptor blocker), renin

is known as "neurogenic hypertension".[97] Low adherence to treatment is an important

angiotensin system blockers and beta-blockers, beta-blockers and centrally acting

cause of resistant hypertension.[98]

medications.[88]Combinations of an ACE-inhibitor or angiotensin IIreceptor antagonist,

a diuretic and an NSAID (including selective COX-2 inhibitors and non-prescribed

Epidemiology

medications such as ibuprofen) should be avoided whenever possible due to a high

Adults

documented risk of acute kidney failure. The combination is known colloquially as a

"triple whammy" in the Australian health industry.[65] Tablets containing fixed combinations

As of 2000, nearly one billion people or ~26% of the adult population of the world had

of two classes of medications are available and while convenient for the people, may be

hypertension.[100] It was common in both developed (333 million) and undeveloped (639

best reserved for those who have been established on the individual components.

million) countries.[100] However, rates vary markedly in different regions with rates as low

[89]

Additionally, the use of treatments with vasoactive agents for people with pulmonary

as 3.4% (men) and 6.8% (women) in rural India and as high as 68.9% (men) and 72.5%

hypertension with left heart disease or hypoxemic lung diseases may cause harm and

(women) in Poland.[101] In Europe hypertension occurs in about 30-45% of people as of

unnecessary expense.[90]

2013.[55]

Elderly

In 1995 it was estimated that 43 million people in the United States had hypertension or
were taking antihypertensive medication, almost 24% of the adult United States

Treating moderate to severe hypertension decreases death rates and

population.[102] The prevalence of hypertension in the United States is increasing and

cardiovascular morbidity and mortality in people aged 60 and older.[91] The recommended

reached 29% in 2004.[103][104] As of 2006 hypertension affects 76 million US adults (34% of

BP goal is advised as <150/90 mm Hg with thiazide diuretic, CCB, ACEI, or ARB being

the population) and African American adults have among the highest rates of

the first line medication in the United States,

hypertension in the world at 44%.[105] It is more common in blacks and less

[92]

and in the revised UK guidelines calcium-

channel blockers are advocated as first line with targets of clinic readings <150/90, or

in whites and Mexican Americans, rates increase with age, and is greater in

<145/85 on ambulatory or home blood pressure monitoring.[85]

the southeastern United States.[3][106] Hypertension is more common in men (though

menopause tends to decrease this difference) and in those of low socioeconomic status.
[3]

Children

warm to touch feel of the body, prominent, distended and tense vessels, fullness of the
pulse, distension of the skin, coloured and dense urine, loss of appetite, weak eyesight,

Rates of high blood pressure in children and adolescents have increased in the last 20
years in the United States.[107] Childhood hypertension, particularly in preadolescents, is
more often secondary to an underlying disorder than in adults. Kidney disease is the

impairment of thinking, yawning, drowsiness, vascular rupture, and hemorrhagic stroke.

[116]

Fullness disease was presumed to be due to an excessive amount of blood within the

blood vessels.

most common secondary cause of hypertension in children and adolescents.

Nevertheless, primary or essential hypertension accounts for most cases. [108]

Descriptions of hypertension as a disease came among others from Thomas Young in

1808 and especially Richard Bright in 1836.[112] The first report of elevated blood pressure

Outcomes

in a person without evidence of kidney disease was made by Frederick Akbar

Main article: Complications of hypertension

Mahomed (18491884).[117]

Hypertension is the most important preventable risk factor for premature

Treatment

death worldwide.[109] It increases the risk of ischemic heart disease[110] strokes,[10] peripheral
vascular disease,[111] and other cardiovascular diseases, including heart failure, aortic

Historically the treatment for what was called the "hard pulse disease" consisted in

aneurysms, diffuse atherosclerosis, chronic kidney disease, and pulmonary embolism.

reducing the quantity of blood by bloodletting or the application of leeches.[112] This was

[10]

Hypertension is also a risk factor for cognitive impairment anddementia.[10] Other

complications include hypertensive retinopathy and hypertensive nephropathy.[54]

advocated by The Yellow Emperor of China, Cornelius Celsus, Galen, and Hippocrates.
[112]

The therapeutic approach for the treatment of hard pulse disease included changes in

lifestyle (staying away from anger and sexual intercourse) and dietary program for

History

patients (avoiding the consumption of wine, meat, and pastries, reducing the volume of

Measurement

food in a meal, maintaining a low-energy diet and the dietary usage of spinach and
vinegar).

Modern understanding of the cardiovascular system began with the work of

physician William Harvey (15781657), who described the circulation of blood in his book

In the 19th and 20th centuries, before effective pharmacological treatment for

"De motu cordis". The English clergyman Stephen Hales made the first published

hypertension became possible, three treatment modalities were used, all with numerous

measurement of blood pressure in 1733.

side-effects: strict sodium restriction (for example the rice

[112][113]

However hypertension as a clinical entity

came into being in 1896 with the invention of the cuff-

diet[112]), sympathectomy (surgical ablation of parts of the sympathetic nervous system),

based sphygmomanometer by Scipione Riva-Rocci in 1896.[114] This allowed the

and pyrogen therapy (injection of substances that caused a fever, indirectly reducing

measurement of blood pressure in the clinic. In 1905, Nikolai Korotkoff improved the

blood pressure).[112][118]

technique by describing the Korotkoff sounds that are heard when the artery is
ausculated with a stethoscope while the sphygmomanometer cuff is deflated. [113]

The first chemical for hypertension, sodium thiocyanate, was used in 1900 but had many
side effects and was unpopular.[112] Several other agents were developed after theSecond

Identification

World War, the most popular and reasonably effective of which

were tetramethylammonium chloride and its derivative hexamethonium; hydralazine;

The symptoms similar to symptoms of patients with hypertensive crisis are discussed in

and reserpine (derived from the medicinal plant Rauwolfia serpentina). A major

medieval Persian medical texts in the chapter of "fullness disease".

breakthrough was achieved with the discovery of the first well-tolerated orally available

[115]

This symptoms

include headache, heaviness in the head, sluggish movements, general redness and

agents. The first was chlorothiazide, the first thiazide diuretic and developed from the

antibiotic sulfanilamide, which became available in 1958.[112][119] Subsequently beta

the challenges of adhering to medicine schedules and making lifestyle changes.

blockers, calcium channel blockers,angiotensin converting enzyme (ACE)

Nonetheless, the achievement of blood pressure goals is possible, and most importantly,

inhibitors, angiotensin receptor blockers and renin inhibitors were developed as

lowering blood pressure significantly reduces the risk of death due to heart disease and

antihypertensive agents.

stroke, the development of other debilitating conditions, and the cost associated with
advanced medical care.

Society and culture

Research

Awareness

Pregnancy
The World Health Organization has identified hypertension, or high blood pressure, as
the leading cause of cardiovascular mortality. The World Hypertension League (WHL),

Regarding research in hypertension that occurs during pregnancy, it has been

an umbrella organization of 85 national hypertension societies and leagues, recognized

recommended that basic research be directed toward increasing understanding of the

that more than 50% of the hypertensive population worldwide are unaware of their

genetics and pathogenesis of oxidative stress in preeclampsia; and that clinical trials be

condition.

initiated to assess which interventions are effective in preventing oxidative stress during

[120]

To address this problem, the WHL initiated a global awareness campaign on

hypertension in 2005 and dedicated May 17 of each year as World Hypertension

pregnancy. Regarding the management of essential hypertension in the woman who

Day (WHD). Over the past three years, more national societies have been engaging in

becomes pregnant, the recommendation is that clinical trials be initiated to assess the

WHD and have been innovative in their activities to get the message to the public. In

effectiveness of various medication regimens, and their effect on mother and fetus. [125]

2007, there was record participation from 47 member countries of the WHL. During the
week of WHD, all these countries in partnership with their local governments,
professional societies, nongovernmental organizations and private industries promoted
hypertension awareness among the public through several media and public rallies.
Using mass media such as Internet and television, the message reached more than 250
million people. As the momentum picks up year after year, the WHL is confident that
almost all the estimated 1.5 billion people affected by elevated blood pressure can be
reached.[121]

Non-drug treatment
One avenue of research investigating more effective treatments for severe resistant
hypertension has focused on the use of selective radiofrequency ablation. It employs a
catheter-based device to cause thermal injury to the sympathetic nerves surrounding the
renal arteries, with the aim to reduce renal sympathetic overactivity (so-called "renal
denervation") and thereby reduce blood pressure. It has been employed in clinical trials
for resistant hypertension.[126] However, a prospective, single-blind, randomized, sham-

Economics

controlled clinical trial failed to confirm a beneficial effect. [127] Infrequent renal artery
dissection, femoral artery pseudoaneurysm, excessive decreases in blood pressure and

High blood pressure is the most common chronic medical problem prompting visits to

heart rate have been reported.[126] A 2014 consensus statement from The Joint UK

primary health care providers in USA. The American Heart Association estimated the

Societies recommended radiofrequency ablation not be used for the treatment of

direct and indirect costs of high blood pressure in 2010 as $76.6 billion.

resistant hypertension,[128] but supported continuing clinical trials. Patient selection, with

[105]

In the US 80%

of people with hypertension are aware of their condition, 71% take some

attention to measurement of pre- and post-procedure sympathetic nerve activity and

antihypertensive medication, but only 48% of people aware that they have hypertension

norepinephrine levels, may help differentiate responders from non-responders to this

adequately control it.

procedure.[129]

[105]

Adequate management of hypertension can be hampered by

inadequacies in the diagnosis, treatment, and/or control of high blood pressure. [122] Health
care providers face many obstacles to achieving blood pressure control, including

Although considered an experimental treatment in the United States and the United

resistance to taking multiple medications to reach blood pressure goals. People also face

Kingdom, it is an approved treatment in Europe, Australia, and Asia.

cause. It is much less common than the other type, called essential hypertension,
affecting only 5% of hypertensive patients. It has many different causes
including endocrine diseases, kidney diseases, and tumors. It also can be a side effect of
many medications.

Hypertensive nephropathy
Hypertensive nephropathy (or "hypertensive nephrosclerosis", or "Hypertensive kidney
disease") is a medical condition referring to damage to the kidney due to chronic high
blood pressure. It should be distinguished from "renovascular hypertension" (I15.0),
which is a form of secondary hypertension.[1][2]
In the kidneys, as a result of benign arterial hypertension, hyaline (pink, amorphous,
homogeneous material) accumulates in the wall of small arteries and arterioles,
producing the thickening of their walls and the narrowing of the lumina
hyaline arteriolosclerosis. Consequent ischemia will produce tubular atrophy, interstitial
fibrosis, glomerular alterations (smaller glomeruli with different degrees of hyalinization from mild to sclerosis of glomeruli) and periglomerular fibrosis. In advanced
stages, kidney failure will occur. Functional nephrons have dilated tubules, often with
hyaline casts in the lumens. Additional complications often associated with hypertensive
nephropathy include glomerular damage resulting in protein and blood in the urine.

Types[edit]

Renovascular hypertension (I15.0)

It has two main causes: fibromuscular dysplasia and atheromatous stenosis. Also
diabetes

See main article at Renovascular hypertension.

Hypertension secondary to other renal disorders (I15.1)

Chronic renal failure

Kidney disease / renal artery stenosis: the normal physiological response to low
blood pressure in the renal arteries is to increase cardiac output (CO) to maintain the
pressure needed for glomerular filtration. Here, however, increased CO cannot solve
the structural problems causing renal artery hypotension, with the result that CO
remains chronically elevated.

Renal segmental hypoplasia (Ask-Upmark kidney)

Hypertension secondary to endocrine disorders (I15.2)

Neurogenic hypertension - excessive secretion of norepinephrine and

epinephrine which promotes vasoconstriction resulting from chronic high activity of
the sympathoadrenal system, the sympathetic nervous system and the adrenal
gland. The specific mechanism involved is increased release of the "stress
hormones", epinephrine (adrenaline) andnorepinephrine which increase blood output
from the heart and constrict arteries. People with neurogenic hypertension respond
poorly to treatment with diuretics as the underlying cause of their hypertension is not

Secondary hypertension
Secondary hypertension (or, less commonly, inessential hypertension) is a type
of hypertension which by definition is caused by an identifiable underlying secondary

addressed.[1][2]

Pheochromocytoma - a tumor which results in an excessive secretion of

norepinephrine and epinephrine which promotes vasoconstriction

Hyperaldosteronism (Conn's syndrome) - idiopathic hyperaldosteronism, liddle's

of hormonal contraception (those containing ethinyl-estradiol) can cause

syndrome (also called pseudoaldosteronism), glucocorticoid remediable

hypertension while in use.

aldosteronism

Heavy alcohol use

Steroid use

Nicotine use.[3]

Cushing's syndrome - an excessive secretion of glucocorticoids causes the

hypertension

Hyperparathyroidism

Acromegaly

Malformed aorta, slow pulse, ischemia: these cause reduced blood flow to the
renal arteries, with physiological responses as already outlined.

Hyperthyroidism

Aortic valve disease: unclear etiology.

Coarcation of the aorta

Atherosclerosis

Hypothyroidism

Other secondary hypertension (I15.8)

Hormonal contraceptives

Neurologic disorders

Anemia: unclear etiology.

Obstructive sleep apnea

Fever: unclear etiology.

Liquorice (when consumed in excessive amounts)

White coat hypertension, that is, elevated blood pressure in a clinical setting but
not in other settings, probably due to the anxiety some people experience during a

Scleroderma

Neurofibromatosis

clinic visit.

Perioperative hypertension is development of hypertension just before, during or

after surgery. It may occur before surgery during the induction of anesthesia;

Pregnancy: unclear etiology.

Cancers: tumours in the kidney can operate in the same way as kidney disease.
More commonly, however, tumors cause inessential hypertension by ectopic
secretion of hormones involved in normal physiological control of blood pressure.

Drugs: In particular, alcohol, nasal decongestants with adrenergic

intraoperatively e.g. by pain-induced sympathetic nervous system stimulation; in the

early postanesthesia period, e.g. by pain-induced sympathetic
stimulation, hypothermia, hypoxia, orhypervolemia from excessive intraoperative
fluid therapy; and in the 24 to 48 hours after the postoperativ period as fluid is
mobilized from the extravascular space. In addition, hypertension may develop
perioperatively because of discontinuation of long-term antihypertensive medication.
[4]

effects, NSAIDs, MAOIs, adrenoceptor stimulants, and combined methods

Adrenal

with Cushing's syndrome develop hypertension., [23] which is accompanied by distinct

symptoms of the syndrome, such as central obesity, lipodystrophy, moon

A variety of adrenal cortical abnormalities can cause hypertension, In

face, sweating, hirsutismand anxiety.[24]

primary aldosteronism there is a clear relationship between the aldosterone-induced

sodium retention and the hypertension.[5]

Kidney

Another related disorder that causes hypertension is apparent mineralocorticoid excess

Other well known causes include diseases of the kidney. This includes diseases such

syndrome which is an autosomal recessive disorder that results from mutations in the

as polycystic kidney disease which is a cystic genetic disorder of the kidneys, PKD is

gene encoding 11-hydroxysteroid dehydrogenase, an enzyme that normally inactivates

characterized by the presence of multiple cysts (hence, "polycystic") in both kidneys, can

circulating cortisol to the less-active metabolite cortisone. At high

also damage the liver, pancreas, and rarely, the heart and brain.[25][26][27][28] It can

concentrations cortisol can cross-react and activate the mineralocorticoid receptor,

beautosomal dominant or autosomal recessive, with the autosomal dominant form being

leading to aldosterone-like effects in the kidney, causing hypertension.[7] This effect can

more common and characterized by progressive cyst development and bilaterally

also be produced by prolonged ingestion of liquorice (which can be of potent strength

enlarged kidneys with multiple cysts, with concurrent development of hypertension, renal

in liquorice candy), by causing inhibition of the 11-hydroxysteroid

insufficiency and renal pain.[29] Or chronic glomerulonephritis which is a disease

dehydrogenase enzyme and likewise leading to secondary apparent mineralocorticoid

characterized byinflammation of the glomeruli, or small blood vessels in the kidneys.[30][31]

excess syndrome.[8][9][10] Frequently, if liquorice is the cause of the high blood pressure, a

[32]

[6]

low blood level of potassium will also be present.[9] Cortisol induced hypertension cannot
be completely explained by the activity of Cortisol on Aldosterone receptors. Experiments

Hypertension can also be produced by diseases of the renal arteries supplying the

show that treatment with Spironolactone(an inhibitor of the aldosterone receptor), does

kidney. This is known as renovascular hypertension; it is thought that decreased

not prevent hypertension with excess cortisol. It seems that inhibition of nitric

perfusion of renal tissue due to stenosis of a main or branch renal artery activates

oxide synthesis may also play a role in cortisol induced hypertension.[11]

the renin-angiotensin system.[33][34][35]

Yet another related disorder causing hypertension is glucocorticoid remediable

Also, some renal tumors can cause hypertension. The differential diagnosis of a renal

aldosteronism, which is an autosomal dominant disorder in which the increase

tumor in a young patient with hypertension includes Juxtaglomerular cell tumor, Wilms'

in aldosteronesecretion produced by ACTH is no longer transient, causing of primary

tumor, and renal cell carcinoma, all of which may produce renin.[36]

hyperaldosteronism, the Gene mutated will result in an aldosterone synthase that

is ACTH-sensitive, which is normally not.[12][13][14][15][16] GRA appears to be the most

Neuroendocrine tumors are also a well known cause of secondary

common monogenic form of human hypertension.[17]

hypertension. Pheochromocytoma[37] (most often located in the adrenal medulla)

Compare these effects to those seen in Conn's disease, an adrenocortical tumor which

excessive stimulation of adrenergic receptors, which results in

causes excess release of aldosterone,[18] that leads to hypertension.[19][20][21]

peripheral vasoconstriction and cardiac stimulation. This diagnosis is confirmed by

increases secretion ofcatecholamines such as epinephrine and norepinephrine, causing

demonstrating increased urinary excretion of epinephrine and norepinephrine and/or

Another adrenal related cause is Cushing's syndrome which is a disorder caused by high
levels of cortisol. Cortisol is a hormone secreted by the cortex of the adrenal glands.
Cushing's syndrome can be caused by taking glucocorticoid drugs, or by tumors that
produce cortisol or adrenocorticotropic hormone (ACTH).[22] More than 80% of patients

their metabolites (vanillylmandelic acid).

Medication side effects

Arsenic exposure

Certain medications, including NSAIDs (Motrin/Ibuprofen) and steroids can cause

Because of the ubiquity of arsenic in ground water supplies and its effect on

hypertension. Other medications include extrogens (such as those found in oral

cardiovascular health, low dose arsenic poisoning should be inferred as a part of the

contraceptives with high estrogenic activity), certain antidepressants (such

pathogenesis of idiopathic hypertension. Idiopathic and essential are both somewhat

as venlafaxine), buspirone, carbamazepine, bromocriptine, clozapine, and cyclosporine.

synonymous with primary hypertension. Arsenic exposure has also many of the same

[3]

High blood pressure that is associated with the sudden withdrawal of

signs of primary hypertension such

various antihypertensive medications is called rebound hypertension.[43][44][45][46][47][48][49] The

as headache, somnolence, [57] confusion, proteinuria [58] visual disturbances,

increases in blood pressure may result in blood pressures greater than when the

and nausea and vomiting [59]

medication was initiated. Depending on the severity of the increase in blood pressure,
rebound hypertension may result in a hypertensive emergency. Rebound hypertension is
avoided by gradually reducing the dose (also known as "dose tapering"), thereby giving
the body enough time to adjust to reduction in dose. Medications commonly associated
with rebound hypertension include centrally-acting antihypertensive agents, such
as clonidine[50] and methyl-dopa.[49]
Other herbal or "natural products" which have been associated with hypertension
include: Ma Huang, St. John's Wart, and licorice.[3]

Pregnancy

Potassium deficiency
Due to the role of intracellular potassium in regulation of cellular pressures related to
sodium, establishing potassium balance has been shown to reverse hypertension.

Diagnosis
The ABCDE mnemonic can be used to help determine a secondary cause of
hypertension

A: Accuracy, Apnea, Aldosteronism

B: Bruits, Bad Kidney

C: Catecholamines, Coarctation of the Aorta, Cushing's Syndrome

Sleep disturbances

D: Drugs, Diet

Another common and under-recognized sign of hypertension is sleep apnea,[54][55] which is

E: Erythropoietin, Endocrine Disorders

Few women of childbearing age have high blood pressure, up to 11%

develop hypertension of pregnancy.[51] While generally benign, it may herald three
complications of pregnancy: pre-eclampsia, HELLP syndrome and eclampsia. Follow-up
and control with medication is therefore often necessary.[52][53]

often best treated with nocturnal nasal continuous positive airway pressure (CPAP), but
other approaches include the Mandibular advancement splint (MAS),
UPPP, tonsillectomy, adenoidectomy, septoplasty, or weight loss. Another cause is an
exceptionally rareneurological disease called Binswanger's disease, causing dementia; it
is a rare form of multi-infarct dementia, and is one of the
neurological syndromes associated with hypertension.[56]

Renovascular hypertension
From Wikipedia, the free encyclopedia

[60]

Renovascular hypertension (or "renal hypertension") is a syndrome which consists of

high blood pressure caused by the kidneys' hormonal response to narrowing of
the arteries supplying the kidneys (renal artery stenosis). When functioning properly this
hormonal axis regulates blood pressure. Due to low local blood flow, the kidneys
mistakenly increases blood pressure of the entire circulatory system. It is a form
of secondary hypertension - a form of hypertension whose cause is identifiable. It
accounts for 5% to 10% of all hypertensive patients in US. Its prevalence is 2% in those
who have a diastolic blood pressure of more than 100 mmHg and approximately 30% in
patients who have diastolic blood pressure more than 130mmHg. Patients with renal
hypertension are at increased risk of end organ dysfunction, including permanent kidney
damage, if inadequate pharmacologic therapies are used to control blood pressure.

patients with normal kidney function and hypertension, the captopril (or enalaprilat)

Signs and symptoms

inhibitors and angiotensin II receptor blocker classes of antihypertensives are

renogram may be used. Lateralization of kidney function [accentuation of the difference

between affected and unaffected (or "less affected") sides] is suggestive of significant
vascular disease. Test results may be falsely negative in the presence of bilateral
disease.

Treatment
Renal hypoperfusion activates renin-angiotensin-aldosterone (RAA) axis; ACE
contraindicated as they might compromise the renal function especially if the stenosis is

Suggestive clinical features include onset of hypertension <30 or >50 years of age,

bilateral. Nitroprusside, labetalol, or calcium antagonists are generally effective in

abdominal or femoral bruits, hypokalemic alkalosis, moderate to severe retinopathy,

lowering blood pressure acutely, although inhibitors of the RAA axis [e.g., ACE inhibitors,

acute onset of hypertension or malignant hypertension, and hypertension resistant to

angiotensin II receptor blockers (ARBs)] are most effective long-term treatment, if

medical therapy.

disease is not bilateral.

Pathogenesis

Treatment may involve angioplasty and stenting of the renal arteries. Surgical
revascularization appears to be superior for ostial lesions characteristic

Narrowing of the arteries supplying the kidneys causes a low perfusion pressure which is

of atherosclerosis. The relative efficacy of surgery compared with angioplasty (especially

detected by the juxtaglomerular apparatus (via the juxtaglomerular cells, which act as

with stenting) for fibromuscular dysplasia or for non-occlusive, non-ostial atherosclerotic

baroreceptors; located on the afferent arteriole wall). This leads to renin secretion that

disease is unclear. Angioplasty (with or without stenting) tends to be temporarily effective

causes the angiotensinogen conversion to angiotensin I. Angiotensin I then proceeds to

for some cases. However, as of early 2011, six randomized controlled trials have failed to

the lung where it is converted to angiotensin II via angiotensin converting enzyme (ACE).

demonstrate any real benefit in blood pressure control or preservation of renal function

Angiotensin II causes blood vessel constriction and aldosterone release leading to water

when using endovascular (angioplasty or stenting) procedures compared to medical

and sodium retention and potassium depletion. The increased blood volume and blood

therapy alone. ACE inhibitors or ARBs are ideal agents for hypertension associated with

vessel constriction contributes to increased blood pressure which can lead to

renal artery stenosis, except in patients with bilateral disease (see "Ischemic

hypertension.

Nephropathy" below) or disease in a solitary kidney (including an allograft).

Diagnosis
Techniques have been developed to diagnose renal hypertension using digital image
processing of radiographs. The "gold standard" in diagnosis of renal artery stenosis is
conventional arteriography. Magnetic resonance angiography (MRA) is used in many
centers, especially among patients with renal insufficiency at higher risk for contrast
nephropathy. MRA may overestimate the severity of stenosis relative to angiography. In

Unstable angina

Angina pectoris

Unstable angina (UA) (also "crescendo angina"; this is a form of acute coronary
syndrome) is defined as angina pectoris that changes or worsens.[1]

From Wikipedia, the free encyclopedia

It has at least one of these three features:

Angina pectoris commonly known as angina is the sensation of chest pain,
pressure, or squeezing, often due toischemia of the heart muscle from obstruction or
spasm of the coronary arteries.[1] While angina pectoris can derive from anemia,cardiac
arrhythmias and heart failure, its main cause is coronary artery disease,
an atherosclerotic process affecting the arteriesfeeding the heart. The term derives from
the Latin angere ("to strangle") and pectus ("chest"), and can, therefore, be translated as
"a strangling feeling in the chest".
There is a weak relationship between severity of pain and degree of oxygen deprivation
in the heart muscle (i.e., there can be severe pain with little or no risk of a myocardial
infarction (heart attack) and a heart attack can occur without pain). In some cases,
angina can be quite severe, and in the early 20th century this was known to be a signal
of impending death.[2] However, given current medical therapies, the outlook has
improved substantially. People with an average age of 62 years, who have moderate to
severe degrees of angina (grading by classes II, III and IV) have a 5-year mortality rate
of approximately 8%.[3]

1. it occurs at rest (or with minimal exertion), usually lasting 35 minutes

2. it is severe and of new onset (i.e., within the prior 46 weeks)
3. it occurs with a crescendo pattern (i.e., distinctly more severe, prolonged, or
frequent than before).
UA may occur unpredictably at rest, which may be a serious indicator of an impending
heart attack. What differentiates stable angina from unstable angina (other than
symptoms) is the pathophysiology of the atherosclerosis. The pathophysiology of
unstable angina is the reduction of coronary flow due to transient platelet aggregation on
apparently normal endothelium, coronary artery spasms, or coronary thrombosis. [5][6] The

Worsening ("crescendo") angina attacks, sudden-onset angina at rest, and angina lasting
more than 15 minutes are symptoms ofunstable angina (usually grouped with similar
conditions as the acute coronary syndrome). As these may precede a heart attack, they
require urgent medical attention and are, in general, treated in similar fashion to
myocardial infarction.

Classification

Stable angina
Also known as effort angina, this refers to the classic type of angina related to myocardial
ischemia. A typical presentation of stable angina is that of chest discomfort and
associated symptoms precipitated by some activity (running, walking, etc.) with minimal

process starts with atherosclerosis, progresses through inflammation to yield an active

unstable plaque, which undergoes thrombosis and results in acute myocardial ischemia,
which, if not reversed, results in cell necrosis (infarction). [6] Studies show that 64% of all
unstable anginas occur between 10 PM and 8 AM when patients are at rest. [6][7]
In stable angina, the developing atheroma is protected with a fibrous cap. This cap may
rupture in unstable angina, allowing blood clots to precipitate and further decrease the
area of the coronary vessel's lumen. This explains why, in many cases, unstable angina
develops independently of activity.[6]

Cardiac syndrome X

or non-existent symptoms at rest or after administration of sublingual nitroglycerin.

[4]

Symptoms typically abate several minutes after activity and recur when activity

Cardiac syndrome X, sometimes known as microvascular angina is characterized by

resumes. In this way, stable angina may be thought of as being similar to

angina-like chest pain, in the context of normal epicardial coronary arteries (the largest

intermittent claudication symptoms. Other recognized precipitants of stable angina

vessels on the surface of the heart, prior to significant branching) on angiography. The

include cold weather, heavy meals, and emotional stress.

original definition of cardiac syndrome X also mandated that the patient display ischemic
changes on exercise EKG (ST depressions with stress) despite normal coronary arteries.
[8]

The primary cause of cardiac syndrome X is unknown, but factors which appear to be

involved are endothelial dysfunction and reduced flow (perhaps due to spasm) in the tiny

A variant form of angina (Prinzmetal's angina) occurs in patients with normal coronary

"resistance" blood vessels of the heart.[9] Since microvascular angina is not characterized

arteries or insignificant atherosclerosis. It is thought to be caused by spasms of the

by major arterial blockages, it is harder to recognize and diagnose. Microvascular angina

artery. It occurs more in younger women.[14]

was previously felt to be a rather benign condition, but more recent data has changed
this attitude. Studies including the Women's Ischemia Syndrome Evaluation (WISE)

Cause

suggest that microvascular angina is part of the pathophysiology of ischemic heart

Major risk factors

disease, perhaps explaining the higher rates of angina in women than in men, as well as
their predilection towards ischemia and acute coronary syndromes in the absence of
obstructive coronary artery disease.[13]
Age ( 45 years for men, 55 for women)

Signs and symptoms

Angina pectoris can be quite painful, but many patients with angina complain of chest
discomfort rather than actual pain: the discomfort is usually described as a pressure,
heaviness, tightness, squeezing, burning, or choking sensation. Apart from chest
discomfort, anginal pains may also be experienced in the epigastrium (upper central
abdomen), back, neck area, jaw, or shoulders. This is explained by the concept
of referred pain, and is due to the fact that the spinal level that receives visceral
sensation from the heart simultaneously receives cutaneous sensation from parts of the
skin specified by that spinal nerve's dermatome, without an ability to discriminate the
two. Typical locations forreferred pain are arms (often inner left arm), shoulders, and
neck into the jaw. Angina is typically precipitated by exertion or emotional stress. It is
exacerbated by having a full stomach and by cold temperatures. Pain may be
accompanied by breathlessness, sweating, and nausea in some cases. In this case, the
pulse rate and the blood pressure increases. Chest pain lasting only a few seconds is
normally not angina (such as precordial catch syndrome).
Myocardial ischemia comes about when the myocardia (the heart muscles) receive
insufficient blood and oxygen to function normally either because of increased oxygen
demand by the myocardia or because of decreased supply to the myocardia. This
inadequate perfusion of blood and the resulting reduced delivery of oxygen and nutrients
are directly correlated to blocked or narrowed blood vessels.
Some experience "autonomic symptoms" (related to increased activity of the autonomic
nervous system) such as nausea, vomiting, and pallor.
Major risk factors for angina include cigarette smoking, diabetes, high cholesterol, high
blood pressure, sedentary lifestyle, and family history of premature heart disease.

Cigarette smoking

Diabetes mellitus (DM)

Dyslipidemia

Family history of premature cardiovascular disease (men <55 years, female <65
years old)

Hypertension (HTN)

Kidney disease (microalbuminuria or GFR<60 mL/min)

Obesity (BMI 30 kg/m2)

Physical inactivity

Prolonged psychosocial stress[16]

Routine counselling of adults to advise them to improve their diet and increase their
physical activity has not been found to significantly alter behaviour, and thus is not
recommended.[17]
Conditions that exacerbate or provoke angina
[18]

Medications

Vasodilators

Excessive thyroid replacement

Vasoconstrictors

Polycythemia which thickens the blood causing it to slow its flow through the
heart muscle

Hypothermia

Hypovolaemia

Hypervolaemia

Hypoxemia

Other cardiac problems

Tachyarrhythmia

Bradyarrhythmia

Valvular heart disease

Hypertrophic cardiomyopathy

Myocardial ischemia can result from:

1. a reduction of blood flow to the heart that can be caused by stenosis,
spasm, or acute occlusion (by an embolus) of the heart's arteries.

One study found that smokers with coronary artery disease had a significantly
increased level of sympathetic nerve activity when compared to those without. This

2. resistance of the blood vessels. This can be caused by narrowing of the

is in addition to increases in blood pressure, heart rate, and peripheral vascular

blood vessels; a decrease in radius.[25] Blood flow is proportional to the radius

resistance associated with nicotine, which may lead to recurrent angina attacks. In

of the artery to the fourth power.[26]

addition, the Centers for Disease Control and Prevention (CDC) reports that the risk
of CHD (Coronary heart disease), stroke, and PVD (Peripheral vascular disease) is

3. reduced oxygen-carrying capacity of the blood, due to several factors such

reduced within 12 years of smoking cessation. In another study, it was found that,

as a decrease in oxygen tension and hemoglobin concentration.[27] This

after one year, the prevalence of angina in smoking men under 60 after an initial
attack was 40% less in those having quit smoking compared to those that continued.

decreases the ability to of hemoglobin to carry oxygen to myocardial tissue.

[28]

Studies have found that there are short-term and long-term benefits to smoking
cessation.

Atherosclerosis is the most common cause of stenosis (narrowing of the blood

Other medical problems

vessels) of the heart's arteries and, hence, angina pectoris. Some people with chest

Profound anemia

patients, vasospasm is a more likely cause for the pain, sometimes in the context

Uncontrolled HTN

Hyperthyroidism

pain have normal or minimal narrowing of heart arteries; in these

of Prinzmetal's angina and syndrome X.
Myocardial ischemia also can be the result of factors affecting blood composition,
such as reduced oxygen-carrying capacity of blood, as seen with severe anemia (low
number of red blood cells), or long-term smoking.

Pathophysiology

flat or downsloping ST depression), the test is considered diagnostic for angina. Even
constant monitoring of the blood pressure and the pulse rate can lead us to some

Angina results when there is an imbalance between the heart's oxygen demand and

conclusion regarding the angina. The exercise test is also useful in looking for other

supply. This imbalance can result from an increase in demand (e.g., during exercise)

markers of myocardial ischaemia: blood pressure response (or lack thereof, in particular

without a proportional increase in supply (e.g., due to obstruction or atherosclerosis

a drop in systolic pressure), dysrhythmia and chronotropic response. Other alternatives

of the coronary arteries).

to a standard exercise test include a thallium scintigram or sestamibi scintigram (in

However, the pathophysiology of angina in females varies significantly as compared

to males. Non-obstructive coronary disease is more common in females.

Diagnosis
Angina should be suspected in people presenting with tight, dull, or heavy chest
discomfort that is:[32]
1. Retrosternal or left-sided, radiating to the left arm, neck, jaw, or back.
2. Associated with exertion or emotional stress and relieved within several minutes
by rest.
3. Precipitated by cold weather or a meal.
Some people present with atypical symptoms, including breathlessness, nausea, or
epigastric discomfort or burping. These atypical symptoms are particularly likely in older
people, women, and those with diabetes.[32]
Anginal pain is not usually sharp or stabbing or influenced by respiration. Antacids and
simple analgesia do not usually relieve the pain. If chest discomfort (of whatever site) is
precipitated by exertion, relieved by rest, and relieved by glyceryl trinitrate, the likelihood
of angina is increased.[32]

patients unable to exercise enough for the purposes of the treadmill tests, e.g., due
to asthma or arthritis or in whom the ECG is too abnormal at rest) or
Stress Echocardiography.
In patients in whom such noninvasive testing is diagnostic, a coronary angiogram is
typically performed to identify the nature of the coronary lesion, and whether this would
be a candidate for angioplasty, coronary artery bypass graft (CABG), treatment only with
medication, or other treatments. There has been research that concludes that a
frequency is attained when there is increase in the blood pressure and the pulse rate.
This frequency varies normally but the range is 4550 kHz for the cardiac arrest or for
the heart failure.[clarification needed] In patients in hospital with unstable angina (or the newer term
of "high-risk acute coronary syndromes"), those with resting ischaemic ECG changes or
those with raised cardiac enzymes such as troponin may undergo coronary angiography
directly.

Treatment[edit]
The most specific medicine to treat angina is nitroglycerin. It is a potent vasodilator that
makes more oxygen available to the heart muscle. Beta blockers and calcium channel
blockers act to decrease the heart's workload, and thus its requirement for oxygen.
Nitroglycerin should not be given if certain inhibitors such
as Sildenafil (Viagra), Tadalafil(Cialis), or Vardenafil (Levitra) have been taken within the
previous 12 hours as the combination of the two could cause a serious drop in blood
pressure. Treatments for angina are balloon angioplasty, in which the balloon is inserted

In angina patients momentarily not feeling any chest pain, an electrocardiogram (ECG) is

at the end of a catheter and inflated to widen the arterial lumen. Stents to maintain the

typically normal, unless there have been other cardiac problems in the past. During

arterial widening are often used at the same time. Coronary bypass surgery involves

periods of pain, depression, or elevation of the ST segment may be observed. To elicit

bypassing constricted arteries with venous grafts. This is much more invasive

these changes, an exercise ECG test ("treadmill test") may be performed, during which

than angioplasty.

the patient exercises to his/her maximum ability before fatigue, breathlessness, or pain
intervenes; if characteristic ECG changes are documented (typically more than 1 mm of

The main goals of treatment in angina pectoris are relief of symptoms, slowing

Microvascular angina in women

progression of the disease, and reduction of future events, especially heart

attacks and death. Beta blockers (e.g., carvedilol, propranolol, atenolol) have a large

Aggressive risk factor modification is required for effective treatment of microvascular

body of evidence in morbidity and mortality benefits (fewer symptoms, less disability and

angina where exercise plays a major role.[38] Several other treatment strategies including

longer life) and short-actingnitroglycerin medications have been used since 1879 for

b-blockers, angiotensin-converting enzyme inhibitors, ranolazine, l-arginine, statin drugs

symptomatic relief of angina.[33] Calcium channel blockers (such as nifedipine (Adalat)

and potentially estrogen replacement therapy have been shown to relieve anginal

and amlodipine), isosorbide mononitrate and nicorandil are vasodilators commonly used

symptoms as well as improve vascular function.[38] Nitrates may be effective for symptom

in chronic stable angina .A new therapeutic class, called If inhibitor, has recently been

relief.[38] Further studies are required to determine whether specific treatments are

made available:Ivabradine provides pure heart rate reduction[34] leading to major anti-

associated with improved survival as well as decreased symptoms.

ischemic and antianginal efficacy. ACE inhibitors are also vasodilators with both
symptomatic and prognostic benefit. Statins are the most frequently used
lipid/cholesterol modifiers, which probably also stabilize existing atheromatous
plaque[citation needed]. Low-dose aspirin decreases the risk of heart attack in patients with
chronic stable angina, and was is part of standard treatment. However, in patients
without established cardiovascular disease, the increase inhaemorrhagic stroke and
gastrointestinal bleeding offsets any benefits and it is no longer advised unless the risk of
myocardial infarction is very high.[35]
Exercise is also a very good long-term treatment for the angina (but only particular
regimens - gentle and sustained exercise rather than intense short bursts), [36] probably

Suspected angina
Hospital admission for people with the following symptoms is recommended, as they
may have unstable angina: pain at rest (which may occur at night), pain on minimal
exertion, angina that seems to be progressing rapidly despite increasing medical
treatment. All people with suspected angina should be urgently referred to a chest pain
evaluation service, for confirmation of the diagnosis and assessment of the severity of
coronary heart disease.[39]

Epidemiology

working by complex mechanisms such as improving blood pressure and promoting

As of 2010, angina due to ischemic heart disease affects approximately 112 million

coronary artery collateralisation.

people (1.6% of the population) being slightly more common in men than women (1.7%

Identifying and treating risk factors for further coronary heart disease is a priority in

to 1.5%).[40]

patients with angina. This means testing for elevated cholesterol and other fats in the

In the United States, 10.2 million are estimated to experience angina with approximately

blood,diabetes and hypertension (high blood pressure), and encouraging smoking

500,000 new cases occurring each year.[4][41] Angina is more often the presenting

cessation and weight optimisation.

symptom of coronary artery disease in women than in men. The prevalence of angina

The calcium channel blocker nifedipine prolongs cardiovascular event- and procedurefree survival in patients with coronary artery disease. New overt heart failures were
reduced by 29% compared to placebo; however, the mortality rate difference between
the two groups was statistically insignificant.[37]

rises with increasing age, with a mean age of onset of 62.3 years.[42] After five years postonset, 4.8% of individuals with angina subsequently died from coronary heart disease.
Men with angina were found to have an increased risk of subsequent acute myocardial
infarction and coronary heart disease related death than women. Similar figures apply in
the remainder of the Western world. All forms of coronary heart disease are much lesscommon in the Third World, as its risk factors are much more common in Western and
Westernized countries; it could, therefore, be termed a disease of affluence. The
adoption of a rich, Westernized diet and subsequent increase of smoking, obesity, and

other risk factors has led to an increase in angina and related diseases in countries such

Management

as China.

Unstable angina
From Wikipedia, the free encyclopedia

Nitroglycerin can be used immediately to widen the coronary arteries and help increase
blood flow to the heart. In addition, nitroglycerin causes peripheral venous and artery
dilation reducing cardiac preload and afterload. These reductions allow for decrease
myocardial oxygen demand. Antiplatelet drugs such as aspirin and clopidogrel can help
reduce the progression of plaque formation, as well as combining these with an
anticoagulant such as a low molecular weight heparin.

Unstable angina (UA) is a type of angina pectoris[1] that is irregular.[2] It is also classified
as a type of acute coronary syndrome.[3]
It can be difficult to distinguish unstable angina from nonQ-wave myocardial infarction.
[4]
Unstable angina (UA) and non-ST elevation (non-Q wave) myocardial infarction
(NSTEMI) differ primarily in whether the ischemia is severe enough to cause sufficient
myocardial damage to release detectable quantities of a marker of myocardial injury.
Unstable angina is considered to be present in patients with ischemic symptoms
suggestive of an ACS and no elevation in troponin, with or without ECG changes
indicative of ischemia (e.g., ST segment depression or transient elevation or new T wave
inversion). Since an elevation in troponin may not be detectable for up to 12 hours after
presentation, UA and NSTEMI are frequently indistinguishable at initial evaluation.

Definition
Unstable angina is angina pectoris caused by disruption of an atherosclerotic plaque with
partial thrombosis and possibly embolization or vasospasm. [5][6] It is characterized by at
least one of the following:
1. Occurs at rest or minimal exertion and usually lasts more than 20 minutes
(if nitroglycerin is not administered)
2. Being severe (at least Canadian Cardiovascular Society Classification 3) and of
new onset (i.e. within 1 month)
3. Occurs with a crescendo pattern (brought on by less activity, more severe, more
prolonged or increased frequency than previously).[7][8]
Fifty percent of people with unstable angina will have evidence of myocardial necrosis
based on elevated cardiac serum markers such as creatine kinase isoenzyme (CK)-MB
and troponin T or I, and thus have a diagnosis of non-ST elevation myocardial infarction.
[8][9]

Prinzmetal's angina
From Wikipedia, the free encyclopedia

Prinzmetal's or Prinzmetal angina (/prntsmtl/, sounds like "prints metal") (also

known as variant angina, angina inversa, orcoronary vessel spasm) is a syndrome
typically consisting of angina (cardiac chest pain) at rest that occurs in cycles. It is
caused by vasospasm, a narrowing of the coronary arteries caused by contraction of the
smooth muscle tissue in the vessel walls rather than directly by atherosclerosis (buildup
of fatty plaque and hardening of the arteries).

Signs and symptoms

fail to produce, or produce very little, nitric oxide. Thus, acetylcholine released by

Symptoms typically occur at rest, rather than on exertion (thus attacks usually occur at

the PSNS at rest will simply cause contraction of the vascular smooth muscle.

night).[1] Two-thirds of patients have concurrent atherosclerosis of a major coronary

artery, but this is often mild or not in proportion to the degree of symptoms.

When the endothelium is dysfunctional, stimulation with acetylcholine will

Thromboxane A2, a vasoconstrictor released by platelets to aid in clot formation,

may also play a role in Prinzmetal's angina. Lipoprotein(a) interferes with fibrinolysis

Prinzmetal's should be suspected by a cardiologist when the pain occurs at rest and/or in
clusters, and in the absence of a positive treadmill stress test, as Prinzmetal's is exercise

by competing with plasminogen. The impaired fibrinolysis triggers thrombus

tolerant and can generally only be diagnosed after other forms of cardiac disease have

formation, which also results in coronary vasospasm in variant angina. [5][6]

been ruled out.

It is associated with specific ECG changes (elevation rather than depression of the ST
segment). However, in order to be diagnosed, these ECG changes can only be tracked
when the electrocardiogram occurs while the patient is experiencing an attack.
Therefore, many experts recommend provocative testing during Electrocardiogram
testing to attempt to induce an attack when Prinzmetal's is suspected.

Increased alpha-adrenergic receptor activity on epicardial coronary arteries leads

to coronary vasospasm.[7]

Diagnosis
Although Prinzmetal's Angina has been documented in between 2% to 10% of angina
patients, it can be overlooked by cardiologists who stop testing protocol after ruling out

Mechanism

typical angina. Rarely, an EKG can capture diffuse ST elevations.

The mechanism that causes such intense vasospasm, as to cause a clinically significant

Patients who develop cardiac chest pain are generally treated empirically as an "acute

narrowing of the coronary arteries is so far unknown. There are three relevant

coronary syndrome", and are generally tested for cardiac enzymes such as creatine

hypotheses:

kinase isoenzymes or troponin I or T. These may or may not show a degree of positivity,
as coronary spasm too can cause myocardial damage or may leave the arteries

Enhanced contractility of coronary vascular smooth muscle due to reduced nitric

oxide bioavailability caused by a defect in the endothelial nitric oxide synthetase
enzyme which leads to endothelial function abnormalities.[2][3]

Acetylcholine is normally released by the parasympathetic nervous

system (PSNS) at rest, and causes dilation of the coronary arteries.[4] While
acetylcholine induces vasoconstriction of vascular smooth muscle cells through

undamaged. Echocardiography or thallium scintigraphy is often performed.

The gold standard is coronary angiography with injection of provocative agents into the
coronary artery. Rarely, an active spasm can documented angiographically (e.g. if the
patient receives an angiogram with intent of performing a primary coronary intervention
with angioplasty). Depending on the local protocol, provocation testing may involve
substances such as ergonovine, methylergonovine oracetylcholine. Exaggerated spasm
is diagnostic of Prinzmetal angina.

a direct mechanism, acetylcholine also stimulates endothelial cells to

produce nitric oxide (NO). NO then diffuses out of the endothelial cells,

Treatment

stimulating relaxation of the nearby smooth muscle cells. In healthy arterial

walls, the overall indirect relaxation induced by acetylcholine (via nitric oxide) is
of greater effect than any contraction that is induced.

Prinzmetal's angina typically responds to nitrates and calcium channel blockers.[8]

Use of a beta blocker such as propranolol is contraindicated in Prinzmetal's angina.

Myocardial infarction
From Wikipedia, the free encyclopedia
(Redirected from Acute myocardial infarction)

Myocardial infarction (MI) or acute myocardial infarction (AMI), commonly known as

a heart attack, occurs when blood flow stops to part of the heart causing damage to
the heart muscle. The most common symptom is chest pain or discomfort which may
travel into the shoulder, arm, back, neck, or jaw. Often it is in the center or left side of the
chest and lasts for more than a few minutes. The discomfort may occasionally feel
like heartburn. Other symptoms may include shortness of breath, nausea, feeling faint,
a cold sweat, or feeling tired.[1] About 30% of people have atypical symptoms,[2] with
women more likely than men to present atypically.[3] Among those over 75 years old,
about 5% have had an MI with little or no history of symptoms.[4] An MI may cause heart
failure, an irregular heartbeat, or cardiac arrest.[5][6]

Signs and symptoms

The onset of symptoms in myocardial infarction (MI) is usually gradual, over several
minutes, and rarely instantaneous.[17] Chest pain is the most common symptom of acute
MI and is often described as a sensation of tightness, pressure, or squeezing. Chest pain
due to ischemia(a lack of blood and hence oxygen supply) of the heart muscle is
termed angina pectoris. Pain radiates most often to the left arm, but may also radiate to
the lower jaw, neck, right arm, back, and upper abdomen,[18] where it may
mimic heartburn. Levine's sign, in which a person localizes the chest pain by clenching

Most MIs occur due to coronary artery disease.[5] Risk factors include high blood
pressure, smoking, diabetes, lack of exercise,obesity, high blood cholesterol, poor diet,
and excessive alcohol, among others.[7][8] The mechanism of an MI often involves the
rupture of an atherosclerotic plaque leading to complete blockage of a coronary artery.
[5]
MIs are less commonly caused by coronary artery spasms which may be due
to cocaine, significant emotional stress, and extreme cold, among others.[9][10] A number of
tests are useful to help with diagnosis including electrocardiograms (ECGs), blood tests,
and coronary angiography.[11] An ECG may confirm an ST elevation MI if ST elevation is
present.[2] Commonly used blood tests include troponin and less often creatine kinase
MB.[11]

their fists over their sternum, has classically been thought to be predictive of cardiac

Aspirin is an appropriate immediate treatment for a suspected MI.

[12]
Nitroglycerin or opioids may be used to help with chest pain; however, they do not
improve overall outcomes.[2][12] Supplemental oxygen should be used in those with low
oxygen levels or shortness of breath.[12] In ST elevation MIs treatments which attempt to
restore blood flow to the heart are typically recommended and include angioplasty,
where the arteries are pushed open, or thrombolysis, where the blockage is removed
using medications.[2]People who have a non-ST elevation myocardial infarction (NSTEMI)
are often managed with the blood thinner heparin, with the additional use angioplasty in
those at high risk.[12] In people with blockages of multiple coronary arteries and
diabetes, bypass surgery (CABG) may be recommended rather than angioplasty.[13] After
an MI lifestyle modifications along with long term treatment with aspirin, beta blockers,
and statins is typically recommended.[2]

massive surge of catecholamines from the sympathetic nervous system,[21] which occurs

Worldwide, more than 3 million people have ST elevation MIs and 4 million have
NSTEMIs each year.[14] STEMIs occur about twice as often in men as women. [15] About
one million people have an MI each year in the United States.[5] In the developed world
the risk of death in those who have had an STEMI is about 10%.[2] Rates of MI for a given
age have decreased globally between 1990 and 2010.

and fatigue. Fatigue, sleep disturbances, and dyspnea have been reported as frequently

chest pain, although a prospective observational study showed it had a poor positive
predictive value.[19]
Shortness of breath (dyspnea) occurs when the damage to the heart limits the output of
the left ventricle, causing left ventricular failureand consequent pulmonary edema. Other
symptoms include diaphoresis (an excessive form of sweating),[20] weakness, lightheadedness,nausea, vomiting, and palpitations. These symptoms are likely induced by a
in response to pain and the blood flow abnormalities that result from dysfunction of the
heart muscle.Loss of consciousness (due to inadequate blood flow to the brain
and cardiogenic shock) and sudden death (frequently due to the development
of ventricular fibrillation) can occur in MIs.[18]
Atypical symptoms are more frequently reported by women, the elderly, and those with
diabetes when compared to their male and younger counterparts. [22][23] Women also report
more numerous symptoms compared with men (2.6 on average vs. 1.8 symptoms in
men).[22] The most common symptoms of MI in women include dyspnea, weakness,
occurring symptoms that may manifest as long as one month before the actual clinically
manifested ischemic event. In women, chest pain may be less predictive of coronary

ischemia than in men.[24] Women may also experience back or jaw pain during an

There is little evidence that reducing dietary saturated fat or increasing polyunsaturated

episode.[25]

fat intake affects heart attack risk.[37] Dietary cholesterol also does not appear to have a
significant effect on blood cholesterol and thus recommendations about its consumption

At least one quarter of all MIs are silent, without chest pain or other symptoms. [4] These

may not be needed.[38] Trans fats do appear to increase risk.[37]

cases can be discovered later on electrocardiograms, using blood enzyme tests, or at

autopsy without a prior history of related complaints. Estimates of the prevalence of silent
MIs vary between 22 and 64%.[4] A silent course is more common in the elderly,[4] in
people with diabetes mellitus[26] and after heart transplantation, probably because
the donor heart is not fully innervated by the nervous system of the recipient. [27] In people
with diabetes, differences in pain threshold, autonomic neuropathy,
and psychological factors have been cited as possible explanations for the lack of
symptoms.[26]

Disease
Diabetes mellitus (type 1 or 2),[39] high blood pressure,[32] dyslipidemia/high levels of blood
cholesterol (abnormal levels of lipoproteins in the blood), particularly high low-density

Any group of symptoms compatible with a sudden interruption of the blood flow to the
heart, which includes STEMI, NSTEMI or unstable angina, are called an acute coronary
syndrome.[28]

lipoprotein, low high-density lipoprotein, high triglycerides,[32] and obesity[40] (defined by

a body mass index of more than 30 kg/m, or alternatively by waist circumference
or waist-hip ratio) have all been linked to MI.

Causes

A number of acute and chronic infections including Chlamydophila

Many of the risk factors for myocardial infarction are modifiable and thus many cases

have been linked to atherosclerosis and myocardial infarction. [41] As of 2013, there is no

may be preventable.

evidence of benefit from antibiotics or vaccination, however, calling the association into

pneumoniae, influenza, Helicobacter pylori, and Porphyromonas gingivalis among others

question.[41][42]Myocardial infarction can also occur as a late consequence of Kawasaki

Lifestyle

disease.[43]

Smoking appears to be the cause of about 36% and obesity the cause of 20%

Genetic

of coronary artery disease.[29] Lack of exercise has been linked to 712% of cases.[29]
[30]

Less common causes include stress-related causes such as job stress, which

accounts for about 3% of cases,[29] and chronic high stress levels.[31]

Genome-wide association studies have found 27 genetic variants that are associated
with an increased risk of myocardial infarction.[44] Strongest association of MI has been
found with the 9p21 genomic locus, which contains genes CDKN2A & 2B, although

Tobacco smoking (including secondhand smoke)

[32]

and short-term exposure to air

the single nucleotide polymorphisms that are implicated are within a non-coding region.
The majority of these variants are in regions that have not been previously implicated

pollution such as carbon monoxide, nitrogen dioxide, and sulfur dioxide (but not ozone)

[44]

have been associated with MI.[33] Other factors that increase the risk of MI and are

in coronary artery disease. The following genes have an association with

associated with worse outcomes after an MI include lack of physical activity[34] and

MI: PCSK9, SORT1,MIA3, WDR12, MRAS, PHACTR1, LPA, TCF21, MTHFDSL, ZC3HC

psychosocial factors including low socioeconomic status, social isolation, and negative

1, CDKN2A, 2B, ABO, PDGF0, APOA5, MNF1ASM283, COL4A1, HHIPC1, SMAD3, AD

emotions. Shift work is also associated with a higher risk of MI.[35] Acute and prolonged

AMTS7, RAS1, SMG6,SMG6, SNF8, LDLR, SLC5A3, MRPS6, KCNE2.[44]

intake of high quantities of alcoholic drinks (3-4 or more) increase the risk of a heart
attack.[36]

Other

process of tissue damage following an MI.[55] As a result, the person's heart will be
permanently damaged. This myocardial scarring also puts the person at risk for

At any given age, men are more at risk than women, particularly before menopause,
[45]

but because in general women live longer than men, ischemic heart disease causes

potentially life-threatening abnormal heart rhythms (arrhythmias), and may result in the
formation of a ventricular aneurysm that can rupture with catastrophic consequences.

slightly more total deaths in women.[34] Family history of ischemic heart disease or MI,
particularly if one has a first-degree relative (father, brother, mother, sister) who suffered

Injured heart tissue conducts electrical impulses more slowly than normal heart tissue.

a 'premature' myocardial infarction (defined as occurring at or younger than age 55 years

The difference in conduction velocity between injured and uninjured tissue can trigger re-

(men) or 65 (women).[34]

entry or a feedback loop that is believed to be the cause of many lethal arrhythmias. The
most serious of these arrhythmias is ventricular fibrillation (V-Fib/VF), an extremely fast

Women who use combined oral contraceptive pills have a modestly increased risk of

and chaotic heart rhythm that is the leading cause ofsudden cardiac death. Another life-

myocardial infarction, especially in the presence of other risk factors, such as smoking.

threatening arrhythmia is ventricular tachycardia (V-tach/VT), which can cause sudden

[46]

Heart attacks appear to occur more commonly in the morning hours, especially

cardiac death. However, VT usually results in rapid heart rates that prevent the heart

between 6AM and noon.[47] Evidence suggests that heart attacks are at least three times

from pumping blood effectively. Cardiac output and blood pressuremay fall to dangerous

more likely to occur in the morning than in the late evening.

levels, which can lead to further coronary ischemia and extension of the infarct.

heart attack.

[48]

Old age increases risk of a

[34]

The cardiac defibrillator device was specifically designed to terminate these potentially

Pathophysiology

fatal arrhythmias. The device works by delivering an electrical shock to the person to

Acute myocardial infarction refers to two subtypes of acute coronary syndrome, namely
non-ST-elevated and ST-elevated MIs, which are most frequently (but not always) a
manifestation of coronary artery disease.[49] The most common triggering event is the
disruption of anatherosclerotic plaque in an epicardial coronary artery, which leads to a
clotting cascade, sometimes resulting in total occlusion of the artery.[50][51] Atherosclerosis

depolarize a critical mass of the heart muscle, in effect "rebooting" the heart. This
therapy is time-dependent, and the odds of successful defibrillation decline rapidly after
the onset of cardiopulmonary arrest.
Myocardial infarction in the setting of plaque results from underlying atherosclerosis.
[18]

Inflammation is known to be an important step in the process of atherosclerotic

is the gradual buildup of cholesterol and fibrous tissue in plaques in the wall

plaque formation.[56] C-reactive protein (CRP) is a sensitive but

of arteries (in this case, thecoronary arteries), typically over decades.[52] Bloodstream

nonspecific marker for inflammation. Elevated CRP blood levels, especially measured

column irregularities visible on angiography reflect artery lumen narrowing as a result of

with high-sensitivity assays, can predict the risk of MI, as well as stroke and development

decades of advancing atherosclerosis.[53] Plaques can become unstable, rupture, and

of diabetes.[56] Moreover, some drugs for MI might also reduce CRP levels.[56] The use of

additionally promote the formation of ablood clot that occludes the artery; this can occur

high-sensitivity CRP assays as a means ofscreening the general population is advised

in minutes. When a severe enough plaque rupture occurs in the coronary arteries, it

against, but it may be used optionally at the physician's discretion in those who already

leads to MI (necrosis of downstream myocardium).[50][51] It is estimated that one billion

present with other risk factors or known coronary artery disease.[57] Whether CRP plays a

cardiac cells are lost in a typical MI.

direct role in atherosclerosis remains uncertain.[56]

[54]

If impaired blood flow to the heart lasts long enough, it triggers a process called

Calcium deposition is another part of atherosclerotic plaque formation. Calcium deposits

the ischemic cascade; the heart cells in the territory of the occluded coronary artery die

in the coronary arteries can be detected with CT scans. Several studies have shown that

(chiefly through necrosis) and do not grow back. A collagen scar forms in their place.

coronary calcium can provide predictive information beyond that of classical risk factors.

Recent studies indicate that another form of cell death, apoptosis, also plays a role in the

[58][59][60]

Hyperhomocysteinemia (high blood levels of the amino acid homocysteine)

Classification

in homocysteinuria is associated with premature atherosclerosis;[61] whether elevated

homocysteine in the normal range is causal is controversial.[62]

Myocardial infarctions are generally classified into ST elevation MI (STEMI) and non-ST
elevation MI (NSTEMI).[49] A STEMI is the combination of symptoms related to poor

Pathological types

oxygenation of the heart with elevation of the ST segments on

the electrocardiogram followed by an increase in proteins in the blood related to heart

The two main types of acute myocardial infarction, based on pathology, are:

muscle's death.[15] They make up about 25 to 40 percent of cases.[15]

The phrase "heart attack" is often used non-specifically to refer to a myocardial infarction

Transmural AMI is associated with atherosclerosis involving a major coronary

artery. It can be subclassified into anterior, posterior, inferior, lateral, or septal.

and to sudden cardiac death. An MI is different frombut can causecardiac arrest,

Transmural infarcts extend through the whole thickness of the heart muscle and are

where the heart is not contracting at all or so poorly that all vital organs cease to function.

usually a result of complete occlusion of the area's blood supply.[63] In addition,

It is also distinct from heart failure, in which the pumping action of the heart is impaired.

on ECG, ST elevation and Q waves are seen.

However, an MI may lead to heart failure.[18]

Subendocardial AMI involves a small area in the subendocardial wall of the left
ventricle, ventricular septum, or papillary muscles. The subendocardial area is
particularly susceptible to ischemia.[63] In addition, ST depression may be seen on

A 2007 consensus document classifies MI into five main types:[66]

such as plaque erosion and/or rupture, fissuring, or dissection

ECG in addition to T wave changes.

Diagnosis

ST elevation or depression, or coronary intervention is diagnostic of MI.[64]

Type 2 MI secondary to ischemia due to either increased oxygen demand or

decreased supply, e.g. coronary artery spasm, coronary embolism, anemia,

Main article: Myocardial infarction diagnosis

A cardiac troponin rise accompanied by either typical symptoms, pathological Q waves,

Type 1 spontaneous MI related to ischemia due to a primary coronary event

arrhythmias, hypertension, or hypotension

Type 3 sudden unexpected cardiac death, including cardiac arrest, often with
symptoms suggestive of myocardial ischemia, accompanied by new ST elevation, or

WHO criteria[65] formulated in 1979 have classically been used to diagnose MI; a patient

new left bundle branch block (LBBB), or evidence of fresh thrombus in a coronary

is diagnosed with MI if two (probable) or three (definite) of the following criteria are

artery by angiography and/or at autopsy, but death occurring before blood samples

satisfied:

could be obtained, or at a time before the appearance of cardiac biomarkers in the

blood

1. Clinical history of ischemic type chest pain lasting for more than 20 minutes
2. Changes in serial ECG tracings
3. Rise and fall of serum cardiac biomarkers
At autopsy, a pathologist can diagnose an MI based on anatomopathological findings.

Type 4 associated with coronary angioplasty or stents:

Type 4a MI associated with percutaneous coronary intervention (PCI)

Type 4b MI associated with stent thrombosis as documented by

angiography or at autopsy

Type 5 MI associated with CABG

stressechocardiography can confirm a diagnosis when a patient's history, physical exam,

Electrocardiogram

ECG, and cardiac biomarkers suggest the likelihood of a problem.[71]

For a person to qualify as having a STEMI, in addition to reported angina, the ECG must

Differential diagnosis

show new ST elevation in two or more adjacent ECG leads.[15] This must be greater than
2 mm (0.2 mV) for males and greater than 1.5 mm (0.15mV) in females if in leads V2 and
V3 or greater than 1 mm (0.1 mV) if it is in other ECG leads.[15] A left bundle branch block
that is believed to be new used to be considered the same as ST elevation; however, this
is no longer the case.[15] In early STEMIs there may just be peaked T waves with ST
elevation developing later.[15]

Cardiac biomarkers
While there are a number of different biomarkers, troponins are considered to be the
best[15] and reliance on older tests (such as CK-MB) or myoglobin is discouraged. [67] This
is not the case in the setting of peri-procedural MI where use of troponin and CK-MB
assays are considered useful.[68] Copeptin may be useful to rule out MI rapidly when used
along with troponin.[69]

The differential diagnosis for MI includes other catastrophic causes of chest pain, such
as pulmonary embolism, aortic dissection, esophageal rupture, tension pneumothorax,
orpericardial effusion causing cardiac tamponade. Other noncatastrophic differentials
include gastroesophageal reflux and Tietze's syndrome.[72]

Prevention
Myocardial infarction and other related cardiovascular diseases can be prevented to a
large extent by a number of interventions in terms of lifestyle and medical treatments.
On a population level, public health measures may be used to reduce unhealthy diets
(excessive salt, saturated fat and trans fat) including food labelling and marketing
requirements as well as requirements for catering and restaurants, and stimulating
physical activity. This may be part of regional cardiovascular disease prevention

Imaging

programmes, or through the health impact assessment of regional and local plans and

A chest radiograph and routine blood tests may indicate complications or precipitating

Lifestyle

causes, and are often performed upon arrival to an emergency department. New regional
wall motion abnormalities on an echocardiogram are also suggestive of an MI, and
echocardiography may therefore be performed.
In stable patients whose symptoms have resolved by the time of evaluation, technetium
(99mTc) sestamibi (i.e. a "MIBI scan") or thallium-201 chloride can be used in nuclear
medicine to visualize areas of reduced blood flow in conjunction with physiological or
pharmacological stress. Thallium may also be used to determine viability of tissue,
distinguishing whether nonfunctional myocardium is actually dead or merely in a state of
hibernation or of being stunned. Medical societies and professional guidelines
recommend that the physician confirm a person is at high risk for myocardial infarction
before conducting imaging tests to make a diagnosis.[70][71] Patients who have a normal
ECG and who are able to exercise, for example, do not merit routine imaging. [71] Imaging
tests such as stress radionuclide myocardial perfusion imaging or

policies.[73]

There is some controversy surrounding the effect of dietary fat on the development of
cardiovascular disease. People are often advised to keep a diet where less than 30% of
the energy intake derives from fat, a diet that contains less than 7% of the energy intake
in the form of saturated fat, and a diet that contains less than 300 mg/day of cholesterol.
[74]

Replacing saturated with mono- polyunsaturated fat is also recommended, [74] as the

consumption of polyunsaturated fat instead of saturated fat may decrease coronary heart
disease.[75] Olive oil, rapeseed oil and related products are to be used instead of
saturated fat.[74] Other recommendations include increasing the intake of wholegrain
starch, reducing sugar intake (particularly of refined sugar), consuming five portions of
fruit and vegetables daily, consuming two or more portions of fish per week, and
consuming 45 portions of unsalted nuts, seeds, or legumes per week. [74] Vitamins and
mineral supplements are of no proven benefit,[76] and neither are plant stanols or sterols.
[74]

Physical activity can reduce the risk of cardiovascular disease, and people at risk are

STEMI

advised to engage in 150 minutes of moderate or 75 minutes of vigorous

intensity aerobic exercise a week.[74] Keeping a healthy weight, drinking alcohol within the

The current definitive treatment modalities for MI with ECG evidence of ST elevation

recommended limits, and quitting smoking are measures that also appear to reduce the

(STEMI) include thrombolysis and percutaneous coronary intervention.[87]

risk of cardiovascular disease.[74]

Thrombolysis involves the administration of medication that activates the enzymes that

Medication

normally destroy blood clots. The first thrombolysis agent was streptokinase, but most
thrombolysis agents used currently are artificial forms of the human enzyme tissue

Aspirin has been studied extensively in people considered at increased risk of

plasminogen activator (tPA): reteplase, alteplase, and tenecteplase. They are

myocardial infarction. Based on numerous studies in different groups (e.g. people with or

administered intravenously. Once a STEMI has been diagnosed, and no

without diabetes), there does not appear to be a benefit strong enough to outweigh the

contraindications are present (such as a high risk of bleeding), thrombolysis can be

risk of excessive bleeding.[77][78] Nevertheless, many clinical practice guidelines continue to

administered in the pre-hospital or in-hospital setting. There is inconclusive evidence

recommend aspirin for primary prevention,[79] and some researchers feel that those with

whether pre-hospital thrombolysis reduces death in people with STEMI compared to in-

very high cardiovascular risk but low risk of bleeding should continue to receive aspirin. [80]

hospital thrombolysis.[88] Pre-hospital thrombolysis reduces time to receipt of thrombolytic

treatment, based on studies conducted in higher income countries. [88] If despite

Cholesterol-lowering drugs from the statin class may be used in those at an elevated risk

thrombolysis there is significant cardiogenic shock, continued severe chest pain, or less

of cardiovascular disease; this can be calculated with validated risk prediction tools such

than a 50% improvement in ST elevation on the ECG recording after 90 minutes, then

as QRISK2.[74]

rescue PCI is indicated emergently.[89][90]

Long term hormone replacement therapy when started around the time of menopause

Primary percutaneous coronary intervention (PCI) is the treatment of choice for STEMI if

may decrease heart disease.[81][82]

it can be performed in a hospital in a timely manner.[87][91]

Management

If PCI cannot be performed within 90 to 120 minutes then thrombolysis, preferably within

Main article: Management of acute coronary syndrome

30 minutes of arrival to hospital, is recommended.[89][91][92] After PCI, people are generally

placed on dual antiplatelet therapy for at least a year (which is generally aspirin

An MI requires immediate medical attention. Treatment attempts to save as much viable

and clopidogrel).[15][87][93]

heart muscle as possible and to prevent further complications, hence the phrase "time is
[heart] muscle".[83] Aspirin and nitroglycerin may be administered. Nitroglycerin

Those who have had cardiac arrest may benefit from targeted temperature

(administered under the tongue or intravenously) may be administered to improve the

management with evaluation for implementation of hypothermia protocols. Furthermore

blood supply to the heart.

those with cardiac arrest, and ST elevation at any time, should usually have angiography.

[67]

[67]

Morphine may be used if nitroglycerin is not effective.

Other analgesics such as nitrous oxide are of unknown benefit.

[84]

In the past, high flow oxygen was recommended for everyone with possible myocardial

[94]

NSTEMI

infarction.[67] More recently, routine use was found to lead to increased mortality and
infarct size.[85][86] Therefore, oxygen is currently only used if oxygen levels are found to be

In the absence of ST elevation, formal diagnosis of MI is delayed until a blood test for

low or someone is in respiratory distress.[67]

biomarkers (usually troponin) can be performed; this is 36 hours after the onset of
symptoms. The scenario is referred to as "non-ST elevation acute coronary syndrome"

(NSTEACS). In the meantime, the calculated risk of further cardiovascular events (e.g.

healthy weight.[98]Exercise is both safe and effective even if people have had stents or

using the GRACE score)[70] and the presence of other ECG changes and clinical

heart failure.[99]

features[67] determines ongoing management.

People are usually started on several long-term medications after an MI, with the aim of
People with an acute coronary syndrome where no ST elevation is demonstrated (non-

preventing further cardiovascular events such as MIs, congestive heart failure,

ST elevation ACS or NSTEACS) are treated with aspirin. [67][70] Clopidogrel is added in

or strokes.

many cases, particularly if the risk of cardiovascular events is felt to be high and early
PCI is being considered.[67][70] Depending on whether early PCI is planned, an inhibitor of

Aspirin as well as another antiplatelet agent such as clopidogrel or ticagrelor

antithrombin (fondaparinux or low molecular weight heparin) may be added.[70] In very

("dual antiplatelet therapy" or DAPT) is continued for up to twelve months, followed

high-risk scenarios, inhibitors of the platelet glycoprotein IIb3a receptor such

by aspirin indefinitely.[98] If someone has another medical condition that requires

as eptifibatideor tirofiban may be used.

anticoagulation (e.g. with warfarin) this may need to be adjusted based on risk of

[67][70]

further cardiac events as well as bleeding risk.[98] In those who have had a stent,

Heparins in those who have had an NSTEMI or unstable angina do not change the risk

more than 12 months of clopidogrel plus aspirin does not affect the risk of death. [100]

of death.[95] They do decrease the risk of having a further myocardial infarction. [95]
As of 2011, P2Y12 inhibitors are recommended for 12 months following NSTEMI in

Beta blocker therapy such as metoprolol or carvedilol is recommended to be

started within 24 hours, provided there is no acute heart failure or heart block.[15][67]

Europe.[96] A 2014 review of P2Y12 inhibitors such as clopidogrel found they do not

The dose should be increased to the highest tolerated. [98] Contrary to what was

change the risk of death when given to people with a suspected NSTEMI prior to PCI.

[98]

They do however increase the risk of bleeding and decrease the risk of further

long believed, the use of beta blockers does not appear to affect the risk of death,

cardiovascular problems. The authors thus concluded that their routine use prior to PCI

possibly because other treatments for MI have improved.[101] They should not be used

is of questionable value.[97]

in those who have recently taken cocaine.[102]

Cardiac rehabilitation

the highest tolerated dose. Those who cannot tolerate ACE inhibitors may be treated

Cardiac rehabilitation benefits many who have experienced myocardial infarction, even if

with anangiotensin II receptor antagonist.[98]

there has been substantial heart damage and resultant left ventricular failure; ideally
other medical conditions that could interfere with participation should be managed
optimally. It should start soon after discharge from hospital. The program may include

ACE inhibitor therapy should be started when stable and continued indefinitely at

Statin therapy has been shown to reduce mortality and morbidity.[103] The
protective effects of statins may be due to more than their LDL lowering effects. The

lifestyle advice, exercise, social support, as well as recommendations about driving,

general consensus is that statins have the ability to stabilize plaques and multiple

flying, sport participation, stress management, and sexual intercourse.[98]

other ("pleiotropic") effects that may prevent myocardial infarction in addition to their

Secondary prevention
A number of lifestyle recommendations are available to those who have experienced

effects on blood lipids.[104]

Aldosterone antagonists (spironolactone or eplerenone) may be used if there is

myocardial infarction. This includes the adoption of a Mediterranean-type

evidence of left ventricular dysfunction after an MI, ideally after beginning treatment

diet, maintaining alcohol intake within recommended limits, exercising to the point of mild

with an ACE inhibitor.[98]

breathlessness for 2030 minutes every day, stopping smoking, and trying to achieve a

Previous studies suggested a benefit from omega-3 fatty acid supplementation

rupture;mitral regurgitation, in particular if the infarction causes dysfunction of the

papillary muscle; Dressler's syndrome; and abnormal heart rhythms, such as ventricular

but this has not been confirmed.[98]

fibrillation, ventricular tachycardia, atrial fibrillation, and heart block. Longer-term

Prognosis

complications include heart failure, atrial fibrillation, and an increased risk of a second

The prognosis after MI varies greatly depending on a person's health, the extent of the

MI.

Epidemiology

heart damage, and the treatment given.

In those who have an STEMI in the United States, between 5 to 6 percent die before

Myocardial infarction is a common presentation of coronary artery disease. The World

leaving the hospital and 7 to 18 percent die within a year.

Health Organization estimated in 2004, that 12.2% of worldwide deaths were from

[15]

ischemic heart disease;[113] with it being the leading cause of death in high- or middleUsing variables available in the emergency room, people with a higher risk of adverse

income countries and second only to lower respiratory infections in lower-income

outcome can be identified. One study found 0.4% of patients with a low-risk profile died

countries.[113]Worldwide, more than 3 million people have STEMIs and 4 million have

after 90 days, whereas in high-risk people it was 21.1%.[105]

NSTEMIs a year.[14] STEMIs occur about twice as often in men as women.[15]

Some risk factors for death include age, hemodynamic parameters (such as heart

Rates of death from ischemic heart disease (IHD) have slowed or declined in most high-

failure, cardiac arrest on admission, systolic blood pressure, or Killip class of two or

income countries, although cardiovascular disease still accounted for one in three of all

greater), ST-segment deviation, diabetes, serum creatinine, peripheral vascular disease,

deaths in the USA in 2008.[114] In contrast, IHD is becoming a more common cause of

and elevation of cardiac markers.[105][106][107] Assessment of left ventricular ejection

death in the developing world. For example in India, IHD had become the leading cause

fraction may increase the predictive power.

of death by 2004, accounting for 1.46 million deaths (14% of total deaths) and deaths

[108]

Prognosis is worse if a mechanical

complication such as papillary muscle or myocardial free wall rupture occurs. [109] Morbidity

due to IHD were expected to double during 19852015. [115] Globally, disability adjusted life

and mortality from myocardial infarction has improved over the years due to better

years (DALYs) lost to ischemic heart disease are predicted to account for 5.5% of total

treatment.[110]

DALYs in 2030, making it the second-most-important cause of disability (after unipolar

Throughout hospital departments, practitioners use TIMI scores to assess mortality risk.
There are TIMI (Thrombolysis in Myocardial Infarction) scores for unstable angina or
NSTEMI

[111]

and STEMI,

[112]

depressive disorder), as well as the leading cause of death by this date. [113]

Society and culture

both using routine patient data from history taking, medication

use and lab results. Both scores have been found effective and reliable in multiple

In the United States, women who have had an MI are often treated with fewer medical

settings, including the emergency room.

interventions than men.[15]

Complications

Economics

Main article: Myocardial infarction complications

In 2011, AMI was one of the top five most expensive conditions seen during inpatient
Complications may occur immediately following the heart attack (in the acute phase), or

hospitalizations in the U.S., with an aggregate cost of about $11.5 billion for 612,000

may need time to develop (a chronic problem). Acute complications may include heart

hospital stays.[116]

failure if the damaged heart is no longer able to pump blood adequately around the
body; aneurysm of the left ventricle myocardium; ventricular septal rupture or free wall

Legal implications
At common law, in general, a myocardial infarction is a disease, but may sometimes be
an injury. This can create coverage issues in administration of no-fault insurance
schemes such as workers' compensation. In general, a heart attack is not covered;
[117]

however, it may be a work-related injury if it results, for example, from unusual

emotional stress or unusual exertion.[118] In addition, in some jurisdictions, heart attacks

suffered by persons in particular occupations such as police officers may be classified as
line-of-duty injuries by statute or policy. In some countries or states, a person having
suffered from an MI may be prevented from participating in activity that puts other
people's lives at risk, for example driving a car or flying an airplane. [119]

Etymology

Hemopericardium

Myocardial infarction Latin: infarctus myocardii.

From Wikipedia, the free encyclopedia

Research

Hemopericardium refers to blood in the pericardial sac of the heart. It is clinically similar
to a pericardial effusion, and, depending on the volume and rapidity with which it
develops, may cause cardiac tamponade.[1]

One study demonstrated that patients who receive stem cell treatment by coronary
artery injections of stem cells derived from their own bone marrow after an MI show small
but statistically significant improvements in left ventricular ejection fraction and enddiastolic volume not seen with placebo. The larger the initial infarct size, the greater the

The condition can be caused by full-thickness necrosis (death) of the myocardium (heart
muscle) after myocardial infarction, as well as trauma, [2] Tuberculosis, and in patients
receiving anticoagulants.[3][4] Other causes include ruptured aneurysm of sinus of Valsalva
and other aneurysms of the aortic arch.

effect of the infusion. Clinical trials of progenitor cell infusion as a treatment approach to
STEMI are underway.[120]
Currently, three biomaterial and tissue engineering approaches are used for the
treatment of post-MI conditions, but these are in an even earlier stage of medical
research. Many questions and issues must be addressed before they can be applied to
patients. The first involves polymeric left ventricular restraints in the prevention of heart
failure. The second uses in vitro-engineered cardiac tissue, which is subsequently
implanted in vivo. The final approach entails injecting cells and/or a scaffold into the
myocardium to create in situ-engineered cardiac tissue.

Atrial septal defect

From Wikipedia, the free encyclopedia

Atrial septal defect (ASD) is a congenital heart defect in which blood flows between
the atria (upper chambers) of theheart. Normally, the atria are separated by a dividing
wall, the interatrial septum. If this septum is defective or absent, then oxygen-rich blood
can flow directly from the left side of the heart to mix with the oxygen-poor blood in the
right side of the heart, or vice versa.[1] This can lead to lower-than-normal oxygen levels
in the arterial blood that supplies the brain, organs, and tissues. However, an ASD may
not produce noticeable signs or symptoms, especially if the defect is small.
A "shunt" is the presence of a net flow of blood through the defect, either from left to right
or right to left. The amount of shunting present, if any, determines the hemodynamic

significance of the ASD. A "right-to-left-shunt" typically poses the more dangerous

scenario.

Classification[edit]

During development of the fetus, the interatrial septum develops to separate

the left and right atria. However, a hole in the septum called the foramen ovale, allows
blood from the right atrium to enter the left atrium during fetal development. This opening
allows blood to bypass the nonfunctional fetal lungs while the fetus obtains its oxygen
from the placenta. A layer of tissue called the septum primum acts as a valve over the
foramen ovale during fetal development. After birth, the pressure in the right side of the
heart drops as the lungs open and begin working, causing the foramen ovale to close
entirely. In approximately 25% of adults,[2] the foramen ovale does not entirely seal.[3] In
these cases, any elevation of the pressure in the pulmonary circulatory system (due
to pulmonary hypertension, temporarily while coughing, etc.) can cause the foramen
ovale to remain open. This is known as a patent foramen ovale (PFO), which is a type of
atrial septal defect.

Although there are several classifications for VSD, the most accepted and unified
classification is that of Congenital Heart Surgery Nomenclature and Database Project.
[4]

The classification is based on the location of the VSD on the right ventricular surface of

the inter ventricular septum and is as follows:

1. Multiple
2. Type 1 (Subarterial) (Supracristal) (Conal septal defect)
(Infundibular)

Found in 5-7% of patients, more in Asians, related to the pulmonary valve

3. Type 2 (Perimembranous) (Paramembranous)

(Conoventricular)

Most common variety found in 70%

4. Type 3 (Inlet) (AV canal type)

Ventricular septal defect

From Wikipedia, the free encyclopedia

Ventricular septal defect

A ventricular septal defect (VSD) is a defect in the ventricular septum, the wall dividing
the left and right ventricles of theheart.
The ventricular septum consists of an inferior muscular and superior membranous
portion and is extensively innervated with conducting cardiomyocytes.
The membranous portion, which is close to the atrioventricular node, is most commonly
affected in adults and older children in the United States.[1] It is also the type that will most
commonly require surgical intervention, comprising over 80% of cases.[2]
Membranous ventricular septal defects are more common than muscular ventricular
septal defects, and are the most common congenital cardiac anomaly.

Commonly associated with atrioventricular septal defect, found in about 5%

5. Type 4 (Muscular)

Located in the muscular septum, found in 20%. Can be sub classified again
based on the location into anterior, apical, posterior and mid

6. Type: Gerbode (Left ventricular to right atrial

communication)
Signs and symptoms
Ventricular septal defect is usually symptomless at birth. It usually manifests a few weeks
after birth.

Symptoms
VSD is an acyanotic congenital heart defect, aka a Left-to-right shunt, so there are no
signs of cyanosis in the early stage. However, uncorrected VSD can increase pulmonary
resistance leading to the reversal of the shunt and corresponding cyanosis.

Signs

This effect is more noticeable in patients with larger defects, who may present with
breathlessness, poor feeding and failure to thrive in infancy. Patients with smaller defects

Pansystolic (Holosystolic) murmur along lower left sternal

may be asymptomatic. Four different septal defects exist, with perimembranous most
common, outlet, atrioventricular, and muscular less commonly.[7]

border(depending upon the size of the defect) +/- palpable thrill (palpable turbulence of
blood flow). Heart sounds are normal. Larger VSDs may cause a parasternal heave, a

Diagnosis

displaced apex beat (the palpable heartbeat moves laterally over time, as the heart
enlarges). An infant with a large VSD will fail to thrive and become sweaty and

A VSD can be detected by cardiac auscultation. Classically, a VSD causes a

tachypnoeic (breathe faster) with feeds.[5]

pathognomonic holo- or pansystolic murmur. Auscultation is generally considered

sufficient for detecting a significant VSD. The murmur depends on the abnormal flow of

The restrictive VSDs (smaller defects) are associated with a louder murmur and more

blood from the left ventricle, through the VSD, to the right ventricle. If there is not much

palpable thrill (grade IV murmur). Larger defects may eventually be associated with

difference in pressure between the left and right ventricles, then the flow of blood through

pulmonary hypertension due to the increased blood flow. Over time this may lead to

the VSD will not be very great and the VSD may be silent. This situation occurs a) in the

an Eisenmenger's_syndrome the original VSD operating with a left-to-right shunt, now

fetus (when the right and left ventricular pressures are essentially equal), b) for a short

becomes a right-to-left shunt because of the increased pressures in the pulmonary

time after birth (before the right ventricular pressure has decreased), and c) as a late

vascular bed.

complication of unrepaired VSD. Confirmation of cardiac auscultation can be obtained by

non-invasive cardiac ultrasound (echocardiography). To more accurately measure

CAUSES: The cause of VSD (ventricular septal defect) includes the incomplete looping

ventricular pressures, cardiac catheterization, can be performed.

of the heart during days 24-28 of development. Faults with NKX2.5 gene can cause this.

Pathophysiology

Treatment

During ventricular contraction, or systole, some of the blood from the left ventricle leaks
into the right ventricle, passes through the lungs and reenters the left ventricle via the

Most cases do not need treatment and heal at the first years of life. Treatment is either

pulmonary veins and left atrium. This has two net effects. First, the circuitous refluxing of

conservative or surgical. Smaller congenital VSDs often close on their own, as the heart

blood causes volume overload on the left ventricle. Second, because the left ventricle

grows, and in such cases may be treated conservatively. Some cases may necessitate

normally has a much higher systolic pressure (~120 mmHg) than the right ventricle

surgical intervention, i.e. with the following indications:

(~20 mmHg), the leakage of blood into the right ventricle therefore elevates right
ventricular pressure and volume, causing pulmonary hypertension with its associated
symptoms.
In serious cases, the pulmonary arterial pressure can reach levels that equal the
systemic pressure. This reverses the left to right shunt, so that blood then flows from the
right ventricle into the left ventricle, resulting in cyanosis, as blood is by-passing the
lungs for oxygenation.[6]

1. Failure of congestive cardiac failure to respond to medications

2. VSD with pulmonic stenosis
3. Large VSD with pulmonary hypertension
4. VSD with aortic regurgitation

For the surgical procedure, a heart-lung machine is required and a median sternotomy is

right heart catheter is inserted into the patient through the femoral vein and the VSD is

performed. Percutaneous endovascular procedures are less invasive and can be done

crossed in a retrograde fashion.[9] The catheter is then replaced with a softer wire.[9] This

on a beating heart, but are only suitable for certain patients. Repair of most VSDs is

new wire is directed into the pulmonary artery, snared, then exteriorized through the

complicated by the fact that the conducting system of the heart is in the immediate

femoral vein.[9] This will form a stable arteriovenous loop.[9] The Amplatzer Septal

vicinity.

Occluder is then pushed to the tip of the delivery cable and the first disc is inserted into
the left ventricle.[9] With a slight pull of the device the middle-connecting waist is released

Ventricular septum defect in infants is initially treated medically with cardiac

and the delivery cable is in the right ventricle of the heart. [9] The right ventricular disc is

glycosides (e.g., digoxin 10-20 g/kg per day),loop diuretics (e.g., furosemide 13 mg/kg

deployed by yet another pull of the delivery cable. [9] TEE is performed before and after

per day) and ACE inhibitors (e.g., captopril 0.52 mg/kg per day).

implantation of the device to ensure proper placement.[9]

Amplatzer Septal Occluder

Advantages and Disadvantages

Composition of the Device

The Amplatzer Septal Occluder was shown to have full closure of the ventricular defect
The Amplatzer Septal Occluden is a device originally used to close openings between

within the 24 hours of placement.[9] It has a low risk of embolism after implantation.

the left and right atrium of the heart.[8] It is now also used to close ventricular septal

[12]

defects (VSD) in the heart. It is a self-expandable device made of Nitril wire consisting

be due from the right ventricular disc.[9] There have been some reports that the

of 2 flat discs separated by a central connecting waist.[10] The discs contain some Dacron

Amplatzer Septal Occluder may cause life-threatening erosion of the tissue inside the

fabric to enhance local thrombosis for proper healing post insertion of the device. [11] The

heart.[13] This occurs in one percent of the patients implanted with the device and requires

diameter of the discs is 8mm larger than the central connecting waist, which determines

immediate open-heart surgery.[13] This erosion occurs due to improper sizing of the device

the size of the device.[10] It contains a higher waist-to-disc ratio compared to other

resulting with it being too large for the defect, causing rubbing of the septal tissue and

occluders.[12] The Amplatzer delivery system of includes a delivery cable and a pusher

erosion.[13]

[9]

catheter to allow for proper insertion of the device into the septal defect. [10] The device is
designed to block the hole in the membranous septum, with the discs lying on both sides
of the wall surrounding the hole.[10] Cardiac tissue is naturally developed around the
Amplatzer, becoming part of the membranous septum and sealing the defective hole.
[10]

Amplatzer is not to be used for patients with infections, extensive cardiac

abnormalities, blood clots or patients who are allergic to nickel or cannot use bloodthinners.[8]
The non-surgical procedure
The Amplatzer Septal Occluder comes in different sizes and the size is determined by
the area of the defect, which is measured at the end of diastole.[9] The non-surgical
installation procedure is done with the aid of trans-esophageal echocardiogram (TEE)
and fluoroscopic monitoring.[9] There is also an angiogram in the long axial oblique view
for viewing of the left ventricle during the procedure. [9] For closure of a VSD, a left and

Some tricuspid valve regurgitation was shown after the procedure that could possibly

Surgery
a) Surgical closure of a Perimembranous VSD is performed on cardiopulmonary bypass
with ischemic arrest. Patients are usually cooled to 28 degrees. Percutaneous Device
closure of these defects is rarely performed in the United States because of the reported
incidence of both early and late onset complete heart block after device closure,
presumably secondary to device trauma to the AV node.
b) Surgical exposure is achieved through the right atrium. The tricuspid valve septal
leaflet is retracted or incised to expose the defect margins.
c) Several patch materials are available, including native pericardium, bovine
pericardium, PTFE (Gore-Tex or Impra), or Dacron.

d) Suture techniques include horizontal pledgeted mattress sutures, and running

A VSD can also form a few days after a myocardial infarction[18] (heart attack) due to

polypropylene suture.

mechanical tearing of the septal wall, before scar tissue forms, when macrophages start
remodeling the dead heart tissue.

e) Critical attention is necessary to avoid injury to the conduction system located on the
left ventricular side of the interventricular septum near the papillary muscle of the conus.
f) Care is taken to avoid injury to the aortic valve with sutures.

Myocardial rupture

g) Once the repair is complete, the heart is extensively deaired by venting blood through
the aortic cardioplegia site, and by infusing Carbon Dioxide into the operative field to
displace air.

Myocardial rupture is a laceration or tearing of the wall of the ventricles or atria of

the heart, of the interatrial or interventricular septum, or of the papillary muscles. It is
most commonly seen as a serious sequela of an acute myocardial infarction (heart
attack).

h) Intraoperative transesophageal echocardiography is used to confirm secure closure of

the VSD, normal function of the aortic and tricuspid valves, good ventricular function, and

It can also be caused by trauma.

the elimination of all air from the left side of the heart.

Etiology

i) The sternum, fascia and skin are closed, with potential placement of a local anesthetic
infusion catheter under the fascia, to enhance postoperative pain control.
j) A video of Perimembranous VSD repair, including the operative technique, and the
daily postoperative recovery, can be seen here: VSD Repair, Perimembranous
Ventricular Septal Defect i

Epidemiology and Etiology

The most common cause of myocardial rupture is a recent myocardial infarction, with the
rupture typically occurring three to five days after infarction.[2] Other causes of rupture
include cardiac trauma, endocarditis (infection of the heart), cardiac tumors, infiltrative
diseases of the heart,[3] and aortic dissection.
Risk factors for rupture after an acute myocardial infarction include female gender,[5]
[6]
[5]

advanced age of the individual,[5][6] first ischemic event, and a low body mass index.
Other presenting signs associated with myocardial rupture include a pericardial friction

VSDs are the most common congenital cardiac abnormalities. They are found in 30-60%

rub, sluggish flow in the coronary artery after it is opened i.e. revascularized with

of all newborns with a congenital heart defect, or about 2-6 per 1000 births. During heart

anangioplasty, the left anterior descending artery being often the cause of the acute MI,[5]

formation, when the heart begins life as a hollow tube, it begins to partition, forming

[6][7]

septa. If this does not occur properly it can lead to an opening being left within the
ventricular septum. It is debatable whether all those defects are true heart defects, or if
some of them are normal phenomena, since most of the trabecular VSDs close
spontaneously.[14]Prospective studies give a prevalence of 2-5 per 100 births of trabecular
VSDs that closes shortly after birth in 80-90% of the cases.[15][16]
Congenital VSDs are frequently associated with other congenital conditions, such
as Down syndrome.[17]

and delay of revascularization greater than 2 hours.[6]

Incidence
The incidence of myocardial rupture has decreased in the era of urgent revascularization
and aggressive pharmacological therapy for the treatment of an acute myocardial
infarction. However, the decrease in the incidence of myocardial rupture is not uniform;
there is a slight increase in the incidence of rupture if thrombolytic agents are used to
abort a myocardial infarction.[8] On the other hand, if primary percutaneous coronary
intervention is performed to abort the infarction, the incidence of rupture is significantly

lowered.[6]The incidence of myocardial rupture if PCI is performed in the setting of an

(wherein the ventricles are incapable of filling and are thus incapable producing

acute myocardial infarction is about 1 percent.[5]

adequate stroke volume).

Classification[edit]
Myocardial ruptures can be classified as one of three types.

Type I myocardial rupture is an abrupt slit-like tear that generally occurs within 24
hours of an acute myocardial infarction.

Type II is an erosion of the infarcted myocardium, which is suggestive of a slow

tear of the dead myocardium. Type II ruptures typically occur more than 24 hours

Signs and symptoms

Symptoms of myocardial rupture are recurrent or persistent chest pain, syncope,
and distension of jugular vein.

Diagnosis

after the infarction occurred.

Due to the acute hemodynamic deterioration associated with myocardial rupture, the

Type III ruptures are characterized by early aneurysm formation and subsequent
rupture of the aneurysm.[9]

diagnosis is generally made based on physical examination, changes in the vital signs,
and clinical suspicion. The diagnosis can be confirmed with echocardiography. The
diagnosis is ultimately made at autopsy.

Another method for classifying myocardial ruptures is by the anatomical portion of the
heart that has ruptured. By far the most dramatic is rupture of the free wall of the left or
right ventricles, as this is associated with immediate hemodynamic collapse and death
secondary to acute pericardial tamponade. Rupture of the interventricular septum will
cause aventricular septal defect. Rupture of a papillary muscle will cause acute mitral
regurgitation.

Treatment
The treatment for myocardial rupture is supportive in the immediate setting and surgical
correction of the rupture, if feasible. A certain small percentage of individuals do not seek
medical attention in the acute setting and survive to see the physician days or weeks
later. In this setting, it may be reasonable to treat the rupture medically and delay or

The rupture will most often occur near the edge of the necrotic myocardium where it

avoid surgery completely, depending on the individual's comorbid medical issues.

abuts healthy (but hyperemic) myocardium where the inflammatory response is at its

Prognosis

greatest. Further, the rupture will occur in an area of greatest shear stress. Within the left
ventricle, these areas are adjacent to both anterior and posterior papillary muscles
(regardless of whether the papillary muscle is involved in the infarction).
Left ventricular free wall rupture almost always results in hemopericardium (the exception
being in the scenario where the patient has had prior open heart surgery and has
obliterative fibrous pericardial adhesions; these would prevent egress of blood) and
pericardial tamponade. An accumulation of as little as 75 ml of blood, acquired acutely in
a patient without pre-existing pericardial effusion, is sufficient to produce tamponade

The prognosis of myocardial rupture is dependent on a number of factors, including

which portion of the myocardium is involved in the rupture. In one case series, if
myocardial rupture involved the free wall of the left ventricle, the mortality rate was
100.0%.[5] The chances of survival rise dramatically if the patient: 1. has a witnessed
initial event; 2. seeks early medical attention; 3. has an accurate diagnosis by the
emergentologist; and 4. happens to be at a facility that has a cardiac surgery service (by
whom a quickand heroicrepair of the rupture can be attempted). Even if the
individual survives the initial hemodynamic sequelae of the rupture, the 30 day mortality
is still significantly higher than if rupture did not occur.

Endothelial cell injury

Causes of injury to the vessel's wall include trauma, surgery, infection or turbulent flow at
bifurcations. The main mechanism is exposure of tissue factor to the blood coagulation
system.[6]

Thrombosis

Disturbed blood flow

Further information: Blood flow

Thrombosis (Greek: ) is the formation of a blood clot (thrombus; Greek:

) inside a blood vessel, obstructing the flow of blood through the circulatory
system. When a blood vessel is injured, the body uses platelets (thrombocytes)
and fibrin to form a blood clot to prevent blood loss. Even when a blood vessel is not
injured, blood clots may form in the body under certain conditions. A clot that breaks free
and begins to travel around the body is known as an embolus.[1][2]
When a thrombus is significantly large enough to reduce the blood flow to a
tissue, hypoxia (oxygen deprivation) can occur and metabolic products such as lactic
acid can accumulate. A larger thrombus causing a much greater obstruction to the blood
flow may result in anoxia, the complete deprivation of oxygen and infarction, tissue
death. There are also a number of other conditions that can arise according to the
location of the thrombus and the organs affected.
Thromboembolism is the combination of thrombosis and its main
complication, embolism.

Causes
Main article: Virchow's triad
The main causes of thrombosis are given in Virchow's triad which

Causes of disturbed blood flow include stagnation of blood flow past the point of injury,
or venous stasis which may occur in heart failure,[6] in or after long periods of sedentary
behavior, such as sitting on a long airplane flight. Also, atrial fibrillation, causes stagnant
blood in the left atrium (LA) or left atrial appendage (LAA), and can lead to a
thromboembolism.[6] Cancers or malignancies such as leukemia may cause increased
risk of thrombosis by possible activation of the coagulation system by cancer cells or
secretion of procoagulant substances (paraneoplastic syndrome), by external
compression on a blood vessel when a solid tumor is present, or (more rarely) extension
into the vasculature (for example, renal cell cancers extending into the renal veins).
[6]

Also, treatments for cancer (radiation, chemotherapy) often cause additional

hypercoagulability.[6]

Classification
There are two distinct forms of thrombosis, venous thrombosis and arterial thrombosis,
each of which can be presented by several subtypes.

lists hypercoagulability, endothelial cell injury, and disturbed blood flow.

Venous thrombosis

Hypercoagulability

Main article: Venous thrombosis

Main article: Thrombophilia

Hypercoagulability or thrombophilia, is caused by, for example, genetic deficiencies or
autoimmune disorders. Recent studies indicate that neutrophils play a pivotal role in
deep vein thrombosis, mediating numerous pro-thrombotic actions.[3][4][5]

Venous thrombosis is the formation of a thrombus (blood clot) within a vein. There are
several diseases which can be classified under this category:
Deep vein thrombosis
Main article: Deep vein thrombosis
Deep vein thrombosis (DVT) is the formation of a blood clot within a deep vein. It most
commonly affects leg veins, such as the femoral vein. Three factors are important in the

formation of a blood clot within a deep veinthese are the rate of blood flow, the

Paget-Schroetter disease is the obstruction of an upper extremity vein (such as

thickness of the blood and qualities of the vessel wall. Classical signs of DVT

the axillary vein or subclavian vein) by a thrombus. The condition usually comes to light

include swelling, pain and redness of the affected area.

after vigorous exercise and usually presents in younger, otherwise healthy people. Men
are affected more than women.

Portal vein thrombosis

Main article: Portal vein thrombosis

Cerebral venous sinus thrombosis

Main article: Cerebral venous sinus thrombosis

Portal vein thrombosis affects the hepatic portal vein, which can lead to
portal hypertension and reduction of the blood supply to the liver.[7] It usually has a

Cerebral venous sinus thrombosis (CVST) is a rare form of stroke which results from the

pathological cause such as pancreatitis, cirrhosis, diverticulitis or cholangiocarcinoma.

blockage of the dural venous sinuses by a thrombus. Symptoms may include headache,
abnormal vision, any of the symptoms of stroke such as weakness of the face and limbs

Renal vein thrombosis

on one side of the body and seizures. The diagnosis is usually made with a CT or MRI

Main article: Renal vein thrombosis

scan. The majority of persons affected make a full recovery. The mortality rate is 4.3%.[9]

Renal vein thrombosis is the obstruction of the renal vein by a thrombus. This tends to

Cavernous sinus thrombosis

lead to reduced drainage from the kidney. Anticoagulation therapy is the treatment of

Main article: Cavernous sinus thrombosis

choice.
Cavernous sinus thrombosis is a specialised form of cerebral venous sinus thrombosis,
Jugular vein thrombosis

where there is thrombosis of the cavernous sinus of the basal skull dura, due to the

Main article: Jugular vein thrombosis

retrograde spread of infection and endothelial damage from the danger triangle of the

Jugular vein thrombosis is a condition that may occur due to infection, intravenous drug
use or malignancy. Jugular vein thrombosis can have a varying list of complications,
including: systemic sepsis, pulmonary embolism, and papilledema. Though characterized
by a sharp pain at the site of the vein, it can prove difficult to diagnose, because it can
occur at random.[8]
Budd-Chiari syndrome

face. The facial veins in this area anastomose with the superior and inferior ophthalmic
veins of the orbit, which drain directly posteriorly into the cavernous sinus through
the superior orbital fissure. Staphyloccoal or Streptococcal infections of the face, for
example nasal or upper lip pustules may thus spread directly into the cavernous sinus,
causing stroke-like symptoms of double vision, squint, as well as spread of infection to
causemeningitis.

Arterial thrombosis

Main article: Budd-Chiari syndrome

Arterial thrombosis is the formation of a thrombus within an artery. In most cases, arterial
Budd-Chiari syndrome is the blockage of the hepatic vein or the inferior vena cava. This

thrombosis follows rupture of atheroma, and is therefore referred to as atherothrombosis.

form of thrombosis presents with abdominal pain, ascites and hepatomegaly. Treatment
varies between therapy and surgical intervention by the use of shunts.

Another common cause of arterial occlusion is atrial fibrillation, which causes a blood
stasis within the atria with easy thrombus formation. In addition, it is well known that the

Paget-Schroetter disease

direct current cardioversion of atrial fibrillation carries a great risk of thromboembolism,

Main article: Paget-Schroetter disease

especially if persisting more than 48 hours. Thromboembolism strikes approximately 5%

of cases not receiving anticoagulant therapy. When cardiac rhythm is restored clots are

Natural history

pushed out from atria to ventricles and from these to the aorta and its branches. [10]
If a thrombus forms inside a blood vessel, without medical intervention the thrombosis
Arterial thrombosis can embolize and is a major cause of arterial embolism, potentially

may proceed to several possible outcomes:[citation needed]

causing infarction of almost any organ in the body.

1. Embolisation: the thrombus detaches from the underlying endothelial wall,
Stroke

leading to distal embolisation and vessel occlusion. An arterial

Main article: Stroke

thromboembolus may lead to astroke, central retinal artery occlusion, ischaemic

A stroke is the rapid decline of brain function due to a disturbance in the supply of blood
to the brain. This can be due to ischemia, thrombus, embolus (a lodged particle)
orhemorrhage (a bleed). In thrombotic stroke, a thrombus (blood clot) usually forms
around atherosclerotic plaques. Since blockage of the artery is gradual, onset of
symptomatic thrombotic strokes is slower. Thrombotic stroke can be divided into two
categorieslarge vessel disease and small vessel disease. The former affects vessels
such as the internal carotids, vertebral and the circle of Willis. The latter can affect
smaller vessels such as the branches of the circle of Willis.

limb, mesenteric ischaemia or some form of localised ischaemia depending on

the arterial circulation of the embolus. A venous thromboembolus may occlude
the pulmonary artery leading to pulmonary embolism.
2. Lysis: the thrombus may be acutely lysed by circulatory plasmin. This is
essentially the physiological equivalent to
pharmacological thrombolysis performed in the hospital.
3. Ischaemia/infarction: if an arterial thrombus cannot be lysed by the body and it

Myocardial infarction

does not embolise, and if the thrombus is large enough to impair or occlude

Main article: Myocardial infarction

blood flow in the involved artery, then local ischaemia or infarction will result.
A venous thrombus may or may not be ischaemic, since veins distribute

Myocardial infarction (MI) or heart attack, is caused by ischemia, (restriction in the blood
supply), often due to the obstruction of a coronary artery by a thrombus. This restriction
gives an insufficient supply of oxygen to the heart muscle which then results in tissue
death,(infarction). A lesion is then formed which is the infarct. MI can quickly become
fatal if emergency medical treatment is not received promptly. If diagnosed within 12
hours of the initial episode (attack) then thrombolytic therapy is initiated.

deoxygenated blood that is less vital for cellular metabolism. Nevertheless, nonischaemic venous thrombosis may still be problematic, due to the swelling
caused by blockage to venous drainage. In deep vein thrombosis this manifests
as pain, redness, and swelling; in retinal vein occlusion this may result
in macular oedema and visual acuity impairment, which if severe enough can
lead to blindness.

Other sites
4. Organisation: following the thrombotic event, residual vascular thrombus will be
Hepatic artery thrombosis usually occurs as a devastating complication after liver

re-organised histologically with several possible outcomes. For an occlusive

transplantation.

thrombus (defined as thrombosis within a small vessel that leads to complete

[11]

An arterial embolus can also form in the limbs.

occlusion), wound healing will reorganise the occlusive thrombus into

collagenous scar tissue, where the scar tissue will either permanently obstruct
the vessel, or contract down with myofibroblastic activity to unblock the lumen.
For a mural thrombus (defined as a thrombus in a large vessel that restricts the

blood flow but does not occlude completely), histological reorganisation of the

and high blood pressure) needs to outweigh the small but known risk of major bleeding

thrombus does not occur via the classic wound healingmechanism. Instead,

associated with the use of warfarin.[18]

the platelet-derived growth factor degranulated by the clotted platelets will attract
a layer of smooth muscle cells to cover the clot, and this layer of mural smooth
muscle will be vascularised by the blood inside the vessel lumen rather than by
the vasa vasorum.

Embolization
Further information: Embolus
If a bacterial infection is present at the site of thrombosis, the thrombus may break down,
spreading particles of infected material throughout the circulatory system (pyemia, septic
embolus) and setting up abscesses of a metastatic nature wherever they come to rest.
Without an infection, the thrombus may become detached and enter circulation as
anembolus, finally lodging in and completely obstructing a blood vessel, which unless
treated very quickly will lead to tissue necrosis (an infarction) in the area past the
occlusion. If the occlusion is in the coronary artery, myocardial ischaemia is likely to
occur, whereby cardiac myocytes cannot function properly due to lack of oxygen. This
lack of oxygen is then likely to result in a myocardial infarction.
Most thrombi, however, become organized into fibrous tissue, and the thrombosed
vessel is gradually unblocked.

Prevention

In people admitted to hospital, thrombosis is a major cause for complications and

occasionally death. In the UK, for instance, the Parliamentary Health Select
Committee heard in 2005 that the annual rate of death due to thrombosis was 25,000,
with at least 50% of these being hospital-acquired.
[19]

Hence thromboprophylaxis (prevention of thrombosis) is increasingly emphasized. In

patients admitted for surgery, graded compression stockings are widely used, and in
severe illness, prolonged immobility and in all orthopedic surgery,professional
guidelines recommend low molecular weight heparin (LMWH) administration, mechanical
calf compression or (if all else is contraindicated and the patient has recently suffered
deep vein thrombosis) the insertion of a vena cava filter.[20][21] In patients with medical
rather than surgical illness, LMWH too is known to prevent thrombosis,[21][22] and in
the United Kingdom the Chief Medical Officer has issued guidance to the effect that
preventative measures should be used in medical patients, in anticipation of formal
guidelines.[19]
However, thromboprophylaxis can lead to complications such as bleeding. There are
new, non-invasive ways to stratify bleeding risk for patients with VTE and PE, by using
tools like the RIETE Registry. The RIETE registry is an interactive database which uses
data from previous and current patients, even groups not typically recruited like women
and elderly as well as those with pre-existing conditions like Cancer or renal failure. The
RIETE Registry offers more personalized options for patients with clotting risk, and it also
has created a predictive calculator based on the registry's findings. [23]

Prophylaxis of venous thromboembolism with heparin in medical patients does not

appear to decrease mortality and while it may decrease the risk of pulmonary
embolism anddeep vein thrombosis it increases the risk of bleeding and thus results in
little or no overall clinical benefit.[13][14] Mechanical measures also appeared of little benefit
in this group and in those with a stroke resulted in harm.[13] Evidence supports the use of
heparin following surgery which has a high risk of thrombosis to reduce the risk of DVTs;
however the effect on PEs or overall mortality is not known.

Treatment
Warfarin and Vitamin K antagonists, are anticoagulants that can be taken orally to reduce
thromboembolic occurrence. Where a more effective response is required, heparin can
be given (by injection) concomitantly. As a side effect of any anticoagulant, the risk
of bleeding is increased, so the international normalized ratio of blood is monitored. Selfmonitoring and self-management are safe options for competent patients, though their

Generally, a risk-benefit analysis is required, as all anticoagulants lead to a small

practice varies. In Germany, about 20% of patients were self-managed while only 1% of

increase in the risk of major bleeding. In atrial fibrillation, for instance, the risk

U.S. patients did home self-testing (according to one 2012 study).

of stroke(calculated on the basis of additional risk factors, such as advanced age

Coronary artery disease

From Wikipedia, the free encyclopedia

Coronary artery disease (CAD), also known as ischemic heart disease (IHD),
[1]
atherosclerotic heart disease,[2]atherosclerotic cardiovascular disease,
[3]
and coronary heart disease,[4] is a group of diseases that includes: stable
angina,unstable angina, myocardial infarction, and sudden coronary death.[5] It is within
the group of cardiovascular diseases of which it is the most common type.[6] A common
symptom is chest pain or discomfort which may travel into the shoulder, arm, back, neck,
or jaw.[7] Occasionally it may feel like heartburn.[7] Usually symptoms occur with exercise
or emotional stress, last less than a few minutes, and gets better with rest. [7] Shortness of
breath may also occur and sometimes no symptoms are present. [7] The first sign is
occasionally a heart attack.[8] Other complications include heart failure or an irregular
heartbeat.[8]
Risk factors include: high blood pressure, smoking, diabetes, lack of
exercise, obesity, high blood cholesterol, poor diet, and excessive alcohol, among
others.[9][10] Other risks include depression.[11] The underlying mechanism
involves atherosclerosis of thearteries of the heart.[10] A number of tests may help with
diagnoses including: electrocardiogram, cardiac stress testing, and coronary
angiogram among others.[12]
Prevention is by eating a healthy diet, regular exercise, maintaining a healthy weight and
not smoking.[13] Sometimes medication for diabetes, high cholesterol, or high blood
pressure are also used.[13] There is limited evidence for screening people who are at low
risk and do not have symptoms.[14] Treatment involves the same measures as prevention.
[15][16]
Additional medications such as aspirin,beta blockers, or nitrogylcerin may be
recommended.[16] Procedures such as percutaneous coronary intervention (PCI)
or coronary artery bypass surgery (CABG) may be used in severe disease.[16][17] In those
with stable CAD it is unclear if PCI or CABG in addition to the other treatments improve
life expectancy or decreases heart attack risk.[18]

In 2013 CAD was the most common cause of death globally, resulting in 8.14 million
deaths (16.8%) up from 5.74 million deaths (12%) in 1990.[6] The risk of death from CAD
for a given age has decreased between 1980 and 2010 especially in the developed
world.[19] The number of cases of CAD for a given age has also decreased between 1990
and 2010.[20] In the United States in 2010 about 20% of those over 65 had CAD, while it
was present in 7% of those 45 to 64, and 1.3% of those 18 to 45. [21] Rates are higher
among men than women of a given age.[21]

Signs and symptoms

Chest pain that occurs regularly with activity, after eating, or at other predictable times is
termed stable angina and is associated with narrowings of the arteries of the heart.

with a protein known as apolipoprotein(a).

Dietary cholesterol does not appear to have a significant effect on blood cholesterol and
thus recommendations about its consumption may not be needed. [34]

Other

factor after a majority of research into the field discovered that TABP's were twice as
likely to exhibit CAD as any other personality type (very controversial due to tobacco
industry funding of these researches).

Risk factors can be classified as: fixed (such as age, sex, family history) and modifiable
(such as smoking, hypertension, diabetes mellitus, obesity, etc.)

Blood fats

High blood cholesterol (specifically, serum LDL concentrations) HDL(high density

lipoprotein)has a protective effect over development of coronary artery disease. [29]

High blood triglycerides may play a role.[30]

Hemostatic factors:[35] High levels of fibrinogen and coagulation factor VII are
associated with an increased risk of CAD. Factor VII levels are higher in individuals

Coronary artery disease has a number of well determined risk factors. The most common
risk factors include smoking, family history, hypertension, obesity, diabetes, lack of
exercise, stress, and high blood lipids.[23] Smoking is associated with about 36% of cases
and obesity 20%.[24] Lack of exercise has been linked to 712% of cases.[24][25]
Job stress appears to play a minor role accounting for about 3% of cases. [24] In one study,
women who were free of stress from work life saw an increase in the diameter of their
blood vessels, leading to decreased progression of atherosclerosis. [26] Contrastingly,
women who had high levels of work-related stress experienced a decrease in the
diameter of their blood vessels and significantly increased disease progression. [26] Also,
having a type A behavior pattern, a group of personality characteristics including time
urgency, competitiveness, hostility, and impatience[27] is linked to an increased risk of
coronary disease.[28]

Type A personality.Type A behaviour is associated with competitive drive,

restlessness,hostility & a sense of impatience. Added in 1981 as an independent risk

Angina that changes in intensity, character or frequency is termed unstable. Unstable

angina may precede myocardial infarction. In adults who go to the emergency with an
unclear cause of pain, about 30% have pain due to coronary artery disease. [22]

Risk factors

High levels of lipoprotein(a), a compound formed when LDL cholesterol combines

with a high intake of dietary fat[ .Decreased fibrinolytic activity has been reported in
patients with coronary atherosclerosis.

Low hemoglobin]* Men over 45; Women over 55[37]

Pathophysiology
Limitation of blood flow to the heart causes ischemia (cell starvation secondary to a lack
of oxygen) of the myocardial cells. Myocardial cells may die from lack of oxygen and this
is called a myocardial infarction (commonly called a heart attack). It leads to heart
muscle damage,heart muscle death and later myocardial scarring without heart
muscle regrowth. Chronic high-grade stenosis of the coronary arteries can induce
transient ischemia which leads to the induction of a ventricular arrhythmia, which may
terminate into ventricular fibrillation leading to death.
Typically, coronary artery disease occurs when part of the smooth, elastic lining inside
a coronary artery (the arteries that supply blood to the heart muscle)
develops atherosclerosis. With atherosclerosis, the artery's lining becomes hardened,
stiffened, and swollen with all sorts of "gunge" - including calcium deposits, fatty
deposits, and abnormal inflammatory cells - to form a plaque. Deposits of calcium
phosphates (hydroxyapatites) in the muscular layer of the blood vessels appear to play
not only a significant role in stiffening arteries but also for the induction of an early phase
of coronary arteriosclerosis. This can be seen in a so-called metastatic mechanism
of calciphylaxis as it occurs in chronic kidney disease and haemodialysis (Rainer Liedtke
2008). Although these patients suffer from a kidney dysfunction, almost fifty percent of

them die due to coronary artery disease. Plaques can be thought of as large "pimples"
that protrude into the channel of an artery, causing a partial obstruction to blood flow.
Patients with coronary artery disease might have just one or two plaques, or might have
dozens distributed throughout their coronary arteries. However, there is a term in
medicine called cardiac syndrome X, which describes chest pain (Angina pectoris) and
chest discomfort in people who do not show signs of blockages in the larger coronary
arteries of their hearts when an angiogram (coronary angiogram) is being performed.[38]

Baseline electrocardiography (ECG)

Exercise ECG Stress test

Exercise radioisotope test (nuclear stress test, myocardial scintigraphy)

No one knows exactly what causes cardiac syndrome X. One explanation

is microvascular dysfunction.[39] It is not completely clear why women are more likely than
men to have it; however, hormones and other risk factors unique to women may play a
role.

Echocardiography (including stress echocardiography)

Coronary angiography

Diagnosis

Intravascular ultrasound

Magnetic resonance imaging (MRI)

For symptomatic patients, stress echocardiography can be used to make a diagnosis for
obstructive coronary artery disease.

[41]

The use of echocardiography, stress cardiac

imaging, and/or advanced non-invasive imaging is not recommended on individuals who

The diagnosis of coronary disease underlying particular symptoms depends largely on

are exhibiting no symptoms and are otherwise at low risk for developing coronary

the nature of the symptoms. The first investigation is an electrocardiogram (ECG/EKG),

disease.[41][42]

both for "stable" angina and acute coronary syndrome. An X-ray of the chest and blood
tests may be performed.

CAD has always been a tough disease to diagnose without the use of invasive or
stressful activities. The development of the Multifunction Cardiogram (MCG) has

Stable angina

changed the way CAD is diagnosed. The MCG consists of a 2 lead resting EKG signal is

Main article: Angina pectoris

transformed into a mathematical model and compared against tens of thousands of

clinical trials to diagnose a patient with an objective severity score, as well as secondary

In "stable" angina, chest pain with typical features occurring at predictable levels of

and tertiary results about the patient's condition. The results from MCG tests have been

exertion, various forms of cardiac stress tests may be used to induce both symptoms and

validated in 8 clinical trials[citation needed] which resulted in a database of over 50,000 patients

detect changes by way of electrocardiography (using an

where the system has demonstrated accuracy comparable tocoronary angiography (90%

ECG), echocardiography (using ultrasound of the heart) or scintigraphy (using uptake

overall sensitivity, 85% specificity). This level of accuracy comes from the application of

of radionuclide by the heart muscle). If part of the heart seems to receive an insufficient

advanced techniques in signal processing and systems analysis combined with a large

blood supply, coronary angiography may be used to identify stenosis of the coronary

scale clinical database which allows MCG to provide quantitative, evidence-based results

arteries and suitability for angioplasty or bypass surgery.

to assist physicians in reaching a diagnosis. The MCG has also been awarded a
Category III CPT code by theAmerican Medical Association in the July 2009 CPT
update[citation needed].
The diagnosis of "Cardiac Syndrome X" - the rare coronary artery disease that is more
common in women, as mentioned, an "exclusion" diagnosis. Therefore, usually the same
tests are used as in any patient with the suspicion of coronary artery disease:

Acute coronary syndrome

Main article: Acute coronary syndrome
Diagnosis of acute coronary syndrome generally takes place in the emergency
department, where ECGs may be performed sequentially to identify "evolving changes"
(indicating ongoing damage to the heart muscle). Diagnosis is clear-cut if ECGs show
elevation of the "ST segment", which in the context of severe typical chest pain is

strongly indicative of an acute myocardial infarction (MI); this is termed a STEMI (ST-

A diet high in fruits and vegetables decreases the risk of cardiovascular disease and

elevation MI), and is treated as an emergency with either urgent coronary

death.[46] Vegetarians have a lower risk of heart disease,[47][48] possibly due to their greater

angiography and percutaneous coronary intervention (angioplasty with or

consumption of fruits and vegetables.[49] Evidence also suggests that the Mediterranean

without stent insertion) or with thrombolysis ("clot buster" medication), whichever is

diet[50] and a high fiber diet lower the risk.[51]

available. In the absence of ST-segment elevation, heart damage is detected by cardiac

markers (blood tests that identify heart muscle damage). If there is evidence of damage

The consumption of trans fat (commonly found in hydrogenated products such

(infarction), the chest pain is attributed to a "non-ST elevation MI" (NSTEMI). If there is

as margarine) has been shown to cause a precursor to atherosclerosis[52] and increase

no evidence of damage, the term "unstable angina" is used. This process usually

the risk of coronary artery disease.[53]

necessitates admission to hospital, and close observation on acoronary care unit for
possible complications (such as cardiac arrhythmias irregularities in the heart rate).

Evidence does not support a beneficial role for omega-3 fatty acid supplementation in

Depending on the risk assessment, stress testing or angiography may be used to identify

death). There is tentative evidence that menaquinone (Vitamin K2), but not phylloquinone

and treat coronary artery disease in patients who have had an NSTEMI or unstable

(Vitamin K1), intake may reduce the risk of CAD mortality.

angina.

preventing cardiovascular disease (including myocardial infarction and sudden cardiac

Secondary prevention

Risk assessment

Secondary prevention is preventing further sequelae of already established disease.

There are various risk assessment systems for determining the risk of coronary artery
disease, with various emphasis on different variables above. A notable example

Lifestyle changes that have been shown to be effective to this goal include:

Weight control

pressure.[43]

Smoking cessation

Prevention

Avoiding the consumption of trans fats (in partially hydrogenated oils)

Prevention involves: exercise, decreasing obesity, treating hypertension, a healthy diet,

Exercise. In people with coronary artery disease, aerobic exercise, like walking,

isFramingham Score, used in the Framingham Heart Study. It is mainly based on age,
gender, diabetes, total cholesterol, HDL cholesterol, tobacco smoking and systolic blood

decreasing cholesterol levels, and stopping smoking. Medications and exercise are

jogging, or swimming, can reduce the risk of mortality.[57] Aerobic exercise can help

roughly equally effective.

decrease blood pressure and the amount of blood cholesterol (LDL) over time. It also

[44]

In diabetes mellitus, there is little evidence that very tight blood sugar control improves
cardiac risk although improved sugar control appears to decrease other problems like
kidney failure and blindness. The World Health Organization (WHO) recommends "low to
moderate alcohol intake" to reduce risk of coronary artery disease although this remains
without scientific cause and effect proof.[45]

increases HDL cholesterol which is considered as "good cholesterol". [58][59] Separate to

the question of the benefits of exercise; it is unclear whether doctors should spend
time counseling patients to exercise. The U.S. Preventive Services Task Force,
found "insufficient evidence" to recommend that doctors counsel patients on
exercise, but "it did not review the evidence for the effectiveness of physical activity
to reduce chronic disease, morbidity and mortality", it only examined the

Diet
Main article: Diet and heart disease

effectiveness of the counseling itself.[60] The American Heart Association, based on a

non-systematic review, recommends that doctors counsel patients on exercise. [61]

Aspirin
In those with no other heart problems aspirin decreases the risk of a myocardial
infarction in men but not women and increases the risk of bleeding, most of which is from

Decrease psychosocial stress.

the stomach. It does not affect the overall risk of death in either men or women. [66] It is

Management

thus only recommended in adults who are at increased risk for coronary artery
disease[67]where increased risk is defined as 'men older than 90 years of age,

There are a number of treatment options for coronary artery disease:

[63]

postmenopausal women, and younger persons with risk factors for coronary artery
disease (for example, hypertension, diabetes, or smoking) are at increased risk for heart

1. Lifestyle changes
2. Medical treatment - drugs (e.g. cholesterol lowering medications, beta-blockers,
nitroglycerin, calcium antagonists, etc.);
3. Coronary interventions as angioplasty and coronary stent;

disease and may wish to consider aspirin therapy'. More specifically, high-risk persons
are 'those with a 5-year risk 3%'
Anti-platelet therapy
Clopidogrel plus aspirin reduces cardiovascular events more than aspirin alone in those
with an STEMI. In others at high risk but not having an acute event the evidence is weak.

4. Coronary artery bypass grafting (CABG)

[68]

In those who have had a stent more than 12 months of clopidogrel plus aspirin does

Medications

not affect the risk of death.[69]

Statins, which reduce cholesterol, reduce risk of coronary disease[64]

Surgery

Nitroglycerin

Revascularization for acute coronary syndrome has a mortality benefit.

[70]

ACE inhibitors, which treat hypertension and may lower the risk of
recurrent myocardial infarction

Calcium channel blockers and/or beta-blockers

Aspirin

It is recommended that blood pressure typically be reduced to less than 140/90 mmHg.
[65]

The diastolic blood pressure however should not be lower than 60 mmHg. Beta

blockers are recommended first line for this use.[65]

Revascularization for stable ischaemic heart disease does not appear to have benefits

over medical therapy alone.[71] In those with disease in more than one artery coronary
artery bypass grafts appear better than percutaneous coronary interventions.[72][73]

Epidemiology
CAD as of 2010 was the leading cause of death globally resulting in over 7 million
deaths.[75] This is up from 5.2 million deaths in 1990.[75]It may affect individuals at any age
but becomes dramatically more common at progressively older ages, with approximately
a tripling with each decade of life.[76] Males are affected more often than females.[76]
It is estimated that 60% of the world's cardiovascular disease burden will occur in the
South Asian subcontinent despite only accounting for 20% of the world's population. This
may be secondary to a combination of genetic predisposition and environmental factors.

Organizations such as the Indian Heart Association are working with the World Heart

on - with first promising results particularly for FGF-1[86][87] and utilization of endothelial

Federation to raise awareness about this issue.[77]

progenitor cells.

Coronary heart disease (CHD) is the leading cause of death for both men and women

Myeloperoxidase has been proposed as a biomarker.

and accounts for approximately 600,000 deaths in the United States every year.
[78]

According to present trends in the United States, half of healthy 40-year-old men will

develop CAD in the future, and one in three healthy 40-year-old women. [79] It is the most
common reason for death of men and women over 20 years of age in the United States.
[80]

The Maasai of Africa have almost no heart disease.

Society and culture

Other terms sometimes used for this condition are "hardening of the arteries" and
"narrowing of the arteries".[81]

Research
Further information: atheroma and atherosclerosis
Recent research efforts focus on new angiogenic treatment modalities (angiogenesis)
and various (adult) stem cell therapies.
A region on Chromosome 17 was confined to families with multiple cases of myocardial
infarction.[82]
A more controversial link is that between Chlamydophila pneumoniae infection and
atherosclerosis.[83] While this intracellular organism has been demonstrated in
atherosclerotic plaques, evidence is inconclusive as to whether it can be considered a
causative factor. Treatment with antibiotics in patients with proven atherosclerosis has
not demonstrated a decreased risk of heart attacks or other coronary vascular diseases.
[84]

Since the 1990s the search for new treatment options for coronary artery disease
patients, particularly for so called "no-option" coronary patients, focused on usage of
angiogenesis[85] and (adult) stem cell therapies. Numerous clinical trials were performed,
either applying protein (angiogenic growth factor) therapies, such as FGF-1 or VEGF, or
cell therapies using different kinds of adult stem cell populations. Research is still going

Coronary thrombosis
From Wikipedia, the free encyclopedia

Coronary thrombosis is the formation of a blood clot inside a blood vessel of the heart
due to various factors including pollution. This blood clot restricts blood flow within the
heart. It is associated with narrowing of blood vessels subsequent to clotting.[1] The
condition is considered as a type of ischaemic heart disease.
Thrombosis in the heart can lead to a myocardial infarction.[2] Coronary thrombosis and
myocardial infarction are sometimes used as synonyms, although this is technically
inaccurate as the thrombosis refers to the blocking of blood vessels, while the infarction
refers to the tissue death due to the consequent loss of blood flow to the heart tissue.
The heart contains many connecting blood vessels, and depending upon the location of
the thrombosis, the infarction may cause no symptoms.
Coronary thrombosis can be a complication associated with drug-eluting stents.

Dressler syndrome

Causes

From Wikipedia, the free encyclopedia

It is believed to result from an autoimmune inflammatory reaction to myocardial neoantigens formed as a result of the MI. A similar pericarditis can be associated with any

Dressler syndrome is a secondary form of pericarditis that occurs in the setting of

injury to the heart or the pericardium (the outer lining of the heart). It consists of fever,
pleuritic pain, pericarditis and/or a pericardial effusion.
Dressler syndrome is also known as postmyocardial infarction syndrome[1] and the
term is sometimes used to refer to post-pericardiotomy pericarditis.

pericardiotomy or trauma to the pericardium or heart surgery.

Differential diagnosis
Dressler syndrome needs to be differentiated from pulmonary embolism, another
identifiable cause of pleuritic (and non-pleuritic) chest pain in people who have been

It was first characterized by William Dressler at Maimonides Medical Center in 1956.[2][3][4]

hospitalized and/or undergone surgical procedures within the preceding weeks.

It should not be confused with the Dressler's syndrome of haemoglobinuria named

for Lucas Dressler, who characterized it in 1854.

Treatment
Dressler syndrome is typically treated with colchicine. In some resistant
cases, corticosteroids can be used but are not preferred due to the high frequency of
relapse when corticosteroid therapy is discontinued. NSAIDs though once used to treat
Dressler syndrome, are less advocated and should be avoided in patients with ischemic
heart disease. One NSAID in particular, indomethacin can inhibit new collagen deposition
thus impairing the healing process for the infarcted region. NSAIDS should only be used
in cases refractory to aspirin. Heparin in Dressler syndrome should be avoided because
it can lead to hemorrhage into the pericardial sac leading to tamponade. The only time
heparin could be used with pericarditis is with coexisting acute MI in order to prevent
further thrombus formation.

Presentation
Dressler syndrome occurs in about 7% of myocardial infarctions,[7] and consists of a
persistent low-grade fever, chest pain (usually pleuritic in nature), pericarditis (usually
evidenced by a pericardial friction rub), and/or a pericardial effusion. The symptoms tend
to occur 23 weeks after myocardial infarction, but can also be delayed for a few months.
It tends to subside in a few days, and very rarely leads to pericardial tamponade.[8] An
elevated ESR is an objective laboratory finding.

Aneurysm of heart
An aneurysm of heart refers to an aneurysm involving cardiac tissue.

Classification

Investigations

See also: Aneurysm

It should not be confused with a coronary artery aneurysm, which is an aneurysm of the

The word aneurysm refers to a bulge or pocketing of the wall or lining of a vessel
commonly occurring in the blood vessels at the base of the septumn, or within the aorta.
When it concerns the heart muscle, it is called a cardiac aneurysm and is usually seen in
the left ventricle of the heart.

vessels supplying the heart, not the heart itself.

It should also not be confused with a pseudoaneurysm or a myocardial rupture (which
involves a hole in the wall, not just a bulge.)

Diagnosis

Ventricular aneurysm
Main article: Ventricular aneurysm

When a person visits the hospital or doctor with other symptoms, especially with a history

Ventricular aneurysms are the most common type of aneurysm of the heart, occurring
most often following a stroke or TIA, due to a weakening of a scarred wall and pressure
from blood flows, particularly during systole.

of heart problems, they will normally be required to undergo an electrocardiogram, which

monitors electrical activity within the heart and shows abnormalities when a cardiac
aneurysm is present. It can also appear as a bulge on a chest x-ray, and a more
accurate diagnosis will then be made using an echocardiogram, which uses ultrasound

Atrial septal aneurysm

to photograph the heart and how it functions while it beats.

Main article: Atrial septal aneurysm

Treatment

Signs and symptoms

As some people live with this type of aneurysm for many years, diagnosis and treatment
As it tends to develop slowly, symptoms may go unnoticed. Often the only way of finding

will not be given. If, however, it has been properly diagnosed, blood thinning agents may

out that it has occurred at all is when other medical conditions present, which are usually

be given to help reduce the likelihood of blood thickening and clots forming, along with

very serious such as blood clots causing strokes and blockages in other blood vessels.

the use of drugs to correct the irregular rhythm of the heart (seen on the

These blood clots form as the blood in the ventricle does not pump out as it should and

electrocardiogram), and occasionally surgery will be offered. If surgery is indicated, it is

can collect and thicken in the bulged area, releasing clots into the system.

often to try to remove the bulge and repair the damaged area and can be quite difficult so

[citation needed]

Causes

will be used as a last option as it carries many risks.

Most people who live with a cardiac aneurysm do so without knowing it. It is far better to

Seen mainly syama in the walls of the left ventricle (lower chamber) of the heart, it is

reduce the risk of heart attack and keep blood pressure within healthy limits in order to

thought to occur here as the blood in this area carries the highest amount of pressure

reduce the likelihood of an aneurysm occurring along with all of the possible side-effects

forcing the walls to bulge. It can develop very slowly over many years and does not often

and consequences. Lifestyle choices play a very important role in this prevention and

cause any problems during this time. Another possible cause of a cardiac aneurysm is as

careful consideration should be given when participating in highly unhealthy activities

a consequence of a heart attack, known medically as a myocardial infarction. Again it

such as heavy drinking which causes dehydration/blood to thicken and smoking which is

develops slowly due to a rise in pressure. It maybe also congenital.

a vasoconstrictor that decreases blood flow, especially to the heart.

On physical examination, the lungs are usually normal. Occasionally, a pleural friction
rub may be audible over the affected area of the lung (mostly in PE with infarct).
A pleural effusion is sometimes present that is exudative, detectable by decreased
percussion note, audible breath sounds and vocal resonance. Strain on the right ventricle
may be detected as a left parasternal heave, a loud pulmonary component of the second

Pulmonary embolism

heart sound, and raised jugular venous pressure.[1] A low-grade fever may be present,

From Wikipedia, the free encyclopedia

As smaller pumonary emboli tend to lodge in more peripheral areas without collateral

Pulmonary embolism (PE) is a blockage of the main artery of the lung or one of its
branches by a substance that has travelled from elsewhere in the body through the
bloodstream (embolism). PE most commonly results from deep vein thrombosis (a blood
clot in the deep veins of the legs or pelvis) that breaks off and migrates to the lung, a
process termed venous thromboembolism (VTE). A small proportion of cases are caused
by the embolization of air, fat, or talc in drugs of intravenous drug abusers or amniotic
fluid. The obstruction of the blood flow through the lungs and the resultant pressure on
the right ventricle of the heart lead to the symptoms and signs of PE. The risk of PE is
increased in various situations, such as cancer or prolonged bed rest.[1]

particularly if there is associated pulmonary hemorrhage or infarction. [2]

circulation they are more likely to cause lung infarction and small effusions (both of which
are painful), but not hypoxia, dyspnea or hemodynamic instability such as tachycardia.
Larger PEs, which tend to lodge more centrally, typically cause dyspnea, hypoxia,
hypotension, tachycardia and syncope, but are often painless because there is no lung
infarction due to collateral circulation. The classic presentation for PE with pleuritic pain,
dyspnea and tachycardia is most likely to be caused by a large embolism that fragments
and thus causes both large and small PEs. Thus, small PEs are often missed because
they cause pleuritic pain alone without any other findings and large PEs are often missed

Symptoms of pulmonary embolism include difficulty breathing, chest pain on inspiration,

and palpitations. Clinical signs include low blood oxygen saturation and cyanosis, rapid
breathing, and a rapid heart rate. Severe cases of PE can lead to collapse, abnormally
low blood pressure, and sudden death.[1]

because they are painless and mimic other conditions often causing EKG changes and
small rises in troponin and BNP levels.[3]
PEs are sometimes described as massive, submassive and nonmassive depending on

Diagnosis is based on these clinical findings in combination with laboratory tests (such
as the D-dimer test) and imaging studies, usually CT pulmonary angiography. Treatment
is typically with anticoagulant medication, including heparin and warfarin. Severe cases
may require thrombolysis using medication such as tissue plasminogen activator (tPA),
or may require surgical intervention viapulmonary thrombectomy.

Signs and symptoms

Symptoms of pulmonary embolism are typically sudden in onset and may include one or
many of the following: dyspnea (shortness of breath), tachypnea (rapid breathing), chest
pain of a "pleuritic" nature (worsened by breathing), cough and hemoptysis (coughing up
blood). More severe cases can include signs such as cyanosis (blue discoloration,
usually of the lips and fingers), collapse, and circulatory instability because of decreased

the clinical signs and symptoms. Although the exact definitions of these are unclear, a
generally accepted definition of massive PE is one in which there is hemodynamic
instability such as sustained hypotension, bradycardia or pulselessness. [4]

Risk factors
The most common sources of embolism are proximal leg deep vein thromboses (DVTs)
or pelvic vein thromboses. Any risk factor for DVT also increases the risk that the venous
clot will dislodge and migrate to the lung circulation, which may happen in as many as
15% of all DVTs. The conditions are generally regarded as a continuum termed venous
thromboembolism (VTE).

blood flow through the lungs and into the left side of the heart. About 15% of all cases

The development of thrombosis is classically due to a group of causes named Virchow's

ofsudden death are attributable to PE.[1]

triad (alterations in blood flow, factors in the vessel wall and factors affecting the
properties of the blood). Often, more than one risk factor is present.

Alterations in blood flow: immobilization (after surgery, injury, pregnancy (also

procoagulant), obesity (also procoagulant), cancer (also procoagulant)

The diagnosis of PE is based primarily on validated clinical criteria combined with

selective testing because the typical clinical presentation (shortness of breath, chest
pain) cannot be definitively differentiated from other causes of chest pain and shortness

Factors in the vessel wall: surgery, catheterizations causing direct injury

("endothelial injury")

of breath. The decision to do medical imaging is usually based on clinical grounds, i.e.
the medical history, symptoms and findings on physical examination, followed by an
assessment of clinical probability.[1]

Factors affecting the properties of the blood (procoagulant state):

The most commonly used method to predict clinical probability, the Wells score, is

Estrogen-containing hormonal contraception

a clinical prediction rule, whose use is complicated by multiple versions being available.
In 1995, Wells et al. initially developed a prediction rule (based on a literature search) to

Genetic thrombophilia (factor V Leiden, prothrombin mutation

G20210A, protein C deficiency, protein S
deficiency, antithrombindeficiency, hyperhomocysteinemia and plasminogen/fibri
nolysis disorders)

Acquired thrombophilia (antiphospholipid syndrome, nephrotic

syndrome, paroxysmal nocturnal hemoglobinuria)

Cancer (due to secretion of pro-coagulants)

Underlying causes
After a first PE, the search for secondary causes is usually brief. Only when a second PE

predict the likelihood of PE, based on clinical criteria.[8] The prediction rule was revised in
1998[9] This prediction rule was further revised when simplified during a validation by
Wells et al. in 2000.[10] In the 2000 publication, Wells proposed two different scoring
systems using cutoffs of 2 or 4 with the same prediction rule.[10] In 2001, Wells published
results using the more conservative cutoff of 2 to create three categories. [11] An additional
version, the "modified extended version", using the more recent cutoff of 2 but including
findings from Wells's initial studies[8][9] were proposed.[12] Most recently, a further study
reverted to Wells's earlier use of a cutoff of 4 points[10] to create only two categories.[13]
There are additional prediction rules for PE, such as the Geneva rule. More importantly,
the use of any rule is associated with reduction in recurrent thromboembolism. [14]
The Wells score:[15]

occurs, and especially when this happens while still under anticoagulant therapy, a
further search for underlying conditions is undertaken. This will include testing

clinically suspected DVT 3.0 points

alternative diagnosis is less likely than PE 3.0 points

inherited coagulation abnormalities.

tachycardia (heart rate > 100) 1.5 points

Diagnosis

immobilization ( 3d)/surgery in previous four weeks 1.5 points

To diagnose pulmonary embolism, medical societies recommend a review of clinical

history of DVT or PE 1.5 points

hemoptysis 1.0 points

("thrombophilia screen") for Factor V Leiden mutation, antiphospholipid

antibodies, protein C and S and antithrombin levels, and later prothrombin
mutation,MTHFR mutation, Factor VIII concentration and rarer

criteria to determine the need for testing, followed by testing to determine a likelihood of
being able to confirm a diagnosis by imaging, followed by imaging if other tests have
shown that there is a likelihood of a PE diagnosis.[5][6][7]

malignancy (with treatment within 6 months) or palliative 1.0 points

recommend tests such as the D-dimer to first provide supporting evidence for the need
for imaging, and imaging would be done if other tests confirmed a moderate or high

Traditional interpretation[10][11][16]

probability of finding evidence to support a diagnosis of PE.[6][21]

Score >6.0 High (probability 59% based on pooled data[17])

CT pulmonary angiography is the recommended first line diagnostic imaging test in most

Score 2.0 to 6.0 Moderate (probability 29% based on pooled data )

this has fallen into disuse with the increased availability of non-invasive techniques. [

Score <2.0 Low (probability 15% based on pooled data[17])

Non-invasive imaging

people.[22] Historically, the gold standard for diagnosis was pulmonary angiography, but
[17]

CT pulmonary angiography (CTPA) is a pulmonary angiogram obtained using computed

Alternative interpretation[10][13]

tomography (CT) with radiocontrast rather than right heart catheterization. Its advantages

Score > 4 PE likely. Consider diagnostic imaging.

are clinical equivalence, its non-invasive nature, its greater availability to people, and the
possibility of identifying other lung disorders from the differential diagnosis in case there

Score 4 or less PE unlikely. Consider D-dimer to rule out PE.

Blood tests

is no pulmonary embolism. Assessing the accuracy of CT pulmonary angiography is

hindered by the rapid changes in the number of rows of detectors available in
multidetector CT (MDCT) machines.[23] According to a cohort study, single-slice spiral

In people with a low or moderate suspicion of PE, a normal D-dimer level (shown in

CT may help diagnose detection among people with suspected pulmonary embolism.

a blood test) is enough to exclude the possibility of thrombotic PE, with a three-month

[24]

risk of thromboembolic events being 0.14%.

a prevalence of detection was 32%, the positive predictive value of 67.0% and negative

[18]

D-dimer is highly sensitive but not very

In this study, the sensitivity was 69% and specificity was 84%. In this study which had

specific (specificity around 50%). In other words, a positive D-dimer is not synonymous

predictive value of 85.2% (click here to adjust these results for people at higher or lower

with PE, but a negative D-dimer is, with a good degree of certainty, an indication of

risk of detection). However, this study's results may be biased due to possible

absence of a PE.

incorporation bias, since the CT scan was the final diagnostic tool in people with

[19]

The typical cut off is 500 ug/L.

[20]

However, in those over the age of

50, changing the cut-off value to the persons age multiplied by 10 ug/L decreases the

pulmonary embolism. The authors noted that a negative single slice CT scan is

number of falsely positive tests without missing any additional cases of PE. [20]

insufficient to rule out pulmonary embolism on its own. A separate study with a mixture of
4 slice and 16 slice scanners reported a sensitivity of 83% and aspecificity of 96%. This

When a PE is being suspected, a number of blood tests are done in order to exclude

study noted that additional testing is necessary when the clinical probability is

important secondary causes of PE. This includes a full blood count, clotting

inconsistent with the imaging results.[25] CTPA is non-inferior to VQ scanning, and

status (PT, aPTT,TT), and some screening tests (erythrocyte sedimentation rate, renal

identifies more emboli (without necessarily improving the outcome) compared to VQ

function, liver enzymes, electrolytes). If one of these is abnormal, further investigations

scanning.[26]

might be warranted.

Imaging
In typical people who are not known to be at high risk of PE, imaging is helpful to confirm
or exclude a diagnosis of PE after simpler first-line tests are used.[5][6][21] Medical societies

A ventilation/perfusion scan (or V/Q scan or lung scintigraphy) shows that some areas of
the lung are being ventilated but not perfusedwith blood (due to obstruction by a clot).
This type of examination is as accurate as multislice CT, but is less used, due to the
greater availability of CT technology. It is particularly useful in people who have an
allergy to iodinated contrast, impaired renal function, or arepregnant (due to its lower

radiation exposure as compared to CT).[27][28] The test can be performed with planar two-

This is occasionally present (occurring in up to 20% of people), but may also occur in

dimensional imaging, or single photon emission tomography (SPECT) which enables

other acute lung conditions, and, therefore, has limited diagnostic value. The most

three-dimensional imaging.[22] Hybrid devices combining SPECT and CT (SPECT/CT)

commonly-seen signs in the ECG are sinus tachycardia, right axis deviation, and right

further enable anatomic characterization of any abnormality.

bundle branch block.[33] Sinus tachycardia, however, is still only found in 869% of people
with PE.[34]

Low probability diagnostic tests/non-diagnostic tests

Echocardiography
Tests that are frequently done that are not sensitive for PE, but can be diagnostic.
In massive and submassive PE, dysfunction of the right side of the heart may be seen

Chest X-rays are often done on people with shortness of breath to help rule-out

on echocardiography, an indication that thepulmonary artery is severely obstructed and

other causes, such as congestive heart failure and rib fracture. Chest X-rays in PE

the right ventricle, a low pressure pump, is unable to match the pressure. Some studies

are rarely normal,[29] but usually lack signs that suggest the diagnosis of PE

(see below) suggest that this finding may be an indication for thrombolysis. Not every

(e.g. Westermark sign,Hampton's hump).

person with a (suspected) pulmonary embolism requires an echocardiogram, but

elevations in cardiac troponins or brain natriuretic peptide may indicate heart strain and

Ultrasonography of the legs, also known as leg doppler, in search of deep

venous thrombosis (DVT). The presence of DVT, as shown on ultrasonography of
the legs, is in itself enough to warrant anticoagulation, without requiring the V/Q or
spiral CT scans (because of the strong association between DVT and PE). This may
be valid approach in pregnancy, in which the other modalities would increase the risk

warrant an echocardiogram,[35] and be important in prognosis.[36]

The specific appearance of the right ventricle on echocardiography is referred to as
the McConnell's sign. This is the finding of akinesia of the mid-free wall but normal
motion of the apex. This phenomenon has a 77% sensitivity and a 94% specificity for the
diagnosis of acute pulmonary embolism in the setting of right ventricular dysfunction. [37]

of birth defects in the unborn child. However, a negative scan does not rule out PE,
and low-radiation dose scanning may be required if the mother is deemed at high

Algorithms

risk of having pulmonary embolism.

Probability testing

Electrocardiogram
Recent recommendations for a diagnostic algorithm have been published by the PIOPED
The primary use of the ECG is to rule out other causes of chest pain.
[30]

An electrocardiogram (ECG) is routinely done on people with chest pain to quickly

diagnose myocardial infarctions (heart attacks), an important differential diagnosis in an

individual with chest pain. While certain ECG changes may occur with PE, none are

investigators; however, these recommendations do not reflect research using 64 slice

MDCT.[17] These investigators recommended:

Low clinical probability. If negative D-dimer, PE is excluded. If positive D-dimer,

obtain MDCT and based treatment on results.

specific enough to confirm or sensitive enough to rule out the diagnosis. [30] An ECG may
show signs of right heart strain or acute cor pulmonale in cases of large PEs the
classic signs are a large S wave in lead I, a large Q wave in lead III, and an inverted T

Moderate clinical probability. If negative D-dimer, PE is excluded. However, the

wave in lead III (S1Q3T3), which occurs in 12-50% of people with the diagnosis, yet also

authors were not concerned that a negative MDCT with negative D-dimer in this

occurs in 12% without the diagnosis.[31][32]

setting has an 5% probability of being false. Presumably, the 5% error rate will fall as
64 slice MDCT is more commonly used. If positive D-dimer, obtain MDCT and based
treatment on results.

High clinical probability. Proceed to MDCT. If positive, treat, if negative, additional

tests are needed to exclude PE.

Anticoagulation
In most cases, anticoagulant therapy is the mainstay of treatment.

Pulmonary embolism rule-out criteria

Unfractionated heparin, low molecular weight heparin (LMWH), or fondaparinux is

The pulmonary embolism rule-out criteria (PERC) help assess people in whom
pulmonary embolism is suspected, but unlikely. Unlike the Wells Score and Geneva
score, which are clinical prediction rules intended to risk stratify patients with suspected
PE, the PERC rule is designed to rule out risk of PE in patients when the physician has
already stratified them into a low-risk category.
People in this low risk category without any of these criteria may undergo no further
diagnostic testing for PE: Hypoxia SaO <95%, unilateral leg swelling, hemoptysis, prior
2

DVT or PE, recent surgery or trauma, age >50, hormone use, tachycardia. The rationale
behind this decision is that further testing (specifically CT angiogram of the chest) may
cause more harm (from radiation exposure and contrast dye) than the risk of PE. [38] The
PERC rule has a sensitivity of 97.4% and specificity of 21.9% with a false negative rate
of 1.0% (16/1666).[39]

administered initially, whilewarfarin, acenocoumarol, or phenprocoumon therapy is

commenced (this may take several days, usually while the patient is in the hospital).
LMWH may reduce bleeding among people with pulmonary embolism as compared to
heparin according to a systematic review of randomized controlled trials by the Cochrane
Collaboration.[45] The relative risk reduction was 40%. For people at similar risk to those in
this study (2.0% had bleeding when not treated with low molecular weight heparin), this
leads to an absolute risk reductionof 0.8%. 125 people must be treated for one to benefit.
Warfarin therapy often requires frequent dose adjustment and monitoring of
the international normalized ratio (INR). In PE, INRs between 2.0 and 3.0 are generally
considered ideal. If another episode of PE occurs under warfarin treatment, the INR
window may be increased to e.g. 2.53.5 (unless there are contraindications) or
anticoagulation may be changed to a different anticoagulant e.g. LMWH. [citation needed]

Prevention

In patients with an underlying malignancy, therapy with a course of LMWH is favored

Pulmonary embolism may be preventable in those with risk factors. For instance, people

as to whether ongoing treatment is required.[46]

admitted to hospital may receive preventative medication and anti-thrombosis stockings

to reduce the risk.[40]
Following the completion of warfarin in those with prior PE, long term aspirin is useful to
prevent re occurrence.[41][42]

Treatment

over warfarin; it is continued for six months, at which point a decision should be reached

Similarly, pregnant women are often maintained on low molecular weight heparin until at
least 6 weeks after delivery to avoid the known teratogenic effects of warfarin, especially
in the early stages of pregnancy.[47]
Warfarin therapy is usually continued for 36 months, or "lifelong" if there have been
previous DVTs or PEs, or none of the usual risk factors is present. An abnormal Ddimer level at the end of treatment might signal the need for continued treatment among

Anticoagulant therapy is the mainstay of treatment. Acutely, supportive treatments, such

patients with a first unprovoked pulmonary embolus.[48] For those with small PEs (known

as oxygen or analgesia, may be required. People are often admitted to hospital in the

as subsegmental PEs) the effects of anticoagulation is unknown as it has not been

early stages of treatment, and tend to remain under inpatient care until the INR has

properly studied as of 2014.[49]

reached therapeutic levels. Increasingly, however, low-risk cases are managed at home
in a fashion already common in the treatment of DVT.[43] Evidence to support one
approach versus the other is weak.[44]

Thrombolysis
Massive PE causing hemodynamic instability (shock and/or hypotension, defined as a
systolic blood pressure <90 mmHg or a pressure drop of 40 mmHg for >15 min if not

caused by new-onset arrhythmia, hypovolemia or sepsis) is an indication

Infirmary in 1957. This study is the only placebo controlled trial ever to examine the place

for thrombolysis, the enzymatic destruction of the clot with medication. In this situation it

of anticoagulants in the treatment of PE, the results of which were so convincing that the

is the best available treatment in those without contraindications and is supported by

trial has never been repeated as to do so would be considered unethical. That said, the

clinical guidelines.

reported mortality rate of 26% in the placebo group is probably an overstatement, given

[7][46][50]

that the technology of the day may have detected only severe PEs. More recent
The use of thrombolysis in non-massive PEs is still debated. [51][52] Some have found that

evidence suggests that up to 10% of symptomatic PEs are fatal within the first hour of

the treatment decreases the risk of death and increases the risk of bleeding

symptoms.[7]

includingintracranial hemorrhage.[53] Others have found no decrease in the risk of death. [52]
There are a number of markers used for risk stratification and these are also

Inferior vena cava filter

independent predictors of adverse outcome. These include hypotension, cardiogenic

If anticoagulant therapy is contraindicated (e.g. shortly after a major operation),

an inferior vena cava filter may be implanted to prevent new emboli from entering the
pulmonary artery and combining with an existing blockage.
soon as it becomes safe to start using anticoagulation.

[46]

It should be removed as

number of ECG changes including S1Q3T3 also correlate with worse short-term
prognosis.[4] There have been a number of other patient-related factors such as COPD
and chronic heart failure thought to also play a role in prognosis.[7]

[46]

Surgery
Surgical management of acute pulmonary embolism (pulmonary thrombectomy) is
uncommon and has largely been abandoned because of poor long-term outcomes.
However, recently, it has gone through a resurgence with the revision of the surgical
technique and is thought to benefit certain people.[54] Chronic pulmonary embolism
leading to pulmonary hypertension (known as chronic thromboembolic hypertension) is
treated with a surgical procedure known as a pulmonary thromboendarterectomy.

Epidemiology
Pulmonary embolism occur in more than 0.6 million people in the United States each
year.[55] It results in between 50,000[55] and 200,000 deaths per year in the United States.
[56]

shock, syncope, evidence of right heart dysfunction, and elevated cardiac enzymes. [7] A

The risk in those who are hospitalized is around 1%.[57] The rate of fatal pulmonary

emboli has declined from 6% to 2% over the last 25 years in the United States. [56]

Prognosis
Mortality from untreated PE is said to be 26%. This figure comes from a trial published in
1960 by Barrit and Jordan,[58] which compared anticoagulation against placebo for the
management of PE. Barritt and Jordan performed their study in the Bristol Royal

Prognosis depends on the amount of lung that is affected and on the co-existence of
other medical conditions; chronic embolisation to the lung can lead to pulmonary
hypertension. After a massive PE, the embolus must be resolved somehow if the patient
is to survive. In thrombotic PE, the blood clot may be broken down by fibrinolysis, or it
may be organized and recanalized so that a new channel forms through the clot. Blood
flow is restored most rapidly in the first day or two after a PE.[59] Improvement slows
thereafter and some deficits may be permanent. There is controversy over whether small
subsegmental PEs need to be treated at all[60] and some evidence exists that patients
with subsegmental PEs may do well without treatment.
Once anticoagulation is stopped, the risk of a fatal pulmonary embolism is 0.5% per year.

the left heart for distribution. In normal circumstances, the right heart pumps blood into
the lungs without any resistance. The lungs usually have minimal pressure, and the right
heart easily pumps blood through to them.[2] However with certain lung diseases
chronically present, like emphysema and chronic bronchitis, each of which is found in the
pathology of chronic obstructive pulmonary disease (COPD), and also pulmonary
hypertension, the blood vessels of the lungs are significantly reduced in number (due to
lung tissue destruction) and/or chronically constricted (due to poor alveolar ventilation in
the case of COPD). The right ventricle is no longer able to push blood into the lungs
effectively, and the chronic overload eventually causes it to fail.

Signs and symptoms

The symptoms of pulmonary heart disease depend on the stage of the disorder. In the
early stages, one may have no symptoms but as pulmonary heart disease progresses,
most individuals will develop the symptoms like:

Shortness of breath which occurs on exertion but when severe can occur at rest

Wheezing

Pulmonary heart disease (New Latin pulmnle, of the lungs), also known as Cor
pulmonale (Latin cor, heart + of the lungs) is the enlargement and failure of the right
ventricle of the heart as a response to increased vascular resistance or high blood
pressure in the lungs (pulmonary hypertension).

Chronic wet cough

Swelling of the abdomen with fluid (ascites)

Chronic pulmonary heart disease usually results in right ventricular hypertrophy (RVH),
whereas acute pulmonary heart disease usually results in dilatation. Hypertrophy is an
adaptive response to a long-term increase in pressure. Individual muscle cells grow
larger (in thickness) and change to drive the increased contractile force required to move
the blood against greater resistance. Dilatation is a stretching (in length) of the ventricle
in response to acute increased pressure, such as when caused by a pulmonary
embolism or ARDS (acute respiratory distress syndrome).

Swelling of the ankles and feet (pedal edema)

Enlargement or prominent neck and facial veins

Raised jugular venous pressure (JVP)

To be classified as pulmonary heart disease, the cause must originate in the pulmonary
circulation system. Two major causes are vascular changes as a result of tissue damage
(e.g. disease, hypoxic injury, chemical agents, etc.), and chronic hypoxic pulmonary
vasoconstriction. If left untreated, then death may result. RVH due to a systemic defect is
not classified as pulmonary heart disease.

Enlargement of the liver

Bluish discoloration of the skin (cyanosis)

Presence of abnormal heart sounds

possible bi-phasic atrial response shown on an EKG due to hypertrophy

Pulmonary heart disease

From Wikipedia, the free encyclopedia

The heart and lungs are intricately related. Whenever the heart is affected by disease,
the lungs will follow and vice versa. Pulmonary heart disease is by definition a condition
when the lungs cause the heart to fail.[1]
The heart has two pumping chambers. The left ventricle pumps blood throughout the
body. The right ventricle pumps blood to the lungs where it is oxygenated and returned to

Complications

Bronchopulmonary dysplasia (in infants)

Blood backs up into the systemic venous system, including the hepatic vein. Chronic
congestion in the centrilobular region of the liver leads to hypoxia and fatty changes of
more peripheral hepatocytes, leading to what is known as nutmeg liver.

Severe thoracic kyphosis

Causes

Acute:

Pulmonary embolism

Acute respiratory distress syndrome (ARDS)

Diagnosis
In many cases, the diagnosis of pulmonary heart disease is not easy as both the lung
and heart disease can produce similar symptoms. Most patients undergo
an electrocardiogram, chest x ray, echocardiogram, CT scan of the chest and a cardiac
catheterization. During a cardiac catheterization, a small flexible tube is inserted from the
groin and under x-ray guidance images of the heart are obtained. Moreover the
technique allows measurement of pressures in the lung and heart which provide a clue to
the diagnosis.[1]

Chronic:

COPD

Primary pulmonary hypertension

Uncontrolled persistent asthma

Chest x ray right ventricular hypertrophy, right atrial dilatation, prominent

pulmonary artery Peripheral lung fields show reduced vascular markings. Patients
of chronic obstructive pulmonary disease show features of hyperinflation that include
widened intercostal space, increased translucency of lung and flattened diaphragm.

ECG right ventricular hypertrophy, right axis deviation, prominent R wave in

lead V1 & inverted T waves in right precordial leads, Large S in Lead I, II and III;
Large Q in lead III, Tall Peaked P waves (P pulmonale) in lead II, III and aVF Not

Loss of lung tissue following trauma or surgery

Pierre Robin sequence

all the above features are found in a single patient; however, different patients show
different combinations of these findings.

Echocardiogram right ventricular hypertrophy or dilatation, possible tricuspid

End stage pneumoconiosis

Sarcoidosis

T1-4 Vertebral subluxation

Pathophysiology

Obstructive sleep apnea(untreated)

There are several mechanisms leading to pulmonary hypertension and pulmonary heart
disease:

Interstitial lung disease

Pulmonary vasoconstriction

Sickle cell anemia

Anatomic changes in vascularization

regurgitation expected

Increased blood viscosity

to pulmonary hypertension. If hematocrit (PCV) is above 60%, then it is better to reduce

the red blood cell count by phlebotomies.

Idiopathic or primary pulmonary hypertension

Mucolytic agents like bromhexine and carbocisteine help bring out excessive bronchial
secretions more easily by coughing.

Prevention
While not all lung diseases can be prevented one can reduce the risk of lung disease.
This means avoiding or discontinuing smoking. Patients with end stage emphysema or
chronic obstructive lung disease always end up with right heart failure. When working in
environments where there are chemicals, wear masks to prevent inhalation of dust
particles.[3]

All patients with pulmonary heart disease are maintained on blood thinning
medications to prevent formation of blood clots.
When medical therapy fails, one may require a transplant. However, since the lungs are
damaged, both the heart and lungs needs to be transplanted. With a shortage of donors
this therapy is only done 10-15 times a year in North America.

Treatment
Elimination of the cause is the most important intervention. Smoking must be stopped,
along with exposure to second-hand smoke. Exposure to dust, flames, household smoke
and to cold weather are to be avoided. If there is evidence of respiratory infection, it
should be treated with appropriate antibiotics after culture and sensitivity. In pulmonary
embolism, thrombolysis (enzymatic dissolution of the blood clot) is advocated by some
authorities[who?] if there is dysfunction of the right ventricle, and is otherwise treated
withanticoagulants. In COPD, long-term oxygen therapy may improve pulmonary heart
disease.
Pulmonary heart disease may lead to congestive heart failure (CHF), with worsening of
respiration due to pulmonary edema, swelling of the legs due to peripheral edema and
painful congestive hepatomegaly (enlargement of the liver due to tissue damage). This
situation requires diuretics (to decrease strain on the heart), sometimes nitrates (to
improve blood flow), phosphodiesterase inhibitors such as sildenafil or tadalafil and
occasionally inotropes (to improve heart contractility). CHF is a negative prognostic
indicator in pulmonary heart disease.
Oxygen is often required to resolve the shortness of breath. Plus, oxygen to the lungs
also helps relax the blood vessels and eases right heart failure. Oxygen is given at the
rate of 2 litres per minute. Excess oxygen can be harmful to patients because hypoxia is
the main stimulus to respiration. If such hypoxia is suddenly corrected by overflow of
oxygen, such stimulus to the respiratory center is suddenly withdrawn and respiratory
arrest occurs. When wheezing is present, majority of the patients
require bronchodilators. A variety of drugs have been developed to relax the blood
vessels in the lung. Calcium channel blockers are used but only work in a few cases.
Other novel medications that need to be inhaled or given intravenously
include prostacyclin derivatives.
Cases of COPD with chronic pulmonary heart disease present with
secondary polycythemia, and if severe it may increase the blood viscosity and contribute

Epidemiology
Each year there are about 20,000 deaths and close to 280,000 hospital admissions
among individuals who have pulmonary heart disease. The majority of individuals
affected by pulmonary heart disease are women less than 65 years of age. Infants who
are born with congenital heart disorders (esp. holes in the heart like a VSD) are prone to
pulmonary artery disease. While pulmonary heart disease is serious, it is much less
common than coronary artery disease.

Pulmonary hypertension
From Wikipedia, the free encyclopedia

Pulmonary hypertension (PH) is an increase of blood pressure in the pulmonary

artery, pulmonary vein, or pulmonary capillaries, together known as the lung vasculature,
leading to shortness of breath, dizziness, fainting, leg swelling and other symptoms.
Pulmonary hypertension can be a severe disease with a markedly decreased exercise
tolerance such as heart failure. It was first identified by Ernst von Romberg in 1891.
[1]
According to the most recent classification, it can be one of six different types (see
below).

Signs and symptoms

Because symptoms may develop very gradually, patients may delay seeing a physician
for years. Common symptoms include shortness of breath, fatigue, nonproductive cough,angina pectoris, fainting or syncope, peripheral edema (swelling
around the ankles and feet), and rarely coughing up blood.

WHO Group I - Pulmonary arterial hypertension (PAH)

Idiopathic PAH

Heritable

Pulmonary venous hypertension typically presents with shortness of breath while lying
flat or sleeping (orthopnea or paroxysmal nocturnal dyspnea), while
pulmonary arterialhypertension (PAH) typically does not.

BMPR2

ALK1, endoglin (with or without hereditary hemorrhagic

telangiectasia)

A detailed family history is established to determine whether the disease might

be familial. A history of exposure to drugs such

as cocaine, methamphetamine, ethanol leading tocirrhosis, and tobacco leading

to emphysema is considered significant.
A physical examination is performed to look for typical signs of pulmonary hypertension,
including a split S2, and loud P2 (pulmonic valve closure sound) and (para)sternal heave

Drug- and toxin-induced

Associated with

indicating a hypertrophied right atrium. Signs of systemic congestion resulting from right
sided heart failure are jugular venous distension, pedal edema, ascites, hepatojugular
reflux, clubbing etc. Evidence of tricuspid insufficiency and pulmonic regurgitation is also
sought and, if present, is consistent with the presence of pulmonary hypertension.

Causes and classification[edit]

A 1973 meeting organized by the World Health Organization was the first to attempt
classification of pulmonary hypertension. A distinction was made between primary and
secondary PH, and primary PH was divided in the "arterial plexiform", "veno-occlusive"
and "thromboembolic" forms.[3] A second conference in 1998 at vian-les-Bains also
addressed the causes of secondary PH (i.e. those due to other medical conditions), [4] and
in 2008, the 4th World Symposium on Pulmonary Arterial Hypertension was convened in
Dana Point to modify the classification based on new understandings of disease
mechanisms. The revised system developed by this group provides the current
framework for understanding pulmonary hypertension. [2] The system includes several

follows:[2]

Connective tissue disease

HIV infection

Portal hypertension

Congenital heart diseases

Schistosomiasis

Chronic hemolytic anemia (including sickle cell disease)

Persistent pulmonary hypertension of the newborn

WHO Group I' - Pulmonary veno-occlusive disease (PVOD)

and/or pulmonary capillary hemangiomatosis (PCH)

improvements over the former 2004 Venice Classification system.

The Dana Point 2008 Updated Clinical Classification system can be summarized as

Unknown

WHO Group II - Pulmonary hypertension owing to left heart disease

Systolic dysfunction

Diastolic dysfunction

Valvular heart disease

Others: tumoral obstruction, fibrosing mediastinitis, chronic kidney

failure on dialysis

WHO Group III - Pulmonary hypertension owing to lung disease and/or hypoxia

Chronic obstructive pulmonary disease (COPD)

Interstitial lung disease

Other pulmonary diseases with mixed restrictive and obstructive pattern

Sleep-disordered breathing

Alveolar hypoventilation disorders

Chronic exposure to high altitude

Developmental abnormalities

Pathogenesis
Whatever the initial cause, pulmonary arterial hypertension (WHO Group I) involves
the narrowing of blood vessels connected to and within the lungs. This makes it harder
for the heart to pump blood through the lungs, much as it is harder to make water flow
through a narrow pipe as opposed to a wide one. Over time, the affected blood vessels
become stiffer and thicker, in a process known as fibrosis. This further increases the
blood pressure within the lungs and impairs their blood flow. In common with other types
of pulmonary hypertension, the increased workload of the heart causes hypertrophy of
the right ventricle, making the heart less able to pump blood through the lungs, ultimately
causing right heart failure (a condition known as cor pulmonale). The right ventricle is
normally part of a low pressure system, with pressures that are around one-sixth of those
that the left ventricle normally encounters. As such, the right ventricle cannot cope as
well to higher pressures, and although hypertrophy of the heart muscle helps initially, it
ultimately leads to a situation where the right ventricular muscle cannot get enough
oxygen to meet its needs and right heart failure follows. As the blood flowing through the
lungs decreases, the left side of the heart receives less blood. This blood may also carry
less oxygen than normal. Therefore it becomes harder and harder for the left side of the
heart to pump to supply sufficient oxygen to the rest of the body, especially during
physical activity.
Pathogenesis in pulmonary hypertension owing to left heart disease (WHO Group II) is

WHO Group IV - Chronic thromboembolic pulmonary hypertension (CTEPH)

WHO Group V - Pulmonary hypertension with unclear multifactorial[disambiguation

needed]

mechanisms

completely different in that constriction or damage to the pulmonary blood vessels is not
the issue. Instead, the left heart fails to pump blood efficiently, leading to pooling of blood
in the lungs and back pressure within the pulmonary system. This causes pulmonary
edemaand pleural effusions.
In hypoxic pulmonary hypertension (WHO Group III), the low levels of oxygen are
thought to cause narrowing of the pulmonary arteries. This phenomenon is

Hematologic diseases: myeloproliferative disease, removal of the spleen

Systemic diseases: sarcoidosis, pulmonary Langerhans

designed to stop too much blood flowing to areas of the lung that are damaged and do
cell histiocytosis: lymphangioleiomyomatosis, neurofibromatosis, vasculitis

called hypoxic pulmonary vasoconstriction and it is initially a protective response

Metabolic disorders: glycogen storage disease, Gaucher disease, thyroid

diseases

not contain oxygen. When the damage is widespread and prolonged, this hypoxiamediated vasoconstriction occurs across a large portion of the pulmonary vascular bed.
In chronic thromboembolic pulmonary hypertension (WHO Group IV), the blood vessels
are blocked or narrowed with recurrent blood clots, and these clots can lead to release of
substances that cause the blood vessels to constrict. This combination of blocked or

narrowed vessels and vasoconstriction once again increases the resistance to blood flow

only GAF-A has the necessary affinity to bind cGMP. This union increases the catalytic

and so the pressure within the system rises.

activity and it is stabilized by a close serine phosphorylation (performed by a kinase).

Consequently, the concentration of cGMP decreases and the vasodilation is stopped. [6]

Molecular pathology
The molecular mechanism of pulmonary arterial hypertension (PAH) is not known yet,
but it is believed that the endothelial dysfunction results in a decrease in the synthesis of
endothelium-derived vasodilators such as nitric oxide and prostacyclin. Moreover, theres
a stimulation of the synthesis of vasoconstrictors such as thromboxane and vascular

Patients with PAH produce less NO and others vasodilators and produce more
vasoconstrictors. Consequently, this molecular pathway doesnt work properly and it
results in a constant vasoconstriction. For this reason, NO and PDE5 inhibitors such as
tadalafil or sildenafil are possible therapies.[7] Tadalafil, for example, causes a
vasodilation mediated by nitric oxide in the pulmonary endothelium.

Diagnosis

endothelial growth factor (VEGF). These results in a severe vasoconstriction and smooth
muscle and adventitial hypertrophy characteristic of patients with PAH.[5]
In normal conditions, the nitric oxide synthase produces nitric oxide from L-arginine in
presence of oxygen. Adenylate-cyclase and gualynate-cyclase are activated in presence

Because pulmonary hypertension can be of five major types, a series of tests must be
performed to distinguish pulmonary arterialhypertension from venous, hypoxic,
thromboembolic, or miscellaneous varieties.

of nitric oxide and these enzymes produce cAMP and cGMP respectively. The cGMP is

Further procedures are required to confirm the presence of pulmonary hypertension and

produced by a type of guanylate cyclase (which is a kind of pyrophosphate-liase

exclude other possible diagnoses. These generally include pulmonary function

cyclase): the soluble guanylate cyclase (or sGC), that catalyzes the formation of cGMP

tests; blood tests to exclude HIV, autoimmune diseases, and liver

from GTP. sGC is a heterodimer made up of one subunit and one sub-unit in each

disease; electrocardiography(ECG); arterial blood gas measurements; X-rays of the

chain. It also contains a prosthetic heme group, required for NO binding. The union of

chest (followed by high-resolution CT scanning if interstitial lung disease is suspected);

NO and sGC produces a conformational enzyme change that stimulates cGMP

and ventilation-perfusion or V/Q scanning to exclude chronic thromboembolic pulmonary

production.

hypertension. Biopsy of the lung is usually not indicated unless the pulmonary

[6]

In the vascular endothelium, cGMP activates cGMP kinase or PKG (protein kinase G),
which is an enzyme that belongs to a type of serine/threonine - specific protein kinase.
PKG is a dimer composed of two similar polypeptides chains that share a common
molecular structure. Each subunit contains a catalytic domain and regulatory domain.
GMP-kinase activates potassium channels and subsequently the inhibition of calcium

hypertension is thought to be due to an underlying interstitial lung disease; further, lung

biopsies are fraught with risks of bleeding due to the high intrapulmonary blood pressure.
Clinical improvement is often measured by a "six-minute walk test", i.e. the distance a
patient can walk in six minutes. Stability and improvement in this measurement correlate
with better survival.

channels. Thus, this process leads to a reduction of intracellular calcium and finally a

Diagnosis of PAH requires the presence of pulmonary hypertension. Although pulmonary

vasodilation.[7]

arterial pressure can be estimated on the basis of echocardiography, pressure

Phosphodiesterase type V (PDE5), which is abundant in the pulmonary tissue, is a

metalohydrolase that hydrolyzes the cyclic bond of cGMP in the presence of divalent
cations (Zn2+). Actually, Zn2+ union is necessary for PDE5 activity. In the N-terminal region
(regulatory domain) of PDE5 there is an aminoacid sequence (residues 142-526) that
joins cGMP. This sequence of PDE5 is divided in two domains; GAF-A and GAF-B; but

measurements with a Swan-Ganz catheter through the right side of the heart provides
the most definite assessment. PAOP (pulmonary artery occlusion pressure) and PVR
(pulmonary vascular resistance) cannot be measured directly withechocardiography.
Therefore diagnosis of PAH requires right-sided cardiac catheterization. A Swan-Ganz

catheter can also measure thecardiac output, which is far more important in measuring

approved for the different condition called pulmonary arterial hypertension. [10] To make the

disease severity than the pulmonary arterial pressure.

distinction, doctors at a minimum will conduct cardiac catheterization of the right heart,
echocardiography, chest CT, a six-minute walk test, and pulmonary function testing.

Normal pulmonary arterial pressure in a person living at sea level has a mean value of
820 mm Hg (10662666 Pa) at rest. Pulmonary hypertension is present when mean

[10]

Using treatments for other kinds of pulmonary hypertension in patients with these

conditions can harm the patient and wastes substantial medical resources. [10]

pulmonary artery pressure exceeds 25 mm Hg (3300 Pa) at rest.[8] Mean pulmonary

artery pressure (mPAP) should not be confused with systolic pulmonary artery pressure

High dose calcium channel blockers are useful in only 5% of IPAH patients who

(sPAP), which is often reported on echocardiogram reports. A systolic pressure of 40 mm

are vasoreactive by Swan-Ganz catheter. Unfortunately, calcium channel blockers have

Hg typically implies a mean pressure of more than 25 mm Hg. Roughly, mPAP =

been largely misused, being prescribed to many patients with non-vasoreactive PAH,

0.61sPAP + 2.

leading to excess morbidity and mortality. The criteria for vasoreactivity have changed.

Physical examination
A physical examination is performed to look for typical signs of pulmonary hypertension.
These include altered heart sounds, such as a widely split S2 or second heart sound, a
loud P2 or pulmonic valve closure sound (part of the second heart sound), (para)sternal

Only those patients whose mean pulmonary artery pressure falls by more than 10 mm
Hg to less than 40 mm Hg with an unchanged or increased cardiac output when
challenged withadenosine, epoprostenol, or nitric oxide are considered vasoreactive.
[11]

Of these, only half of the patients are responsive to calcium channel blockers in the

long term.[12]

heave, possible S3 or third heart sound, and pulmonary regurgitation. Other signs include

A number of agents have recently been introduced for primary and secondary PAH. The

an elevated jugular venous pressure, peripheral edema(swelling of the ankles and

trials supporting the use of these agents have been relatively small, and the only

feet), ascites (abdominal swelling due to the accumulation of fluid), hepatojugular reflux,

measure consistently used to compare their effectivity is the "6 minute walk test". Many

and clubbing.

have no data on mortality benefit or time to progression. [13]

Echocardiography

Vasoactive substances

A meta-analysis of Doppler echocardiography for predicting right heart catheterization

Many pathways are involved in the abnormal proliferation and contraction of the smooth

reported a sensitivity and specificity of 88% and 56%, respectively.[9]

muscle cells of the pulmonary arteries in patients with pulmonary arterial hypertension.

Treatment
Treatment is determined by whether the PH is arterial, venous, hypoxic, thromboembolic,
or miscellaneous. Since pulmonary venoushypertension is synonymous with congestive
heart failure, the treatment is to optimize left ventricular function by the use
of diuretics, beta blockers, ACE inhibitors etc., or to repair/replace the mitral

Three of these pathways are important since they have been targeted with drugs
endothelin receptor antagonists, phosphodiesterase type 5 (PDE-5) inhibitors, and
prostacyclin derivatives.
Because inexpensive generic drugs for this disease are not widely available, the World
Health Organization does not include them in its model list of essential medicines.

valve or aortic valve.

Prostaglandins

Patients with left heart failure or hypoxemic lung diseases (groups II or III pulmonary

Prostacyclin (prostaglandin I2) is commonly considered the most effective treatment for

hypertension) should not routinely be treated with vasoactive agents including

PAH. Epoprostenol (synthetic prostacyclin, marketed as Flolan) is given via continuous

prostanoids, phosphodiesterase inhibitors, or endothelin antagonists, as these are

infusion that requires a semi-permanent central venous catheter. This delivery system

can cause sepsis and thrombosis. Prostacyclin is unstable, and therefore has to be kept

and the T1/2 (biological half-life) hovers around 17.5 hours in healthy subjects.

on ice during administration. Since it has a half-life of 3 to 5 minutes, the infusion has to

[17]

be continuous (24/7), and interruption can be fatal. Other prostanoids have therefore

would pay of the cost of sildenafil therapy.[18] However, there are some adverse effects

been developed. Treprostinil (Remodulin) can be given intravenously or subcutaneously,

of this drug such as headache, diarrhea, nausea, back

but the subcutaneous form can be very painful. An increased risk of sepsis with

pain, dyspepsia, flushing and myalgia.[19]

Moreover, if we consider pharmacoeconomic implications, patients that take tadalafil

intravenous Remodulin has been reported by the CDC. Iloprost (Ilomedin) is also used in
Europe intravenously and has a longer half life. Iloprost (marketed as Ventavis) was the
only inhaled form of prostacyclin approved for use in the US and Europe, until the
inhaled form of treprostinil was approved by the FDA in July 2009 and is marketed under
the trade name Tyvaso. The inhaled form of administration has the advantage of
selective deposition in the lungs with less systemic side effects, however coughing and

Activators of soluble guanylate cyclase

Soluble guanylate cyclase (sGC) is the intracellular receptor for NO. As of April 2009, the
sGC activators cinaciguat and riociguat were undergoing clinical trials for the treatment
of PAH. In October 2013, riociguat (Adempas), was FDA approved for the treatment of

throat irritation commonly occur. Oral and inhaled forms of Remodulin are under

PAH. It is the first of its class.

development. Beraprost is an oral prostanoid available in South Korea and Japan.

Surgical

Endothelin receptor antagonists

The dual (ETA and ETB) endothelin receptor antagonist bosentan (marketed as Tracleer)
was approved in 2001. Sitaxentan (Thelin), a selective endothelin receptor antagonist
that blocks only the action of ETA, was approved for use in Canada, Australia, and the
European Union.[14] but not in the United States. In 2010, Pfizer withdrew Thelin
worldwide because of fatal liver complications. A similar drug, ambrisentan is marketed
as Letairis in U.S. by Gilead Sciences.[15] In addition, another dual/nonselective
endothelin antagonist, Actelion-1, from the makers of Tracleer, will enter clinical trials in
2008.
Phosphodiesterase type 5 inhibitors
The U.S. FDA approved Sildenafil, a selective inhibitor of cGMP specific
phosphodiesterase type 5 (PDE5), for the treatment of PAH in 2005. It is marketed for
PAH as Revatio. In 2009, they also approved Tadalafil, another PDE5 inhibitor, marketed
under the name Adcirca.[16] PDE5 inhibitors are believed to increase pulmonary artery
vasodilation, and inhibit vascular remodeling, thus lowering pulmonary arterial pressure
and pulmonary vascular resistance.[citation needed]
Tadalafil is taken orally, as well as sildenafil, and it is rapidly absorbed (serum levels are
detectable at 20 minutes). The recommended dose is 40 mg in one single dose per day

Atrial septostomy is a surgical procedure that creates a communication between the right
and left atria. It relieves pressure on the right side of the heart, but at the cost of lower
oxygen levels in blood (hypoxia).
Lung transplantation cures pulmonary arterial hypertension, but leaves the patient with
the complications of transplantation, and a post-surgical median survival of just over five
years.[20]
Pulmonary thromboendarterectomy (PTE) is a surgical procedure that is used for chronic
thromboembolic pulmonary hypertension. It is the surgical removal of an
organizedthrombus (clot) along with the lining of the pulmonary artery; it is a very difficult,
major procedure that is currently performed in a few select centers.
Treatment regimens for hypoxic and miscellaneous varieties of pulmonary hypertension
have not been established. However, studies of several agents are currently enrolling
patients. Many physicians will treat these diseases with the same medications as for
PAH, until better options become available. Such treatment is called off-label use.

Monitoring

almost three times as likely to present with IPAH than adult males. The presentation of
IPAH within children is more evenly split along gender lines.

Established clinical practice guidelines dictate the frequency of pulmonary nodule

evaluation and surveillance. [10] Patients are normally monitored through commonly

Other forms of PAH are far more common. In scleroderma the incidence has been

available tests such as:

estimated to be 6 to 60% of all patients, in rheumatoid arthritis up to 21%, in systemic

lupus erythematosus 4 to 14%, in portal hypertension between 2 to 5%, in HIV about

pulse oximetry

0.5%, and in sickle cell disease ranging from 20 to 40%.

arterial blood gas tests

Diet pills such as Fen-Phen produced an annual incidence of 25-50 per million per year.

chest X-rays

Pulmonary venous hypertension is exceedingly common, since it occurs in most patients

symptomatic with congestive heart failure.

serial ECG tests

Up to 4% of people who suffer a pulmonary embolism go on to develop chronic

serial echocardiography

thromboembolic disease including pulmonary hypertension.

spirometry or more advanced lung function studies

Only about 1.1% of patients with COPD develop pulmonary hypertension with no other

Prognosis

disease to explain the high pressure. Sleep apnea is usually associated with only very
mild pulmonary hypertension, typically below the level of detection. On the other
hand obesity-hypoventilation syndrome is very commonly associated with right heart

The NIH IPAH registry from the 1980s showed an untreated median survival of 23 years

failure due to pulmonary hypertension.

from time of diagnosis, with the cause of death usually being right ventricular failure (cor
pulmonale).[citation needed] A recent outcome study of those patients who had started treatment
with bosentan (Tracleer) showed that 89% patients were alive at 2 years. [21] With new
therapies, survival rates are increasing.[22] For 2,635 patients enrolled in The Registry to
Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management
(REVEAL Registry) from March 2006 to December 2009, 1-, 3-, 5-, and 7-year survival
rates were 85%, 68%, 57%, and 49%, respectively. For patients with idiopathic/familial
PAH, survival rates were 91%, 74%, 65%, and 59%.[23]
Levels of mortality are very high in pregnant women with severe pulmonary
hypertension.[24] Pregnancy is sometimes described as contraindicated in these women.

Epidemiology
Idiopathic pulmonary arterial hypertension is a rare disease with an incidence of about 23 cases per million per year[29] and a prevalence of about 15 per million. Adult females are

Arteriovenous fistula
An arteriovenous fistula is an abnormal connection or passageway between
an artery and a vein. It may be congenital, surgically created
for hemodialysis treatments, or acquired due to pathologic process, such as trauma or
erosion of an arterial aneurysm.

Causes
Congenital (developmental defect)

Pulmonary circulation

Rupture of arterial aneurysm into an adjacent vein

Penetrating injuries

Pulmonary circulation is the portion of the cardiovascular system which

carries deoxygenated blood away from the heart, to the lungs, and returns oxygenated
(oxygen-rich) blood back to the heart. The term pulmonary circulation is readily paired
and contrasted with the systemic circulation. A separate system known as the bronchial
circulation supplies blood to the tissue of the larger airways of the lung.

Inflammatory necrosis of adjacent vessels

Route

Intentionally created (for example, Cimino fistula as vascular access for

hemodialysis)

Mechanism

Pulmonary circulation is the movement of blood from the heart, to the lungs, and back to
the heart again. Deoxygenated blood leaves the heart, goes to the lungs, and then reenters the heart; Deoxygenated blood leaves through the right ventricle through the
pulmonary artery. From the right atrium, the blood is pumped through the tricuspid
valve (or right atrioventricular valve), into the right ventricle. Blood is then pumped from
the right ventricle through the pulmonary valve and into the pulmonary trunk of
the pulmonary artery.

When an arteriovenous fistula is formed involving a major artery like the abdominal aorta,
it can lead to a large decrease in peripheral resistance. This lowered peripheral
resistance causes the heart to increase cardiac output to maintain proper blood flow to
all tissues. The physical manifestations of this would be a relatively normal systolic blood

Arteries
From the right ventricle, blood is pumped through the pulmonary semi-lunar valve into
the left and right pulmonary arteries (one for each lung) and travels through the lungs.

pressure with a decreased diastolic blood pressure resulting in a wide pulse pressure.

Lungs
Normal blood flow in the brachial artery is 85 to 110 milliliters per minute (mL/min). After
the creation of a fistula, the blood flow increases to 400500 mL/min immediately, and
7001,000 mL/min within 1 month. A bracheocephalic fistula above the elbow has a
greater flow rate than a radiocephalic fistula at the wrist. Both the artery and the vein
dilate and elongate in response to the greater blood flow and shear stress, but the vein
dilates more and becomes "arterialized". In one study, the cephalic vein increased from
2.3 mm to 6.3 mm diameter after 2 months. When the vein is large enough to
allow cannulation, the fistula is defined as "mature." [1]
An arteriovenous fistula can increase preload.[2] AV shunts also decrease the afterload of
the heart. This is because the blood bypasses the arterioles which results in a decrease
in the total peripheral resistance (TPR). AV shunts increase both the rate and volume of
blood returning to the heart.

The pulmonary arteries carry deoxygenated blood to the lungs, where it releases carbon
dioxide and picks up oxygen during respiration. Arteries are further divided in to very fine
branches called the capillaries. In structure the capillaries are very thin walled. Their
function is to assist in the carrying of blood to all cells of the body. The pulmonary vein
returns oxygenated blood to the left atrium of the heart.

Veins
The oxygenated blood then leaves the lungs through pulmonary veins, which return it to
the left heart, completing the pulmonary cycle. This blood then enters the left atrium,
which pumps it through the bicuspid valve, also called the mitral or left atrioventricular
valve, into the left ventricle. The blood is then distributed to the body through the
systemic circulation before returning again to the pulmonary circulation.

History
Pulmonary circulation was first described by Ibn al-Nafis in his Commentary on Anatomy
in Avicenna's Canon (1242). Ibn al-Nafis described pulmonary circulation as: [1][2]

"the blood from the right chamber of the heart must arrive at the left chamber but there is
no direct pathway between them. The thick septum of the heart is not perforated and
does not have visible pores as some people thought or invisible pores as Galen thought.
The blood from the right chamber must flow through the vena arteriosa (pulmonary
artery) to the lungs, spread through its substances, be mingled there with air, pass
through the arteria venosa (pulmonary vein) to reach the left chamber of the heart and
there form the vital spirit..."
It was later described by Michael Servetus in the "Manuscript of Paris"[3] (near 1546,
never published) and later published in his Christianismi Restitutio (1553). Since it was a
theology work condemned by most of the Christian factions of his time, the discovery
remained mostly unknown until the dissections of William Harvey in 1616.

Embryonic
The pulmonary circulation loop is virtually bypassed in fetal circulation. The fetal lungs
are collapsed, and blood passes from the right atrium directly into the left atrium through
the foramen ovale: an open conduit between the paired atria, or the ductus arteriosus: a
shunt between the pulmonary artery and the aorta. When the lungs expand at birth, the
pulmonary pressure drops and blood is drawn from the right atrium into the right ventricle
and through the pulmonary circuit. Over the course of several months, the foramen ovale
closes, leaving a shallow depression known as the fossa ovalis in the adult heart.

Pulmonary artery
From Wikipedia, the free encyclopedia

Structure
In the human heart, the pulmonary trunk (pulmonary artery or main pulmonary
artery) begins at the base of the right ventricle. It is short and wideapproximately 5
centimetres (2.0 in) in length and 3 centimetres (1.2 in) in diameter. It then branches into
two pulmonary arteries (left and right), which deliver deoxygenated blood to the
corresponding lung.

Embryology
The pulmonary arteries originate from the truncus arteriosus and the sixth pharyngeal
arch. The truncus arteriosis is a structure that forms during the development of the
heart as a successor to the conus arteriosus. [1]
By the third week of embryological life, the endocardial tubes have developed a swelling
in the part closest to the heart. The swelling is known as the bulbus cordis and the upper
part of this swelling develops into the truncus arteriosus [2] The structure is ultimately
mesodermal in origin.[1] During development of the heart, the heart tissues undergo
folding, and the truncus arteriosus is exposed to what will eventually be both the left and

right ventricles. As a septum develops between the two ventricles of the heart, two
bulges form on either side of the truncus arteriosus. These progressively enlarge until the
trunk splits into the aorta and pulmonary arteries.[3]
During embryological life, the ductus arteriosis connects the pulmonary trunk and
the arch of aorta, allowing blood to bypass the lungs.

Function
The pulmonary artery carries deoxygenated blood from the right ventricle to the lungs.
The blood here passes through capillaries adjacent to alveoli and
becomes oxygenated as part of the process of respiration.
In contrast to the pulmonary arteries, the bronchial arteries supply nutrition to the lungs
themselves.

Pulmonary artery pressure

The pulmonary artery pressure (PA pressure) is a measure of the blood
pressure found in the pulmonary artery. This is measured by inserting a catheter into the
pulmonary artery.[5] :190191 The mean pressure is typically 9 - 18 mmHg,[6] and the wedge
pressure measured in the left atrium may be 6-12mmHg. The wedge pressure may be
elevated in left heart failure,[5]:190191 mitral valve stenosis, and other conditions, such
as sickle cell disease.

Clinical significance
The pulmonary artery is relevant in a number of clinical states. Pulmonary
hypertension is used to describe an increase in the pressure of the pulmonary artery, and
may be defined as a mean pulmonary artery pressure of greater than 25mmHg. [5]:720 This
may occur as a result of heart problems such as heart failure, lung or airway disease
such asCOPD or scleroderma, or thromboembolic disease such as pulmonary
embolism or emboli seen in sickle cell anaemia.[5]:720721
Pulmonary embolism refers to an embolus that lodges in the pulmonary circulation. This
may arise from a deep venous thrombosis, especially after a period of immobility. A
pulmonary embolus is a common cause of death in patients with cancer and stroke. [5]:720
721

A large pulmonary embolus affecting the pulmonary trunk is called a saddle embolus.

Pulmonary valve stenosis

From Wikipedia, the free encyclopedia

Pulmonary valve stenosis is a heart valve disorder in which outflow of blood from
the right ventricle of the heart is obstructed at the level of the pulmonic valve. This results
in the reduction of flow of blood to the lungs. Valvular pulmonic stenosis accounts for

80% of right ventricular outflow tract obstruction.[1] While the most common cause of
pulmonary valve stenosis is congenital heart disease, it may also be due to rheumatic
heart disease or a malignant carcinoid tumor.[1] Both stenosis of the pulmonary artery and
pulmonary valve stenosis are causes of pulmonic stenosis.

Symptoms and Signs

Symptoms include jugular vein distension, cyanosis (usually visible in the nailbeds), right
ventricular hypertrophy, and general symptoms of lowered oxygenation of the blood.
When the stenosis is mild, it can go unnoticed for many years and have no negative
symptoms. If stenosis is severe, sudden fainting or dizziness many occur when

From Wikipedia, the free encyclopedia

Pulmonary insufficiency (or incompetence, or regurgitation) is a condition where

the pulmonary valve is incompetent and allowsbackflow to the right ventricle of
the heart during diastole. While a small amount of pulmonary regurgitation may occur in
healthy individuals, it is usually detectable only by an echocardiogram and is harmless.
More pronounced regurgitation that is noticed through a routine physical examination is
a medical sign of disease and warrants further investigation.
If it is secondary to pulmonary hypertension it is referred to as a Graham Steell
murmur.The three primary pathological mechanisms causing pulmonary insufficiency,
are dilatation of the pulmonic valve ring, acquired alteration of pulmonic valve leaflet
morphology, orcongenital absence or malformation of the valve.

exercising. An enlarged liver (hepatomegaly) and swelling in the legs (edema) may also
be apparent.

Signs and symptoms

Evaluation

Mild cases are usually asymptomatic. Because pulmonic regurgitation is the result of
other factors in the body, any noticeable symptoms are ultimately caused by an
underlying medical condition rather than the regurgitation itself. However, more severe
regurgitation may contribute to right ventricular enlargement by dilation , and in later
stages, right heart failure.

The initial evaluation of pulmonary valve stenosis involves echocardiography. The

degree of stenosis is typically determined by the peak pressure gradient across the
valve.[1]Pulmonary stenosis is mild if the valve area is larger than 1.0 cm2 per square
meter and the trans-valvular gradient is 30-50 mmHg, or the peak RV systolic pressure is
less than 75 mmHg. The stenosis is moderate if valve area is 0.5-1.0 cm2 per square
meter, trans-valvular gradient is 50-75 mmHg, or right ventricle systolic pressure is 75100 mmHg. It is severe when the valve area is less than 0.5 cm , and the gradient is

A decrescendo murmur can sometimes be identified early in diastole, heard best over the
left lower sternal border.

Causes

more than 75 mmHg.[2]

Treatment
Valve replacement or surgical repair (depending upon whether the stenosis is in the
valve or vessel) may be indicated. If the valve stenosis is of congenital origin, balloon
valvuloplasty is another option, depending on the case.

Pulmonary insufficiency

Pulmonary hypertension

Infective endocarditis

Rheumatic heart disease

Congenital absence of the pulmonary valve

Carcinoid syndrome

Congestive abnormalities

Tetralogy of Fallot, a malformation of the heart characterized by four co-occurring

defects: a ventricular septal defect, a misplaced origin of the aorta causing it to

override the septal defect, narrowing of the pulmonary artery, and enlargement of the
right ventricle.

valve.[1]Pulmonary stenosis is mild if the valve area is larger than 1.0 cm2 per square
meter and the trans-valvular gradient is 30-50 mmHg, or the peak RV systolic pressure is
less than 75 mmHg. The stenosis is moderate if valve area is 0.5-1.0 cm2 per square
meter, trans-valvular gradient is 50-75 mmHg, or right ventricle systolic pressure is 75100 mmHg. It is severe when the valve area is less than 0.5 cm 2, and the gradient is
more than 75 mmHg.[2]

Iatrogenic (post surgical repair for congenital heart disease)

Chest trauma

Treatment

Prosthetic heart valve dysfunction

Valve replacement or surgical repair (depending upon whether the stenosis is in the
valve or vessel) may be indicated. If the valve stenosis is of congenital origin, balloon
valvuloplasty is another option, depending on the case.

Treatment
Asymptomatic cases do not require treatment.
Pulmonic regurgitation is generally treated by addressing the underlying condition. In
certain cases, the pulmonary valve may be surgically replaced.

Pulmonary valve stenosis

Pulmonary valve stenosis is a heart valve disorder in which outflow of blood from
the right ventricle of the heart is obstructed at the level of the pulmonic valve. This results
in the reduction of flow of blood to the lungs. Valvular pulmonic stenosis accounts for
80% of right ventricular outflow tract obstruction.[1] While the most common cause of
pulmonary valve stenosis is congenital heart disease, it may also be due to rheumatic
heart disease or a malignant carcinoid tumor.[1] Both stenosis of the pulmonary artery and
pulmonary valve stenosis are causes of pulmonic stenosis.

Symptoms and Signs

Symptoms include jugular vein distension, cyanosis (usually visible in the nailbeds), right
ventricular hypertrophy, and general symptoms of lowered oxygenation of the blood.
When the stenosis is mild, it can go unnoticed for many years and have no negative
symptoms. If stenosis is severe, sudden fainting or dizziness many occur when
exercising. An enlarged liver (hepatomegaly) and swelling in the legs (edema) may also
be apparent.

Evaluation
The initial evaluation of pulmonary valve stenosis involves echocardiography. The
degree of stenosis is typically determined by the peak pressure gradient across the

Cardiomyopathy
From Wikipedia, the free encyclopedia

Cardiomyopathy (literally "heart muscle disease") is the measurable deterioration for

any reason of the ability of the myocardium(the heart muscle) to contract, usually leading
to heart failure. Common symptoms include dyspnea (breathlessness) and peripheral
edema (swelling of the legs). Those with cardiomyopathy are often at risk of dangerous
forms of irregular heart rate and sudden cardiac death.[1] The most common form of
cardiomyopathy is dilated cardiomyopathy.[2][3] Although the term "cardiomyopathy" could
theoretically apply to almost any disease affecting the heart, it is usually reserved for
"severe myocardial disease leading to heart failure".[4]
Cardiomyopathy and myocarditis, resulted in 443,000 deaths in 2013 up from 294,000 in
1990.

Classification
The term 'cardiomyopathy' only came into use about 50 years ago. The definition has
advanced as knowledge has increased and new diagnostic tests have been introduced.
In 2008, the European Society of Cardiology defined it as a myocardial disorder in which
the heart muscle was structurally abnormal and functioned abnormally.[6] [7] [8] Two years
earlier, the American Heart Association had pointed out that cardiomyopathies were
either confined to the heart or were part of a generalized disorder, both often leading to
death or progressive heart failure. Both groups excluded heart disease due to coronary
artery disease, hypertension, abnormalities of the heart valves, and heart disease

present at birth from the definition. Earlier, simpler, categories such as intrinsic, (defined
as weakness of the heart muscle without an identifiable external cause), and extrinsic,
(where the primary pathology arose outside the myocardium itself), became more difficult
to sustain. For example, as more external causes were recognized, the intrinsic category
became smaller. Alcoholism, for example, has been identified as a cause of dilated
cardiomyopathy, as has drug toxicity, and certain infections (including Hepatitis C). On
the other hand, molecular biology and genetics have given rise to the recognition of
various genetic causes, increasing the intrinsic category. For example, mutations in the
cardiac desmosomal genes as well as in the DES gene may cause arrhythmogenic right
ventricular cardiomyopathy (ARVC).[9][10]
At the same time, a more clinical categorization of cardiomyopathy as 'hypertrophied',
'dilated', or 'restrictive',[11] became difficult to maintain when it became apparent that some
of the conditions could fulfill more than one of those three categories at any particular
stage of their development.
The current American Heart Association definition divides cardiomyopathies into primary,
which affect the heart alone, and secondary, which are the result of illness affecting other
parts of the body. These categories are further broken down into subgroups which
incorporate new genetic and molecular biology knowledge.[12]

Peripartum cardiomyopathy

Takotsubo cardiomyopathy

Loeffler endocarditis

Secondary/extrinsic cardiomyopathies

Metabolic/storage

amyloidosis

hemochromatosis

Types

Inflammatory

"viral myocarditis"

Chagas disease

Primary/intrinsic cardiomyopathies

Genetic

Endocrine

Hypertrophic cardiomyopathy (HCM or HOCM)

diabetic cardiomyopathy

hyperthyroidism

acromegaly

Arrhythmogenic right ventricular cardiomyopathy (ARVC)

Isolated ventricular non-compaction

Mitochondrial myopathy

Toxicity

Mixed

chemotherapy

Alcoholic cardiomyopathy

Dilated cardiomyopathy (DCM)

Restrictive cardiomyopathy (RCM)

Neuromuscular

Acquired

muscular dystrophy

Nutritional diseases

Obesity-associated cardiomyopathy[13]
Other

"Ischemic cardiomyopathy" is a weakness in the muscle of the

heart due to inadequate oxygen delivery to the myocardium with coronary
artery disease being the most common cause. Not supported by current

Dilated cardiomyopathy
From Wikipedia, the free encyclopedia

cardiomyopathies classification schemes.[14][15]

Signs and symptoms

Symptoms and signs may mimic those of almost any form of heart disease. Chest pain is
common. Mild myocarditis or cardiomyopathy is frequently asymptomatic; severe cases
are associated with heart failure, arrhythmias, and systemic embolization. Manifestations
of the underlying disease (e.g., Chagas' disease) may be prominent. Most patients with
biopsy-proven myocarditis report a recent viral prodrome preceding cardiovascular
symptoms.
ECG abnormalities are often present, although the changes are frequently nonspecific. A
pattern characteristic of left ventricular hypertrophy may be present. Flat or inverted T
waves are most common, often with low-voltage QRS complexes. Intraventricular
conduction defects and bundle branch block, especially left bundle branch block, are also
common. An echocardiogram is useful to detect wall motion abnormalities or a
pericardial effusion. Chest radiographs can be normal or can show evidence of
congestive heart failure with pulmonary edema or cardiomegaly.

Treatment

Not to be confused with hypertrophic cardiomyopathy or any other cardiomyopathy.

Dilated cardiomyopathy or DCM is a condition in which the heart becomes weakened
and enlarged and cannot pump blood efficiently. The decreased heart function can affect
the lungs, liver, and other body systems.
DCM is one of the cardiomyopathies, a group of diseases that affect primarily
the myocardium (the muscle of the heart). Different cardiomyopathies have different
causes and affect the heart in different ways. In DCM a portion of the myocardium is
dilated, often without any obvious cause. Left or right ventricular systolic pump function
of the heart is impaired, leading to progressive cardiac enlargement and hypertrophy, a
process called remodeling.[1]
Dilated cardiomyopathy is the most common form of non-ischemic cardiomyopathy. It
occurs more frequently in men than in women, and is most common between the ages of
20 and 60 years.[2] About one in three cases of congestive heart failure (CHF) is due to
dilated cardiomyopathy.[1] Dilated cardiomyopathy also occurs in children.

Signs and symptoms

Main article: Heart failure Signs and symptoms

Treatment depends on the type of cardiomyopathy and condition of disease, but may
include medication (conservative treatment) or iatrogenic/implanted pacemakers for slow
heart rates, defibrillators for those prone to fatal heart rhythms, ventricular assist
devices (VADs) for severe heart failure, or ablation for recurring dysrhythmias that cannot
be eliminated by medication or mechanical cardioversion. The goal of treatment is often
symptom relief, and some patients may eventually require a heart transplant. Treatment
of cardiomyopathy (and other heart diseases) using alternative methods such as stem
cell therapy is commercially available but is not supported by convincing evidence.

Dilated cardiomyopathy may not cause symptoms significant enough to impact on quality
of life A minority of people can experience significant symptoms. These might include: [
Shortness of breath

Syncope

Angina, but only in the presence of ischemic heart disease

A person suffering from dilated cardiomyopathy may have an enlarged heart,

with pulmonary edema and an elevated jugular venous pressure and a low pulse

pressure. Signs of mitral and tricuspid regurgitation may be present. A fast heart rate with
no change during the respiratory cycle may also be found. [citation needed]

Causes
Although in many cases no cause is apparent, dilated cardiomyopathy is probably the
result of damage to the myocardiumproduced by a variety of toxic, metabolic, or
infectious agents. It may be due to fibrous change of the myocardium from a
previous myocardial infarction. Or, it may be the late sequelae of acute viral myocarditis,
such as with Coxsackie B virus and other enteroviruses[3] possibly mediated through an
immunologic mechanism.[4] In cats, taurine deficiency is the most common cause of
dilated cardiomyopathy.
Other causes include:

Chagas disease, due to Trypanosoma cruzi. This is the most common infectious
cause of dilated cardiomyopathy in Latin America[5]

Pregnancy. Dilated cardiomyopathy occurs late in gestation or several weeks to

months postpartum as a peripartum cardiomyopathy.[3] It is reversible in half of
cases.[3]

Alcohol abuse (Alcoholic cardiomyopathy), although the cause-and-effect

relationship with alcohol alone is debated.[3] Nonalcoholic toxic insults include
administration of certain chemotherapeutic agents, in
particular doxorubicin (Adriamycin), and cobalt.[3]

Genetics
About 2535% of affected individuals have familial forms of the disease, [3] with
most mutations affecting genes encoding cytoskeletal proteins,[3] while some affect other
proteins involved in contraction.[10] The disease is genetically heterogeneous, but the
most common form of its transmission is an autosomal dominant pattern.[3] Autosomal
recessive (as found, for example, in Alstrm syndrome[3]), X-linked (as in Duchenne
muscular dystrophy), and mitochondrial inheritance of the disease is also found.[11] Some
relatives of those affected by dilated cardiomyopathy have preclinical, asymptomatic
heart-muscle changes.[12]
Other cytoskeletal proteins involved in DCM include -cardiac actin, desmin, and the
nuclear lamins A and C.[3] Mitochondrial deletions and mutations presumably cause DCM
by altering myocardial ATP generation.[3]

Pathophysiology
The progression of heart failure is associated with left ventricular remodeling, which
manifests as gradual increases in left ventricular end-diastolic and end-systolic volumes,
wall thinning, and a change in chamber geometry to a more spherical, less elongated
shape. This process is usually associated with a continuous decline in ejection fraction.
The concept of cardiac remodeling was initially developed to describe changes that
occur in the days and months following myocardial infarction. [13]
Death is due to either congestive heart failure or ventricular tachy- or bradyarrhythmias.

Computational models of eccentric cardiac growth

Cardiac dilation is a transversely isotropic, irreversible process resulting from excess
strains on the myocardium.[14] A computation model of volumetric, isotropic, and cardiac
wall growth predicts the relationship between cardiac strains (e.g. volume overload after
myocardial infarction) and dilation using the following governing equations:

Thyroid disease, stimulant use, and chronic uncontrolled tachycardia.

Autoimmune mechanisms are also suggested as a cause for dilated cardiomyopathy.[6]

Recent studies have shown that those subjects with an extremely high occurrence
(several thousands a day) of premature ventricular contractions (extrasystole) can
develop dilated cardiomyopathy. In these cases, if the extrasystole are reduced or
removed (for example, via ablation therapy) the cardiomyopathy usually regresses. [7][8]
Although the disease is more common in African-Americans than in Caucasians, [9] it may
occur in any patient population.

where
is elastic volume stretch that is reversible and
volume growth described by:

is irreversible, isotropic

where
is a vector, which points along a cardiomyocyte's long axis and
is the
cardiomyocyte stretch due to growth. The total cardiomyocyte growth is given by:

The above model reveals a gradual dilation of the myocardium, especially the ventricular
myocardium, to support the blood volume overload in the chambers. Dilation manifests
itself in an increase in total cardiac mass and cardiac diameter. Cardiomyocytes reach
their maximum length of 150 m in the endocardium and 130 m in the epicardium by
the addition of sarcomeres.[15] Due to the increase in diameter, the dilated heart appears
spherical in shape, as opposed the elliptical shape of a healthy human heart. In addition,
the ventricular walls maintain the same thickness, characteristic of pathophysiological
cardiac dilation.

Diagnosis
Generalized enlargement of the heart is seen upon normal chest X-ray. Pleural
effusion may also be noticed, which is due to pulmonary venous hypertension.
Serial 12-lead ECGs from a 49-year-old black man with cardiomyopathy. (TOP): Sinus tachycardia (rate
about 101/min) with LBBB accompanied by RAD (here about 108). Frequent multifocal PVCs (both

The electrocardiogram often shows sinus tachycardia or atrial fibrillation, ventricular

arrhythmias, left atrial enlargement, and sometimes intraventricular conduction defects
and low voltage. When left bundle-branch block (LBBB) is accompanied by right axis
deviation (RAD), the rare combination is considered to be highly suggestive of dilated or
congestive cardiomyopathy.[16][17] Echocardiogram shows left ventricular dilatation with
normal or thinned walls and reduced ejection fraction.
Cardiac catheterization and coronary angiography are often performed to exclude
ischemic heart disease.
Genetic testing can be important, since one study has shown that gene mutations in the
TTN gene (which codes for a protein called titin) are responsible for "approximately 25%
of familial cases of idiopathic dilated cardiomyopathy and 18% of sporadic cases." [18] The
results of the genetic testing can help the doctors and patients understand the underlying
cause of the dilated cardiomyopathy. Genetic test results can also help guide decisions
on whether a patient's relatives should undergo genetic testing (to see if they have the
same genetic mutation) and cardiac testing to screen for early findings of dilated
cardiomyopathy.

There is some evidence for the benefits of Coenzyme Q10 in treating heart failure.[20][21]
[22]
Other supplements provided may include L-Carnitine, Taurine and D-Ribose.

Procedures and Surgery

Artificial pacemakers may be used in patients with intraventricular conduction delay,
and implantable cardioverter-defibrillators in those at risk of arrhythmia. These forms of
treatment have been shown to improve symptoms and reduce hospitalization.
In patients with advanced disease who are refractory to medical therapy, heart
transplantation may be considered.

Reverse remodeling
This refers to reversing the remodelling that has occurred. Therapies that support
reverse remodeling have been investigated, and this may suggests a new approach to
the prognosis of cardiomyopathies (see ventricular remodeling).[13]

Dilated cardiomyopathy in animals

Dilated cardiomyopathy is a heritable disease in some dog breeds, including
the Boxer, Dobermann, Great Dane, Irish Wolfhound, and St Bernard.[23] Treatment is
based on medication, including ACE inhibitors, loop diuretics, and phosphodiesterase
inhibitors.
Dilated cardiomyopathy is also a disease affecting some cat breeds, including
the Oriental Shorthair, Burmese, Persian, and Abyssinian. As opposed to these
hereditary forms, non-hereditary DCM used to be common in the overall cat population
before the addition of taurine to commercial cat food.
There is also a high incidence of heritable dilated cardiomyopathy in captive Golden
Hamsters (Mesocricetus auratus), due in no small part to their being highly inbred. The
incidence is high enough that several strains of Golden Hamster have been developed to
serve as animal models in clinical testing for human forms of the disease.

Cardiac magnetic resonance imaging (cardiac MRI) may also provide helpful diagnostic
information in patients with dilated cardiomyopathy.[19]

Treatment
Management and treatment of dilated cardiomyopathy has improved significantly in the
last decade. Drug therapy can slow down progression and in some cases even improve
the heart condition. Standard therapy may include salt restriction, ACE
inhibitors, diuretics, and digitalis. Anticoagulants may also be used. Alcohol should be
avoided.[

Hypertrophic cardiomyopathy
From Wikipedia, the free encyclopedia

Not to be confused with dilated cardiomyopathy or any other cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a primary disease of

the myocardium (the muscle of the heart) in which a portion of the myocardium
is hypertrophied (thickened) without any obvious cause, creating functional impairment of
the cardiac muscle.[1][2][3][4][5][6]It is a leading cause of sudden cardiac death in young
athletes.[7] The occurrence of hypertrophic cardiomyopathy is a significant cause of
sudden unexpected cardiac death in any age group and as a cause of disabling cardiac
symptoms. Younger people are likely to have a more severe form of hypertrophic
cardiomyopathy.
HCM is frequently asymptomatic until sudden cardiac death, and for this reason some
suggest routinely screening certain populations for this disease.[8]

treatment with diuretics, a mainstay of CHF treatment, will exacerbate symptoms in

hypertrophic obstructive cardiomyopathy by decreasing ventricular preload volume and
thereby increasing outflow resistance (less blood to push aside the thickened obstructing
tissue).
Major risk factors for sudden death in individuals with HCM include prior history of
cardiac arrest or ventricular fibrillation, spontaneous sustained ventricular tachycardia,
family history of premature sudden death, unexplained syncope, LV thickness greater
than or equal to 30 mm, abnormal exercise blood pressure and nonsustained ventricular

A cardiomyopathy is a disease that affects the muscle of the heart. With HCM,
the myocytes (cardiac contractile cells) in the heart increase in size, which results in the
thickening of the heart muscle. In addition, the normal alignment of muscle cells is
disrupted, a phenomenon known as myocardial disarray. HCM also causes disruptions of
the electrical functions of the heart. HCM is most commonly due to a mutation in one of 9
sarcomeric genes that results in a mutated protein in the sarcomere, the primary
component of the myocyte (the muscle cell of the heart). These are predominantly
single-point missense mutations in the genes for beta-myosin heavy chain (MHC),
myosin-binding protein C, cardiac troponinT, or tropomyosin. These mutations cause
myofibril and myocyte structural abnormalities and possible deficiencies in force
generation.

tachycardia.[10]

While most literature so far focuses on European, American, and Japanese populations,
HCM appears in all racial groups. The prevalence of HCM is about 0.2% to 0.5% of the
general population.

mutations occur in the myosin heavy chain gene on chromosome 14 q11.2-3, while

Signs and symptoms

of inheriting the disease-causing mutation. Whenever a mutation is identified through

The clinical course of HCM is variable. Many patients are asymptomatic or mildly
symptomatic. The symptoms of HCM include dyspnea (shortness of breath) due to
stiffening and decreased blood filling of the ventricles, exertional chest pain (sometimes
known as angina) due to reduced or restricted blood flow to the coronary arteries,
uncomfortable awareness of the heart beat (palpitations) due to the aforementioned
ischemia, as well as disruption of the electrical system running through the abnormal
heart muscle,lightheadedness, fatigue, fainting (called syncope) and sudden cardiac
death. As mentioned, Dyspnea is largely due to increased stiffness of the left ventricle,
which impairs filling of the ventricles, but also leads to elevated pressure in the left

Genetics
Familial hypertrophic cardiomyopathy is inherited as an autosomal dominant trait and is
attributed to mutations in one of a number of genes that encode for one of
the sarcomere proteins.
About 50-60% of patients with a high index of clinical suspicion for HCM will have a
mutation identified in at least 1 of 9 sarcomeric genes. Approximately 45% of these
approximately 35% involve the cardiac myosin binding protein C gene. Since HCM is
typically an autosomal dominant trait, children of a single HCM parent have 50% chance
genetic testing, family-specific genetic testing can be used to identify relatives at-risk for
the disease.[11]
In individuals without a family history of HCM, the most common cause of the disease is
a de novo mutation of the gene that produces the -myosin heavy chain.
An insertion/deletion polymorphism in the gene encoding for angiotensin converting
enzyme (ACE) alters the clinical phenotype of the disease. The D/D (deletion/deletion)
genotype of ACE is associated with more marked hypertrophy of the left ventricle and
may be associated with higher risk of adverse outcomes.

ventricle and left atrium, causing back pressure and interstitial congestion in the lungs.

Some mutations could have more malignant potential compared to others ( myosin

Symptoms are not closely related to the presence or severity of an outflow tract gradient.

heavy chain). For example, troponin T mutations were originally associated with a 50%

[9]

Often, symptoms mimic those of congestive heart failure (esp. activity intolerance &

dyspnea), but treatment of each is different. Beta blockers are used in both cases, but

mortality before the age of 40. However, a more recent and larger study found a similar

septum. But SAM onset is observed to be a low velocity phenomenon: SAM begins at

risk to other sarcomeric protein mutations [14]

velocities no different from those measured in normal hearts.[16][17] Hence, the magnitude
and importance of Venturi forces in the outflow tract are much less than previously

Pathophysiology

thought, and Venturi forces cannot be the main force that initiates SAM.

Individuals with HCM have some degree of left ventricular hypertrophy. Usually this is an

Recent echocardiographic evidence indicates that drag, the pushing force of flow is the

asymmetric hypertrophy, involving the inter-ventricular septum, and is known as

dominant hydrodynamic force on the mitral leaflets. In obstructive HCM the mitral leaflets

asymmetric septal hypertrophy.

are often large [22] and are anteriorly positioned in the LV cavity due to anteriorly

[15]

This is in contrast to the concentric hypertrophy seen

in aortic stenosis or hypertension. About two-thirds of individuals with HCM have

positioned papillary muscles[16] that at surgery are often "agglutinated" onto the LV

asymmetric septal hypertrophy.

anterior wall by abnormal attachments. [20][21]

About 25% of individuals with HCM demonstrate an obstruction to the outflow of blood

The mid-septal bulge aggravates the malposition of the valve and redirects outflow so

from the left ventricle during rest. In as much as 70% of patients however obstruction can

that it comes from a lateral and posterior direction.[18] The abnormally directed outflow

be provoked under certain conditions. This is known as dynamic outflow obstruction,

may be visualized behind and lateral to the enlarged mitral valve, where it catches it, and

because the degree of obstruction is variable and is dependent on the loading conditions

pushes it into the septum. There is a crucial overlap between the inflow and outflow

(ventricular filling and arterial blood pressure) and the contractility state of the left

portions of the left ventricle.[24] As SAM progresses in early systole the angle between

ventricle.

outflow and the protruding mitral leaflet increases. A greater surface area of the leaflets is

Myocardial hypertrophy and extracellular fibrosis predispose to increased left ventricular

stiffness which in concert with compromised cellular energetics and abnormal calcium
handling lead to diastolic dysfunction manifested as dyspnea and exercise intolerance.
The altered structure of the coronary vessels and increased diastolic pressure (reduced
blood supply) together with the hypertrophy and the outflow tract obstruction (increased
demand) cause myocardial ischemia that is manifested as angina and may be
responsible for the triggering of ventricular arrhythmias.
In about 30% of patients there are abnormal vascular responses and inability to increase
systolic blood pressure during exercise. This is attributed to exaggerated cardiac
inhibitory reflexes initiated by increased myocardial wall stress and to elevated levels of
vasodilating substances (natriuretic peptides).
Dynamic outflow obstruction (when present in HCM) is usually due to systolic anterior
motion of the anterior leaflet of the mitral valve. Systolic anterior motion of the mitral
valve (SAM) was initially thought to be due to the septal subaortic bulge, narrowing the
outflow tract, causing high velocity flow and a Venturi effecta local underpressure in
the outflow tract. Low pressure was thought to suck the mitral valve anteriorly into the

now exposed to drag which amplifies the force on the leaflets drag increases with
increasing angle relative to flow.[18] An analogy is an open door in a drafty corridor: the
door starts by moving slowly and then accelerates as it presents a greater surface area
to the wind and finally it slams shut. The necessary conditions that predispose to SAM
are: anterior position of the mitral valve in the LV, altered LV geometry that allows flow to
strike the mitral valve from behind, and chordal slack. SAM may be considered anteriorly
directed mitral prolapse. In both conditions the mitral valve is enlarged and is displaced
in systole by the pushing force of flow resulting in mitral regurgitation.
Because the mitral valve leaflet doesn't get pulled into the left ventricular outflow tract
(LVOT) until after the aortic valve opens, the initial upstroke of the arterial pulse will be
normal. When the mitral valve leaflet gets pushed into the LVOT, the arterial pulse will
momentarily collapse and be followed by a second rise, as the left ventricular pressure
overcomes the increased obstruction that SAM of the mitral valve causes. This can be
seen on the physical examination as a double tap upon palpation of the apical impulse
and as a double pulsation upon palpation of the carotid pulse, known as bifid pulse.[25]

Screening
Main article: Hypertrophic cardiomyopathy screening

Although HCM may be asymptomatic, affected individuals may present with symptoms

1 death per 220,000 athletes.[35] Lastly, genetic testing would provide a definitive

ranging from mild to critical heart failure and sudden cardiac death at any point from

diagnosis; however, due to the numerous HCM-causing mutations, this method of

early childhood to seniority.[26][27] HCM is the leading cause of sudden cardiac death in

screening is complex, and is not cost-effective.[2] Therefore, genetic testing in the United

young athletes in the United States, and the most common genetic cardiovascular

States is limited to individuals which exhibit clear symptoms of HCM. This ensures that

disorder. One study found that the incidence of sudden cardiac death in young

the test is not wasted on detecting other causes of ventricular hypertrophy (due to its low

competitive athletes declined in the Veneto region of Italy by 89% since introduction of

sensitivity), and that family members of the individual are educated on the potential risk

routine Hypertrophic Cardiomyopathy Screening of athletes.

of being carriers of the mutant gene(s).[36]

[28]

[29]

As of 2010, however,

studies have shown that the incidence of sudden cardiac death, among all HCM patients,
has declined to one percent, or less.[30] HCM can be detected with

In the United States such screening is not routine and the American Heart

an echocardiogram with 80%+ accuracy,[citation needed] which can be preceded by screening

Association has "consistently opposed" routine screening.[8]

with an electrocardiogram (ECG) to test for heart abnormalities. Cardiac magnetic

resonance imaging (CMR), considered the gold standard for determining the physical
properties of the left ventricular wall, can serve as an alternative screening tool when an
echocardiogram provides inconclusive results.[31] For example, the identification of
segmental lateral ventricular hypertrophy cannot be accomplished with echocardiography
alone. Also, left ventricular hypertrophy may be absent in children under thirteen years of
age. This undermines the results of pre-adolescents echocardiograms. [27] Researchers,

Canada
Canadian genetic testing guidelines and recommendations for individuals diagnosed with
HCM are as follows.

however, have studied asymptomatic carriers of a HCM-causing mutation through the

The main purpose genetic testing is for screening family members. [37]

use of CMR and have been able to identify crypts in the interventricular septal tissue in

or avoid extensive testing.[37]

these patients. It has been proposed that the formation of these crypts is an indication of
myocyte disarray and altered vessel walls that may later result in the clinical expression
of HCM.[31] Lastly, giving warning of heart abnormalities in only 3% of patients before

sudden cardiac death, the gathering of family history and physical examination alone are

Genetic testing is not meant for confirming a diagnosis.[37]

ineffective.[8] A possible explanation for this is that the gathering of family history only

events. Furthermore, given the several factors necessary to be considered at risk for

sudden cardiac death, and that no factor is more important than another, there exists

There are several potential challenges associated with routine screening for HCM in the
United States.[33] First, the U.S. athlete population of 15 million is almost twice as large as
Italy's estimated athlete population.[33] Second, these events are extremely rare in the
U.S., with fewer than 100 deaths due to HCM in competitive athletes per year,[34] or about

Genetic testing is not intended for risk assessment or treatment decisions. [37]

ambiguity regarding when to implement special treatment. [32]

United States

If the diagnosed individual has no relatives that are at risk, then genetic
testing is not required.[37]

focuses on whether sudden death occurred or not. It fails to acknowledge the age at
which relatives suffered sudden cardiac death, as well as the frequency of the cardiac

According to the results, at-risk relatives may be encouraged to undergo

Evidence only supports clinical testing in predicting the progression and

risk of developing complications of HCM.[37]

For individuals suspected of having HCM

Genetic testing is not recommended for determining other causes of left

ventricular hypertrophy (such as athlete's heart, hypertension, and cardiac
amyloidosis).[37]

HCM may be differentiated from other hypertrophy-causing conditions

using clinical history and clinical testing.[37]

Diagnosis
A diagnosis of hypertrophic cardiomyopathy is based upon a number of features of the
disease process. While there is use of echocardiography, cardiac catheterization, or
cardiac MRI in the diagnosis of the disease, other important factors
include ECG and genetic test (although not primarily used for diagnosis)[37] findings and if
there is any family history of HCM or unexplained sudden death in otherwise healthy
individuals.

Obstructive and non-obstructive

Depending on whether the distortion of normal heart anatomy causes an obstruction of
the outflow of blood from the left ventricle of the heart, HCM can be defined as
obstructive or non-obstructive.

The obstructive variant of HCM, hypertrophic obstructive cardiomyopathy

The BrockenbroughBraunwaldMorrow sign is observed in individuals with HCM with

outflow tract gradient. This sign can be used to differentiate HCM from aortic stenosis. In
individuals with aortic stenosis, after a premature ventricular contraction (PVC), the
following ventricular contraction will be more forceful, and the pressure generated in the
left ventricle will be higher. Because of the fixed obstruction that the stenotic aortic valve
represents, the post-PVC ascending aortic pressure will increase as well. In individuals
with HCM, however, the degree of obstruction will increase more than the force of
contraction will increase in the post-PVC beat. The result of this is that the left ventricular
pressure increases and the ascending aortic pressure decreases, with an increase in the
LVOT gradient.
While the BrockenbroughBraunwaldMorrow sign is most dramatically demonstrated
using simultaneous intra-cardiac and intra-aortic catheters, it can be seen on routine
physical examination as a decrease in the pulse pressure in the post-PVC beat in
individuals with HCM.

Treatment

Asymptomatic patient

(HOCM) has also historically been known as idiopathic hypertrophic subaortic

A significant number of patients with hypertrophic cardiomyopathy do not have any

stenosis (IHSS) and asymmetric septal hypertrophy (ASH).

symptoms and will have normal life expectancies, though they should be counseled to

Another, non-obstructive variant of HCM is apical hypertrophic cardiomyopathy,

[38]

also called Yamaguchi Syndrome or Yamaguchi Hypertrophy, first described in

individuals of Japanese descent.

avoid particularly strenuous activities or competitive athletics. These patients should also
be screened for risk factors for sudden cardiac death. In patients with resting or inducible
outflow obstructions, situations that will cause dehydration or vasodilation (such as the
use of vasodilatory or diuretic blood pressure medications) should be avoided. Septal

Physical examination

reductions therapy is not recommended in asymptomatic patients.[39]

Upon cardiac catheterization, catheters can be placed in the left ventricle and the

Medications

ascending aorta, to measure the pressure difference between these structures. In normal
individuals, during ventricular systole, the pressure in the ascending aorta and the left
ventricle will equalize, and the aortic valve is open. In individuals with aortic stenosis or
with HCM with an outflow tract gradient, there will be a pressure gradient (difference)
between the left ventricle and the aorta, with the left ventricular pressure higher than the
aortic pressure. This gradient represents the degree of obstruction that has to be
overcome in order to eject blood from the left ventricle.

The primary goal of medications is to relieve symptoms such as chest pain, shortness of
breath, and palpitations. Beta blockers are considered first-line agents, as they can slow
down the heart rate. For patients who cannot tolerate beta blockers or do not have good
control of symptoms with beta blockers, nondihydropyridine calcium channel
blockers such as verapamil can be used. These medications also decrease the heart
rate, though their use in patients with severe outflow obstruction, elevated pulmonary
artery wedge pressure and low blood pressures should be done with caution.

Dihydropyridine calcium channel blockers should be avoided in patients with evidence of

myomectomy). In a select population with symptoms secondary to a high outflow tract

obstruction. For patients who continue to have symptoms despite the above

gradient, alcohol septal ablation can reduce the symptoms of HCM. In addition, older

treatments, disopyramide can be considered for further symptom relief. Diuretics can be

individuals and those with other medical problems, for whom surgical myectomy would

considered for patients with evidence of fluid overload, though cautiously used in those

pose increased procedural risk, would likely benefit from the lesser invasive septal

with evidence of obstruction. Patients who continue to have symptoms despite drug

ablation procedure.[2][5][45]

therapy can consider more invasive therapies.[39]

When performed properly, an alcohol septal ablation induces a controlled heart attack, in

Surgical myectomy

which the portion of the interventricular septum that involves the left ventricular outflow
tract is infarcted and will contract into a scar. Which patients are best served by surgical

Surgical septal myectomy is an open heart operation done to relieve symptoms in

myectomy, alcohol septal ablation, or medical therapy is an important topic and one

patients who remain severely symptomatic despite medical therapy. It has been

which is intensely debated in medical scientific circles.[46]

performed successfully for more than 25 years. Surgical septal myectomy uniformly
decreases left ventricular outflow tract obstruction and improves symptoms, and in

Ventricular pacing[edit]

experienced centers has a surgical mortality of less than 1%, as well as 85% success
rate.[26] It involves a median sternotomy (general anesthesia, opening the chest, and

The use of a pacemaker has been advocated in a subset of individuals, in order to cause

cardiopulmonary bypass) and removing a portion of the interventricular septum.

asynchronous contraction of the left ventricle. Since the pacemaker activates the

[2]

Surgical myectomy resection focused just on the subaortic septum, to increase the size

interventricular septum before the left ventricular free wall, the gradient across the left

of the outflow tract to reduce Venturi forces may be inadequate to abolish systolic

ventricular outflow tract may decrease. This form of treatment has been shown to provide

anterior motion (SAM) of the anterior leaflet of the mitral valve. With this limited sort of

less relief of symptoms and less of a reduction in the left ventricular outflow tract gradient

resection the residual mid-septal bulge still redirects flow posteriorly: SAM persists

when compared to surgical myectomy.[47] Technological advancements have also lead to

because flow still gets behind the mitral valve. It is only when the deeper portion of the

the development of a dual-chamber pacemaker, which is only turned on when needed (in

septal bulge is resected that flow is redirected anteriorly away from the mitral valve,

contrast to a regular pacemaker which provides a constant stimulus). Although the dual-

abolishing SAM.[3][42] With this in mind, a modification of the Morrow myectomy termed

chamber pacemaker has shown to decrease ventricular outflow tract obstruction,

extended myectomy, mobilization and partial excision of the papillary muscles has

experimental trials have only found few individuals with improved symptoms.

become the excision of choice. In selected patients with particularly large redundant
mitral valves, anterior leaflet plication may be added to complete separation of the mitral
valve and outflow.[43][44] Complications of septal myectomy surgery include possible death,
arrhythmias, infection,incessant bleeding, septal perforation/defect, stroke. [26]

[32]

Unfortunately, researchers suspect that these reports of "improved" symptoms are due

to a placebo effect.[26]

Procedure includes an incision on the anterolateral area below the clavicle. Two
leads are then inserted; one into the right atria and the other into the right ventricular

Alcohol septal ablation

Alcohol septal ablation, introduced by Ulrich Sigwart in 1994, is a percutaneous
technique that involves injection of alcohol into one or more septal branches of the left
anterior descending artery. This is a technique with results similar to the surgical septal
myectomy procedure but is less invasive, since it does not involve general anaesthesia
and opening of the chest wall and pericardium (which are done in a septal

apex via the subclavian veins. Once in place, they are secured and attached to the
generator which will remain inside the patient's fascia, anterior to the pectoral
muscle.[26]Complications of this procedure include infection, electrical lead and
generator malfunction which will require replacement. [26]

Cardiac transplantation

The Ontario Hockey League's Mickey Renaud Captain's Trophy honors former Windsor
Spitfires captain Mickey Renaud, who died of HCM at age 19. [71]

In cases that are refractory to all other forms of treatment, cardiac transplantation is one
option. It is also the only treatment available for end-stage heart failure. [32] However,

On December 10, 2008, NBA player Cuttino Mobley announced his retirement due to

transplantation must occur before the onset of symptoms such as pulmonary vessel

HCM.[72]

hypertension, kidney malfunction, and thromboembolism in order for it to be successful.

Studies have indicated a seven-year survival rate of 94% in patients after transplantation.

The disease also ended the career of former Wake Forest star Robert O'Kelley, after a

[32]

mandatory EKG in Brazil discovered his condition in 2006.[73]

Society and culture

Current University of Denver assistant hockey coach David Carle was originally recruited

Notable cases

to play for the team, but retired from playing after being diagnosed with HCM at the NHL
draft combine. He was nonetheless drafted in the 7th round by the Tampa Bay Lightning.

British comedy actor Leonard Rossiter died from hypertrophic cardiomyopathy in 1984
Former Arsenal and Watford goalkeeper Manuel Almunia announced his retirement on

while waiting to go onstage at the Lyric Theatre, London.

August 26, 2014 after being diagnosed with HCM. [74]

After the death of Marc-Vivien Fo of Cameroon during a 2003 FIFA Confederations
Cup match, his autopsy revealed hypertrophic cardiomyopathy.[48] Mikls "Miki" Fehr, a
Hungarian football player who died during a match on January 25, 2004, also suffered
from HCM.[49][50]

In children
Hypertrophic cardiomyopathy (HCM) is one of the most uncommon cardiac
malformations encountered in pediatric cardiology. This attributed largely to the

The autopsy of actor Corey Haim identified HCM as one of the contributing causes
(along with pneumonia and coronary arteriosclerosis) for his death in 2010.[51]

phenotypes is usually absent, incomplete, or delayed into adulthood. Most of current

information pertaining HCM arises from studies in adult populations, and the implication
of these observations for pediatric population is often uncertain. [75] Nonetheless, recent

Internet personality Ben Breedlove of Austin, Texas died on December 25, 2011, from

studies in pediatric cardiology have revealed that HCM accounts for 42% of childhood

HCM at age 18.[52][53]

cardiomyopathies with an incidence report of 0.47/100,000 in children. [76] Further, in

asymptomatic cases, sudden death is considered one of the most feared complications

English footballer Mitchell Cole died from HCM on December 1, 2012 after retiring earlier

associated with the disease in select pediatric population. Consequently, the

in the year due to the condition.

recommended practice is to start screening children of affected individuals throughout

[54]

childhood to detect cardiac abnormalities at an early stage in hope to prevent further

Other noted athletes believed or suspected to have died from HCM

complication of the disease.[77]

include NFL players Thomas Herrion,[55] Mitch Frerotte,[56] Gaines Adams,[57][58] and Derrick
Faison;[59] NBAplayers Reggie Lewis,[60][61] Jason Collier,[58] and Kevin Duckworth;
[62]

NHL player Sergei Zholtok;

[55]

long distance runner Ryan Shay;

[63]

Marymount basketball star Hank Gathers;

[64]

Generally, the diagnosis of HCM in a pediatric population is made during assessment for
murmur, congestive heart failure, physical exhaustion, and genetic testing of children of

Loyola

Loyola Marymount soccer player David

affected individuals.[75] Specifically, echocardiogram (ECHO) has been used as a

Kucera;[65] Western Kentucky University basketball player Danny Rumph;[66] Kansas

definitive noninvasive diagnostic tool in nearly all children. ECHO assesses cardiac

State football player Anthony Bates; LSU baseball player Wally Pontiff Jr.;

ventricular size, wall thickness, systolic and diastolic function, and outflow obstruction.

[67]

hockey star Alexei Cherepanov;

[69]

[68]

and American strongman Jesse Marunde.

Russian ice

[70]

Thus, ECHO has been chosen as an ideal means to detect excessive wall thickening of

to the terminal aorta creating acute pain and rear limb paralysis (see below). Sudden

cardiac muscle in HCM.[75]

death can also occur but appears to be uncommon.

In HCM, treatment strategies aimed to reduce disease symptoms and lower the risk of

There is no cure for feline HCM. Many but not all cats have a heart murmur. Many cats

sudden death.

that have a heart murmur do not have HCM. Frequently the first signs that a cat has

[78]

Due to the heterogeneity of the disease, treatment is usually modified

according to individual patients needs.[78] -blockers improve left ventricular filling and

HCM are tachypnea/dyspnea due to heart failure or acute pain and paralysis due to

relaxation and thereby improve symptoms. In some pediatric patients, blockers drugs

systemic thromboembolism. While medication is commonly given to cats with HCM that

(e.g. propranolol) were shown to effectively reduce the risk of sudden death. [78] Further,

have no clinical signs, no medication has been shown to be helpful at this stage and it

calcium channel blockers (verapamil) and antiarrhythmic drugs maybe used as an

has been shown that an ACE inhibitor is not beneficial until heart failure is present

adjunct therapy to -blockers in symptomatic children. Nonetheless, further testing is

which time a diuretic is most beneficial). Diltiazem generally produces no demonstrable

needed to determine their definitive benefits.

benefit. Atenolol is commonly administered when severe systolic anterior motion of the

[78]

[84]

(at

mitral valve is present.

Other animals

Feline arterial thromboembolism (FATE) is relatively common and devastating

Feline hypertrophic cardiomyopathy (HCM) is the most common heart disease in

complication of feline HCM and other feline cardiomyopathies. The thrombus generally

domestic cats; the disease process and genetics are believed to be similar to the disease

forms in the left atrium, most commonly the left auricle. Formation is thought to be

in humans.[79] In Maine Coon cats, HCM has been confirmed as an autosomal dominant

primarily due to blood flow stasis. Classically the thromboembolus lodges at the iliac

inherited trait.[80] Numerous cat breeds have HCM as a problem in the breed. The first

trifurcation of the aorta, occluding either one or both of the common iliac arteries.

genetic mutation (in cardiac myosin binding protein C) responsible for feline HCM was

Clinically this presents as a cat with complete loss of function in one or both hind limbs.

discovered in 2005 in Maine Coon cats.

The hind limbs are cold and the cat is in considerable pain. Emboli may, rarely, lodge in

[82]

[81]

A test for this mutation (A31P) is available.

About one third of Maine Coon cats tested for the mutation are either heterozygous or

other locations, most commonly the right front limb and the renal arteries.

homozygous for the mutation, although many of the cats that are heterozygous have no
overt evidence of the disease on an echocardiogram (low penetrance). Some Maine

Clopidogrel (Plavix) is used to try to prevent left atrial thrombus formation in cats with

Coon cats with clinical evidence of hypertrophic cardiomyopathy test negative for this

HCM and a large left atrium. The FATCAT study at Purdue University demonstrated that

mutation, strongly suggesting that another cause exists in the breed. The cardiac myosin

it is superior to aspirin for the prevention of a second thrombus from forming in cats that

binding protein C mutation identified in Maine Coon cats has not been found in any other

have already experienced a clot. Thrombolytic agents (e.g., tissue plasminogen

breed of cat with HCM but more recently another myosin binding protein C mutation has

activator) have been used with some success to break down an existing aortic

been identified in Ragdoll cats with HCM.

thromboembolus, but their cost is high and outcome appears to be no better than giving

[83]

As in humans, feline HCM is not present at

birth but develops over time. It has been identified for the first time in cats as young as 6

a cat time (4872 hours) to break down its own clot. Pain management is extremely

months of age and at least as old as 7 years of age.

important. The prognosis for cats with FATE is often poor as they are likely to have
significant HCM already and a recurrent bout of FATE is likely. For this reason

Clinically cats with hypertrophic cardiomyopathy commonly have systolic anterior motion
of the mitral valve (see graphic). Cats with severe HCM often develop left heart failure
(pulmonary edema; pleural effusion) because of severe diastolic dysfunction of the left
ventricle. They may also develop a left atrial thrombus that embolizes, most commonly,

euthanasia is often a valid consideration.

In July 2013, Rigo, a 42-year-old Western lowland gorilla, resident in Melbourne Zoo and
father of Mzuri, the first gorilla born by artificial insemination, died unexpectedly as a
result of HCM. The condition is not uncommon in male gorillas over the age of 30, and in
many cases there is no sign of the disease until the individual's sudden death.

Cardiac muscle
From Wikipedia, the free encyclopedia
(Redirected from Endomyocardial)

Cardiac muscle (heart muscle) is involuntary striated muscle that is found in the walls
and histological foundation of the heart, specifically the myocardium. Cardiac muscle is
one of three major types of muscle, the others being skeletal and smooth muscle. These
three types of muscle all form in the process of myogenesis. The cells that constitute
cardiac muscle, called cardiomyocytes or myocardiocytes, contain only three nuclei.
The myocardium is the muscle tissue of the heart, and forms a thick middle layer
between the outer epicardium layer and the inner endocardium layer.
Coordinated contractions of cardiac muscle cells in the heart propel blood out of
the atria and ventricles to the blood vessels of the left/body/systemic and
right/lungs/pulmonary circulatory systems. This complex mechanism illustrates systole of
the heart.
Cardiac muscle cells, unlike most other tissues in the body, rely on an available blood
and electrical supply to deliver oxygen and nutrients and remove waste products such
as carbon dioxide. The coronary arteries help fulfill this function.

Striation
Cardiac muscle has cross striations formed by rotating segments of thick and thin protein
filaments. Like skeletal muscle, the primary structural proteins of cardiac muscle are
myosin and actin. The actin filaments are thin, causing the lighter appearance of the I
bandsin striated muscle, whereas the myosin filament is thicker, lending a darker
appearance to the alternating A bands as observed withelectron microscopy. However, in
contrast to skeletal muscle, cardiac muscle cells are typically branch-like instead of
linear.

T-tubules
Another histological difference between cardiac muscle and skeletal muscle is that the Ttubules in the cardiac muscle are bigger and wider and track laterally to the Z-discs.
There are less T-tubules in comparison with skeletal muscle. The diad is a structure in
the cardiacmyocyte located at the sarcomere Z-line. It is composed of a single Ttubule paired with a terminal cisterna of the sarcoplasmic reticulum. The diad plays an
important role in excitation-contraction coupling by juxtaposing an inlet for the action
potential near a source of Ca2+ions. This way, the wave of depolarization can be coupled
to calcium-mediated cardiac muscle contraction via the sliding filament mechanism.
Cardiac muscle forms these instead of the triads formed between the sarcoplasmic
reticulum in skeletal muscle and T-tubules. T-tubules play critical role in excitationcontraction coupling (ECC). Recently, the action potentials of T-tubules were recorded
optically by Guixue Bu et al.[3]

Intercalated discs
Main article: Intercalated disc
The cardiac syncytium is a network of cardiomyocytes connected to each other
by intercalated discs that enable the rapid transmission of electrical impulses through the
network, enabling the syncytium to act in a coordinated contraction of the myocardium.
There is an atrial syncytium and a ventricular syncytium that are connected by
cardiac connection fibres.[4] Electrical resistance through intercalated discs is very low,
thus allowing free diffusion of ions. The ease of ion movement along cardiac muscle
fibers axes is such that action potentials are able to travel from one cardiac muscle cell
to the next, facing only slight resistance. Each syncyntium obeys the all or none law.[5]
Intercalated discs are complex adhering structures that connect the single
cardiomyocytes to an electrochemicalsyncytium (in contrast to the skeletal muscle, which
becomes a multicellular syncytium during mammalian embryonic development). The
discs are responsible mainly for force transmission during muscle contraction.
Intercalated discs are described to consist of three different types of cell-cell junctions:
the actin filament anchoring adherens junctions, the intermediate filament
anchoring desmosomes , and gap junctions. They allow action potentials to spread
between cardiac cells by permitting the passage of ions between cells, producing
depolarization of the heart muscle. However, novel molecular biological and
comprehensive studies unequivocally showed that intercalated discs consist for the most
part of mixed-type adhering junctions named area composita (pl. areae compositae)
representing an amalgamation of typical desmosomal and fascia adhaerens proteins (in
contrast to various epithelia).[6][7][8] The authors discuss the high importance of these
findings for the understanding of inherited cardiomyopathies (such asarrhythmogenic
right ventricular cardiomyopathy).
Under light microscopy, intercalated discs appear as thin, typically dark-staining lines
dividing adjacent cardiac muscle cells. The intercalated discs run perpendicular to the
direction of muscle fibers. Under electron microscopy, an intercalated disc's path appears
more complex. At low magnification, this may appear as a convoluted electron dense

structure overlying the location of the obscured Z-line. At high magnification, the
intercalated disc's path appears even more convoluted, with both longitudinal and
transverse areas appearing in longitudinal section. [9]

Physiology
In contrast to skeletal muscle, cardiac muscle requires extracellular calcium ions for
contraction to occur. Like skeletal muscle, the initiation and upshoot of the action
potential in ventricular muscle cells is derived from the entry of sodium ions across
the sarcolemma in a regenerative process. However, an inward flux of extracellular
calcium ions through L-type calcium channels sustains the depolarization of cardiac
muscle cells for a longer duration. The reason for the calcium dependence is due to the
mechanism of calcium-induced calcium release (CICR) from the sarcoplasmic
reticulum that must occur under normal excitation-contraction (EC) coupling to cause
contraction. Once the intracellular concentration of calcium increases, calcium ions bind
to the protein troponin, which initiate extracellular fluid and intracellular stores, and
skeletal muscle, which is only activated by calcium stored in the sarcoplasmic reticulum.

Regeneration of heart muscle cells

Until recently, it was commonly believed that cardiac muscle cells could not be
regenerated. However, a study reported in the April 3, 2009 issue of Science contradicts
that belief.[10] Olaf Bergmann and his colleagues at the Karolinska
Institute in Stockholm tested samples of heart muscle from people born before 1955 who
had very little cardiac muscle around their heart, many showing with disabilities from this
abnormality. By using DNA samples from many hearts, the researchers estimated that a
20-year-old renews about 1% of heart muscle cells per year, and about 45 percent of the
heart muscle cells of a 50-year-old were generated after he or she was born.
One way that cardiomyocyte regeneration occurs is through the division of pre-existing
cardiomyocytes during the normal aging process.[11] The division process of pre-existing
cardiomyocytes has also been shown to increase in areas adjacent to sites of myocardial
injury. In addition, certain growth factors promote the self-renewal of endogenous
cardiomyocytes and cardiac stem cells. For example, insulin-like growth factor
1, hepatocyte growth factor, and high-mobility group protein B1 increase cardiac stem
cell migration to the affected area, as well as the proliferation and survival of these cells.
[12]
Some members of the fibroblast growth factorfamily also induce cell-cycle re-entry of
small cardiomyocytes. Vascular endothelial growth factor also plays an important role in
the recruitment of native cardiac cells to an infarct site in addition to its angiogenic effect.
Based on the natural role of stem cells in cardiomyocyte regeneration, researchers and
clinicians are increasingly interested in using these cells to induce regeneration of
damaged tissue. Various stem cell lineages have been shown to be able to differentiate
into cardiomyocytes, including bone marrow stem cells. For example, in one study,
researchers transplanted bone marrow cells, which included a population of stem cells,
adjacent to an infarct site in a mouse model. Nine days after surgery, the researchers
found a new band of regenerating myocardium.[13] However, this regeneration was not

observed when the injected population of cells was devoid of stem cells, which strongly
suggests that it was the stem cell population that contributed to the myocardium
regeneration. Other clinical trials have shown that autologous bone marrow cell
transplants delivered via the infarct-related artery decreases the infarct area compared to
patients not given the cell therapy.[14]

Clinical significance
Occlusion (blockage) of the coronary arteries by atherosclerosis and/or thrombosis can
lead to myocardial infarction (heart attack), where part of the myocardium is injured due
toischemia (not receiving enough oxygen). Certain viruses lead
to myocarditis (inflammation of the myocardium). Cardiomyopathies are inherent
diseases of the myocardium, many of which are caused by genetic mutations.

Loeffler endocarditis
Loeffler endocarditis is a form of restrictive cardiomyopathy which affects
the endocardium and occurs with white blood cell proliferation, specifically of eosinophils.
[1]
Restrictive cardiomyopathy is defined as a disease of the heart muscle which results in
impaired filling of the heart ventricles during diastole. [1][2]

Pathogenesis
Eosinophilic states that may occur in association with Loeffler endocarditis include
hypereosinophilic syndrome, eosinophilic leukemia, carcinoma, lymphoma, drug
reactions or parasites, as reported in multiple case series. [1] Hypereosinophilia can be
caused by a worm (helminth) that invokes the chronic persistence of these eosinophils,
resulting in a condition known as hypereosinophilic syndrome.[3]
The eosinophilia and eosinophilic penetration of the cardiac myocytes leads to a fibrotic
thickening of portions of the heart (similar to that of endomyocardial fibrosis). Commonly
the heart will develop large mural thrombi (thrombi which lay against ventricle walls) due
to the deterioration of left ventricular wall muscle. Symptoms include edema and
breathlessness. The disease is commonly contracted in temperate climates (due to the
favorable conditions for parasites), and is rapidly fatal.

Endocardial fibroelastosis

Characteristics
EFE is characterized by a thickening of the innermost lining of the heart chambers
(the endocardium) due to an increase in the amount of supporting connective tissue and
elastic fibers. It is an uncommon cause of unexplained heart failure in infants and
children, and is one component of HEC syndrome. Fibroelastosis is strongly seen as a
primary cause of restrictive cardiomyopathy in children, along with cardiac amyloidosis,
which is more commonly seen in progressive multiple myeloma patients and the elderly.

Cause and Genetics

A recent review cites references to 31 different diseases and other stresses associated
with the EFE reaction.[2] These include infections, cardiomyopathies, immunologic
diseases, congenital malformations, even electrocution by lightning strike. EFE has two
distinct genetic forms, each having a different mode of inheritance. An x-linked
recessiveform,[3] and an autosomal recessive form[4] have both been observed.

History
An infant with dilated, failing heart was no rarity on the pediatric wards of hospitals in the
mid-twentieth century. When such patients came to the autopsy table, most of the hearts
showed the thickened endocardial layer noted above. This was thought to be a disease
affecting both the heart muscle and the endocardium and it was given various names
such as: idiopathic hypertrophy of the heart, endocardial sclerosis, cardiac enlargement
of unknown cause, etc. Some of these hearts also had overt congenital anomalies ,
especially aortic stenosis and coarctation of the aorta.
The term "endocardial fibroelastosis" was introduced by Weinberg and Himmelfarb in
1943.[5] In their pathology laboratory they noted that usually the endocardium was pearly
white or opaque instead of normally thin and transparent and microscopically showed a
systematic layering of collagenous and elastic fibers. they felt their new term was more
adequately descriptive, and, indeed it was quickly and widely adopted. Clinicians began
applying it to any infant with a dilated, failing heart, in spite of the fact that the only way to
definitively establish the presence of EFE was to see it at autopsy. EFE had quickly
become the name of a disease, and it continues to be used by many physicians in this
way, though many patients with identical symptoms do not have the endocardial reaction
of EFE.
In the latter decades of the twentieth century new discoveries and new thinking about
heart muscle disease gave rise to the term "cardiomyopathy". Many of the cases of
infantile cardiac failure were accordingly called "primary cardiomyopathy" as well as
"primary EFE", while those with identifiable congenital anomalies stressing the heart
were called "secondary EFE". In 1957 Black-Schaffer proposed a unitary explanation
that stress on the ventricle, of any kind, may trigger the endocardial reaction, so that all
EFE could be thought of as secondary.[6] This prescient paper convinced few readers at
the time.

Evidence gradually accumulated as to the role of infection as one such type of stress.
The studies of Fruhling and colleagues in 1962 were critical. [7] They followed a series of
epidemics of Coxsackie virus infection in their part of France. After each epidemic there
were increased numbers of cases with EFE coming to autopsy. On closer study there
were cases of pure acute myocarditis, cases of mixed myocarditis and EFE, and cases
where myocarditis had healed, leaving just EFE. They were able to culture Coxsackie
virus from the tissues of many of the cases at all stages of this apparent progression. A
similar progression from myocarditis to EFE was later observed at Johns Hopkins but no
virology was done.[8]
Noren and colleagues at University of Minnesota, acting on an idea floated at a pediatric
meeting, were able to show a relation between exposure to maternal mumps in fetal life,
EFE, and a positive skin test for mumps in infants.[9] This brought on a large ongoing
controversy and finally prompted a virologist colleague of theirs to inject embryonated
eggs with mumps virus.[10] The chicks at first showed the changes of myocarditis, about a
year later, typical EFE, and transitional changes in between. Despite this, the controversy
about the role of mumps continued as the actual incidence of EFE plummeted. The
proponents of mumps etiology pointed to this as the effect of the recent implementation
of widespread mumps immunization.
Evidence that viral infection may play a role as a cause or trigger of EFE was greatly
reinforced by the study directed by Towbin in the virus laboratory of Texas Children's
Hospital.[11] They applied the methods of today's genetics to old preserved specimens
from autopsies of patients with EFE done well before mumps immunization began and
found mumps genome in the tissues of over 80% of these patients. It seems undeniable
that transplacental mumps infection had been in the past the major cause of EFE, and
that immunization was indeed the cause of EFE having become rare.
Non-infectious causes of EFE have also been studied, spurred by the opening of new
avenues of genetics research. Now there are specific named genes associated with
certain cardiomyopathies, some of which show the characteristic reaction of EFE. A
typical example is Barth syndrome and the responsible gene, tafazzin. [12]
Developments in echocardiography, both the technology of the machines and the skill of
the operators, have made it no longer necessary to see the endocardium at autopsy.
EFE can now be found non-invasively by the recording of increased endocardial echos.
Fetal echocardiography has shown that EFE can begin to accumulate as early as 14
weeks of gestation, and increase with incredible rapidity[13] and even that it can be
reversed if the stress can be removed early in fetal life. [14]
The North American Pediatric Cardiomyopathy Registry was founded in 2000 and has
been supported since by the National Heart, Lung and Blood Institute. Because of the
logic of the diagnostic tree, where EFE applies to many branches of the tree and thus
cannot occupy a branch, it is not listed by the Registry as a cause but rather, "with EFE"
is a modifier that can be applied to any cause.[15]

Thus, the past half century has seen EFE evolve from a mysterious but frequently
observed disease to a rare but much better understood reaction to many diseases and
other stresses.

Treatment
The cause should be identified and, where possible, the treatment should be directed to
that cause. A last resort form of treatment is heart transplant.

Presentation
Rhythmicity and contractility of the heart may be normal, but the stiff walls of the heart
chambers (atria and ventricles) keep them from adequately filling,
reducing preload and end-diastolic volume.
Thus, blood flow is reduced, and blood volume that would normally enter the heart is
backed up in the circulatory system. In time, restrictive cardiomyopathy patients develop
diastolic dysfunction and eventually heart failure.
Untreated hearts with RCM often develop the following characteristics: Biatrial
enlargement, thickened LV walls (with normal chamber size), thickened RV free wall
(with normal chamber size), elevated right atrial pressure (>12mmHg),
moderate pulmonary hypertension, normal systolic function, poor diastolic function,
typically Grade III - IV Diastolic heart failure.

Causes
It is possible to divide the causes into primary and secondary.[3]

Primary

Lffler's endocarditis

endocardial fibroelastosis

Secondary

infiltrative

Restrictive cardiomyopathy

cardiac amyloidosis

Restrictive cardiomyopathy (RCM) (a.k.a. Obliterative cardiomyopathy, once known as

"constrictive cardiomyopathy"[1]) is a form of cardiomyopathy in which the walls are rigid,
[2]
and the heart is restricted from stretching and filling with blood properly.

haemochromatosis

sarcoidosis

It is the least common of Goodwin's three original subtypes of cardiomyopathy, which

includes hypertrophic and dilated as well as restrictive.[1]
It should not be confused with constrictive pericarditis, a disease which presents similarly
but is very different in treatment and prognosis.[1]

interstitial

postradiation fibrosis

Other causes include scleroderma, Churg-Strauss

syndrome, cystinosis, lymphoma, Gaucher's disease, Fabry's disease, pseudoxanthoma

elasticum, hypereosinophilic syndrome,carcinoid, Noonan's syndrome, reactive arthritis,

and Werner's syndrome.[4]

Fatigue, weakness, faintness

Treatment

Decreased alertness or concentration

Therapy for restrictive cardiomyopathy is limited.[5]

Cough containing mucus, or pink, frothy material

Diuretics may help relieve symptoms. Calcium channel blockers may improve diastolic
function in selected individuals.

Decreased urine output (oliguria)

Heart failure resulting from restrictive cardiomyopathy will usually eventually have to be
treated by cardiac transplantation.

Need to urinate at night (nocturia)

Palpitations

Irregular or rapid pulse

Alcoholic cardiomyopathy
From Wikipedia, the free encyclopedia

Alcoholic cardiomyopathy is a disease in which the chronic long-term abuse

of alcohol (i.e. ethanol) leads to heart failure.[1]Alcoholic cardiomyopathy is a type
of dilated cardiomyopathy. Due to the direct toxic effects of alcohol on heart muscle, the
heart is unable to pump blood efficiently, leading to heart failure. It can affect other parts
of the body if the heart failure is severe. It is most common in males between the ages of
35-50.

Diagnosis
Abnormal heart sounds, murmurs, ECG abnormalities, and enlarged heart on chest x-ray
may lead to the diagnosis. Echocardiogram abnormalities and cardiac
catheterization orangiogram to rule out coronary artery blockages, along with a history of
alcohol abuse can confirm the diagnosis.

Treatment

Signs and symptoms presented by the occurrence of alcoholic cardiomyopathy are the
result of the heart failing and usually occur after the disease has progressed to an
advanced stage. Therefore the symptoms have a lot in common with other forms
of cardiomyopathy. These symptoms can include the following:[2]

Treatment for alcoholic cardiomyopathy involves lifestyle changes, including complete

abstinence from alcohol use, a low sodium diet, and fluid restriction, as well as
medications. Medications may include ACE inhibitors, beta blockers, and diuretics which
are commonly used in other forms of cardiomyopathy to reduce the strain on the heart.
Persons with congestive heart failure may be considered for surgical insertion of
an ICD or a pacemaker which can improve heart function. In cases where the heart
failure is irreversible and worsening, heart transplant may be considered.

Ankle, feet, and leg swelling

Treatment will possibly prevent the heart from further deterioration, and the

Overall swelling

Loss of appetite

Shortness of breath, especially with activity

Breathing difficulty while lying down

Signs and symptoms

cardiomyopathy is largely reversible if complete abstinence from alcohol is maintained.

ARVD is often found in association with diffuse palmoplantar keratoderma, and woolly
hair, because their genes are nearby and often inherited together

[1]:513[2]

ARVC/D is an important cause of ventricular arrhythmias in children and young adults. It

Genetics
It is usually inherited in an autosomal dominant pattern, with variable expression. Novel
studies showed that mutations (point mutations) in genes encoding for desmosomal
proteins (see intercalated disc) are the main causatives for the development of this
disease. Recently it could be shown, that mutations in the DES gene could cause ARVC.
[3]

Desmin is an intermediate filament protein, which is linked to the desmosomes.

Different DES muations cause an abnormal aggregation of desmin and associated

proteins.[4] Thepenetrance is 2035% in general, but significantly higher in Italy. Seven
gene loci have been implicated in ARVD. However, about 50% of families that express
ARVD that undergo genetic screening do not show linkage with any of the
known chromosomal loci. It is unclear whether the pathogenesis varies with the different
loci involved. Standard genetic screening test are currently tested and evaluated in
different state of the art cardiovascular research centres and hospitals. Types include:

Incidence

Arrhythmogenic right ventricular dysplasia

The incidence of ARVD is about 1/10,000 in the general population in the United States,
although some studies have suggested that it may be as common as 1/1,000. Recently,

Arrhythmogenic right ventricular dysplasia (ARVD), also called arrhythmogenic

1/200 were found to be carriers of mutations that predispose to ARVC[5] It accounts for up

right ventricular cardiomyopathy (ARVC) orarrhythmogenic right ventricular

to 17% of all sudden cardiac deaths in the young. In Italy, the incidence is 40/10,000,

dysplasia/cardiomyopathy (ARVD/C), is an inherited heart disease.

making it the most common cause of sudden cardiac death in the young population.

ARVD is caused by genetic defects of the parts of heart muscle (also

Presentation

called myocardium or cardiac muscle) known as desmosomes, areas on the surface of

heart muscle cells which link the cells together. The desmosomes are composed of

Up to 80% of individuals with ARVD present with syncope or sudden cardiac death. The

several proteins, and many of those proteins can have harmful mutations.

remainder frequently present with palpitations or other symptoms due to right ventricular
outflow tract (RVOT) tachycardia (a type of monomorphic ventricular tachycardia).

The disease is a type of nonischemic cardiomyopathy that involves primarily the right
ventricle. It is characterized by hypokineticareas involving the free wall of the right

Symptoms are usually exercise-related. In populations where hypertrophic

ventricle, with fibrofatty replacement of the right ventricular myocardium, with

cardiomyopathy is screened out prior to involvement in competitive athletics, it is a

associatedarrhythmias originating in the right ventricle.

common cause of sudden cardiac death.

The first clinical signs of ARVD are usually during adolescence. However, signs of ARVD

cases. Involvement of the ventricular septum is rare. The areas involved are prone to

have been demonstrated in infants.

aneurysm formation.

Pathogenesis

Ventricular arrhythmias

The pathogenesis of ARVD is largely unknown. Apoptosis (programmed cell death)

appears to play a large role. It is unclear why only the right ventricle is involved. The

Ventricular arrhythmias due to ARVD typically arise from the diseased right ventricle. The
type of arrhythmia ranges from frequentpremature ventricular complexes (PVCs)
to ventricular tachycardia (VT) to ventricular fibrillation (VF).

disease process starts in the subepicardial region and works its way towards the
endocardial surface, leading to transmural involvement (possibly accounting for the

While the initiating factor of the ventricular arrhythmias is unclear, it may be due to

aneurysmal dilatation of the RV). Residual myocardium is confined to the subendocardial

triggered activity or reentry.

region and the trabeculae of the RV. These trabeculae may become hypertrophied.
Ventricular arrhythmias are usually exercise-related, suggesting that they are sensitive to
Aneurysmal dilatation is seen in 50% of cases at autopsy. It usually occurs in the

catecholamines. The ventricular beats typically have a right axis deviation. Multiple

diaphragmatic, apical, and infundibular regions (known as the triangle of dysplasia). The

morphologies of ventricular tachycardia may be present in the same individual,

left ventricle is involved in 50-67% of individuals. If the left ventricle is involved, it is

suggesting multiple arrhythmogenic foci or pathways.

usually late in the course of disease, and confers a poor prognosis.

Right ventricular outflow tract (RVOT) tachycardia is the most common VT seen in
There are two pathological patterns seen in ARVD, Fatty infiltration and fibro-fatty

individuals with ARVD. In this case, the EKG shows a left bundle branch block (LBBB)

infiltration.

morphology with an inferior axis.

Fatty infiltration

Diagnosis

The first, fatty infiltration, is confined to the right ventricle. This involves a partial or near-

The differential diagnosis for the ventricular tachycardia due to ARVD include:

complete substitution of myocardium with fatty tissue without wall thinning. It involves
predominantly the apical and infundibular regions of the RV. The left ventricle and

ventricular septum are usually spared. No inflammatory infiltrates are seen in fatty
infiltration. There is evidence of myocyte (myocardial cell) degeneration and death seen
in 50% of cases of fatty infiltration.

Congenital heart disease

Repaired tetralogy of Fallot

Ebstein's anomaly

Uhl's anomaly

Atrial septal defect

Partial anomalous venous return

Fibro-fatty infiltration
The second, fibro-fatty infiltration, involves replacement of myocytes with fibrofatty tissue.
A patchy myocarditis is involved in up to 2/3 of cases, with inflammatory infiltrates
(mostlyT cells) seen on microscopy. Myocardial atrophy is due to injury and apoptosis.
This leads to thinning of the RV free wall (to < 3 mm thickness) Myocytes are replaced
with fibrofatty tissue. The regions preferentially involved include the RV inflow tract, the
RV outflow tract, and the RV apex. However, the LV free wall may be involved in some

Acquired heart disease

Tricuspid valve disease

Ventricular ectopy seen on a surface EKG in the setting of ARVD is typically of left
bundle branch block (LBBB) morphology, with a QRS axis of -90 to +110 degrees. The

Pulmonary hypertension

Right ventricular infarction

origin of the ectopic beats is usually from one of the three regions of fatty degeneration
(the "triangle of dysplasia"): the RV outflow tract, the RV inflow tract, and the RV apex.
Signal averaged ECG

Bundle-branch re-entrant tachycardia

Signal averaged ECG (SAECG) is used to detect late potentials and epsilon waves in

Miscellaneous

individuals with ARVD.

Pre-excited AV re-entry tachycardia

Echocardiography

Idiopathic RVOT tachycardia

Echocardiography may reveal an enlarged, hypokinetic right ventricle with a paper-thin

Sarcoidosis

RV free wall. The dilatation of the RV will cause dilatation of the tricuspid valve annulus,

Clinical testing
In order to make the diagnosis of ARVD, a number of clinical tests are employed,
including the electrocardiogram (EKG), echocardiography, right ventricular angiography,
cardiac MRI, and genetic testing.
Electrocardiogram
90% of individuals with ARVD have some EKG abnormality. The most common EKG
abnormality seen in ARVD is T wave inversion in leads V1 to V3. However, this is a nonspecific finding, and may be considered a normal variant in right bundle branch
block (RBBB), women, and children under 12 years old.
RBBB itself is seen frequently in individuals with ARVD. This may be due to delayed
activation of the right ventricle, rather than any intrinsic abnormality in the right bundle
branch. The epsilon wave is found in about 50% of those with ARVD. This is described
as a terminal notch in the QRS complex. It is due to slowed intraventricular conduction.
The epsilon wave may be seen on a surface EKG; however, it is more commonly seen
on signal averaged EKGs.

with subsequent tricuspid regurgitation. Paradoxical septal motion may also be present.
Cardiac MRI
Fatty infiltration of the RV free wall can be visible on cardiac MRI. Fat has increased
intensity in T1-weighted images. However, it may be difficult to differentiate
intramyocardial fat and the epicardial fat that is commonly seen adjacent to the normal
heart. Also, the sub-tricuspid region may be difficult to distinguish from the
atrioventricular sulcus, which is rich in fat.
Cardiac MRI can visualize the extreme thinning and akinesis of the RV free wall.
However, the normal RV free wall may be about 3 mm thick, making the test less
sensitive.
Right ventricular angiography
Right ventricular angiography is considered the gold standard for the diagnosis of ARVD.
Findings consistent with ARVD are an akinetic or dyskinetic bulging localized to the
infundibular, apical, and subtricuspid regions of the RV. The specificity is 90%; however,
the test is observer dependent.

Right ventricular biopsy

Major Criteria

Transvenous biopsy of the right ventricle can be highly specific for ARVD, but it has low

Right ventricular dysfunction

sensitivity. False positives include other conditions with fatty infiltration of the ventricle,

such as chronic alcohol abuse and Duchenne/Becker muscular dystrophy.

Severe dilatation and reduction of RV ejection fraction with little or no LV

impairment

False negatives are common, however, because the disease progresses typically from
the epicardium to the endocardium (with the biopsy sample coming from the

Localized RV aneurysms

Severe segmental dilatation of the RV

endocardium), and the segmental nature of the disease. Also, due to the paper-thin right
ventricular free wall that is common in this disease process, most biopsy samples are
taken from the ventricular septum, which is commonly not involved in the disease
process.

A biopsy sample that is consistent with ARVD would have > 3% fat, >40% fibrous tissue,

Tissue characterization

Fibrofatty replacement of myocardium on endomyocardial biopsy

and <45% myocytes.

Conduction abnormalities

Autopsy
A post mortem histological demonstration of full thickness substitution of the RV
myocardium by fatty or fibro-fatty tissue is consistent with ARVD.
Genetic Testing

the disease causing mutation. Whenever a mutation is identified by genetic testing,

Localized prolongation (>110 ms) of QRS in V1 - V3

Family history

ARVD patients have a mutation identified in one of several genes encoding components
autosomal dominant trait, children of an ARVD patient have a 50% chance of inheriting

Epsilon waves in V1 - V3.

ARVD is an autosomal dominant trait with reduced penetrance. Approximately 40-50% of

of the desmosome, which can help confirm a diagnosis of ARVD.[6] Since ARVD is an

Familial disease confirmed on autopsy or surgery

Minor Criteria

Right ventricular dysfunction

family-specific genetic testing can be used to differentiate between relatives who are atrisk for the disease and those who are not. ARVD genetic testing is clinically available. [7]

Diagnostic Criteria[edit]
There is no pathognomonic feature of ARVD. The diagnosis of ARVD is based on a
combination of major and minor criteria. To make a diagnosis of ARVD requires either 2
major criteria or 1 major and 2 minor criteria or 4 minor criteria.

Mild global RV dilatation and/or reduced ejection fraction with normal LV.

Mild segmental dilatation of the RV

Regional RV hypokinesis
Tissue characterization

Conduction abnormalities

ARVD is a progressive disease. Over time, the right ventricle becomes more involved,
leading to right ventricular failure. The right ventricle will fail before there is left ventricular

Inverted T waves in V2 and V3 in an individual over 12 years old, in the

absence of a right bundle branch block (RBBB)

dysfunction. However, by the time the individual has signs of overt right ventricular
failure, there will be histological involvement of the left ventricle. Eventually, the left
ventricle will also become involved, leading to bi-ventricular failure. Signs and symptoms

Late potentials on signal averaged EKG.

of left ventricular failure may become evident, including congestive heart failure, atrial
fibrillation, and an increased incidence of thromboembolic events.

Ventricular tachycardia with a left bundle branch block (LBBB)

morphology

Frequent PVCs (> 1000 PVCs / 24 hours)

Family history

Family history of sudden cardiac death before age 35

Family history of ARVD

Management
The goal of management of ARVD is to decrease the incidence of sudden cardiac death.
This raises a clinical dilemma: How to prophylactically treat the asymptomatic patient
who was diagnosed during family screening.
A certain subgroup of individuals with ARVD are considered at high risk for sudden
cardiac death. Characteristics associated with high risk of sudden cardiac death include:

Young age

Competitive sports activity

Malignant familial history

Extensive RV disease with decreased right ventricular ejection fraction.

Left ventricular involvement

Syncope

Episode of ventricular arrhythmia

Natural history
There is a long asymptomatic lead-time in individuals with ARVD. While this is a
genetically transmitted disease, individuals in their teens may not have any
characteristics of ARVD on screening tests.
Many individuals have symptoms associated with ventricular tachycardia, such as
palpitations, light-headedness, or syncope. Others may have symptoms and signs
related to right ventricular failure, such as lower extremity edema, or liver congestion with
elevated hepatic enzymes. Unfortunately, sudden death may be the first manifestation of
disease.

Management options include pharmacological, surgical, catheter ablation, and placement

of an implantable cardioverter-defibrillator.
Prior to the decision of the treatment option, programmed electrical stimulation in
the electrophysiology laboratory may be performed for additional prognostic information.
Goals of programmed stimulation include:

Assessment of the disease's arrhythmogenic potential

Implantable cardioverter-defibrillator

Evaluate the hemodynamic consequences of sustained VT

An ICD is the most effective prevention against sudden cardiac death. Due to the
prohibitive cost of ICDs, they are not routinely placed in all individuals with ARVD.

Determine whether the VT can be interrupted via antitachycardia pacing.

Indications for ICD placement in the setting of ARVD include:

Regardless of the management option chosen, the individual is typically suggested to

Cardiac arrest due to VT or VF

to begin an exercise regimen, an exercise stress test may have added benefit.

Symptomatic VT that is not inducible during programmed stimulation

Pharmacologic management

Failed programmed stimulation-guided drug therapy

Pharmacologic management of ARVD involves arrhythmia suppression and prevention of

Severe RV involvement with poor tolerance of VT

Sudden death of immediate family member

undergo lifestyle modification, including avoidance of strenuous exercise, cardiac

stimulants (i.e.: caffeine, nicotine, pseudoephedrine) and alcohol. If the individual wishes

thrombus formation.
Sotalol, a beta blocker and a class III antiarrhythmic agent, is the most effective
antiarrhythmic agent in ARVD. Other antiarrhythmic agents used include amiodarone and

Since ICDs are typically placed via a transvenous approach into the right ventricle, there

conventional beta blockers (i.e.: metoprolol). If antiarrhythmic agents are used, their

are complications associated with ICD placement and follow-up.

efficacy should be guided by series ambulatory holter monitoring, to show a reduction in

Due to the extreme thinning of the RV free wall, it is possible to perforate the RV during

arrhythmic events.

implantation, potentially causing pericardial tamponade. Because of this, every attempt is

While angiotensin converting enzyme inhibitors (ACE Inhibitors) are well known for

made at placing the defibrillator lead on the ventricular septum.

slowing progression in other cardiomyopathies, they have not been proven to be helpful
After a successful implantation, the progressive nature of the disease may lead to fibro-

in ARVD.

fatty replacement of the myocardium at the site of lead placement. This may lead to
Individuals with decreased RV ejection fraction with dyskinetic portions of the right

undersensing of the individual's electrical activity (potentially causing inability to sense

ventricle may benefit from long term anticoagulation with warfarin to prevent thrombus

VT or VF), and inability to pace the ventricle.

formation and subsequent pulmonary embolism.

Cardiac transplant surgery

Catheter ablation
Cardiac transplant surgery may be performed in ARVD. It may be indicated if the
Catheter ablation may be used to treat intractable ventricular tachycardia. It has a 60-

arrhythmias associated with the disease are uncontrollable or if there is severe bi-

90% success rate. Unfortunately, due to the progressive nature of the disease,

ventricular heart failure that is not manageable with pharmacological therapy.

[8]

recurrence is common (60% recurrence rate), with the creation of new arrhythmogenic
foci. Indications for catheter ablation include drug-refractory VT and frequent recurrence
of VT afterICD placement, causing frequent discharges of the ICD.

Family screening
All first degree family members of the affected individual should be screened for ARVD.

Heart failure

This is used to establish the pattern of inheritance. Screening should begin during the
teenage years unless otherwise indicated. Screening tests include:

Echocardiogram

EKG

Signal averaged EKG

Holter monitoring

Cardiac MRI

Exercise stress test

From Wikipedia, the free encyclopedia

Heart failure (HF), often used to mean chronic heart failure (CHF), occurs when
the heart is unable to pump sufficiently to maintain blood flow to meet the body's needs.[1]
[2][3]
The terms congestive heart failure (CHF) or congestive cardiac failure(CCF) are
often used interchangeably with chronic heart failure.[4] Signs and symptoms commonly
include shortness of breath,excessive tiredness, and leg swelling.[5] The shortness of
breath is usually worse with exercise, while lying down, and may wake the person at
night.[5] A limited ability to exercise is also a common feature.[6]
Common causes of heart failure include coronary artery disease including a
previous myocardial infarction (heart attack), high blood pressure, atrial
fibrillation, valvular heart disease, excess alcohol use, infection, and cardiomyopathy of
an unknown cause.[5][7] These cause heart failure by changing either the structure or the
functioning of the heart.[5] There are two main types of heart failure: heart failure due to
left ventricular dysfunction and heart failure with normal ejection fraction depending on if
the ability of the left ventricle to contract is affected, or the heart's ability to relax. [5] The
severity of disease is usually graded by the degree of problems with exercise. [8] Heart
failure is not the same as myocardial infarction (in which part of the heart muscle dies)
or cardiac arrest (in which blood flow stops altogether).[9][10] Other diseases that may have
symptoms similar to heart failure include obesity, kidney failure, liver
problems, anemia and thyroid disease.[8]
The condition is diagnosed based on the history of the symptoms and a physical
examination with confirmation byechocardiography.[11] Blood tests, electrocardiography,
and chest radiography may be useful to determine the underlying cause. [11]Treatment
depends on the severity and cause of the disease. [11] In people with chronic stable mild
heart failure, treatment commonly consists of lifestyle modifications such as stopping
smoking,[12] physical exercise,[13] and dietary changes, as well as medications.[12]In those
with heart failure due to left ventricular dysfunction, angiotensin converting enzyme
inhibitors or angiotensin receptor blockers along with beta blockers are recommended.
[11]
For those with severe disease, aldosterone antagonists, or hydralazine plus
a nitrate may be used.[11] Diuretics are useful for preventing fluid retention.[12] Sometimes,
depending on the cause, an implanted device such as a pacemaker or an implantable
cardiac defibrillator may be recommended.[11] In some moderate or severe casescardiac
resynchronization therapy (CRT) may be suggested[14] or cardiac contractility
modulation may be of benefit.[15] A ventricular assist device or occasionally a heart
transplant may be recommended in those with severe disease despite all other
measures.[12]
Heart failure is a common, costly, and potentially fatal condition.[7] In developed countries,
around 2% of adults have heart failure and in those over the age of 65, this increases to
610%.[7][16] In the year after diagnosis the risk of death is about 35% after which it

decreases to below 10% each year.[5] This is similar to the risks with a number of types of
cancer.[5] In the United Kingdom the disease is the reason for 5% of emergency hospital
admissions.[5] Heart failure has been known since ancient times with the Ebers
papyrus commenting on it around 1550 BCE.[6]

Terminology
Heart failure is a physiological state in which cardiac output is insufficient to meet the
needs of the body and lungs. The termed "congestive heart failure" (CHF) is often used
as one of the common symptoms is swelling or water retention. [17]
Heart failure is divided into two different types: heart failure due to reduced ejection
fraction (HFREF) also known as heart failure due to left ventricular systolic dysfunction or
systolic heart failure and heart failure with preserved ejection fraction (HFPEF) also
known as diastolic heart failure or heart failure with normal ejection fraction (HFNEF).[5]
[13]
Heart failure with reduced ejection fraction occurs when the ejection fraction is less
than 40%.[18] In diastolic heart failure, the heart muscle contracts well but the ventricle
does not fill with blood well in the relaxation phase. [5] Ejection fraction is the proportion of
blood in the heart pumped out of the heart during a single contraction. [19] It is a
percentage with normal being between 50 and 75%.[19]
The term "acute" is used to mean rapid onset, and "chronic" refers to long duration.
Chronic heart failure is a long term situation, usually with stable treated
symptomatology.Acute decompensated heart failure is worsening or decompensated
heart failure, referring to episodes in which a person can be characterized as having a
change in heart failure signs and symptoms resulting in death or an urgent need for
therapy or hospitalization.[20] Heart failure may also occur in situations of "high output,"
(termed "high output cardiac failure") where the ventricular systolic function is normal but
the heart cannot deal with an important augmentation of blood volume. [21]

Signs and symptoms

Heart failure symptoms are traditionally and somewhat arbitrarily divided into "left" and
"right" sided, recognizing that the left and right ventricles of the heart supply different
portions of the circulation. However, heart failure is not exclusively backward failure (in
the part of the circulation which drains to the ventricle).
There are several other exceptions to a simple left-right division of heart failure
symptoms. Additionally, the most common cause of right-sided heart failure is left-sided
heart failure.[22] The result is that patients commonly present with both sets of signs and
symptoms.

Left-sided failure
Common respiratory signs are increased rate of breathing and increased work of
breathing (non-specific signs of respiratory distress).Rales or crackles, heard initially in

the lung bases, and when severe, throughout the lung fields suggest the development
of pulmonary edema (fluid in the alveoli). Cyanosis which suggests severe hypoxemia, is
a late sign of extremely severe pulmonary edema.
Additional signs indicating left ventricular failure include a laterally displaced apex
beat (which occurs if the heart is enlarged) and a gallop rhythm (additional heart sounds)
may be heard as a marker of increased blood flow, or increased intra-cardiac
pressure. Heart murmursmay indicate the presence of valvular heart disease, either as a
cause (e.g. aortic stenosis) or as a result (e.g. mitral regurgitation) of the heart failure.
Backward failure of the left ventricle causes congestion of the lungs' blood vessels, and
so the symptoms are predominantly respiratory in nature. Backward failure can be
subdivided into failure of the left atrium, the left ventricle or both within the left circuit. The
patient will havedyspnea (shortness of breath) on exertion and in severe cases, dyspnea
at rest. Increasing breathlessness on lying flat, called orthopnea, occurs. It is often
measured in the number of pillows required to lie comfortably, and in orthopnea, the
patient may resort to sleeping while sitting up. Another symptom of heart failure
is paroxysmal nocturnal dyspnea: a sudden nighttime attack of severe breathlessness,
usually several hours after going to sleep. Easy fatigability and exercise intolerance are
also common complaints related to respiratory compromise.
"Cardiac asthma" or wheezing may occur.
Compromise of left ventricular forward function may result in symptoms of poor systemic
circulation such as dizziness, confusion and cool extremities at rest.

Right-sided failure
Physical examination may reveal pitting peripheral edema, ascites, and liver
enlargement. Jugular venous pressure is frequently assessed as a marker of fluid status,
which can be accentuated by eliciting hepatojugular reflux. If the right ventricular
pressure is increased, a parasternal heave may be present, signifying the compensatory
increase in contraction strength.
Backward failure of the right ventricle leads to congestion of systemic capillaries. This
generates excess fluid accumulation in the body. This causes swelling under the skin
(termed peripheral edema or anasarca) and usually affects the dependent parts of the
body first (causing foot and ankle swelling in people who are standing up,
and sacraledema in people who are predominantly lying down). Nocturia (frequent
nighttime urination) may occur when fluid from the legs is returned to the bloodstream
while lying down at night. In progressively severe cases, ascites (fluid accumulation in
the abdominal cavity causing swelling) and liver enlargement may develop. Significant
liver congestion may result in impaired liver function, and jaundice and
even coagulopathy (problems of decreased blood clotting) may occur.

Biventricular failure
Dullness of the lung fields to finger percussion and reduced breath sounds at the bases
of the lung may suggest the development of a pleural effusion (fluid collection in between
the lung and the chest wall). Though it can occur in isolated left- or right-sided heart
failure, it is more common in biventricular failure because pleural veins drain into both the
systemic and pulmonary venous systems. When unilateral, effusions are often right
sided.

4. Hypertension 11%
5. Other 5%
Rarer causes of heart failure include the following:

Viral myocarditis (an infection of the heart muscle)

Infiltrations of the muscle such as amyloidosis

HIV cardiomyopathy (caused by human immunodeficiency virus)

Connective tissue diseases such as systemic lupus erythematosus

Abuse of drugs such as alcohol and cocaine

Pharmaceutical drugs such as chemotherapeutic agents

1. Ischemic heart disease 62%

Arrhythmias.

2. Cigarette smoking 16%

Obstructive sleep apnea (a condition of sleep wherein disordered breathing overlaps with
obesity, hypertension, and/or diabetes) is regarded as an independent cause of heart
failure.

Causes
Congestive heart failure
Heart failure may also occur in situations of "high output," (termed "high output cardiac
failure") where the ventricular systolic function is normal but the heart cannot deal with
an important augmentation of blood volume.[21] This can occur in overload situation (blood
or serum infusions), renal diseases, chronic severe anemia, beriberi (vitamin B1/thiamine
deficiency), thyrotoxicosis, Paget's disease, arteriovenous fistulae, or arteriovenous
malformations.
A study of healthy adults in the United States found the following risk factors: [23]

3. Hypertension (high blood pressure) 10%

Acute decompensation
4. Obesity 8%
5. Diabetes 3%
6. Valvular heart disease 2% (much higher in older populations)
Italians had the following underlying causes:[24]

Main article: Acute decompensated heart failure

Chronic stable heart failure may easily decompensate. This most commonly results from
an intercurrent illness (such as pneumonia), myocardial infarction (a heart
attack),arrhythmias, uncontrolled hypertension, or a patient's failure to maintain a fluid
restriction, diet, or medication.[25] Other well recognized factors that may worsen CHF
include the following: anemia and hyperthyroidism which place additional strain on the
heart muscle, excessive fluid or salt intake, and medication that causes fluid retention
such as NSAIDsand thiazolidinediones.[26] NSAIDs in general increase the risk twofold.[27]

1. Ischemic heart disease 40%

Pathophysiology

2. Dilated cardiomyopathy 32%

Heart failure is caused by any condition which reduces the efficiency of the myocardium,
or heart muscle, through damage or overloading. As such, it can be caused by a wide
number of conditions, including myocardial infarction (in which the heart muscle is
starved of oxygen and dies), hypertension (which increases the force of contraction

3. Valvular heart disease 12%

needed to pump blood) and amyloidosis (in which protein is deposited in the heart
muscle, causing it to stiffen). Over time these increases in workload will produce
changes to the heart itself:

Enlargement of the ventricles, contributing to the enlargement and spherical

shape of the failing heart. The increase in ventricular volume also causes a reduction
in stroke volume due to mechanical and inefficient contraction of the heart. [30]

Reduced force of contraction, due to overloading of the ventricle. In a healthy

heart, increased filling of the ventricle results in increased force of contraction (by
the FrankStarling law of the heart) and thus a rise in cardiac output. In heart failure
this mechanism fails, as the ventricle is loaded with blood to the point where heart

The general effect is one of reduced cardiac output and increased strain on the heart.
This increases the risk of cardiac arrest (specifically due to ventricular dysrhythmias),
and reduces blood supply to the rest of the body. In chronic disease the reduced cardiac
output causes a number of changes in the rest of the body, some of which are
physiological compensations, some of which are part of the disease process:

muscle contraction becomes less efficient. This is due to reduced ability to crosslink actin and myosin filaments in over-stretched heart muscle.[28]

sinus and aortic arch which link to the nucleus tractus solitarii. This center in the

A reduced stroke volume, as a result of a failure of systole, diastole or both.

brain increases sympathetic activity, releasing catecholamines into the blood stream.

Increased end systolic volume is usually caused by reduced contractility.

Binding to alpha-1 receptors results in systemic arterial vasoconstriction. This helps

Decreased end diastolic volume results from impaired ventricular filling as occurs

restore blood pressure but also increases the total peripheral resistance, increasing

when the compliance of the ventricle falls (i.e. when the walls stiffen).

the workload of the heart. Binding to beta-1 receptors in the myocardium increases
the heart rate and makes contractions more forceful in an attempt to increase

Reduced spare capacity. As the heart works harder to meet normal metabolic

cardiac output. This also, however, increases the amount of work the heart has to

demands, the amount cardiac output can increase in times of increased oxygen

perform.

demand (e.g. exercise) is reduced. This contributes to the exercise intolerance

commonly seen in heart failure. This translates to the loss of one's cardiac reserve,

Arterial blood pressure falls. This destimulates baroreceptors in the carotid

or the ability of the heart to work harder during strenuous physical activity. Since the

Increased sympathetic stimulation also causes the posterior pituitary to

secrete vasopressin (also known as antidiuretic hormone or ADH), which causes

heart has to work harder to meet the normal metabolic demands, it is incapable of

fluid retention at the kidneys. This increases the blood volume and blood pressure.

meeting the metabolic demands of the body during exercise.

Increased heart rate, stimulated by increased sympathetic activity[29] in order to

Reduced perfusion (blood flow) to the kidneys stimulates the release of renin
an enzyme which catalyses the production of the potent vasopressor angiotensin.

maintain cardiac output. Initially, this helps compensate for heart failure by

Angiotensin and its metabolites cause further vasoconstriction, and stimulate

maintaining blood pressure and perfusion, but places further strain on the

increased secretion of the steroid aldosterone from the adrenal glands. This

myocardium, increasing coronary perfusion requirements, which can lead to

promotes salt and fluid retention at the kidneys.

worsening of ischemic heart disease. Sympathetic activity may also cause potentially
fatal arrhythmias.

Hypertrophy (an increase in physical size) of the myocardium, caused by the

terminally differentiated heart muscle fibres increasing in size in an attempt to
improve contractility. This may contribute to the increased stiffness and decreased
ability to relax during diastole.

The chronically high levels of circulating neuroendocrine hormones such

as catecholamines, renin, angiotensin, and aldosterone affects the myocardium
directly, causing structural remodelling of the heart over the long term. Many of these
remodelling effects seem to be mediated by transforming growth factor beta (TGFbeta), which is a common downstream target of the signal transduction cascade

initiated by catecholamines[31] and angiotensin II,[32] and also by epidermal growth

factor (EGF), which is a target of the signaling pathway activated by aldosterone [33]

Reduced perfusion of skeletal muscle causes atrophy of the muscle fibres. This
can result in weakness, increased fatigueability and decreased peak strength all
contributing to exercise intolerance.[34]

The increased peripheral resistance and greater blood volume place further strain on the
heart and accelerates the process of damage to the myocardium. Vasoconstriction and
fluid retention produce an increased hydrostatic pressure in the capillaries. This shifts the
balance of forces in favour of interstitial fluid formation as the increased pressure forces
additional fluid out of the blood, into the tissue. This results in edema (fluid build-up) in
the tissues. In right-sided heart failure this commonly starts in the ankles where venous
pressure is high due to the effects of gravity (although if the patient is bed-ridden, fluid
accumulation may begin in the sacral region.) It may also occur in the abdominal cavity,
where the fluid build-up is called ascites. In left-sided heart failure edema can occur in
the lungs this is called cardiogenic pulmonary edema. This reduces spare capacity for
ventilation, causes stiffening of the lungs and reduces the efficiency of gas exchange by
increasing the distance between the air and the blood. The consequences of this
aredyspnea (shortness of breath), orthopnea and paroxysmal nocturnal dyspnea.
The symptoms of heart failure are largely determined by which side of the heart fails. The
left side pumps blood into the systemic circulation, whilst the right side pumps blood into
the pulmonary circulation. Whilst left-sided heart failure will reduce cardiac output to the
systemic circulation, the initial symptoms often manifest due to effects on the pulmonary
circulation. In systolic dysfunction, the ejection fraction is decreased, leaving an
abnormally elevated volume of blood in the left ventricle. In diastolic dysfunction, enddiastolic ventricular pressure will be high. This increase in volume or pressure backs up
to the left atrium and then to the pulmonary veins. Increased volume or pressure in the
pulmonary veins impairs the normal drainage of the alveoli and favors the flow of fluid
from the capillaries to the lung parenchyma, causing pulmonary edema. This impairs gas
exchange. Thus, left-sided heart failure often presents with respiratory symptoms:
shortness of breath, orthopnea and paroxysmal nocturnal dyspnea.
In severe cardiomyopathy, the effects of decreased cardiac output and poor perfusion
become more apparent, and patients will manifest with cold and clammy extremities,
cyanosis, claudication, generalized weakness, dizziness, and syncope.
The resultant hypoxia caused by pulmonary edema causes vasoconstriction in the
pulmonary circulation, which results in pulmonary hypertension. Since the right ventricle
generates far lower pressures than the left ventricle (approximately 20 mmHg versus
around 120 mmHg, respectively, in the healthy individual) but nonetheless generates
cardiac output exactly equal to the left ventricle, this means that a small increase in
pulmonary vascular resistance causes a large increase in amount of work the right
ventricle must perform. However, the main mechanism by which left-sided heart failure

causes right-sided heart failure is actually not well understood. Some theories invoke
mechanisms that are mediated by neurohormonal activation. [35] Mechanical effects may
also contribute. As the left ventricle distends, the intraventricular septum bows into the
right ventricle, decreasing the capacity of the right ventricle.

Systolic dysfunction
Heart failure caused by systolic dysfunction is more readily recognized. It can be
simplistically described as failure of the pump function of the heart. It is characterized by
a decreased ejection fraction (less than 45%). The strength of ventricular contraction is
attenuated and inadequate for creating an adequate stroke volume, resulting in
inadequate cardiac output. In general, this is caused by dysfunction or destruction of
cardiac myocytes or their molecular components. In congenital diseases such
as Duchenne muscular dystrophy, the molecular structure of individual myocytes is
affected. Myocytes and their components can be damaged by inflammation (such as
in myocarditis) or by infiltration (such as in amyloidosis). Toxins and pharmacological
agents (such as ethanol, cocaine, doxorubicin, and amphetamines) cause intracellular
damage and oxidative stress. The most common mechanism of damage is ischemia
causing infarction and scar formation. After myocardial infarction, dead myocytes are
replaced by scar tissue, deleteriously affecting the function of the myocardium. On
echocardiogram, this is manifest by abnormal wall motion (hypokinesia) or absent wall
motion (akinesia).
Because the ventricle is inadequately emptied, ventricular end-diastolic pressure and
volumes increase. This is transmitted to the atrium. On the left side of the heart, the
increased pressure is transmitted to the pulmonary vasculature, and the resultant
hydrostatic pressure favors extravasation of fluid into the lung parenchyma, causing
pulmonary edema. On the right side of the heart, the increased pressure is transmitted to
the systemic venous circulation and systemic capillary beds, favoring extravasation of
fluid into the tissues of target organs and extremities, resulting in dependent peripheral
edema.

Diastolic dysfunction
Heart failure caused by diastolic dysfunction is generally described as the failure of the
ventricle to adequately relax and typically denotes a stiffer ventricular wall. This causes
inadequate filling of the ventricle, and therefore results in an inadequate stroke volume.
The failure of ventricular relaxation also results in elevated end-diastolic pressures, and
the end result is identical to the case of systolic dysfunction (pulmonary edema in left
heart failure, peripheral edema in right heart failure).
Diastolic dysfunction can be caused by processes similar to those that cause systolic
dysfunction, particularly causes that affect cardiac remodeling.
Diastolic dysfunction may not manifest itself except in physiologic extremes if systolic
function is preserved. The patient may be completely asymptomatic at rest. However,
they are exquisitely sensitive to increases in heart rate, and sudden bouts of tachycardia

(which can be caused simply by physiological responses to exertion, fever, or

dehydration, or by pathological tachyarrhythmias such as atrial fibrillation with rapid
ventricular response) may result in flash pulmonary edema. Adequate rate control
(usually with a pharmacological agent that slows down AV conduction such as a calcium
channel blocker or a beta-blocker) is therefore key to preventing decompensation.
Left ventricular diastolic function can be determined through echocardiography by
measurement of various parameters such as the E/A ratio (early-to-atrial left ventricular
filling ratio), the E (early left ventricular filling) deceleration time, and the isovolumic
relaxation time.

Diagnosis
No system of diagnostic criteria has been agreed on as the gold standard for heart
failure. The National Institute for Health and Care Excellence recommends
measuring brain natriuretic peptide followed by ultrasound of the heart if positive.[36]

Imaging
Echocardiography is commonly used to support a clinical diagnosis of heart failure. This
modality uses ultrasound to determine the stroke volume (SV, the amount of blood in the
heart that exits the ventricles with each beat), the end-diastolic volume (EDV, the total
amount of blood at the end of diastole), and the SV in proportion to the EDV, a value
known as the ejection fraction (EF). In pediatrics, the shortening fraction is the preferred
measure of systolic function. Normally, the EF should be between 50% and 70%; in
systolic heart failure, it drops below 40%. Echocardiography can also identify valvular
heart disease and assess the state of the pericardium (the connective tissue sac
surrounding the heart). Echocardiography may also aid in deciding what treatments will
help the patient, such as medication, insertion of an implantable cardioverterdefibrillator or cardiac resynchronization therapy. Echocardiography can also help
determine if acute myocardial ischemia is the precipitating cause, and may manifest as
regional wall motion abnormalities on echo.
Chest X-rays are frequently used to aid in the diagnosis of CHF. In a person who is
compensated, this may show cardiomegaly (visible enlargement of the heart), quantified
as the cardiothoracic ratio (proportion of the heart size to the chest). In left ventricular
failure, there may be evidence of vascular redistribution ("upper lobe blood diversion" or
"cephalization"), Kerley lines, cuffing of the areas around the bronchi, and interstitial
edema. Ultrasound of the lung may also be able to detect Kerley lines.[37]

Electrophysiology
An electrocardiogram (ECG/EKG) may be used to identify arrhythmias, ischemic heart
disease, right and left ventricular hypertrophy, and presence of conduction delay or
abnormalities (e.g. left bundle branch block). Although these findings are not specific to
the diagnosis of heart failure a normal ECG virtually excludes left ventricular systolic
dysfunction.[38]

Blood tests
Blood tests routinely performed include electrolytes (sodium, potassium), measures
of renal function, liver function tests, thyroid function tests, a complete blood count, and
oftenC-reactive protein if infection is suspected. An elevated B-type natriuretic
peptide (BNP) is a specific test indicative of heart failure. Additionally, BNP can be used
to differentiate between causes of dyspnea due to heart failure from other causes of
dyspnea. If myocardial infarction is suspected, various cardiac markers may be used.
According to a meta-analysis comparing BNP and N-terminal pro-BNP (NTproBNP) in
the diagnosis of heart failure, BNP is a better indicator for heart failure and left ventricular
systolic dysfunction. In groups of symptomatic patients, a diagnostic odds ratio of 27 for
BNP compares with a sensitivity of 85% and specificity of 84% in detecting heart failure.
[39]

Angiography
Heart failure may be the result of coronary artery disease, and its prognosis depends in
part on the ability of the coronary arteries to supply blood to the myocardium (heart
muscle). As a result, coronary catheterization may be used to identify possibilities for
revascularisation through percutaneous coronary intervention or bypass surgery.

Monitoring
Various measures are often used to assess the progress of patients being treated for
heart failure. These include fluid balance (calculation of fluid intake and excretion),
monitoring body weight (which in the shorter term reflects fluid shifts).[40]

Classification
There are many different ways to categorize heart failure, including:

the side of the heart involved (left heart failure versus right heart failure). Right
heart failure compromises pulmonary flow to the lungs. Left heart failure
compromises aortic flow to the body and brain. Mixed presentations are common;
left heart failure often leads to right heart failure in the longer term.

whether the abnormality is due to insufficient contraction (systolic dysfunction), or

due to insufficient relaxation of the heart (diastolic dysfunction), or to both.

whether the problem is primarily increased venous back pressure (preload), or

Stage A: Patients at high risk for developing HF in the future but no functional or
structural heart disorder.

Stage B: a structural heart disorder but no symptoms at any stage.

Stage C: previous or current symptoms of heart failure in the context of an

failure to supply adequate arterial perfusion (afterload).

whether the abnormality is due to low cardiac output with high systemic vascular

underlying structural heart problem, but managed with medical treatment.

resistance or high cardiac output with low vascular resistance (low-output heart
failure vs. high-output heart failure).

Stage D: advanced disease requiring hospital-based support, a heart transplant

or palliative care.

the degree of functional impairment conferred by the abnormality (as reflected in

the New York Heart Association Functional Classification[41])

the degree of coexisting illness: i.e. heart failure/systemic hypertension, heart

failure/pulmonary hypertension, heart failure/diabetes, heart failure/kidney failure,
etc.

Functional classification generally relies on the New York Heart Association functional
classification. The classes (I-IV) are:

Class I: no limitation is experienced in any activities; there are no symptoms from

ordinary activities.

Class II: slight, mild limitation of activity; the patient is comfortable at rest or with

The ACC staging system is useful in that Stage A encompasses "pre-heart failure" a
stage where intervention with treatment can presumably prevent progression to overt
symptoms. ACC Stage A does not have a corresponding NYHA class. ACC Stage B
would correspond to NYHA Class I. ACC Stage C corresponds to NYHA Class II and III,
while ACC Stage D overlaps with NYHA Class IV.

Algorithms
There are various algorithms for the diagnosis of heart failure. For example, the
algorithm used by the Framingham Heart Study adds together criteria mainly from
physical examination. In contrast, the more extensive algorithm by the European Society
of Cardiology (ESC) weights the difference between supporting and opposing
parameters from themedical history, physical examination, further medical tests as well
as response to therapy.
Framingham criteria

Class III: marked limitation of any activity; the patient is comfortable only at rest.

By the Framingham criteria, diagnosis of congestive heart failure (heart failure with
impaired pumping capability)[17] requires the simultaneous presence of at least 2 of the
following major criteria or 1 major criterion in conjunction with 2 of the following minor
criteria:

Class IV: any physical activity brings on discomfort and symptoms occur at rest.

Major criteria include the following:[44]

mild exertion.

This score documents severity of symptoms, and can be used to assess response to
treatment. While its use is widespread, the NYHA score is not very reproducible and
does not reliably predict the walking distance or exercise tolerance on formal testing. [42]
In its 2001 guidelines the American College of Cardiology/American Heart
Association working group introduced four stages of heart failure:[43]

Cardiomegaly on chest radiography

S3 gallop (a third heart sound)

Acute pulmonary edema

Paroxysmal nocturnal dyspnea

Differential diagnosis

Crackles on lung auscultation

There are several terms which are closely related to heart failure, and may be the cause
of heart failure, but should not be confused with it:

Central venous pressure of more than 16 cm H

2O at the right atrium

Jugular vein distension

Positive abdominojugular test

Weight loss of more than 4.5 kg in 5 days in response to treatment (sometimes

classified as a minor criterion[45])

Minor criteria include the following:[44]

Cardiac arrest and asystole refer to situations in which there is no cardiac output
at all. Without urgent treatment these result in sudden death.

Myocardial infarction ("Heart attack") refers to heart muscle damage due to

insufficient blood supply, usually as a result of a blocked coronary artery.

Cardiomyopathy refers specifically to problems within the heart muscle, and

these problems can result in heart failure. Ischemic cardiomyopathy implies that the
cause of muscle damage is coronary artery disease. Dilated cardiomyopathy implies
that the muscle damage has resulted in enlargement of the heart. Hypertrophic
cardiomyopathyinvolves enlargement and thickening of the heart muscle.

Tachycardia of more than 120 beats per minute

Nocturnal cough

Dyspnea on ordinary exertion

Pleural effusion

Decrease in vital capacity by one third from maximum recorded

Hepatomegaly

Bilateral ankle edema

Management
Main article: Management of heart failure
Treatment focuses on improving the symptoms and preventing the progression of the
disease. Reversible causes of the heart failure also need to be addressed
(e.g. infection,alcohol ingestion, anemia, thyrotoxicosis, arrhythmia, hypertension).
Treatments include lifestyle and pharmacological modalities, and occasionally various
forms of device therapy and rarely cardiac transplantation.

Acute decompensation
Main article: Acute decompensated heart failure

Minor criteria are acceptable only if they can not be attributed to another medical
condition such as pulmonary hypertension, chronic lung disease, cirrhosis, ascites, or
thenephrotic syndrome.[44] The Framingham Heart Study criteria are 100% sensitive and
78% specific for identifying persons with definite congestive heart failure. [44]
ESC algorithm
The ESC algorithm weights the following parameters in establishing the diagnosis of
heart failure:[46]

In acute decompensated heart failure (ADHF), the immediate goal is to re-establish

adequate perfusion and oxygen delivery to end organs. This entails ensuring that airway,
breathing, and circulation are adequate. Immediate treatments usually involve some
combination of vasodilators such as nitroglycerin, diuretics such as furosemide, and
possiblynon invasive positive pressure ventilation (NIPPV).

Chronic management
The goals of treatment for people with chronic heart failure are the prolongation of life,
the prevention of acute decompensation and the reduction of symptoms, allowing for
greater activity.

Heart failure can result from a variety of conditions. In considering therapeutic options, it
is important to first exclude reversible causes, including thyroid disease, anemia,
chronictachycardia, alcohol abuse, hypertension and dysfunction of one or more heart
valves. Treatment of the underlying cause is usually the first approach in treating heart
failure. However, in the majority of cases, either no primary cause is found or treatment
of the primary cause does not restore normal heart function. In these
cases, behavioral, medicaland device treatment strategies exist which can provide
significant improvement in outcomes, including the relief of symptoms, exercise
tolerance, and a decrease in the likelihood of hospitalization or death.

In people who are intolerant of ACE-I and ARBs or who have significant renal
dysfunction, the use of combined hydralazine and a long-acting nitrate, such as
isosorbide dinitrate, are an effective alternative. This regimen has been shown to reduce
mortality in people with moderate heart failure.[53] It is especially beneficial in AfricanAmericans (AA).[53] In AAs who are symptomatic, hydralazine and isosorbide dinitrate
(H+I) can be added to ACE-I or ARBs.

Lifestyle

Second-line drugs for CHF do not confer a mortality benefit. Digitalis is one such drug. Its
narrow therapeutic window, high degree of toxicity, and the failure of multiple trials to
show a mortality benefit have reduced its role in clinical practice. It is now used in only a
small number of people with refractory symptoms, who are in atrial fibrillation and/or who
have chronic hypotension.

Behavioral modification is a primary consideration in any chronic heart failure

management program, with dietary guidelines regarding fluid and salt intake being of
particular importance.[47]
Exercise should be encouraged and tailored to suit individual capabilities. The inclusion
of regular physical conditioning as part of a cardiac rehabilitation program can
significantly improve quality of life and reduce the risk of hospital admission for
worsening symptoms however there is no evidence for a reduction in mortality rates as a
result of exercise. Furthermore, it is not clear whether this evidence can be extended to
people with heart failure with preserved ejection fraction (HFpEF) or to those whose
exercise regimen takes place entirely at home.[48]
Home visits and regular monitoring at heart failure clinics reduce the need for
hospitalization and improve life expectancy.[49]
Medication
First-line therapy for people with heart failure due to reduced systolic function should
include angiotensin-converting enzyme (ACE) inhibitors (ACE-I) or Angiotensin receptor
blockers (ARBs). Use of medicines from this class are associated with improved survival
and quality of life in people with heart failure.[50]
Beta-adrenergic blocking agents (beta blockers) also form part of the first line of
treatment, adding to the improvement in symptoms and mortality provided by ACEI/ARB.[50] The mortality benefits of beta blockers in people with systolic dysfunction who
also have atrial fibrillation (AF) is more limited than in those who do not have AF.[51] If the
ejection fraction is not diminished (HFpEF), the benefits of beta blockers is more modest;
a decrease in mortality has been observed but reduction in hospital admission for
uncontrolled symptoms has not been observed.[52]

In people with markedly reduced ejection fraction, the use of an aldosterone antagonist,
in addition to beta blockers and ACE-I, can improve symptoms and reduce mortality.[54][55]

Diuretics have been a mainstay of treatment for treatment of fluid accumulation, and
include diuretics classes such as loop diuretics, thiazide-like diuretic, and potassiumsparing diuretic. Although widely used, evidence on their efficacy and safety is limited,
with the exception of spironolactone antagonists.[54][56] A recent Cochrane review found
that in small studies, the use of diuretics appeared to have improved mortality in
individuals with heart failure.[57] However, the extent to which these results can be
extrapolated to a general population is unclear due to the small number of participants in
the cited studies.[56]
Anemia is an independent factor in mortality in people with chronic heart failure. The
treatment of anemia significantly improves quality of life for those with heart failure, often
with a reduction in severity of the NYHA classification, and also improves mortality rates.
[58][59]
The latest European guidelines (2012) recommend screening for iron-deficient
anemia and treating with parenteral iron if anemia is found.[60]
Minimally invasive therapies
In people with severe cardiomyopathy (left ventricular ejection fraction below 35%), or in
those with recurrent VT or malignant arrhythmias, treatment with an automatic
implantable cardioverter defibrillator (AICD) is indicated to reduce the risk of severe lifethreatening arrhythmias. The AICD does not improve symptoms or reduce the incidence
of malignant arrhythmias, but does reduce mortality from those arrhythmias, often in
conjunction with antiarrhythmic medications. In people with left ventricular ejection
(LVEF) below 35%, the incidence of ventricular tachycardia (VT) or sudden cardiac
death is high enough to warrant AICD placement. Its use is therefore recommended
in AHA/ACC guidelines.[14]
Cardiac contractility modulation (CCM) is a treatment for people with moderate to
severe left ventricular systolic heart failure (NYHA class IIIV) which enhances both the
strength of ventricular contraction and the hearts pumping capacity. The CCM
mechanism is based on stimulation of the cardiac muscle by non-excitatory electrical

signals (NES), which are delivered by a pacemaker-like device. CCM is particularly

suitable for the treatment of heart failure with normal QRS complex duration (120 ms or
less) and has been demonstrated to improve the symptoms, quality of life and exercise
tolerance.[61][62][63][15][64] CCM is approved for use in Europe, but not currently in North
America.[65][66]
About one third of people with LVEF below 35% have markedly altered conduction to the
ventricles, resulting in dyssynchronous depolarization of the right and left ventricles. This
is especially problematic in people with left bundle branch block (blockage of one of the
two primary conducting fiber bundles that originates at the base of the heart and carries
depolarizing impulses to the left ventricle). Using a special pacing algorithm,
biventricular cardiac resynchronization therapy (CRT) can initiate a normal sequence of
ventricular depolarization. In people with LVEF below 35% and prolonged QRS duration
on ECG (LBBB or QRS of 150 ms or more) there is an improvement in symptoms and
mortality when CRT is added to standard medical therapy.[67] However, in the two thirds of
people without prolonged QRS duration, CRT may actually be harmful.[14][15][68]

Prognosis
Prognosis in heart failure can be assessed in multiple ways including clinical prediction
rules and cardiopulmonary exercise testing. Clinical prediction rules use a composite of
clinical factors such as lab tests and blood pressure to estimate prognosis. Among
several clinical prediction rules for prognosing acute heart failure, the 'EFFECT rule'
slightly outperformed other rules in stratifying patients and identifying those at low risk of
death during hospitalization or within 30 days.[72] Easy methods for identifying low risk
patients are:

and systolic blood pressure at least 115 mm Hg have less than 10% chance of
inpatient death or complications.

Surgical therapies
People with the most severe heart failure may be candidates for ventricular assist
devices (VAD). VADs have commonly been used as a bridge to heart transplantation, but
have been used more recently as a destination treatment for advanced heart failure. [69]
In select cases, heart transplantation can be considered. While this may resolve the
problems associated with heart failure, the person must generally remain on an
immunosuppressive regimen to prevent rejection, which has its own significant
downsides.[70] A major limitation of this treatment option is the scarcity of hearts available
for transplantation.

ADHERE Tree rule indicates that patients with blood urea nitrogen < 43 mg/dl

BWH rule indicates that patients with systolic blood pressure over 90 mm Hg,
respiratory rate of 30 or less breaths per minute, serum sodium over 135 mmol/L, no
new ST-T wave changes have less than 10% chance of inpatient death or
complications.

People with CHF often have significant symptoms, such as shortness of breath and
chest pain. Both palliative care and cardiology are trying to get palliative care involved
earlier in the course of patients with heart failure, and some would argue any patient with
NYHA class III CHF should have a palliative care referral. Palliative care can not only
provide symptom management, but also assist with advanced care planning, goals of
care in the case of a significant decline, and making sure the patient has a
medical power of attorneyand discussed his or her wishes with this individual.[71]

A very important method for assessing prognosis in advanced heart failure patients is
cardiopulmonary exercise testing (CPX testing). CPX testing is usually required prior to
heart transplantation as an indicator of prognosis. Cardiopulmonary exercise testing
involves measurement of exhaled oxygen and carbon dioxide during exercise. The peak
oxygen consumption (VO2 max) is used as an indicator of prognosis. As a general rule, a
VO2 max less than 1214 cc/kg/min indicates a poor survival and suggests that the
patient may be a candidate for a heart transplant. Patients with a VO2 max<10 cc/kg/min
have clearly poorer prognosis. The most recent International Society for Heart and Lung
Transplantation (ISHLT) guidelines[73] also suggest two other parameters that can be used
for evaluation of prognosis in advanced heart failure, the heart failure survival score and
the use of a criterion of VE/VCO2 slope > 35 from the CPX test. The heart failure survival
score is a score calculated using a combination of clinical predictors and the VO2 max
from the cardiopulmonary exercise test.

Without transplantation, heart failure may not be reversible and cardiac function typically
deteriorates with time. The growing number of patients with Stage IV heart failure
(intractable symptoms of fatigue, shortness of breath or chest pain at rest despite optimal
medical therapy) should be considered for palliative care or hospice, according to
American College of Cardiology/American Heart Association guidelines. [71]

Heart failure is associated with significantly reduced physical and mental health, resulting
in a markedly decreased quality of life.[74][75] With the exception of heart failure caused by
reversible conditions, the condition usually worsens with time. Although some people
survive many years, progressive disease is associated with an overall annual mortality
rate of 10%.[76]

Palliative care

Epidemiology

Sex

Heart failure is associated with a high health expenditure, mostly because of the cost of
hospitalizations; costs have been estimated to amount to 2% of the total budget of
theNational Health Service in the United Kingdom, and more than $35 billion in the
United States.[77][78]

Men have a higher incidence of heart failure, but the overall prevalence rate is similar in
both sexes, since women survive longer after the onset of heart failure. [89] Women tend to
be older when diagnosed with heart failure (after menopause), they are more likely than
men to have diastolic dysfunction, and seem to experience a lower overall quality of life
than men after diagnosis.[89]

Heart failure is the leading cause of hospitalization in people older than 65. [79] In
developed countries, the mean age of patients with heart failure is 75 years old. In
developing countries, two to three percent of the population have heart failure, but in
those 70 to 80 years old, it occurs in 2030 percent.
More than 20 million people have heart failure worldwide. [80][81] The prevalence and
incidence of heart failure are increasing, mostly because of increasing life span, but also
because of increased prevalence of risk factors (hypertension, diabetes, dyslipidemia,
and obesity) and improved survival rates from other types of cardiovascular disease
(myocardial infarction, valvular disease, and arrhythmias).[81][82]
In the United States, heart failure affects 5.8 million people, and each year 550,000 new
cases are diagnosed.[80] In 2011, congestive heart failure was the most common reason
for hospitalization for adults aged 85 years and older, and the second most common for
adults aged 6584 years.[83] It is estimated that one in five adults at age 40 will develop
heart failure during their remaining lifetime and about half of people who develop heart
failure die within 5 years of diagnosis.[84] Heart failure is much higher in African
Americans, Hispanics, Native Americans and recent immigrants from the eastern bloc
countries like Russia. This high prevalence in these ethnic minority populations has been
linked to high incidence of diabetes and hypertension. In many new immigrants to the
U.S., the high prevalence of heart failure has largely been attributed to lack of preventive
health care or substandard treatment.[85] Nearly one out of every four patients (24.7%)
hospitalized in the U.S. with congestive heart failure are readmitted within 30 days.
[86]
Additionally, more than 50% of patients seek re-admission within 6 months after
treatment and the average duration of hospital stay is 6 days.
In tropical countries, the most common cause of HF is valvular heart disease or some
type of cardiomyopathy. As underdeveloped countries have become more affluent, there
has also been an increase in the incidence of diabetes, hypertension and obesity, which
have in turn raised the incidence of heart failure.[87]
Congestive heart failure is a leading cause of hospital readmissions in the U.S. In a study
of 18 States, Medicare patients aged 65 and older were readmitted at a rate of 24.5 per
100 admissions in 2011. In the same year, Medicaid patients were readmitted at a rate of
30.4 per 100 admissions, and uninsured patients were readmitted at a rate of 16.8 per
100 admissions. These are the highest readmission rates for both patient categories.
Notably, congestive heart failure was not among the top ten conditions with the most 30day readmissions among the privately insured. [88]

Economics
In 2011, non-hypertensive congestive heart failure was one of the ten most expensive
conditions seen during inpatient hospitalizations in the U.S., with aggregate inpatient
hospital costs of more than $10.5 billion.[90]

Research
There is low quality evidence that stem cell therapy may help.[91] Although this evidence
positively indicated benefit, the evidence was of lower quality than other evidence that
does not indicate benefit.

Associated symptoms
Main article: VACTERL association
Congenital heart defects are associated with an increased incidence of some other
symptoms, together being called the VACTERL association:

V Vertebral anomalies

A Anal atresia

C Cardiovascular anomalies

T Tracheoesophageal fistula

Congenital heart defect

E Esophageal atresia

From Wikipedia, the free encyclopedia

R Renal (Kidney) and/or radial anomalies

L Limb defects

Congenital heart defect (CHD) or congenital heart anomaly[2] is a defect in the

structure of the heart and great vessels that is present at birth. Many types of heart
defects exist, most of which either obstruct blood flow in the heart or vessels near it, or
cause blood to flow through the heart in an abnormal pattern. Other defects, such
as long QT syndrome, affect the heart's rhythm. Heart defects are among the most
common birth defects and are the leading cause of birth defect-related deaths.
Approximately 9 people in 1000 are born with a congenital heart defect. [3] Many defects
do not need treatment, but some complex congenital heart defects require medication or
surgery.
Congenital heart defects resulted in 323,000 deaths in 2013 down from 366,000 deaths
in 1990.[4]

Signs and symptoms

Signs and symptoms are related to type and severity of the heart defect. Symptoms
frequently present early in life, but it is possible for some CHDs to go undetected
throughout life.[5] Some children have no signs while others may exhibit shortness of
breath, cyanosis,fainting,[6] heart murmur, under-development of limbs and muscles, poor
feeding or growth, or respiratory infections. Congenital heart defects cause abnormal
heart structure resulting in production of certain sounds called heart murmur. These can
sometimes be detected by auscultation; however, not all heart murmurs are caused by
congenital heart defects.

Ventricular septal defect (VSD), atrial septal defects, and tetralogy of Fallot are the most
common congenital heart defects seen in the VACTERL association. Less common
defects in the association are truncus arteriosus and transposition of the great arteries.

Causes
The cause of congenital heart disease may be either genetic or environmental, but is
usually a combination of both.[7]

Genetic
Most of the known causes of congenital heart disease are sporadic genetic changes,
either focal mutations or deletion or addition of segments of DNA.[8] Large chromosomal
abnormalities such as trisomies 21, 13, and 18 cause about 58% of cases of CHD,
[7]
with trisomy 21 being the most common genetic cause. [8] Small chromosomal
abnormalitiesalso frequently lead to congenital heart disease, and examples include
microdeletion of the long arm of chromosome 22 (22q11, DiGeorge syndrome), the long
arm ofchromosome 1 (1q21), the short arm of chromosome 8 (8p23) and many other,
less recurrent regions of the genome, as shown by high resolution genome-wide
screening (Array comparative genomic hybridization).[9] A database of genes involved in
congenital heart defects is available as the collaborative knowledge base CDHWiki.

The genes regulating the complex developmental sequence have only been partly
elucidated. Some genes are associated with specific defects. A number of genes have
been associated with cardiac manifestations. Mutations of a heart muscle protein, myosin heavy chain (MYH6) are associated with atrial septal defects. Several proteins
that interact with MYH6 are also associated with cardiac defects. The transcription
factor GATA4 forms a complex with the TBX5 which interacts with MYH6. Another factor,
the homeobox(developmental) gene, NKX2-5 also interacts with MYH6. Mutations of all
these proteins are associated with both atrial and ventricular septal defects; In addition,
NKX2-5 is associated with defects in the electrical conduction of the heart and TBX5 is
related to the Holt-Oram syndrome which includes electrical conduction defects and
abnormalities of the upper limb. Another T-box gene, TBX1, is involved in velo-cardiofacial syndrome DiGeorge syndrome, the most common deletion which has extensive
symptoms including defects of the cardiac outflow tract including tetralogy of Fallot.[10]
The notch signaling pathway, a regulatory mechanism for cell growth and differentiation,
plays broad roles in several aspects of cardiac development. Notch elements are
involved in determination of the right and left sides of the body plan, so the directional
folding of the heart tube can be impacted. Notch signaling is involved early in the
formation of the endocardial cushions and continues to be active as the develop into the
septa and valves. It is also involved in the development of the ventricular wall and the
connection of the outflow tract to the great vessels. Mutations in the gene for one of the
notch ligands, Jagged1, are identified in the majority of examined cases of arteriohepatic
dysplasia (Alagille syndrome), characterized by defects of the great vessels (pulmonary
artery stenosis), heart (tetralogy of Fallot in 13% of cases), liver, eyes, face, and bones.
Though less than 1% of all cases, where no defects are found in the Jagged1 gene,
defects are found in Notch2 gene. In 10% of cases, no mutation is found in either gene.
For another member of the gene family, mutations in the Notch1 gene are associated
with bicuspid aortic valve, a valve with two leaflets instead of three. Notch1 is also
associated with calcification of the aortic valve, the third most common cause of heart
disease in adults.[12][13]
Mutations of a cell regulatory mechanism, the Ras/MAPK pathway are responsible for a
variety of syndromes, including Noonan syndrome, LEOPARD syndrome, Costello
syndrome and cardiofaciocutaneous syndrome in which there is cardiac involvement.
[14]
While the conditions listed are known genetic causes, there are likely many other
genes which are more subtle. It is known that the risk for congenital heart defects is
higher when there is a close relative with one.[8]

Environmental
Known antenatal environmental factors include
maternal infections (Rubella), drugs (alcohol, hydantoin, lithium and thalidomide) and
maternal illness (diabetes mellitus,phenylketonuria, and systemic lupus erythematosus).
[15]

Maternal obesity
As noted in several studies following similar body mass index (BMI) ranges, prepregnant
and gestating women, who were obese (BMI 30), carried a statistically significant risk
of birthing children with congenital heart defects (CHD) compared to normal-weight
women (BMI= 1924.9).[16][17][18] Although there are minor conflicting reports,[16] there was
significant support for the risk of fetal CHD development in overweight mothers (BMI=
25-29.9).[17][18] Additionally, as maternal obesity increased, the risk of heart defects did too
indicating a trend between BMI and CHD odds.[16] Altogether, these results present
reasonable concern for women to achieve a normal-weight BMI prior to pregnancy to
help decrease risk for fetal heart defects.
A distinct physiological mechanism has not been identified to explain the link between
maternal obesity and CHD, but both prepregnancy folate deficiency and diabetes have
been implicated in some studies.[19] Identification of the mechanism could aid health
officials to develop reduction strategies and curb CHDs prevalence in this preventable
situation.

Embryology
Main article: Heart development
There is a complex sequence of events that result in a well formed heart at birth and
disruption of any portion may result in a defect.[8] The orderly timing of cell growth, cell
migration, and programmed cell death ("apoptosis") has been studied extensively and
the genes that control the process are being elucidated. [10] Around day 15 of
development, the cells that will become the heart exist in two horseshoe shaped bands
of the middle tissue layer (mesoderm),[10] and some cells migrate from a portion of the
outer layer (ectoderm), the neural crest, which is the source of a variety of cells found
throughout the body. On day 19 of development, a pair of vascular elements, the
"endocardial tubes", form. The tubes fuse when cells between then undergo
programmed death and cells from the first heart field migrate to the tube, and form a ring
of heart cells (myocytes) around it by day 21. On day 22, the heart begins to beat and by
day 24, blood is circulating.[20]
At day 22, the circulatory system is bilaterally symmetrical with paired vessels on each
side and the heart consisting of a simple tube located in the midline of the body layout.
The portions that will become the atria and will be located closest to the head are the
most distant from the head. From days 23 through 28, the heart tube folds and twists,
with the future ventricles moving left of center (the ultimate location of the heart) and the
atria moving towards the head.[20]
On day 28, areas of tissue in the heart tube begin to expand inwards; after about two
weeks, these expansions, the membranous "septum primum" and the muscular
"endocardial cushions", fuse to form the four chambers of the heart. A failure to fuse
properly will result in a defect that may allow blood to leak between chambers. After this
happens, cells which have migrated from the neural crest begin to divide the bulbus
cordis, the main outflow tract is divided in two by the growth a spiraling septum,

becoming the great vesselsthe ascending segment of the aorta and the pulmonary
trunk. If the separation is incomplete, the result is a "persistent truncus arteriosis". The
vessels may be reversed ("transposition of the great vessels"). The two halves of the
split tract must migrate into the correct positions over the appropriate ventricles. A failure
may result in some blood flowing into the wrong vessel (e.g.overriding aorta). The fourchambered heart and the great vessels have features required for fetal growth. The
lungs are unexpanded and cannot accommodate the full circulatory volume. Two
structures exist to shunt blood flow away from the lungs. Cells in part of the septum
primum die creating a hole while muscle cells, the "septum secundum", grow along the
right atrial side the septum primum, except for one region, leaving a gap through which
blood can pass from the right artium to the left atrium, the foramen ovale. A small vessel,
the ductus arteriosus allows blood from the pulmonary artery to pass to the aorta.[20]

Changes at birth
The ductus arteriosus stays open because of circulating factors including prostaglandins.
The foramen ovale stays open because of the flow of blood from the right atrium to the
left atrium. As the lungs expand, blood flows easily through the lungs and the
membranous portion of the foramen ovale (the septum primum) flops over the muscular
portion (the septum secundum). If the closure is incomplete, the result is a patent
foramen ovale. The two flaps may fuse, but many adults have a foramen ovale that stays
closed only because of the pressure difference between the atria.[20]

Theories
Rokitansky (1875) explained congenital heart defects as breaks in heart development at
various ontogenesis stages.[21] Spitzer (1923) treats them as returns to one of
thephylogenesis stages.[22] Krimsky (1963), synthesizing two previous points of view,
considered congenital heart diseases as a stop of development at the certain stage of
ontogenesis, corresponding to this or that stage of the phylogenesis. [23] Hence these
theories can explain feminine and neutral types of defects only.

Classification
A number of classification systems exist for congenital heart defects. In 2000 the
International Congenital Heart Surgery Nomenclature was developed to provide a
generic classification system.[24]

Hypoplasia

the heart. In both conditions, the presence of a patent ductus arteriosus (and, when
hypoplasia affects the right side of the heart, a patent foramen ovale) is vital to the
infant's ability to survive until emergency heart surgery can be performed, since without
these pathways blood cannot circulate to the body (or lungs, depending on which side of
the heart is defective). Hypoplasia of the heart is generally a cyanotic heart defect.[25]

Obstruction defects
Main article: Ventricular outflow tract obstruction
Obstruction defects occur when heart valves, arteries, or veins are abnormally
narrow or blocked. Common defects include pulmonic stenosis, aortic stenosis,
and coarctation of the aorta, with other types such as bicuspid aortic valve stenosis and
subaortic stenosis being comparatively rare. Any narrowing or blockage can cause heart
enlargement orhypertension.[26]

Septal defects
The septum is a wall of tissue which separates the left heart from the right heart. Defects
in the interatrial septum or the interventricular septum allow blood to flow from the right
side of the heart to the left, reducing the heart's efficiency.[26] Ventricular septal
defects are collectively the most common type of CHD,[27] although approximately 30% of
adults have a type of atrial septal defect called probe patent foramen ovale.[28]

Cyanotic defects
Cyanotic heart defects are called such because they result in cyanosis, a bluish-grey
discoloration of the skin due to a lack of oxygen in the body. Such defects
include persistent truncus arteriosus, total anomalous pulmonary venous
connection, tetralogy of Fallot, transposition of the great vessels, and tricuspid atresia.[26]

Defects

Aortic stenosis

Atrial septal defect (ASD)

Atrioventricular septal defect (AVSD)

Bicuspid aortic valve

Dextrocardia

Double inlet left ventricle (DILV)

Main articles: Hypoplastic left heart syndrome and Hypoplastic right heart syndrome
Hypoplasia can affect the heart, typically resulting in the underdevelopment of the right
ventricle or the left ventricle. This causes only one side of the heart to be capable of
pumping blood to the body and lungs effectively. Hypoplasia of the heart is rare but is the
most serious form of CHD. It is called hypoplastic left heart syndrome when it affects the
left side of the heart and hypoplastic right heart syndrome when it affects the right side of

Double outlet right ventricle (DORV)

Ebstein's anomaly

Partial anomalous pulmonary venous connection (PAPVC)

Hypoplastic left heart syndrome (HLHS)

Total anomalous pulmonary venous connection (TAPVC)

Hypoplastic right heart syndrome (HRHS)

Some constellations of multiple defects are commonly found together.

Mitral stenosis

tetralogy of Fallot (ToF)

Pulmonary atresia

pentalogy of Cantrell

Pulmonary stenosis

Shone's syndrome/ Shone's complex / Shone's anomaly

Transposition of the great vessels

dextro-Transposition of the great arteries (d-TGA)

levo-Transposition of the great arteries (l-TGA)

Scimitar syndrome (SS)

Diagnosis
Many congenital heart defects can be diagnosed prenatally by fetal echocardiography.
This is a test which can be done during the second trimester of pregnancy, when the
woman is about 1824 weeks pregnant.[29][30] It can be an abdominal
ultrasound or transvaginal ultrasound.

Tricuspid atresia

If a baby is born with cyanotic heart disease, the diagnosis is usually made shortly after
birth due to the blue colour of their skin (called cyanosis).[30]

Persistent truncus arteriosus

If a baby is born with a septal defect or an obstruction defect, often their symptoms are
only noticeable after several months or sometimes even after many years. [30]

Ventricular septal defect (VSD)

Treatment

Wolff-Parkinson-White syndrome (WPW)

Sometimes CHD improves without treatment. Other defects are so small that they do not
require any treatment. Most of the time CHD is serious and requires surgery and/or
medications. Medications include diuretics, which aid the body in eliminating water, salts,
and digoxin for strengthening the contraction of the heart. This slows the heartbeat and
removes some fluid from tissues. Some defects require surgical procedures to restore
circulation back to normal and in some cases, multiple surgeries are needed.

Some conditions affect the great vessels or other vessels in close proximity to the heart,
but not the heart itself, but are often classified as congenital heart defects.

Coarctation of the aorta (CoA)

Interrupted aortic arch (IAA)

Patent ductus arteriosus (PDA)

Interventional cardiology now offers patients minimally invasive alternatives to surgery for
some patients. The Melody Transcatheter Pulmonary Valve (TPV), approved in Europe in
2006 and in the U.S. in 2010 under a Humanitarian Device Exemption (HDE), is
designed to treat congenital heart disease patients with a dysfunctional conduit in their
right ventricular outflow tract (RVOT). The RVOT is the connection between the heart
and lungs; once blood reaches the lungs, it is enriched with oxygen before being pumped
to the rest of the body. Transcatheter pulmonary valve technology provides a less-

invasive means to extend the life of a failed RVOT conduit and is designed to allow
physicians to deliver a replacement pulmonary valve via a catheter through the patients
blood vessels.
Most patients require lifelong specialized cardiac care, first with a pediatric cardiologist
and later with an adult congenital cardiologist. There are more than 1.8 million adults
living with congenital heart defects.[31]

Epidemiology
Congenital heart defects resulted in about 223,000 deaths globally in 2010 down from
278,000 deaths in 1990.