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htm
Heart Failure
Article Last Updated: Jan 2, 2006
Author: Michael E Zevitz, MD

INTRODUCTION
Background
Heart failure is the pathophysiologic state in which the heart, via an abnormality of cardiac
function (detectable or not), fails to pump blood at a rate commensurate with the requirements of
the metabolizing tissues and/or pumps only from an abnormally elevated diastolic filling pressure.
Heart failure may be caused by myocardial failure but may also occur in the presence of nearnormal cardiac function under conditions of high demand. Heart failure always causes circulatory
failure, but the converse is not necessarily the case because various noncardiac conditions (eg,
hypovolemic shock, septic shock) can produce circulatory failure in the presence of normal,
modestly impaired, or even supranormal cardiac function.
In terms of incidence, prevalence, morbidity, and mortality, the epidemiologic magnitude of
congestive heart failure (CHF) is staggering. In the United States, the estimated annual cost of
heart failure is $60 billion; the estimated annual cost of inpatient care of patients with CHF is $23
billion. Approximately 1 million US hospital admissions per year are attributable to a primary
diagnosis of acutely decompensated heart failure. For additional resources, please visit Heart
Failure Resource Center.
Pathophysiology
Inadequate adaptation of the cardiac myocytes to increased wall stress in order to maintain
adequate cardiac output following myocardial injury (whether of acute onset or over several
months to years, whether a primary disturbance in myocardial contractility or an excessive
hemodynamic burden placed on the ventricle, or both), is the inciting event in CHF.
Most important among these adaptations are the (1) Frank-Starling mechanism, in which an
increased preload helps to sustain cardiac performance; (2) myocardial hypertrophy with or
without cardiac chamber dilatation, in which the mass of contractile tissue is augmented; and (3)
activation of neurohumoral systems, especially the release of norepinephrine (NE) by adrenergic
cardiac nerves, which augments myocardial contractility and the activation of the reninangiotensin-aldosterone system (RAAS) and other neurohumoral adjustments that act to maintain
arterial pressure and perfusion of vital organs. In acute heart failure, the finite adaptive
mechanisms that may be adequate to maintain the overall contractile performance of the heart at
relatively normal levels become maladaptive when trying to sustain adequate cardiac
performance.
The primary myocardial response to chronic increased wall stress includes myocyte hypertrophy
and remodeling, usually of the eccentric type. The reduction of cardiac output following
myocardial injury sets into motion a cascade of hemodynamic and neurohormonal derangements
that provoke activation of neuroendocrine systems, most notably the above-mentioned adrenergic
systems and RAAS. The release of epinephrine (E) and NE, along with the vasoactive
substances endothelin-1 (ET-1) and vasopressin (V), causes vasoconstriction, which increases
afterload, and, via an increase in cyclic adenosine monophosphate (cAMP), causes an increase
in cytosolic calcium entry. The increased calcium entry into the myocytes augments myocardial
contractility and impairs myocardial relaxation (lusitropy).
The calcium overload may also induce arrhythmias and lead to sudden death. The increase in
afterload and myocardial contractility (known as inotropy) and the impairment in myocardial
lusitropy lead to an increase in myocardial energy expenditure and a further decrease in cardiac
output. The increase in myocardial energy expenditure leads to myocardial cell death, resulting in

heart failure and further reduction in cardiac output, thus starting an accelerating cycle of further
increased neurohumoral stimulation and further adverse hemodynamic and myocardial
responses as described above.
In addition, the activation of the RAAS leads to salt and water retention, resulting in increased
preload and further increases in myocardial energy expenditure. Increases in renin, mediated by
decreased stretch of the glomerular afferent arteriole, reduced delivery of chloride to the macula
densa, and increased beta1-adrenergic activity as a response to decreased cardiac output,
results in an increase in angiotensin II (Ang II) levels and, in turn, aldosterone levels. This results
in stimulation of release of aldosterone. Ang II, along with ET-1, is crucial in maintaining effective
intravascular homeostasis mediated by vasoconstriction and aldosterone-induced salt and water
retention.
Some evidence indicates that local cardiac Ang II production, with a resultant decrease in
lusitropy, increase in inotropy, and increase in afterload, leads to increased myocardial energy
expenditure. In this fashion, Ang II has similar actions to NE in CHF.
Ang II also mediates myocardial cellular hypertrophy and may promote progressive loss of
myocardial function. The neurohumoral factors above lead to myocyte hypertrophy and interstitial
fibrosis, resulting in increased myocardial volume and increased myocardial mass, as well as
myocyte loss. The increase in myocardial volume results in myocyte slippage, which also results
in further increases in myocardial volume and mass. These features, namely the increased
myocardial volume and mass, along with myocyte loss, are the hallmark of myocardial
remodeling. This remodeling process leads to early adaptive mechanisms, such as augmentation
of stroke volume (Starling mechanism) and decreased wall stress (Laplace mechanism), and
later, maladaptive mechanisms such as increased myocardial oxygen demand, myocardial
ischemia, impaired contractility, and arrhythmogenesis.
As heart failure advances and/or becomes progressively decompensated, there is a relative
decline in the counterregulatory effects of endogenous vasodilators, including nitric oxide (NO),
prostaglandins (PGs), bradykinin (BK), atrial natriuretic peptide (ANP), and B-type natriuretic
peptide (BNP). This occurs simultaneously with the increase in vasoconstrictor substances from
the RAAS and adrenergic systems. This fosters further increases in vasoconstriction and thus
preload and afterload, leading to cellular proliferation, adverse myocardial remodeling, and
antinatriuresis with total body fluid excess and worsening CHF symptoms.
Both systolic and diastolic heart failure result in a decrease in stroke volume. This leads to
activation of peripheral and central baroreflexes and chemoreflexes that are capable of eliciting
marked increases in sympathetic nerve traffic. While there are commonalities in the
neurohormonal responses to decreased stroke volume, the neurohormone-mediated events that
follow have been most clearly elucidated for individuals with systolic heart failure. The ensuing
elevation in plasma NE directly correlates with the degree of cardiac dysfunction and has
significant prognostic implications. NE, while being directly toxic to cardiac myocytes, is also
responsible for a variety of signal-transduction abnormalities, such as down-regulation of beta1adrenergic receptors, uncoupling of beta2-adrenergic receptors, and increased activity of
inhibitory G-protein. Changes in beta1-adrenergic receptors result in overexpression and promote
myocardial hypertrophy.
ANP and BNP are endogenously generated peptides activated in response to atrial and
ventricular volume/pressure expansion. ANP and BNP are released from the atria and ventricles,
respectively, and both promote vasodilation and natriuresis. Their hemodynamic effects are
mediated by decreases in ventricular filling pressures, owing to reductions in cardiac preload and
afterload. BNP, in particular, produces selective afferent arteriolar vasodilation and inhibits sodium
reabsorption in the proximal convoluted tubule. BNP inhibits renin and aldosterone release and,
possibly, adrenergic activation as well. Both ANP and BNP are elevated in chronic heart failure.
BNP, in particular, has potentially important diagnostic, therapeutic, and prognostic implications.
Other vasoactive systems that play a role in the pathogenesis of CHF include the ET receptor
system, adenosine receptor system, V, and tumor necrosis factor-alpha (TNF-alpha). ET, a
substance produced by the vascular endothelium, may contribute to the regulation of myocardial
function, vascular tone, and peripheral resistance in CHF. Elevated levels of ET-1 closely
correlate with the severity of heart failure. ET-1 is a potent vasoconstrictor and has exaggerated
vasoconstrictor effects in the renal vasculature, reducing renal plasma blood flow, glomerular

filtration rate (GFR), and sodium excretion. TNF-alpha has been implicated in response to various
infectious and inflammatory conditions. Elevations in TNF-alpha levels have been consistently
observed in CHF and seem to correlate with the degree of myocardial dysfunction. Experimental
studies suggest that local production of TNF-alpha may have toxic effects on the myocardium,
thus worsening myocardial systolic and diastolic function.
Thus, in individuals with systolic dysfunction, the neurohormonal responses to decreased stroke
volume result in temporary improvement in systolic blood pressure and tissue perfusion.
However, in all circumstances, the existing data support the notion that these neurohormonal
responses accelerate the downward spiral of myocardial dysfunction in the long term.
In diastolic heart failure, the same pathophysiologic processes to decreased cardiac output that
occur in systolic heart failure also occur, but they do so in response to a different set of
hemodynamic and circulatory environmental factors that depress cardiac output.
In diastolic heart failure, altered relaxation of the ventricle (due to delayed calcium uptake by the
myocyte sarcoplasmic reticulum and delayed calcium efflux from the myocyte) occurs in response
to an increase in ventricular afterload (pressure overload). The impaired relaxation of the ventricle
leads to impaired diastolic filling of the left ventricle (LV).
An increase in LV chamber stiffness occurs secondary to any one of the following 3 mechanisms
or to a combination thereof: (1) a rise in filling pressure (ie, movement of the ventricle up along its
pressure-volume curve to a steeper portion, as may occur in conditions such as volume overload
secondary to acute valvular regurgitation or acute LV failure due to myocarditis); (2) a shift to a
steeper ventricular pressure-volume curve, occurring most commonly as a result of not only
increased ventricular mass and wall thickness, as observed in (a) aortic stenosis and (b) longstanding hypertension, but also in (c) infiltrative disorders such as amyloidosis, (d)
endomyocardial fibrosis, and (e) myocardial ischemia; and (3) a parallel upward displacement of
the diastolic pressure-volume curve, generally referred to as a decrease in ventricular
distensibility, usually caused by extrinsic compression of the ventricles.
Whereas volume overload, as observed in chronic aortic and/or mitral valvular regurgitant
disease, shifts the entire diastolic pressure-volume curve to the right, indicating increased
chamber stiffness, pressure overload that leads to concentric LV hypertrophy (as occurs in aortic
stenosis, hypertension, and hypertrophic cardiomyopathy) shifts the diastolic pressure-volume
curve to the left along its volume axis so that at any diastolic volume ventricular diastolic pressure
is abnormally elevated, although chamber stiffness may or may not be altered. Increases in
diastolic pressure lead to increased myocardial energy expenditure, remodeling of the ventricle,
increased myocardial oxygen demand, myocardial ischemia, and eventual progression of the
maladaptive mechanisms of the heart that lead to decompensated heart failure.
Frequency
United States
CHF is the fastest-growing clinical cardiac disease entity in the United States, affecting 2% of the
population. Nearly 1 million hospital admissions for acute decompensated CHF occur in the
United States yearly, almost double the number seen 15 years ago. The rehospitalization rates
during the 6 months following discharge are as much as 50%. Nearly 2% of all hospital
admissions in the United States are for decompensated CHF, and heart failure is the most
frequent cause of hospitalization in patients older than 65 years. The average duration of
hospitalization is about 6 days. An estimated $23 billion are spent on inpatient management of
CHF every year, and another $40 billion are spent in the outpatient setting on patients with
compensated or mildly decompensated heart failure every year. Despite aggressive therapies,
hospital admissions for CHF continue to increase, reflecting the prevalence of this malady.
International
CHF is a worldwide problem, but few accurate financial data are available. As discussed
elsewhere, the most common cause of CHF in industrialized countries is ischemic
cardiomyopathy. Other causes, including Chagas disease, assume a more important role in
underdeveloped countries than in the United States.
Mortality/Morbidity

Despite recent advances in the management of patients with heart failure, morbidity and mortality
rates remain high, with an estimated 5-year mortality rate of 50%.
Assigning figures for inpatient mortality rates is difficult because the causes and the
severity of heart failure vary considerably. The most recent estimates of inpatient
mortality rates indicate that death occurs in up to 5-20% of patients.
Hypoxemia that occurs in decompensated CHF, which may be severe, may result in
myocardial ischemia or infarction.
Respiratory failure with hypercapnic respiratory acidosis may occur in severe
decompensated CHF, requiring mechanical ventilation if medical therapy is delayed or
unsuccessful. Endotracheal intubation and mechanical ventilation are associated with
their own risks, including aspiration (during the intubation process), mucosal trauma
(more common with nasotracheal intubation than orotracheal intubation), and
barotrauma.
In patients with CHF, the risk of cardiac sudden death from ventricular tachycardia (VT) or
ventricular fibrillation is considerable, and the degree of risk is correlated with the degree
of decompensation and the degree of LV dysfunction. Recognition of the role of
ventricular arrhythmias and advances in their treatment have resulted in decreased
mortality rates in individuals with CHF.
Progressive renal insufficiency due to decreased renal blood flow and GFR are common
in patients with long-standing CHF.
Liver dysfunction due to passive hepatic congestion is particularly common in patients
with right-sided CHF with elevated right ventricular (RV) pressure that is transmitted back
into the portal vein.
o Mild jaundice, mild abnormalities in coagulation, and derangements in liver
metabolism of medications, some of which are used in the treatment of heart
failure, may result from this liver dysfunction.
o Toxic levels of medications such as warfarin, theophylline, phenytoin, and digoxin
can result from delayed liver metabolic clearance of these drugs in the presence
of decompensated CHF, thereby leading to potentially fatal bleeding, cardiac
dysrhythmias, and neurologic abnormalities.
Race
The incidence and prevalence of CHF are higher in African Americans, Hispanic persons, Native
Americans, and recent immigrants from nonindustrialized nations, Russia, and the former Soviet
republics.
The higher prevalence of CHF in African Americans, Hispanic persons, and Native
Americans is directly related to the higher incidence and prevalence of hypertension and
diabetes. This problem is particularly exacerbated by a lack of access to health care and
to substandard preventive health care of the most indigent of these and other groups;
many persons within these groups are without adequate health insurance coverage.
The higher incidence and prevalence of CHF among recent immigrants from
nonindustrialized nations is largely due to a lack of prior preventive health care and to a
lack of treatment or to substandard treatment for common conditions such as
hypertension, diabetes, rheumatic fever, and ischemic heart disease.
Sex
Men and women have equivalent incidence and prevalence of CHF. CHF in women tends to
occur later in life compared to men.
Age
The prevalence of CHF increases with age, being most common in individuals older than 65
years. In the United States, CHF is the most common reason for hospital admission in patients
older than 65 years. Nonetheless, CHF can occur at any age, depending on the cause.

CLINICAL
History
Breathlessness, a cardinal sign of LV failure, may manifest with progressively increasing severity
as (1) exertional dyspnea, (2) orthopnea, (3) paroxysmal nocturnal dyspnea, (4) dyspnea at rest,
and (5) acute pulmonary edema. The New York Heart Association (NYHA) Classification of Heart
Failure (see Staging), which varies slightly from the above categorization of CHF symptoms, is
widely used in practice and in clinical studies to quantify clinical assessment of CHF.
Exertional dyspnea

o The principal difference between exertional dyspnea in subjects who are healthy
and exertional dyspnea in patients with heart failure is the degree of activity
necessary to induce the symptom. As heart failure first develops, exertional
dyspnea may simply appear to be an aggravation of the breathlessness that
occurs in healthy persons during activity.
o As LV failure advances, the intensity of exercise resulting in breathlessness
progressively declines; however, subjective exercise capacity and objective
measures of LV performance at rest in patients with heart failure are not closely
correlated. Exertional dyspnea, in fact, may be absent in sedentary patients.
Orthopnea

o This early symptom of CHF may be defined as dyspnea that develops in the
recumbent position and is relieved with elevation of the head with pillows. As in
the case of exertional dyspnea, the change in the number of pillows required is
important.
o In the recumbent position, decreased pooling of blood in the lower extremities
and abdomen occurs. Blood is displaced from the extrathoracic to the thoracic
compartment. The failing LV, operating on the flat portion of the Starling curve,
cannot accept and pump out the extra volume of blood delivered to it without
dilating. As a result, pulmonary venous and capillary pressures rise further,
causing interstitial pulmonary edema, reduced pulmonary compliance, increased
airway resistance, and dyspnea.
o In contrast to paroxysmal nocturnal dyspnea, orthopnea occurs rapidly, often
within a minute or two of recumbency, and develops when the patient is awake.
Orthopnea may occur in any condition in which the vital capacity is low. Marked
ascites, whatever its etiology, is an important cause of orthopnea. In advanced
LV failure, orthopnea may be so severe that the patient cannot lie down and must
sleep sitting up in a chair or slumped over a table.
o Cough, particularly during recumbency, may be an "orthopnea equivalent." This
nonproductive cough may be caused by pulmonary congestion and is relieved by
treatments for heart failure.
Paroxysmal nocturnal dyspnea

o Attacks of paroxysmal nocturnal dyspnea usually occur at night. This symptom of

CHF is defined by a sudden awakening of the patient, after a couple hours of
sleep, with a feeling of severe anxiety, breathlessness, and suffocation. The
patient may bolt upright in bed and gasp for breath. Bronchospasm increases
ventilatory difficulty and the work of breathing and is a common complicating
factor of paroxysmal nocturnal dyspnea. On chest auscultation, the
bronchospasm associated with a CHF exacerbation can be difficult to distinguish
from an acute asthma exacerbation, although other clues from the cardiovascular

examination should lead the examiner to the correct diagnosis. Both types of
bronchospasm can be present in the same individual.
o In contrast to orthopnea, which may be relieved by immediately sitting up in bed,
attacks of paroxysmal nocturnal dyspnea may require 30 minutes or longer in this
position for relief. Episodes of this may be so frightening that the patient may be
afraid to resume sleeping, even after the symptoms have abated.
Dyspnea at rest - Mechanisms of dyspnea in heart failure
o Decreased pulmonary function
Decreased compliance
Increased airway resistance
o Increased ventilatory drive
Hypoxemia due to increased pulmonary capillary wedge pressure
(PCWP)
Ventilation/perfusion (V/Q) mismatching due to increased PCWP and
cardiac output
Increased carbon dioxide production
o Respiratory muscle dysfunction
Decreased respiratory muscle strength
Decreased endurance
Ischemia
Fatigue and weakness

o These symptoms are often accompanied by a feeling of heaviness in the limbs.

o Fatigue and weakness are generally related to poor perfusion of the skeletal
muscles in patients with a lowered cardiac output. Although generally a constant
feature of advanced CHF, episodic fatigue and weakness are common in earlier
stages.
Nocturia

o Nocturia may occur relatively early in the course of heart failure. Recumbency
reduces the deficit in cardiac output in relation to oxygen demand; renal
vasoconstriction diminishes and urine formation increases. This may be
troublesome for the patient with heart failure because it may prevent the patient
from obtaining much-needed rest.
o Oliguria is a late finding in CHF and is found in patients with markedly reduced
cardiac output from severely reduced LV function.
Cerebral symptoms: Confusion, memory impairment, anxiety, headaches, insomnia, bad
dreams or nightmares, and rarely, psychosis with disorientation, delirium, or
hallucinations may occur in elderly patients with advanced heart failure, particularly in
those with cerebrovascular atherosclerosis.
Predominant right-sided heart failure

o Ascites, congestive hepatomegaly, and anasarca due to elevated right-sided

heart pressures transmitted backward into the portal vein circulation may result in
increased abdominal girth and epigastric and right upper quadrant (RUQ)
abdominal pain. Other gastrointestinal symptoms, owing to congestion of the
hepatic and gastrointestinal venous circulation, include anorexia, bloating,
nausea, and constipation. In preterminal heart failure, inadequate bowel
perfusion can cause abdominal pain, distention, and bloody stools. Distinguishing
right-sided CHF from hepatic failure is often clinically difficult.
o Dyspnea, prominent in LV failure, becomes less prominent in isolated right-sided
heart failure because of the absence of pulmonary congestion. On the other
hand, when cardiac output becomes markedly reduced in patients with terminal

right-sided heart failure (as may occur in isolated RV infarction and in the late
stages of primary pulmonary hypertension and pulmonary thromboembolic
disease), severe dyspnea may occur as a consequence of the reduced cardiac
output, poor perfusion of respiratory muscles, hypoxemia, and metabolic
acidosis.
Physical
General appearance
o Patients with mild heart failure appear to be in no distress after a few minutes of
rest, but they may be obviously dyspneic during and immediately after moderate
activity. Patients with LV failure may be dyspneic when lying flat without elevation
of the head for more than a few minutes. Those with severe heart failure appear
anxious and may exhibit signs of air hunger in this position.
o Patients with recent onset of heart failure are generally well nourished, but those
with chronic severe heart failure are often malnourished and sometimes even
cachectic.
o Chronic marked elevation of systemic venous pressure may produce
exophthalmos and severe tricuspid regurgitation and may lead to visible
pulsation of the eyes and of the neck veins.
o Central cyanosis, icterus, and malar flush may be evident in patients with severe
heart failure.
o In mild or moderate heart failure, stroke volume is normal at rest; in severe heart
failure, it is reduced, as reflected by a diminished pulse pressure and a dusky
discoloration of the skin.
o With very severe heart failure, particularly if cardiac output has declined acutely,
systolic arterial pressure may be reduced. The pulse may be weak, rapid, and
thready; the proportional pulse pressure (pulse pressure/systolic pressure) may
be markedly reduced. The proportional pulse pressure correlates reasonably well
with cardiac output. In one study, when pulse pressure was less than 25%, it
usually reflected a cardiac index of less than 2.2 L/min/m 2.
Evidence of increased adrenergic activity
o Increased adrenergic activity is manifested by tachycardia, diaphoresis, pallor,
peripheral cyanosis with pallor and coldness of the extremities, and obvious
distention of the peripheral veins secondary to venoconstriction.
o Diastolic arterial pressure may be slightly elevated.
Pulmonary rales
o Rales heard over the lung bases are characteristic of CHF of at least moderate
severity. With acute pulmonary edema, rales are frequently accompanied by
wheezing and expectoration of frothy, blood-tinged sputum.
o The absence of rales, however, certainly does not exclude elevation of
pulmonary capillary pressure due to LV failure.
Systemic venous hypertension: This is manifested by jugular venous distention. Normally,
jugular venous pressure declines with respiration; however, it increases in patients with
heart failure, a finding known as the Kussmaul sign (also found in constrictive
pericarditis).
Hepatojugular reflux: This is found in patients with right-sided heart failure and is helpful
in differentiating hepatic enlargement due to heart failure from that caused by other
conditions.
Edema
o Although a cardinal manifestation of CHF, edema does not correlate well with the
level of systemic venous pressure. In patients with chronic LV failure and low
cardiac output, extracellular fluid volume may be sufficiently expanded to cause
edema in the presence of only slight elevations in systemic venous pressure.

Usually, a substantial gain of extracellular fluid volume (ie, a minimum of 5 L in

adults) must occur before peripheral edema is manifested.
o Edema, in the absence of dyspnea or other signs of LV or RV failure, is not solely
indicative of heart failure and can be observed in many other conditions,
including chronic venous insufficiency, nephrotic syndrome, or other syndromes
of hypoproteinemia or osmotic imbalance.
Hepatomegaly
o Hepatomegaly is prominent in patients with chronic right-sided heart failure, but it
may occur rapidly in acute heart failure.
o When occurring acutely, the liver is usually tender.
o In patients with considerable tricuspid regurgitation, a prominent systolic
pulsation of the liver, attributable to an enlarged right atrial V wave, is often
noted. A presystolic pulsation of the liver, attributable to an enlarged right atrial A
wave, can occur in tricuspid stenosis, constrictive pericarditis, restrictive
cardiomyopathy involving the RV, and pulmonary hypertension (primary or
secondary).
Hydrothorax (pleural effusion)
o Hydrothorax is most commonly observed in patients with hypertension involving
both systemic and pulmonary systems. Hydrothorax is usually bilateral, although
when unilateral, it is usually confined to the right side of the chest.
o When hydrothorax develops, dyspnea usually intensifies because of further
reductions in vital capacity.
Ascites
o This finding occurs in patients with increased pressure in the hepatic veins and in
the veins draining into the peritoneum.
o Ascites usually reflects long-standing systemic venous hypertension.
Protodiastolic (S3) gallop: This is the earliest cardiac physical finding in decompensated
heart failure in the absence of severe mitral or tricuspid regurgitation or left-to-right
shunts.
Cardiomegaly
o A nonspecific finding, cardiomegaly nonetheless occurs in most patients with
chronic heart failure.
o Notable exceptions include heart failure from acute myocardial infarction,
constrictive pericarditis, restrictive cardiomyopathy, valve or chordae tendineae
rupture, or heart failure due to tachyarrhythmias or bradyarrhythmias.
Pulsus alternans
o Pulsus alternans occurs most commonly in heart failure due to increased
resistance to LV ejection, as occurs in hypertension, aortic stenosis, coronary
atherosclerosis, and dilated cardiomyopathy.
o It is usually associated with an S3 gallop, signifies advanced myocardial disease,
and often disappears with treatment of heart failure.
Accentuation of P2 heart sound, S3 gallop, and systolic murmurs
o This accentuation is a cardinal sign of increased pulmonary artery pressure. It
disappears or improves after treatment of heart failure.
o Mitral and tricuspid regurgitation murmurs are often present in patients with
decompensated heart failure because of ventricular dilatation. These murmurs
often disappear or diminish when compensation is restored. Note that correlation
between the intensity of the murmur of mitral regurgitation and its significance in
patients with CHF is poor. Severe mitral regurgitation may be accompanied by an
unimpressively soft murmur.
o The presence of an S3 gallop in adults is important, pathologic, and often the
most apparent finding on cardiac auscultation in patients with significant CHF.
Cardiac cachexia
o

Cardiac cachexia is found in long-standing heart failure, particularly of the RV,

because of anorexia from hepatic and intestinal congestion and sometimes
because of digitalis toxicity. Occasionally, impaired intestinal absorption of fat and
(rarely) protein-losing enteropathy occur.
o Patients with heart failure may also exhibit increased total metabolism secondary
to augmentation of myocardial oxygen consumption, excessive work of
breathing, low-grade fever, and elevated levels of circulating TNF.
Fever: Fever may be present in severe decompensated heart failure because of
cutaneous vasoconstriction and impairment of heat loss.
o

Causes
From a clinical standpoint, it is useful to classify the causes of heart failure into 3 broad
categories: (1) underlying causes, comprising structural abnormalities (congenital or acquired)
that affect the peripheral and coronary arterial circulation, pericardium, myocardium, or cardiac
valves, thus leading to the increased hemodynamic burden or myocardial or coronary
insufficiency responsible for heart failure; (2) fundamental causes, comprising the biochemical
and physiological mechanisms, through which either an increased hemodynamic burden or a
reduction in oxygen delivery to the myocardium results in impairment of myocardial contraction;
and (3) precipitating causes, including the specific causes or incidents that precipitate heart
failure in most episodes of heart failure.
Note that most patients who present with significant heart failure do so because of an inability to
provide adequate cardiac output in that setting. This is often a combination of the causes listed
above in the setting of an abnormal myocardium. The list of causes responsible for presentation
of a patient with a CHF exacerbation is very long, and it is important to search for the proximate
cause in order to optimize therapeutic interventions.
Overt heart failure may be precipitated by progression of the underlying heart disease. A
previously stable compensated patient may develop heart failure that is clinically apparent for the
first time when the intrinsic process has advanced to a critical point, such as with further
narrowing of a stenotic aortic valve or mitral valve. Alternatively, decompensation may occur as a
result of failure or exhaustion of the compensatory mechanisms but without any change in the
load on the heart in patients with persistent severe pressure or volume overload.
Precipitating causes of heart failure

o Inappropriate reduction of therapy: The most common cause of decompensation

in a previously compensated patient with heart failure is inappropriate reduction
in the intensity of treatment, whether dietary sodium restriction, physical activity
reduction, drug regimen reduction, or, most commonly, a combination of these
measures.
o Arrhythmias
Tachyarrhythmias, most commonly atrial fibrillation
Marked bradycardia
Atrioventricular dissociation
Abnormal intraventricular conduction
o Systemic infection or development of unrelated illness
Systemic infection precipitates heart failure by increasing total
metabolism as a consequence of fever, discomfort, and cough, which
increases the hemodynamic burden on the heart.
Septic shock, in particular, can precipitate heart failure by the release of
endotoxin-induced factors that can depress myocardial contractility.
o Pulmonary embolism: Patients with CHF, particularly when confined to bed, are
at high risk of developing pulmonary emboli, which can increase the
hemodynamic burden on the RV by further elevating RV systolic pressure,
possibly causing fever, tachypnea, and tachycardia.

Physical, environmental, and emotional excesses: Intense, prolonged physical

exertion or severe fatigue, such as may result from prolonged travel or emotional
crises, or severe climate changes, either to a hot, humid environment or to a
bitterly cold environment, are relatively common precipitants of cardiac
decompensation.
o Cardiac infection and inflammation
Myocarditis or infective endocarditis may directly impair myocardial
function and exacerbate existing heart disease. The anemia, fever, and
tachycardia that frequently accompany these processes are also
deleterious.
In the case of infective endocarditis, the additional valvular damage that
ensues may precipitate cardiac decompensation.
o Excessive intake of water and/or sodium
o Administration of cardiac depressants or drugs that cause salt retention
o High-output states: Profound anemia, thyrotoxicosis, myxedema, Paget disease
of bone, Albright syndrome, multiple myeloma, glomerulonephritis, cor
pulmonale, polycythemia vera, obesity, carcinoid syndrome, pregnancy, or
nutritional deficiencies (eg, thiamine deficiency, beriberi) can precipitate the
clinical presentation of CHF because of increased myocardial oxygen
consumption and demand beyond a critical level (ie, beyond the ability of the
underlying myocardial oxygen supply to meet these demands). In particular,
consider whether the patient has underlying coronary artery disease or valvular
heart disease.
o Development of a second form of heart disease
Patients with one form of underlying heart disease that may be well
compensated can develop heart failure when a second form of heart
disease ensues.
For example, a patient with chronic hypertension and asymptomatic LV
hypertrophy may be asymptomatic until a myocardial infarction develops
and precipitates heart failure.
Underlying causes

o Dominant systolic heart failure

Ischemic myocardial disease, coronary artery disease
Alcoholic cardiomyopathy
Diabetic cardiomyopathy
Cocaine cardiomyopathy
Drug-induced cardiomyopathy (eg, doxorubicin)
Idiopathic cardiomyopathy
Peripartum cardiomyopathy
Myocarditis
Preterminal valvular heart disease
Congenital heart disease with severe pulmonary hypertension
Terminal ventricular septal defect or atrial septal defect
o Dominant diastolic heart failure
Hypertension
Severe aortic stenosis
Hypertrophic cardiomyopathy
Restrictive cardiomyopathy
Ischemic myocardial disease, coronary artery disease
o Acute heart failure
Acute mitral or aortic regurgitation
Rupture of valve leaflets or supporting structures
o

Infective endocarditis with acute valve incompetence

Myocardial infarction
o High-output heart failure
Anemia
Systemic arteriovenous fistulas
Hyperthyroidism
Beriberi heart disease
Paget disease of bone
Albright syndrome (fibrous dysplasia)
Multiple myeloma
Pregnancy
Glomerulonephritis
Cor pulmonale
Polycythemia vera
Carcinoid syndrome
Obesity
Fundamental causes: See Pathophysiology.

DIFFERENTIALS
Other Problems to be Considered
CHF should be differentiated from pulmonary edema associated with injury to the alveolarcapillary membrane caused by diverse etiologies (ie, noncardiogenic pulmonary edema, adult
respiratory distress syndrome [ARDS]). Increased capillary permeability is observed in trauma,
hemorrhagic shock, sepsis, respiratory infections, administration of various drugs, and ingestion
of toxins such as heroin, cocaine, and toxic gases.
Several features may differentiate cardiogenic heart failure from noncardiogenic pulmonary
edema. In CHF, a history of an acute cardiac event or that of progressive symptoms of heart
failure is usually present. The physical examination reveals a low-flow state, S 3 gallop, elevated
jugular venous distention, and crackles upon auscultation.
Patients with noncardiogenic pulmonary edema have a warm periphery, a bounding pulse, and an
absence of S3 gallop and jugular venous distention. Differentiation is often made based on PCWP
measurements from invasive hemodynamic monitoring. PCWP is generally more than 18 mm Hg
in CHF and is less than 18 mm Hg in noncardiogenic pulmonary edema, but superimposition of
chronic pulmonary vascular disease can make this distinction more difficult to discern. With the
advent of BNP level testing, reliably differentiating cardiac causes of pulmonary congestion from
noncardiac causes is now possible.
WORKUP
Lab Studies
CBC count: This study aids in the assessment of severe anemia, which may cause or
aggravate heart failure. Leukocytosis may signal underlying infection. Otherwise, CBC
counts are usually of little diagnostic help.
Electrolytes
o Serum electrolyte values are generally within reference ranges in patients with
mild-to-moderate heart failure before treatment. However, in severe heart failure,
prolonged, rigid sodium restriction, coupled with intensive diuretic therapy and
the inability to excrete water, may lead to dilutional hyponatremia, which occurs
because of a substantial expansion of extracellular fluid volume and a normal or
increased level of total body sodium.
o Potassium levels are usually within reference ranges, although the prolonged
administration of diuretics may result in hypokalemia. Hyperkalemia may occur in
patients with severe heart failure who show marked reductions in GFR and

inadequate delivery of sodium to the distal tubular sodium-potassium exchange

sites of the kidney, particularly if they are receiving potassium-sparing diuretics
and/or ACE inhibitors.
Renal function tests
o BUN and creatinine levels can be within reference ranges in patients with mild-tomoderate heart failure and normal renal function, although elevated BUN and
BUN/creatinine ratios may also be present.
o Patients with severe heart failure, particularly those on large doses of diuretics
for long periods, may have elevated BUN and creatinine levels indicative of renal
insufficiency because of chronic reductions of renal blood flow from reduced
cardiac output. Diuretics may aggravate renal insufficiency when these patients
are overmedicated with diuretics and become volume depleted.
Liver function tests
o Congestive hepatomegaly and cardiac cirrhosis are often associated with
impaired hepatic function, which is characterized by abnormal values of
aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactic
dehydrogenase (LDH), and other liver enzymes.
o Hyperbilirubinemia, secondary to an increase in both the directly and indirectly
reacting bilirubin, is common. In severe cases of acute RV or LV failure, frank
jaundice may occur.
o Acute hepatic venous congestion can result in severe jaundice, with a bilirubin
level as high as 15-20 mg/dL, elevation of AST to more than 10 times the upper
reference range limit, elevation of the serum alkaline phosphatase level, and
prolongation of the prothrombin time. Both the clinical and the laboratory pictures
may resemble viral hepatitis, but the impairment of hepatic function is rapidly
resolved by successful treatment of heart failure. In patients with long-standing
heart failure, albumin synthesis may be impaired, leading to hypoalbuminemia
and intensifying the accumulation of fluid.
o Fulminant hepatic failure is an uncommon, late, and sometimes terminal
complication of cardiac cirrhosis.
B-type natriuretic peptide
o BNP is a 32-amino acid polypeptide containing a 17-amino acid ring structure
common to all natriuretic peptides. Unlike ANP, whose major storage sites are in
both the atria and ventricles, the major source of plasma BNP is the cardiac
ventricles, suggesting that BNP may be a more sensitive and specific indicator of
ventricular disorders than other natriuretic peptides. The release of BNP appears
to be in direct proportion to ventricular volume expansion and pressure overload.
BNP is an independent predictor of high LV end-diastolic pressure and is more
useful than ANP or NE levels for assessing mortality risk in patients with CHF.
o BNP levels rise with age. Mean BNP levels are 26.2 +/- 1.8 pg/mL in the group
aged 55-64 years, 31.0 +/- 2.4 pg/mL for the group aged 65-74 years, and 63.7
+/- 6 pg/mL for the group aged 75 years and older. Additionally, women without
CHF tend to have somewhat higher BNP levels than their male cohorts of the
same age, with women 75 years and older having a mean BNP level of 76.5 +/3.5 pg/mL. Although the reason is unknown, aging women possibly have stiffer
ventricles than age-matched men.
o BNP levels correlate closely with the NYHA Classification of Heart Failure as well
as the Goldman Activity Classification of Heart Failure.
o BNP levels of more than 100 pg/mL have better than a 95% specificity and
greater than a 98% sensitivity when comparing patients without CHF to all
patients with CHF. Even BNP levels of more than 80 pg/mL have greater than a
93% specificity and 98% sensitivity in the diagnosis of heart failure. Furthermore,
BNP levels, in several pilot studies, had a strong correlation with the severity of
illness and were very reliable in differentiating CHF from pulmonary disease.

BNP levels also correlate highly with the change in PCWP pressure. It has been
proposed that BNP levels may be a useful surrogate indicator of PCWP, although
this is not common in clinical practice. BNP may help in tailoring treatment of the
decompensated patient.
In a pilot study, BNP levels correlated highly with clinical outcomes. Patients with
decreased BNP levels during their hospital stay, along with decreases in NYHA
classification, had good outcomes, whereas patients whose hospital stay ended
in death or readmission within 30 days of discharge had only minimal decreases
of BNP levels or rising levels of BNP despite improvement or no change in their
NYHA classification. In addition, the last measured BNP level was the single
most reliable variable in predicting short-term outcomes in patients with CHF.

Imaging Studies
Chest radiography
o Chest radiographs are very helpful in distinguishing cardiogenic pulmonary
edema (CPE) from other pulmonary causes of severe dyspnea.
o Classic radiographic findings demonstrate cardiomegaly (in patients with
underlying CHF) and alveolar edema with pleural effusions and bilateral infiltrates
in a butterfly pattern. The other signs are loss of sharp definition of pulmonary
vasculature, haziness of hilar shadows, and thickening of interlobular septa
(Kerley B lines).
o Chest radiographs in patients with abrupt onset are usually helpful but can be
limited because a delay of as long as 12 hours is possible from the onset of
dyspnea due to acute heart failure to the development of classic abnormal
findings on x-ray films.
Echocardiography
o This is the easiest and least-expensive method of determining LV function, both
systolic and diastolic. Echocardiography is also the easiest and least-expensive
method of determining the presence of valvular heart disease, LV wall thickness,
chamber sizes, presence of pericardial disease, and regional wall motion
abnormalities that may suggest ischemic coronary artery disease as the cause.
Echocardiography is very reliable in diagnosing the cause or causes of heart
failure.
o Transesophageal echocardiography is particularly useful in patients who are on
mechanical ventilation or morbidly obese and in patients whose transthoracic
echocardiogram was suboptimal in its imaging. It is an easy and safe alternative
to conventional transthoracic echocardiography and provides superior imaging
quality compared to conventional transthoracic echocardiography.
Radionuclide multiple gated acquisition scan
o Radionuclide multiple gated acquisition (MUGA) scan is a very reliable imaging
technique for determining global heart function. LV ejection fraction, as
determined by MUGA scanning, is often used for serial assessment of LV
function because of its reliability.
o However, this study is limited in its assessment of valvular heart disease and
pericardial disease.
Other Tests
Arterial blood gases
o ABGs usually reveal mild hypoxemia in patients who have mild-to-moderate
heart failure. ABGs are more accurate than pulse oximetry for measuring oxygen
saturation. Patients with severe heart failure may have signs and symptoms
ranging from severe hypoxemia, or even hypoxia, along with hypercapnia, to
decreased vital capacity and poor ventilation.
o ABGs help to assess the presence of hypercapnia, a potential early marker for
impending respiratory failure. Hypoxemia and hypocapnia occur in stages 1 and

2 of pulmonary edema because of V/Q mismatch. In stage 3 of pulmonary

edema, right-to-left intrapulmonary shunt develops secondary to alveolar flooding
and further contributes to hypoxemia. In more severe cases, hypercapnia and
respiratory acidosis are usually observed. The decision regarding intubation and
use of mechanical ventilation is frequently based on the presence of hypercapnic
respiratory failure with acidosis discovered on ABGs in patients with fulminant
pulmonary edema.
Pulse oximetry
o Pulse oximetry is highly accurate at assessing the presence of hypoxemia and,
therefore, the severity of heart failure.
o Patients with mild-to-moderate heart failure show modest reductions in oxygen
saturation, whereas patients with severe heart failure may have severe oxygen
desaturation, even at rest.
o Patients with mild-to-moderate heart failure may have normal oxygen saturations
at rest, but they may exhibit marked reductions in oxygen saturations during
physical exertion or recumbency, necessitating the use of continuous oxygen
until compensation either returns oxygen saturation to normal during exertion and
recumbency or on a permanent basis if oxygen desaturation during exertion
and/or recumbency exist during compensated severe heart failure.
o Pulse oximetry is useful for monitoring the patient's response to supplemental
oxygen and other therapies.
Electrocardiography
o The presence of left atrial enlargement and LV hypertrophy is sensitive (although
nonspecific) for chronic LV dysfunction.
o ECG may suggest an acute tachyarrhythmia or bradyarrhythmia as the cause of
heart failure.
o ECG may aid in the diagnosis of acute myocardial ischemia or infarction as the
cause of heart failure or may suggest the likelihood of prior myocardial infarction
or presence of coronary artery disease as the cause of heart failure.
o ECG is of limited help when an acute valvular abnormality or LV systolic
dysfunction is considered to be the cause of heart failure; however, the presence
of left bundle branch block (LBBB) on an ECG is a strong marker for diminished
LV systolic function.
Procedures
Right-sided heart catheterization
o PCWP can be measured by using a pulmonary arterial catheter (Swan-Ganz
catheter), and this helps differentiate cardiogenic causes of decompensated
heart failure from noncardiogenic causes such as ARDS, which occurs
secondary to injury to the alveolar-capillary membrane rather than to alteration in
Starling forces. A PCWP exceeding 18 mm Hg in a patient not known to have
chronically elevated left atrial pressure is indicative of cardiogenic
decompensated heart failure. In patients with chronic pulmonary capillary
hypertension, capillary wedge pressures exceeding 30 mm Hg are generally
required to overcome the pumping capacity of the lymphatics and produce
pulmonary edema.
o Large V waves may sometimes be observed in the PCWP tracing with acute
mitral regurgitation because large volumes of blood regurgitate into a poorly
compliant left atrium. This raises pulmonary venous pressure and causes acute
pulmonary edema. The pulmonary artery waveform appears falsely elevated
because of the large V wave reflected from the left atrium through the compliant
pulmonary vasculature. The Y descent of the waveform is quite rapid as the
overdistended left atrium quickly empties. Patients with long-standing mitral
regurgitation and left atrial enlargement may demonstrate much less impressive
V waves even in the setting of very significant mitral regurgitation.

Cardiogenic shock is the result of a severe depression in myocardial function.

Although many definitions for cardiogenic shock have been proposed, the
following provides a useful guideline: Cardiogenic shock is present when systolic
blood pressure is less than 80 mm Hg, the cardiac index is less than 1.8
L/min/m2, and the PCWP is greater than 18 mm Hg. This form of shock can occur
from a direct insult to the myocardium (eg, large acute myocardial infarction,
severe cardiomyopathy) or from a mechanical problem that overwhelms the
functional capacity of the myocardium (eg, acute severe mitral regurgitation,
acute ventricular septal defect). The prognosis of patients with cardiogenic shock
is poor, with in-hospital mortality rates of 50-90%.
Left-sided heart catheterization and coronary angiography
o Left-sided heart catheterization and coronary angiography should be undertaken
when the etiology of heart failure cannot be determined by clinical or noninvasive
imaging methods or when the etiology is likely to be due to acute myocardial
ischemia or myocardial infarction. Coronary angiography is particularly helpful in
patients with LV systolic dysfunction and known or suspected coronary artery
disease in whom myocardial ischemia is thought to play a dominant role in the
reduction of LV systolic function and the worsening of heart failure. As a general
rule, most patients with clinically significant CHF should undergo cardiac
catheterization to exclude the reversible causes listed above.
o Specific rationales for right- and left-sided heart catheterization include the need
to determine the etiologic significance and severity of mitral and/or aortic valvular
disease in patients with heart failure in whom the cause-effect relationship of
valvular heart disease with regard to heart failure is unclear. Furthermore, rightand left-sided heart catheterization should be performed in patients in whom
constrictive pericarditis is considered a likely cause of heart failure.
o

Staging
A classification of patients with heart disease based on the relation between symptoms
and the amount of effort required to provoke them has been developed by the NYHA.
o Class I: No limitations. Ordinary physical activity does not cause undue fatigue,
dyspnea, or palpitations.
o Class II: Slight limitation of physical activity. Such patients are comfortable at
rest. Ordinary physical activity results in fatigue, palpitations, dyspnea, or angina.
o Class III: Marked limitation of physical activity. Although patients are comfortable
at rest, less-than-ordinary activity leads to fatigue, dyspnea, palpitations, or
angina.
o Class IV: Symptomatic at rest. Symptoms of CHF are present at rest; discomfort
increases with any physical activity.
The Goldman Activity Classification of Heart Failure is based on estimated metabolic cost
of various activities, and classes correlate to NYHA classes.
o Class I: Patients can perform to completion any activity up to 7 metabolic
equivalents (METS).
o Class II: Patients can perform to completion any activity up to 5 METS of activity
but cannot perform to completion any activities equal to or more than 7 METS.
o Class III: Patients can perform to completion any activity up to 2 METS of activity
but cannot perform to completion any activities equal to or more than 5 METS.
o Class IV: Patients cannot perform to completion activities equal to or more than 2
METS.
TREATMENT
Medical Care

Medical therapy of heart failure focuses on 3 main goals: (1) preload reduction, (2) reduction of
systemic vascular resistance (afterload reduction), and (3) inhibition of both the RAAS systems
and vasoconstrictor neurohumoral factors produced by the sympathetic nervous system in
patients with heart failure. The first 2 goals provide symptomatic relief. While reducing symptoms,
inhibition of the RAAS and neurohumoral factors also results in significant reductions in morbidity
and mortality rates.
Preload reduction results in decreased pulmonary capillary hydrostatic pressure and reduction of
fluid transudation into the pulmonary interstitium and alveoli. Afterload reduction results in
increased cardiac output and improved renal perfusion, which allows for diuresis in the patient
with fluid overload. Inhibition of the RAAS and sympathetic nervous system results in favored
vasodilation and reduction of neurohumoral vasoconstrictors, thereby increasing cardiac output
and reducing blood volume and myocardial oxygen demand.
Patients with severe LV dysfunction or acute valvular disorders may present with hypotension.
These patients may not tolerate medications to reduce their preload and afterload and may
require inotropic support to maintain adequate blood pressure.
Patients who remain hypoxic despite supplemental oxygen or who demonstrate severe
respiratory distress require mechanical ventilation, in addition to maximal medical therapy.
Preload reduction
o Nitroglycerin
Nitroglycerine (NTG) is the most effective, predictable, and rapid-acting
medication available for preload reduction.
Multiple studies comparing NTG to furosemide or morphine sulfate have
demonstrated greater efficacy and safety and a faster onset of action for
NTG.
Use of sublingual NTG is associated with preload reduction within 5
minutes and some afterload reduction.
Topical NTG may be as effective as sublingual NTG in most patients with
heart failure, but it should be avoided in patients with severe LV failure
because of poor skin perfusion (manifesting as skin pallor or mottling)
and resultant poor absorption.
Intravenous NTG at higher dosages provides rapid and titratable preload
and afterload reduction and has been demonstrated to be an excellent
single-agent therapy for patients with severe decompensated CHF.
o Loop diuretics
Loop diuretics are the cornerstone of heart failure treatment and have
been considered as such for many decades. Furosemide is most
commonly used. Bumetanide has a higher bioavailability and may be
more effective in patients with severe CHF.
Loop diuretics are presumed to decrease preload through 2
mechanisms: diuresis and direct pulmonary artery vasodilation and
venodilation.
In most patients, diuresis does not occur for at least 20-90 minutes; thus,
the effect is delayed.
In some patients with heart failure, particularly those with diastolic heart
failure who are minimally fluid overloaded, continued diuretic use after
resolution of acute symptoms may be associated with adverse outcomes,
including electrolyte derangements and hypotension.
Use of medications that decrease preload (eg, NTG) and afterload (eg,
ACE inhibitors), either concomitantly or before the administration of loop
diuretics, can prevent potential adverse hemodynamic changes.
o Potassium-sparing diuretics
Numerous studies have shown spironolactone to be as beneficial in the
management of CHF as loop diuretics.
Some of the beneficial effects of spironolactone may be due to its
neurohormonal actions.

Morphine sulfate
Morphine sulfate use in acute CHF for preload reduction has been
commonplace for many years.
Use should be weighed against potential adverse effects (eg,
nausea/vomiting, local or systemic allergic reactions, respiratory
depression) that may outweigh any potential benefit, especially given the
availability of much more effective medications for preload reduction (eg,
NTG).
Any beneficial hemodynamic effect probably is due to anxiolysis, with a
resulting decrease in catecholamine production and systemic vascular
resistance.
Vasodilators (combined afterload and preload reducers)
o ACE inhibitors
Although initial studies focused on the efficacy of ACE inhibitors in the
treatment of chronic CHF, recent studies have demonstrated excellent
results for treatment of acute decompensated CHF.
Studies demonstrate that the use of ACE inhibitors in acute heart failure
is associated with reduced admission rates to ICUs and decreased
endotracheal intubation rates.
Hemodynamic effects of ACE inhibitors include reduced afterload,
improved stroke volume and cardiac output, and reduced preload.
ACE inhibitors must be initiated with extreme care in individuals
presenting with borderline hemodynamic parameters.
When administered by intravenous (enalapril 1.25 mg) or sublingual
routes, hemodynamic and subjective improvements are noted within 10
minutes; improvements occur more slowly with the oral route.
ACE inhibitors prolong survival in heart failure. Furthermore, compared to
the combination of hydralazine and long-acting nitrates, ACE inhibitors
showed a trend to a greater prolongation of survival, had improved
hemodynamics, and were better tolerated.
o Ang II receptor inhibitors
Ang receptor inhibitors, such as losartan and candesartan, are highly
recommended alternatives to ACE inhibitors in patients who cannot
tolerate ACE inhibitors because of adverse effects, most notably,
coughing.
Furthermore, these agents have gained wider use based on their low
adverse effect profile and early study findings, which indicated that
combined ACE inhibition and Ang II receptor inhibition is beneficial.
o Hydralazine
Hydralazine was the first oral balanced (afterload and preload reduction)
vasodilator and was popular before the availability of ACE inhibitors. It is
a direct vasodilator, unlike ACE inhibitors or Ang receptor inhibitors,
which are vasodilators through inhibition of the RAAS system.
When combined with long-acting nitrates, hydralazine was shown, in the
Veterans Administration Heart Failure Trial (VHEFT) studies, to prolong
survival in patients with CHF.
Hydralazine has one main advantage over ACE inhibitors in that it is safe
in pregnancy. It also is not known to worsen renal function in patients
with heart failure who have reduced renal function and is not associated
with the risk of hyperkalemia. Additionally, hydralazine use is
recommended in patients who cannot tolerate ACE inhibitors.
Hydralazine, as a single agent, has less reduction in myocardial oxygen
demand than ACE inhibitors because of a slight increase in heart rate
that usually results from its use.
o

Nitroprusside
Nitroprusside results in simultaneous preload and afterload reduction
through direct smooth muscle relaxation, although it has a greater effect
on afterload.
Afterload reduction is associated with increased cardiac output.
Potency and rapidity of onset and offset of effect make this an ideal
medication for patients who are critically ill.
It may induce precipitous falls in blood pressure; intraarterial blood
pressure monitoring often is recommended.
Use nitroprusside cautiously in the setting of acute myocardial infarction
because of its potential to induce hypotension.
If nitroprusside is used, convert patients to oral or alternative intravenous
vasodilator therapy as soon as possible because prolonged use is
associated with thiocyanate toxicity.
Use in pregnancy is associated with fetal thiocyanate toxicity.
Inotropic support
o Digoxin (cardiac glycoside)
Digoxin has been a cornerstone for the treatment of heart failure for
decades and is the only oral inotropic support agent currently used in
clinical practice.
Digoxin acts by inhibiting the Na+/K+ATPase transport pump and inhibits
sodium and potassium transport across cell membranes. This increases
the velocity and shortening of cardiac muscle, resulting in a shift upward
and to the left of the ventricular function (Frank-Starling) curve relating
stroke volume to filling volume or pressure. This occurs in healthy as well
as failing myocardium and in atrial as well as ventricular muscle. The
positive inotropic effect is due to an increase in the availability of
cytosolic calcium during systole, thus increasing the velocity and extent
of myocardial sarcomere shortening.
No evidence indicates that digoxin affects peripheral vascular resistance
or systemic blood pressure.
All evidence suggests that digoxin provides, even in the short term, a
moderate and metabolically efficient positive inotropic effect, an
important consideration in ischemic cardiomyopathies.
Although the incidence and severity of digitalis intoxication is decreasing,
vigilance for this important complication of therapy is essential. Drugs
that interact with digoxin are numerous and include amiodarone,
propafenone, quinidine, verapamil, nifedipine, diltiazem, levothyroxine,
cyclosporine, flecainide, disopyramide, omeprazole, tetracycline, and
erythromycin. These agents affect clearance or absorption of digoxin,
thus necessitating dose alteration of digoxin in patients taking these
medications. Furthermore, patients with renal insufficiency may need to
have their digoxin dose adjusted downward to avoid digitalis intoxication.
Numerous studies confirm that digoxin does not prolong survival in
patients with systolic heart failure, but it is associated with reduced
hospital admissions, improved functional class, reduced symptoms of
heart failure, and improved quality of life.
Digoxin is also an effective agent against atrial tachyarrhythmias at rest
in patients with LV dysfunction, but it has limited efficacy in controlling the
ventricular rate of atrial arrhythmias during exertion.
o Dobutamine (sympathomimetic agent)
Dobutamine mainly serves as a beta1-receptor agonist, although it has
some beta2-receptor and minimal alpha-receptor activity.
o

Intravenous dobutamine induces significant positive inotropic effects with

mild chronotropic effects. It also induces mild peripheral vasodilation
(decrease in afterload).
The combination effect of increased inotropy with decreased afterload
results in a significant increase in cardiac output.
Combination use with intravenous NTG may be ideal for patients with
myocardial infarction and decompensated heart failure and mild
hypotension in order to provide simultaneous preload reduction with
increased cardiac output. In the setting of acute myocardial infarction,
dobutamine use could increase infarct size because of the increase in
myocardial oxygen consumption that may ensue.
In general, avoid dobutamine in patients with moderate or severe
hypotension (eg, systolic blood pressure <80 mm Hg) because of the
peripheral vasodilation.
Dopamine (sympathomimetic agent)
Vascular and myocardial receptor effects are dose dependent.
Low dosages (0.5-3 mcg/kg/min) cause stimulation of dopaminergic
receptors within the renal and splanchnic vascular beds, causing
vasodilation and increased diuresis.
Moderate dosages (3-10 mcg/kg/min) cause stimulation of betareceptors in the myocardium, resulting in increased cardiac contractility
and heart rate.
High dosages (10-20 mcg/kg/min) cause stimulation of alpha-receptors,
resulting in peripheral vasoconstriction (increased afterload), increased
blood pressure, and no further improvement in cardiac output.
As with other inotropic agents, moderate and high dosages are
arrhythmogenic and also result in increased myocardial oxygen demand
(potential for myocardial ischemia); therefore, use dopamine only in
patients with heart failure who cannot tolerate the use of dobutamine
because of severe hypotension (eg, systolic blood pressure <60-80 mm
Hg).
NE (sympathomimetic agent)
NE primarily stimulates alpha-receptors, resulting in significant increases
in afterload (and potential myocardial ischemia) and reduced cardiac
output.
Use of NE is generally reserved for patients with profound hypotension
(eg, systolic blood pressure <60 mm Hg). Once blood pressure is
restored, add other medications to maintain cardiac output.
Phosphodiesterase inhibitors (milrinone, amrinone)
Phosphodiesterase inhibitors (PDIs) increase intracellular cAMP, which
results in a positive inotropic effect on the myocardium and peripheral
vasodilation (decreased afterload) and a reduction in pulmonary vascular
resistance (decreased preload).
PDIs, unlike catecholamine inotropes, are not dependent on
adrenoreceptor activity; therefore, patients are less likely to develop
tolerance to these medications. Tolerance to catecholamine inotropes
can develop rapidly through down-regulation of the adrenoreceptors.
PDIs are less likely than catecholamine inotropes to cause adverse
effects that are typically associated with adrenoreceptor activity (eg,
increased myocardial oxygen demand, myocardial ischemia).
Several studies directly comparing the use of PDIs (milrinone, amrinone)
to dobutamine in patients with heart failure have demonstrated that
milrinone produced equal or greater improvements in stroke volume,
cardiac output, PCWPs (preload), and systemic vascular resistance

(afterload). They are also associated with less tachycardia and

myocardial oxygen consumption. However, PDIs have been associated
with a significantly greater incidence of adverse events (eg,
tachyarrhythmias) than has dobutamine.
At present, oral PDIs have no role. Their use was associated with a 53%
increase in mortality rates in patients with NYHA Class IV heart failure in
the Prospective Randomized Milrinone Survival Evaluation (PROMISE)
trial, prompting an early termination of that study.
Unfavorable results were also evident in a smaller trial that compared
oral milrinone to digoxin or placebo. Furthermore, sustained
hemodynamic improvement with oral milrinone was lacking, and the
incidence of adverse events, particularly cardiac arrhythmias, was
greater.
Beta-adrenergic blocking agents (metoprolol, carvedilol)
o A large and increasing body of evidence indicates that these agents improve
symptoms, exercise tolerance, cardiac hemodynamics, and LV ejection fraction
and that they decrease mortality rates in patients with heart failure, particularly
those with both ischemic and idiopathic cardiomyopathy.
o A growing body of evidence suggests that long-term beta-adrenergic antagonist
administration improves cardiac function, reduces myocardial ischemia, improves
ventricular-arterial coupling, and decreases myocardial oxygen consumption.
These agents may also reduce the incidence of sudden death due to primary
ventricular arrhythmias in patients with heart failure, although this latter benefit
has yet to be definitively proven.
o Detectable improvements in ventricular function are usually not apparent for a
minimum of 1-3 months, and longer-term structural changes, such as a decline in
ventricular volume or mass, may take 12-18 months.
o Beta-adrenergic antagonists with vasodilator activity, such as carvedilol and
labetalol, have the added benefit of further afterload reduction because of arterial
vasodilation from alpha1-receptor blockade.
Treatment of heart failure with predominant diastolic dysfunction: The therapeutic
approach to diastolic dysfunction has 2 major components. The first involves attempts to
reverse the abnormal cardiac diastolic properties. The second is directed toward reducing
LV filling pressure and thereby venous congestion.
o Treatment of diastolic dysfunction
Pericardiectomy for constrictive pericarditis
Relief of ventricular systolic overload
o ACE inhibitors and Ang receptor inhibitors slow, arrest, or even reverse
myocardial fibrosis in the presence of systolic overload, thus improving diastolic
dysfunction.
o Anti-ischemic agents, such as beta-adrenergic blocking agents, calcium channel
blocking agents, and nitroglycerin, are effective in immediately improving diastolic
dysfunction in patients with coronary artery disease by eliminating or reducing
myocardial ischemia, thus improving ventricular relaxation. Thrombolysis,
mechanical revascularization (percutaneous transluminal coronary angioplasty
[PTCA]), and coronary artery bypass graft surgery (CABGS), in combination with
anti-ischemic agents or alone, all improve diastolic function in patients with acute
and chronic myocardial ischemia by improving ventricular relaxation.
o Calcium channel antagonists, especially verapamil, accelerate ventricular
relaxation, particularly in patients with hypertensive heart disease and
hypertrophic cardiomyopathy, and are useful in the treatment of diastolic
dysfunction.
o Regression of ventricular hypertrophy

Aggressive control of hypertension with beta-adrenergic blocking agents, calcium

channel blocking agents, diuretics, ACE inhibitors, Ang receptor inhibitors, and centralacting antihypertensive agents (eg, methyldopa) reduces ventricular hypertrophy, thereby
improving diastolic function.
Aortic valve replacement for aortic stenosis also reduces ventricular hypertrophy and
improves diastolic function.
Relief of valvular, supravalvular, and subvalvular obstruction to ventricular outflow by
operation or balloon valvuloplasty improves diastolic function by relieving ventricular
pressure overload, thus regressing ventricular hypertrophy.
Reduction of ventricular filling pressure and secondary venous congestion: These
approaches are usually highly effective in patients presenting with a CHF exacerbation
primarily caused by a diastolic dysfunction. Indeed, a hallmark of diastolic dysfunction is
the rapid improvement in response to the therapies described below.
o Restriction of dietary sodium
o Administration of diuretics and venodilators
o Administration of NTG or long-acting nitrates
o Maintenance of normal heart rate and rhythm: Digoxin has no established place
in the management of patients with predominant diastolic dysfunction and wellpreserved ventricular ejection fraction, and it could potentially have an adverse
effect in this group of patients.
Newer therapies for heart failure
Nesiritide, a recombinant BNP, is from an exciting new class of peptides that has several
unique properties.
o Nesiritide is a balanced vasodilator, slightly more venous than arterial, rapidly
improves symptoms of congestion, does not increase heart rate, decreases
myocardial oxygen demand, and is not proarrhythmic.
o Nesiritide decreases aldosterone and ET-1 release through neurohumoral
suppression, does not exhibit tachyphylaxis, and induces a mild diuresis and
natriuresis. It significantly reduces ventricular filling pressures to a greater extent
than standard care with ACE inhibitors and diuretics, even more than the
combination of ACE inhibitors, diuretics, and nitroglycerin.
o Nesiritide should be avoided in patients with systolic blood pressure of less than
80-85 mm Hg. The primary adverse event (occurring in 4% of the patients in the
Veterans Administration Medical Center [VAMC] study on nesiritide) was
hypotension.
o Nesiritide has no drug interactions with any of the other treatments used in CHF,
thus making it useful as an effective adjunct in patients with severe, acute
decompensated CHF without cardiogenic shock.
o Study results indicate that treatment with nesiritide could lead to a reduced length
of stay in the critical care unit, decreased recurrence of decompensation, and
less likelihood of rehospitalization.
Eplerenone, a selective aldosterone-blocking agent, has been shown to reduce rates of
all-cause mortality, cardiovascular mortality, and sudden cardiac death in patients with
myocardial infarction and left ventricular systolic dysfunction who are in CHF and already
being treated with a beta-blocker and an ACE inhibitor or Ang II blocker. Close monitoring
of potassium levels and appropriate dosage adjustments or use of diuretics are
necessary because a small percentage of patients taking eplerenone develop
hyperkalemia.

Surgical Care
Kantrowitz initially described intraaortic balloon pumping (IABP) in 1953, but the procedure was
first used clinically in 1969 in a patient with cardiogenic shock. Since the 1980s, IABP has been
increasingly used in various clinical situations as a lifesaving intervention to obtain hemodynamic
stabilization prior to definite therapy.

Procedure

o The intraaortic balloon pump is inserted percutaneously via the femoral artery
using a modified Seldinger technique. The distal end of the pump is placed just
distal to the aortic knob and the origin of left subclavian artery.
o Fluoroscopy may be used for correct positioning of the balloon, and a
subsequent chest radiograph should be obtained to document satisfactory
balloon placement.
Proper timing of IABP for optimal hemodynamic support
o Proper timing of counterpulsation is necessary for maximum hemodynamic
support. The timings of balloon inflation and deflation are best evaluated and
adjusted at a pump frequency of 1:2.
o Inflation of the balloon should occur in early diastole, just after aortic valve
closure, and should correspond to the dicrotic notch of the aortic pressure
waveform. Balloon deflation should occur in early systole, just before the aortic
valve opens.
o Proper inflation leads to an assisted peak diastolic pressure higher than the
unassisted peak systolic arterial pressure. Proper deflation results in assisted
aortic end-diastolic pressure approximately 10 mm Hg lower than the unassisted
end-diastolic pressure.
o Diastolic augmentation enhances perfusion of the coronary circulation and
carotid arteries. The reduction in end-diastolic pressure decreases aortic
impedance (afterload) and augments systole.
o IABP reduces aortic impedance and systolic pressure, leading to a 15-25%
reduction in LV wall stress. This level of afterload reduction improves LV volume,
LV emptying, and myocardial oxygen consumption.
o Diastolic aortic pressure augmentation enhances myocardial perfusion and
coronary blood flow. The effects on coronary blood flow may be variable but
generally range from a boost of 10-20% in ischemic territories.
o IABP can decrease LV filling pressures by 20-25% and can improve cardiac
output by 20% in patients with cardiogenic shock; therefore, IABP reduces
myocardial oxygen demand significantly, although the beneficial effect of
increased oxygen supply to the myocardium may also occur in some clinical
situations.
Indications for IABP
o IABP is very effective in providing temporary support to patients in cardiogenic
shock while definite therapies such as angioplasty or cardiac bypass surgery are
undertaken. At most institutions, IABP is generally considered to be a bridge to a
definite revascularization procedure or to implementation of an LV assist device.
o IABP is effective in stabilizing patients with unstable angina refractory to medical
therapy prior to a definitive revascularization procedure.
o IABP may be a lifesaving intervention in patients with acute mitral regurgitation
secondary to papillary muscle ischemia, infarction, and other causes such as
infectious endocarditis or myxomatous degeneration. IABP reduces afterload
(thereby reducing the severity of mitral regurgitation), enhances forward cardiac
output, reduces left atrial pressure, and improves pulmonary edema.
o IAPB is used to stabilize patients, which allows time to plan the definitive surgical
procedure in patients who are hemodynamically unstable.
o IABP could also provide hemodynamic support in the perioperative and
postoperative period.
Contraindications and complications
o The absolute contraindications for IABP counterpulsation are aortic dissection,
severe aortic regurgitation, presence of a large arteriovenous shunt, and severe
coagulopathy.

The relative contraindications are severe peripheral vascular disease, recent

thrombolytic therapy, and bleeding diathesis.
o IABP can cause several complications that should be monitored while the patient
is maintained on IABP support. Generally, a mild reduction in platelet counts
occurs; however, these usually do not fall below 100,000/L
o Complications may occur during cannulation of the femoral artery and include
perforation, laceration, or dissection of the artery (1-6%). Thrombosis of the
iliofemoral artery and distal emboli may also occur (1-7%), and limb ischemia has
been reported in up to 40% of patients. The limb ischemia is reversible upon
removing the intraaortic balloon pump unless thrombosis has developed, which
requires embolectomy to save the limb.
o The other complications are localized bleeding (3-5%), infection (2-4%),
thrombocytopenia ( <1%), and intestinal ischemia ( <1%).
Ventricular assist device: This is generally considered a short-term therapy (eg, acute
myocarditis) or bridge to transplant, though a recent study suggested improved survival
when used long term.
Biventricular pacing (cardiac resynchronization): A new therapy, biventricular pacing may
improve left ventricular pumping efficacy in patients with relatively severe cardiomyopathy
and wide QRS complex.
Cardiac transplantation
o

Consultations
Consultation with subspecialists depends on the underlying cause of CHF. Heart failure is now an
area of subspecialization within cardiology.
If the acute episode is attributed to an acute myocardial infarction, acute cardiac
ischemia, or acute dysrhythmia, consultation with a cardiologist is warranted.
If the episode is attributed to fluid overload in patients with renal failure, consultation with
a nephrologist is indicated for emergent/urgent hemodialysis.
If heart failure results from acute valvular dysfunction, consultation with a cardiothoracic
surgeon and a cardiologist for urgent valve replacement may be indicated, depending on
the integrity of the valve involved.
In patients who develop cardiogenic shock, consultation with a cardiologist is generally
indicated in order to rapidly diagnose and aggressively treat with various modalities
(pharmacologic and/or mechanical), to maximize cardiac performance and improve
hemodynamics, and, in some cases, to place an intraaortic balloon pump to serve as a
temporizing measure prior to surgery (ie, for valve replacement or coronary
revascularization).
Diet
Patients admitted with heart failure or pulmonary edema should maintain a low-salt diet in order
to minimize fluid overload. Monitor fluid balance closely.
Activity
Patients with decompensated heart failure should be placed on complete bed rest until
their decompensation is resolved. This is necessary to maximally reduce myocardial
oxygen demand and to avoid exacerbation of the abnormal hemodynamics and
symptoms of heart failure.
Once the patient with heart failure has been stabilized, activity should be gradually and
progressively increased. Emphasize the importance of cardiac rehabilitation to all
patients with heart failure who require improved cardiac fitness. Encourage patients to
exercise daily for at least 20-30 minutes in a low-intensity, endurance-enhancing activity
such as walking, biking, or swimming. Regular exercise improves the quality of life for
these patients and improves efficiency of oxygen utilization at the tissue level, thus

reducing the workload of the heart in the role of oxygen delivery to end organs and
muscles.
MEDICATION
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Drug Category: Human B-type natriuretic peptides (hBNPs)
Dilate veins and arteries. Used in the treatment of acute severe CHF.
Drug Name

Nesiritide (Natrecor)

Description

Recombinant DNA form of hBNP, which dilates veins and arteries.

hBNP binds to particulate guanylate cyclase receptor of vascular
smooth muscle and endothelial cells. Binding to receptor causes
increase in cGMP, which serves as second messenger to dilate veins
and arteries. Reduces PCWP and improves dyspnea in patients with
acutely decompensated CHF.

Adult Dose

2 mcg/kg IV bolus over 60 sec; follow by 0.01 mcg/kg/min continuous

infusion; bolus volume (mL) = 0.33 X patient weight (kg); infusion flow
rate of bolus (mL/h) = 0.1 X patient weight (kg)

Pediatric Dose

Not established

Documented hypersensitivity; systolic blood pressure <90 mm Hg;

patients suspected of having or known to have low cardiac filling
Contraindications pressures, severe aortic or mitral stenosis, restrictive or obstructive
cardiomyopathy, constrictive pericarditis, pericardial tamponade,
conditions in which cardiac output is dependent upon venous return
Interactions

Concurrent administration with ACE inhibitors and other vasodilators

may cause hypotension

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Do not initiate at dose higher than recommended; may affect renal

function in patients whose renal function may depend on activity of
RAAS; may cause hypotension (administer in settings where blood
pressure can be monitored closely); discontinue drug if hypotension
develops; VT, nonsustained VT, headache, abdominal pain, back
pain, insomnia, anxiety, angina pectoris, nausea, and vomiting may
occur

Drug Category: Diuretics

May improve symptoms of venous congestion through elimination of retained fluid and preload
reduction. Used in CHF. Help counteract the sodium and water retention caused by activation of
the RAAS.
Drug Name

Furosemide (Lasix); Bumetanide (Bumex); Torsemide (Demadex)

Description

Increase excretion of water by interfering with chloride-binding

cotransport system, which in turn inhibits sodium and chloride
reabsorption in ascending loop of Henle and distal renal tubule.
Bumetanide does not appear to act in the distal renal tubule. Dose
must be individualized to patient. Depending on response, administer
at small dose increments until desired diuresis occurs.

Adult Dose

Furosemide: 20-80 mg/d PO/IV/IM; titrate up to 600 mg/d for severe

edematous states; depending on response, administer at increments
of 20-40 mg no sooner than 6-8 h after previous dose

Bumetanide: 0.5-2 mg/dose PO 1-2 times/d; titrate dose upward until

desired diuretic effect reached; not to exceed 10 mg/d; alternatively,
0.5-1 mg/dose IV/IM; not to exceed 10 mg/d
Torsemide: 10-20 mg PO/IV qd; not to exceed 200 mg/d; titrate dose
upward by approximately doubling the dose until desired diuretic
effect reached; doses >200 mg/d not adequately studied
Pediatric Dose

Contraindications

Furosemide: 1-2 mg/kg/dose PO; not to exceed 6 mg/kg/dose; not to

administer more frequently than q6h
Bumetanide: Not established
Torsemide: Not established
Documented hypersensitivity; hepatic coma, anuria, increasing
anuria, and state of severe electrolyte depletion

Interactions

Potential for salicylate toxicity in patients on high doses of salicylates

and loop diuretics significant (salicylates and loop diuretics compete
for secretion by renal tubules); NSAIDs may decrease efficacy of loop
diuretics; loop diuretics increase potential for lithium toxicity;
simultaneous use of loop diuretics and cholestyramine not
recommended as cholestyramine decreases absorption of loop
diuretics; probenecid decreases effect loop diuretics;
coadministration with aminoglycosides may increase ototoxicity;
enzyme inducers, including phenytoin, carbamazepine, and
phenobarbital, may reduce efficacy of loop diuretics; hypotensive
effects of ACE inhibitors may increase when administered
concomitantly with loop diuretics; arrhythmias may occur in patients
taking digoxin if diuretic-induced electrolyte disturbances occur

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Torsemide is pregnancy category B; perform frequent serum

electrolyte, CO2, glucose, creatinine, uric acid, calcium, and BUN
determinations during first few months of therapy and periodically
thereafter; profound diuresis with fluid and electrolyte loss may occur;
caution in hepatic failure

Drug Name

Spironolactone (Aldactone)

Description

For management of edema resulting from excessive aldosterone

excretion. Competes with aldosterone for receptor sites in distal renal
tubules, increasing water excretion while retaining potassium and
hydrogen ions.

Adult Dose

25-200 mg/d PO qd or divided bid

Pediatric Dose

1.5-3.5 mg/kg/d PO qd or divided qid

Contraindications Documented hypersensitivity; anuria, renal failure, hyperkalemia

Interactions

May decrease effect of anticoagulants; potassium and potassiumsparing diuretics may increase toxicity of spironolactone

Pregnancy

D - Unsafe in pregnancy

Precautions

Caution in renal and hepatic impairment

Drug Category: Angiotensin receptor blockers

Interfere with the binding of formed Ang II to its endogenous receptor. Used primarily when
patients are intolerant of ACE inhibitors because of adverse effects but are gaining wider use as
first-line vasodilator agents. Equally effective as ACE inhibitors.
Drug Name

Losartan (Cozaar); Candesartan (Atacand); Valsartan (Diovan)

Description

Block the vasoconstrictor and aldosterone-secreting effects of Ang II.

May induce more complete inhibition of RAAS than ACE inhibitors, do
not affect response to BK, and are less likely to be associated with
cough and angioedema. For patients unable to tolerate ACE
inhibitors.

Adult Dose

Losartan: 25-100 mg PO qd/bid

Candesartan: 8-16 mg/d PO initially; not to exceed 32 mg/d
Valsartan: 80 mg/d PO; may increase to 160 mg/d if needed

Pediatric Dose

Not established

Contraindications Documented hypersensitivity

Interactions

Ketoconazole, sulfaphenazole, and phenobarbital may decrease

effects; cimetidine may increase effects of losartan and candesartan

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Category D in second and third trimesters of pregnancy; caution in

renal impairment (serum creatinine >3.5), severe aortic stenosis,
unilateral or bilateral renal artery stenosis or severe CHF; watch for
serum potassium

Drug Category: ACE inhibitors

Inhibit renal systemic and tissue generation of Ang II by ACE; decrease metabolism of bradykinin
(BK). Their blockade of Ang II and the delayed clearance of BK by ACE blocks the direct
vasoconstriction of Ang II, as well as the activation of the sympathetic nervous system, and
promotes arterial and venous dilation. In addition, ACE inhibitors reduce intracavitary pressures
and diminish Wass stress, thereby decreasing myocardial oxygen demand. They inhibit the
release of aldosterone, thereby reducing intravascular volume and preload. Among vasodilators,
the ACE inhibitors are the most balanced vasodilators, having an equal effect on reducing both
afterload and preload.
Drug Name

Captopril (Capoten); Enalapril (Vasotec); Quinapril (Accupril)

Description

Lisinopril (Prinivil, Zestril); Ramipril (Altace); Fosinopril (Monopril)-Prevent conversion of Ang I to Ang II (a potent vasoconstrictor),
resulting in increased levels of plasma renin and a reduction in
aldosterone secretion.

Adult Dose

Captopril: 6.25-12.5 mg PO tid; not to exceed 150 mg tid

Enalapril: 2.5-5 mg/d PO (increase as necessary); dosing range: 1040 mg/d PO in 1-2 divided doses; alternatively, 1.25 mg/dose IV over
5 min q6h
Quinapril: 10 mg PO qd
Lisinopril: 10 mg/d PO qd or divided bid; increase by 5-10 mg/d at 1to 2-wk intervals; not to exceed 80 mg/d
Ramipril: 2.5 mg PO bid initially; titrate up to 5 mg bid when possible
Fosinopril: 10 mg/d PO initially; may increase to 20-40 mg/d qd or
divided bid

Pediatric Dose

Not established

Contraindications Documented hypersensitivity; renal impairment, angioedema

Interactions

NSAIDs may reduce hypotensive effects of ACE inhibitors; ACE

inhibitors may increase digoxin, lithium, and allopurinol levels;
rifampin decreases ACE inhibitor levels; probenecid may increase
ACE inhibitor levels; hypotensive effects of ACE inhibitors may be
enhanced when concurrently administered with diuretics

Pregnancy

D - Unsafe in pregnancy

Precautions

Category D in second and third trimester of pregnancy; caution in

renal impairment, valvular stenosis, or severe CHF

Drug Category: Vasodilators

The use of a vasodilators reduces SVR, thus allowing more forward flow and improving cardiac
output. Indicated for CHF.
Drug Name

Nitroglycerin (Nitrostat, Deponit, Transderm-Nitro Patch)

Description

Isosorbide dinitrate (Isordil), Isosorbide mononitrate (Imdur)--First-line

therapy for patients who are not hypotensive. Provides excellent and
reliable preload reduction. Higher doses provide mild afterload
reduction. Has rapid onset and offset (both within minutes), allowing
rapid clinical effects and rapid discontinuation of effects in adverse
clinical situations.

Adult Dose

Nitroglycerin
Topical: Apply topically 1/2-2" q6h
Transdermal: 0.3-0.6 mg/h qd
Intravenous: 0.2-10 mcg/kg/min IV infusion; titrate by 10 mcg/min
increments until desired hemodynamic effect achieved or until
maximally tolerated dose reached
Spray: Single spray (0.4 mg), which is equivalent to single 1/150
sublingual; dose may be repeated q3-5min as hemodynamics permit,
up to maximum of 1.2 mg
Isosorbide dinitrate: 10-80 mg PO bid/qid
Isosorbide mononitrate: 30-90 PO mg qd

Pediatric Dose

Not established

Documented sensitivity; hypotension; severe anemia; shock; postural

Contraindications hypotension; head trauma; closed-angle glaucoma; cerebral
hemorrhage

Interactions

Sildenafil (Viagra) taken within 24 h may induce precipitous and

potentially lethal decreases in blood pressure; aspirin may increase
nitrate serum concentrations; marked symptomatic orthostatic
hypotension may occur with coadministration of calcium channel
blockers (dose adjustment of either agent may be necessary)

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Extreme caution in right ventricle infarction because of importance of

adequate preload in maintaining cardiac output; caution in patients
with severe aortic stenosis because of needed adequate preload to
maintain cardiac output

Drug Name

Hydralazine (Apresoline)

Description

Decreases systemic resistance through direct vasodilation of

arterioles.

Adult Dose

10-25 mg PO tid/qid initially; adjust dose based on individual

response; typical dose range is 200-600 mg PO qd in 2-4 divided
doses

Pediatric Dose

Not established

Contraindications Documented hypersensitivity; mitral valve rheumatic heart disease

Interactions

MAOIs and beta-blockers may increase hydralazine toxicity;

pharmacologic effects of hydralazine may be decreased by
indomethacin

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Hydralazine has been implicated in myocardial infarction; caution in

suspected coronary artery disease

Drug Name

Isosorbide dinitrate and hydralazine (BiDil)

Description

Fixed-dose combination of isosorbide dinitrate (20 mg/tab), a

vasodilator with effects on both arteries and veins, and hydralazine
(37.5 mg/tab), a predominantly arterial vasodilator. Indicated for heart
failure in black patients, based in part on results from the African
American Heart Failure Trial. Two previous trials in the general
population of patients with severe heart failure found no benefit but
suggested a benefit in black patients. Compared with placebo, black
patients showed a 43% reduction in mortality rate, a 39% decrease in
hospitalization rate, and a decrease in symptoms from heart failure.

Adult Dose

1 tab PO tid; may titrate upward, not to exceed 2 tab tid

Pediatric Dose

Not established

Contraindications Documented hypersensitivity; allergy to organic nitrates

Interactions

Hydralazine may increase propranolol, metoprolol, and lisinopril AUC

and Cmax; isosorbide dinitrate may cause additive vasodilating effects
with other vasodilators (eg, sildenafil [Viagra], vardenafil [Levitra]),
especially when coadministered with alcohol

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

May cause symptomatic hypotension even with small doses; careful

hemodynamic monitoring required if administered in patients with
acute MI
Hydralazine: May cause SLE-like symptoms, including
glomerulonephritis, tachycardia, hypotension, and peripheral neuritis
(pyridoxine therapy may be required)
Isosorbide dinitrate: If hypotension exists, may aggravate angina
associated with hypertrophic cardiomyopathy

Drug Name

Nitroprusside (Nitropress)

Description

Produces vasodilation and increases inotropic activity of the heart. At

higher dosages, may exacerbate myocardial ischemia by increasing
heart rate.

Adult Dose

Begin infusion at 0.3-0.5 mcg/kg/min IV and use increments of 0.5

mcg/kg/min; titrate to desired effect; average dose is 1-6 mcg/kg/min
Infusion rates >10 mcg/kg/min IV may lead to cyanide toxicity

Pediatric Dose

Administer as in adults

Documented hypersensitivity; subaortic stenosis, decreased cerebral

perfusion, arteriovenous shunt or coarctation of aorta (eg,
Contraindications
compensatory hypertension); relatively contraindicated in atrial
fibrillation or flutter with rapid ventricular rate
Interactions

Effects are additive when administered with other hypotensive agents

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Caution in increased intracranial pressure, hepatic failure, severe

renal impairment, and hypothyroidism; in renal or hepatic
insufficiency, nitroprusside levels may increase and can cause
cyanide toxicity; sodium nitroprusside has ability to lower blood
pressure and thus should be used only in those patients with mean

arterial pressures >70 mm Hg

Drug Category: Inotropic agents
Augment both coronary and cerebral blood flow present during the low flow states. Used in
severe acute CHF with low cardiac output.
Drug Name

Digoxin (Lanoxin, Lanoxicaps)

Description

Cardiac glycoside with direct inotropic effects in addition to indirect

effects on cardiovascular system. Acts directly on cardiac muscle,
increasing myocardial systolic contractions. Indirect actions result in
increased carotid sinus nerve activity and enhanced sympathetic
withdrawal for any given increase in mean arterial pressure.

Adult Dose

0.125-0.375 mg PO qd

Pediatric Dose

Not established

Documented hypersensitivity; beriberi heart disease, idiopathic

Contraindications hypertrophic subaortic stenosis, constrictive pericarditis, and carotid
sinus syndrome

Interactions

IV calcium may produce arrhythmias in digitalized patients;

medications that may increase digoxin levels include alprazolam,
benzodiazepines, bepridil, captopril, cyclosporine, propafenone,
propantheline, quinidine, diltiazem, aminoglycosides, oral
amiodarone, anticholinergics, diphenoxylate, erythromycin,
felodipine, flecainide, hydroxychloroquine, itraconazole, nifedipine,
omeprazole, quinine, ibuprofen, indomethacin, esmolol, tetracycline,
tolbutamide, and verapamil; medications that may decrease serum
digoxin levels include aminoglutethimide, antihistamines,
cholestyramine, neomycin, penicillamine, aminoglycosides, oral
colestipol, hydantoins, hypoglycemic agents, antineoplastic treatment
combinations (including carmustine, bleomycin, methotrexate,
cytarabine, doxorubicin, cyclophosphamide, vincristine,
procarbazine), aluminum or magnesium antacids, rifampin,
sucralfate, sulfasalazine, barbiturates, kaolin/pectin, and
aminosalicylic acid

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Hypokalemia may reduce positive inotropic effect of digitalis;

hypercalcemia predisposes patient to digitalis toxicity, and
hypocalcemia can make digoxin ineffective until serum calcium levels
are normal; magnesium replacement therapy must be instituted in
patients with hypomagnesemia to prevent digitalis toxicity; patients
diagnosed with incomplete AV block may progress to complete block
when treated with digoxin; exercise caution in hypothyroidism,
hypoxia, and acute myocarditis; adjust dose in renal impairment;
highly toxic (overdoses can be fatal)

Drug Name

Dobutamine (Dobutrex)

Description

Produces vasodilation and increases inotropic state. At higher

dosages may cause increased heart rate, exacerbating myocardial
ischemia.

Adult Dose

0.5 mcg/kg/min IV initially; titrate until desired therapeutic effect

attained

Pediatric Dose

Administer as in adults

Contraindications Documented hypersensitivity; idiopathic hypertrophic subaortic

stenosis and atrial fibrillation or flutter

Interactions

Beta-adrenergic blockers antagonize effects of dobutamine; general

anesthetics may increase toxicity

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Following a myocardial infarction use with extreme caution;

hypovolemic state should be corrected before using this drug

Drug Name

Dopamine (Intropin)

Description

Naturally occurring catecholamine that acts as a precursor to NE.

Stimulates both adrenergic and dopaminergic receptors.
Hemodynamic effect is dose-dependent. Low-dose use is associated
with dilation within renal and splanchnic vasculature, resulting in
enhanced diuresis. Moderate doses enhance cardiac contractility and
heart rate. Higher doses cause increased afterload through
peripheral vasoconstriction.
Administer by continuous IV infusion. Usually used in severe heart
failure. Reserved for patients with moderate hypotension (eg, systolic
blood pressure 70-90 mm Hg). Typically, moderate or higher doses
used.

Adult Dose

5 mcg/kg/min IV continuous infusion initially; titrate to blood pressure

stabilization; not to exceed 20 mcg/kg/min

Pediatric Dose
Contraindications

Not established
Documented hypersensitivity; pheochromocytoma; ventricular
fibrillation; obstructive hypertrophic cardiomyopathy

Interactions

Phenytoin, alpha- and beta-adrenergic blockers, general anesthesia,

and MAOIs increase and prolong effects of dopamine

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Monitor urine flow, cardiac output, pulmonary wedge pressure, and

blood pressure closely during infusion; prior to infusion, correct
hypovolemia with either whole blood or plasma as indicated;
monitoring central venous pressure or LV filling pressure may be
helpful in detecting and treating hypovolemia; 10- to 20-mcg/kg/min
doses increase levels of peripheral vasoconstriction and afterload;
may increase tachyarrhythmias and cause greater myocardial oxygen
consumption and cardiac ischemia; alkaline solutions may inactivate
dopamine if administered through same IV line

Drug Name

Norepinephrine (Levophed)

Description

Naturally occurring catecholamine with potent alpha-receptor and

mild beta-receptor activity. Stimulates beta1- and alpha-adrenergic
receptors, resulting in increased cardiac muscle contractility, heart
rate, and vasoconstriction. Increases blood pressure and afterload.
Increased afterload may result in decreased cardiac output,
increased myocardial oxygen demand, and cardiac ischemia.
Generally reserved for use in patients with severe hypotension (eg,
systolic blood pressure <70 mm Hg) or hypotension unresponsive to
other medication.

Adult Dose

0.5-1 mcg/min IV infusion initially, titrated to effect; not to exceed 30

mcg/min

Pediatric Dose

Not established

Documented hypersensitivity; obstructive hypertrophic

Contraindications cardiomyopathy; peripheral or mesenteric vascular thrombosis
because ischemia may be increased and area of infarct extended
Interactions

Enhances pressor response of NE by blocking reflex bradycardia

caused by NE

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

May cause tachyarrhythmia (especially sinus tachycardia), increased

myocardial oxygen demand, and cardiac ischemia; alkaline solutions
may inactivate NE if administered through same IV line; extravasation
may cause severe tissue necrosis, (administer into a large vein); if
extravasation occurs, immediately infiltrate 5-10 mg of phentolamine
(diluted in 10-15 mL of isotonic sodium chloride solution) to prevent
necrosis; caution in occlusive vascular disease; if possible, correct
blood-volume depletion before administration

Drug Category: Phosphodiesterase enzyme inhibitors

Inhibition of type III cAMP phosphodiesterase(s) and other mechanisms. Bipyridine-positive
inotropic agents and vasodilators with little chronotropic activity. Different from both digitalis
glycosides and catecholamines in mode of action. These agents are balanced vasodilators,
having equal reduction in both afterload and preload, to same degree as ACE inhibitors.
Drug Name

Milrinone (Primacor), Amrinone (Inocor)

Description

Milrinone: Positive inotropic agent and vasodilator. Results in reduced

afterload, reduced preload, and increased cardiac output. Several
studies comparing milrinone to dobutamine have demonstrated that
milrinone showed greater improvements in preload and afterload and
improvements in cardiac output, without significant increases in
myocardial oxygen consumption.
Amrinone: Produces vasodilation and increases inotropic state. More
likely to cause tachycardia than dobutamine; may exacerbate
myocardial ischemia.

Adult Dose

Milrinone: 50 mcg/kg IV loading dose over 10 min, followed by

continuous infusion at 0.25-1.0 mcg/kg/min; titrate to maintain
adequate systolic blood pressure and cardiac output
Amrinone: 0.75 mg/kg IV bolus slowly over 2-3 min; maintenance
infusion is 5.0-10 mcg/kg/min; not to exceed 10 mg/kg; adjust dose
according to patient response; not to exceed 10 mg/kg

Pediatric Dose

Milrinone: Not established

Amrinone: Administer as in adults

Milrinone: Documented hypersensitivity; obstructive hypertrophic

Contraindications cardiomyopathy
Amrinone: Documented hypersensitivity
Interactions

Milrinone: Precipitates in presence of furosemide

Amrinone: Coadministration with diuretics may result in hypovolemia
and decrease in filling pressure; cardiac glycosides have additive
effects on amrinone

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Milrinone: Monitor fluids, electrolyte changes, and renal function

during therapy; excessive diuresis may increase potassium loss and
predispose digitalized patients to arrhythmias (correct hypokalemia
with potassium supplementation prior to treatment); slow rates or
stop infusion in patients showing excessive decreases in blood

pressure; previous vigorous diuretic therapy has caused significant

decreases in cardiac filling pressure; administer cautiously and
monitor blood pressure, heart rate, and clinical symptomatology
Amrinone: Discontinue therapy if symptoms of liver toxicity develop;
correct hypokalemic states before administering therapy
Drug Category: Beta-adrenergic blockers
Inhibit chronotropic, inotropic, and vasodilatory responses to beta-adrenergic stimulation.
Particularly useful in the patient with elevated blood pressure and relative tachycardia. Inhibits
sympathetic nervous stimulation, particularly E and NE and blocks alpha1-adrenergic
vasoconstrictor activity. Has moderate afterload reduction properties and results in slight preload
reduction as well.
Drug Name

Carvedilol (Coreg)

Description

Nonselective beta- and alpha1-adrenergic blocker. Does not appear

to have intrinsic sympathomimetic activity. May reduce cardiac output
and decrease peripheral vascular resistance.

Adult Dose

3.125 mg PO bid; maintain for 1-2 wk if tolerated and double dose

q1-4wk to maximally tolerated dose or to maximum of 50 mg bid

Pediatric Dose

Not established

Contraindications

Documented hypersensitivity; hypotension; bradycardia; AV/SA node

disease; cardiogenic shock; overt cardiac failure

Interactions

Rifampin, barbiturates, cholestyramine, colestipol, NSAIDs,

salicylates, and penicillins may decrease effects; carvedilol may
increase effects of antidiabetic agents, digoxin, and calcium channel
blockers; concurrent administration with clonidine may increase blood
pressure and decrease heart rate; carvedilol may decrease effect of
sulfonylureas; cimetidine, fluoxetine, paroxetine, and propafenone
may increase carvedilol levels

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Caution in CHF being treated with digitalis, diuretics, or ACE

inhibitors (AV conduction may be slowed); discontinue if liver
impairment occurs; caution in peripheral vascular disease,
hyperthyroidism, and diabetes mellitus

Drug Name

Metoprolol XL (Toprol)

Description

Selective beta1-adrenergic blocker at lower doses; inhibits beta2receptors at higher doses. Does not have intrinsic sympathomimetic
activity. May reduce cardiac output, but does not appear to decrease
peripheral vascular resistance to any significant degree.

Adult Dose

100 mg PO qd; titrate to maximum dose of 400 mg/d PO in 1-2

divided doses.

Pediatric Dose
Contraindications
Interactions

Not established
Documented hypersensitivity; hypotension; bradycardia; AV/SA node
disease; cardiogenic shock; overt cardiac failure
Rifampin, barbiturates, cholestyramine, colestipol, NSAIDs,
salicylates, and penicillins may decrease effects; high doses of
metoprolol XL may increase effects of antidiabetic agents, digoxin,
and calcium-channel blockers because of beta2-receptor inhibition;
concurrent administration with clonidine may increase blood pressure
and decrease heart rate; metoprolol XL may decrease effect of

sulfonylureas; cimetidine, fluoxetine, paroxetine, and propafenone

may increase levels
Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Caution in CHF being treated with digitalis, diuretics, or ACE

inhibitors (AV conduction may be slowed); discontinue if liver
impairment occurs; caution in peripheral vascular disease (at higher
doses) and hyperthyroidism

FOLLOW-UP
Further Inpatient Care
After the patient has been initially stabilized and the decompensation of heart failure has
been resolved, further inpatient care depends on the underlying cause of CHF.
Place patients with heart failure in a monitored bed to watch for acute dysrhythmias. Pay
strict attention to the patient's fluid balance by closely monitoring fluid input and output.
Maintain patients who are fluid-overloaded in negative fluid balance through the use of
diuretics, or, if necessary in patients with renal failure, hemodialysis with ultrafiltration.
Check cardiac enzymes to evaluate for myocardial infarction. Slight elevations in cardiac
enzymes can occur with decompensated heart failure in the absence of myocardial
infarction because of coronary thrombosis.
Perform coronary angiography on patients whose decompensated heart failure resulted
from an acute coronary syndrome, either unstable angina or myocardial infarction. Stress
testing can also be performed later during hospitalization to evaluate for reversible
ischemia in patients without acute coronary syndromes but who have prior symptoms of
angina or who have a high likelihood of coronary artery disease as the cause of LV
dysfunction.
Order echocardiography at the earliest possible moment to evaluate for evidence of
acute valvular dysfunction and wall motion abnormalities and to assess the patient's
systolic and diastolic function. Since the long-term therapy of patients with heart failure
differs significantly between those with predominantly systolic dysfunction and those with
predominantly diastolic dysfunction, it is absolutely essential that all patients with heart
failure have echocardiographic evaluation of cardiac function, chamber size, and valve
function.
In most patients with decompensated heart failure, oral vasodilator therapy, most
commonly ACE inhibitors, can be used as first-line therapy to reverse the cardiac
decompensation and to restore optimal cardiac function. The clinician must be extremely
cautious with vasodilator therapy only in patients with severe aortic or mitral stenosis or in
those with obstructive cardiomyopathy. Patients who required intravenous inotropic
support should be weaned off as quickly as possible and should have their vasodilator
therapy maximized quickly in order to avoid the risk of adverse cardiac events from
increased myocardial oxygen consumption leading to ischemia.
Patients in whom pulmonary edema was caused by dietary factors or medication
noncompliance need strict counseling and education to help prevent recurrence.
Further Outpatient Care
Focus further outpatient care of patients with heart failure on maximizing some or all of
the medical modalities used in their treatment. Undertake further assessment of the
clinical and hemodynamic effects of that therapy fairly soon after discharge and at regular
intervals.
Precise definition and aggressive treatment of all reversible causes for heart failure is
absolutely essential. For instance, patients with myocardial ischemia (particularly those
with reduced systolic function) should be promptly evaluated with noninvasive and/or
invasive evaluations of coronary perfusion, and they should be promptly referred for

revascularization if they are suitable candidates for such revascularization. Similarly,

patients with severe valvular disease, assessed clinically and echocardiographically,
should be promptly referred for cardiac catheterization. If a patient is a suitable candidate
for valve replacement or repair, he or she should undergo prompt surgical therapy.
Patients with nonreversible NYHA class IV heart failure who are younger than 65 years
and facing the likely prospect of death within the next 6-24 months, despite maximal
medical therapy, and who are not candidates for beneficial surgical therapy, should be
promptly referred to a cardiac transplant center for consideration of cardiac
transplantation.
Screen patients with cardiomyopathy and heart failure for candidacy for
cardioverter/defibrillator implantation because the risk of sudden death in these patients
is considerable.
In/Out Patient Meds
See Treatment and Medications.
Transfer
Transfer of patients to a tertiary receiving hospital generally is indicated if the presenting
hospital lacks adequate resources to care for such patients. Most patients with heart
failure can be well managed at community hospitals. However, if the cause of heart
failure is determined to require definitive surgery for stabilization, transfer is often
indicated. Note the following examples:

o Patients with heart failure that develops as a result of acute valvular dysfunction
requiring urgent valve replacement may require transfer to a tertiary care facility
that performs open heart surgery.
o Patients with acute myocardial infarction resulting in cardiogenic shock
hypotension may require transfer for emergency PTCA or CABGS. Thrombolysis
may be attempted at the presenting hospital, but outcome is generally poor
without angioplasty or CABGS.
o Patients with severe heart failure with hemodynamic complications should be
transferred from presenting hospitals that lack sufficient resources for, or
experience with, managing patients with heart failure who require complex
inotropic support or hemodialysis.
o Patients with NYHA class IV heart failure who are younger than 65 years and
facing the likely prospect of death within the next 6-12 months, despite maximal
medical therapy, and who are not candidates for coronary revascularization,
should be transferred to a cardiac transplant center for consideration of cardiac
transplantation if they cannot be stabilized enough to be discharged home on
maximal medical and mechanical therapy.
Complications
The major complications associated with heart failure are sudden cardiac death from
ventricular tachyarrhythmias or bradyarrhythmias and pump failure with cardiovascular
collapse. Approximately half of patients with heart failure eventually die from fatal
ventricular arrhythmias. Prompt diagnosis and treatment usually prevent this complication
in the acute setting. Prompt diagnosis of CHF and prompt treatment to reduce pulmonary
venous congestion, reduce afterload, and improve cardiac output is essential in
preventing cardiovascular and respiratory failure.
Prognosis
In general, the inpatient mortality rate for patients with heart failure is 5-20%.
Heart failure associated with acute myocardial infarction is associated with an inpatient
mortality rate of 20-40%; mortality approaches 80% in patients who are also hypotensive
(eg, cardiogenic shock).
Patient Education

To help prevent recurrence, counsel and educate patients in whom heart failure was
caused by dietary factors or medication noncompliance with regard to the importance of
proper diet and the necessity of medication compliance.
For excellent patient education resources, visit eMedicine's Heart Center, Cholesterol
Center, Diabetes Center. Also, see eMedicine's patient education articles Congestive
Heart Failure, High Cholesterol, Chest Pain, Heart Rhythm Disorders, Coronary Heart
Disease, and Heart Attack.

Congestive Heart Failure and Pulmonary Edema

Shamai Grossman, MD, MS, David FM Brown, MD
INTRODUCTION
Background: Congestive heart failure (CHF) is an imbalance in pump function in which the heart
fails to maintain the circulation of blood adequately. The most severe manifestation of CHF,
pulmonary edema, develops when this imbalance causes an increase in lung fluid secondary to
leakage from pulmonary capillaries into the interstitium and alveoli of the lung.
CHF can be categorized as forward or backward ventricular failure. Backward failure is secondary
to elevated systemic venous pressure, while left ventricular failure is secondary to reduced
forward flow into the aorta and systemic circulation. Furthermore, heart failure can be subdivided
into systolic and diastolic dysfunction. Systolic dysfunction is characterized by a dilated left
ventricle with impaired contractility, while diastolic dysfunction occurs in a normal or intact left
ventricle with impaired ability to relax and receive as well as eject blood.
The New York Heart Association's functional classification of CHF is one of the most useful. Class
I describes a patient who is not limited with normal physical activity by symptoms. Class II occurs
when ordinary physical activity results in fatigue, dyspnea, or other symptoms. Class III is
characterized by a marked limitation in normal physical activity. Class IV is defined by symptoms
at rest or with any physical activity.
Pathophysiology: CHF is summarized best as an imbalance in Starling forces or an imbalance
in the degree of end-diastolic fiber stretch proportional to the systolic mechanical work expended
in an ensuing contraction. This imbalance may be characterized as a malfunction between the
mechanisms that keep the interstitium and alveoli dry and the opposing forces that are
responsible for fluid transfer to the interstitium.
Maintenance of plasma oncotic pressure (generally about 25 mm Hg) higher than pulmonary
capillary pressure (about 7-12 mm Hg), maintenance of connective tissue and cellular barriers

relatively impermeable to plasma proteins, and maintenance of an extensive lymphatic system

are the mechanisms that keep the interstitium and alveoli dry.
Opposing forces responsible for fluid transfer to the interstitium include pulmonary capillary
pressure and plasma oncotic pressure. Under normal circumstances, when fluid is transferred
into the lung interstitium with increased lymphatic flow, no increase in interstitial volume occurs.
When the capacity of lymphatic drainage is exceeded, however, liquid accumulates in the
interstitial spaces surrounding the bronchioles and lung vasculature, thus creating CHF. When
increased fluid and pressure cause tracking into the interstitial space around the alveoli and
disruption of alveolar membrane junctions, fluid floods the alveoli and leads to pulmonary edema.
Etiologies of pulmonary edema may be placed in the following 6 categories:
1. Pulmonary edema secondary to altered capillary permeabilityincludes acute respiratory
deficiency syndrome (ARDS), infectious causes, inhaled toxins, circulating exogenous
toxins, vasoactive substances, disseminated intravascular coagulopathy (DIC),
immunologic processes reactions, uremia, near drowning, and other aspirations.
2. Pulmonary edema secondary to increased pulmonary capillary pressurecomprises
cardiac causes and noncardiac causes, including pulmonary venous thrombosis, stenosis
or veno-occlusive disease, and volume overload.
3. Pulmonary edema secondary to decreased oncotic pressure found with
hypoalbuminemia
4. Pulmonary edema secondary to lymphatic insufficiency
5. Pulmonary edema secondary to large negative pleural pressure with increased end
expiratory volume
6. Pulmonary edema secondary to mixed or unknown mechanisms including high altitude
pulmonary edema (HAPE), neurogenic pulmonary edema, heroin or other overdoses,
pulmonary embolism, eclampsia, postcardioversion, postanesthetic, postextubation, and
postcardiopulmonary bypass
This chapter is limited to cardiac causes of pulmonary edema and CHF and its relevant
emergency care.
Frequency:
In the US: More than 3 million people have CHF, and more than 400,000 new patients
present yearly. Prevalence of CHF is 1-2% of the general population.
Mortality/Morbidity:
Approximately 30-40% of patients with CHF are hospitalized every year. CHF is the
leading diagnosis-related group (DRG) among hospitalized patients older than 65 years.
The 5-year mortality rate after diagnosis was reported in 1971 as 60% in men and 45% in
women. In 1991, data from the Framingham heart study showed the 5-year mortality rate
for CHF essentially remaining unchanged, with a median survival of 3.2 years for males
and 5.4 years for females. This may be secondary to an aging US population with
declining mortality due to other diseases.
The most common cause of death is progressive heart failure, but sudden death may
account for up to 45% of all deaths. After auditing data on 4606 patients hospitalized with
CHF between 1992-1993, the total in-hospital mortality rate was 19%, with 30% of deaths
occurring from noncardiac causes.
Patients with coexisting insulin-dependent diabetes mellitus have a significantly
increased mortality rate.
Race:
African Americans are 1.5 times more likely to die of CHF than whites are. Nevertheless,
African American patients appear to have similar or lower in-hospital mortality rates than
white patients.
Sex:
Prevalence is greater in males than in females for patients aged 40-75 years.
No sex predilection exists for patients older than 75 years.
Age:

Prevalence of CHF increases with increasing age and affects about 10% of the
population older than 75 years.

CLINICAL
History:
Anxiety
Dyspnea at rest
Dyspnea on exertion has been found to be the most sensitive symptom reported, yet the
specificity for dyspnea is less than 60%.
Orthopnea and paroxysmal nocturnal dyspnea (PND) are symptoms; however, sensitivity
for orthopnea and PND is only 20-30%.
Cough productive of pink, frothy sputum is highly suggestive of CHF.
Edema
Nonspecific symptoms reported include the following:
o Weakness
o Lightheadedness
o Abdominal pain
o Malaise
o Wheezing
o Nausea
Past medical history may include the following:
o Cardiomyopathy
o Valvular heart disease
o Alcohol use
o Hypertension
o Angina
o Prior myocardial infarction
o Familial heart disease
Physical:
Findings such as peripheral edema, jugular venous distention, and tachycardia are highly
predictive of CHF. Overall specificity of physical examination has been reported at 90%;
however, this same study reported a sensitivity of only 10-30%.
Tachypnea, using accessory muscles of respiration
Hypertension
Pulsus alternans (alternating weak and strong pulse indicative of depressed left ventricle
[LV] function)
Skin may be diaphoretic or cold, gray, and cyanotic.
Jugular venous distention (JVD) frequently is present.
Wheezing or rales may be heard on lung auscultation.
Apical impulse frequently is displaced laterally.
Cardiac auscultation may reveal aortic or mitral valvular abnormalities, S 3 or S4.
Lower extremity edema also may be noted, especially in the subacute process.
Causes:
A variety of cardiac diseases cause CHF and pulmonary edema.
The most common cause of heart failure is coronary artery disease, which is secondary
to loss of left ventricular muscle, ongoing ischemia, or decreased diastolic ventricular
compliance.
Other disease processes include hypertension, valvular heart disease, congenital heart
disease, other cardiomyopathies, myocarditis, and infectious endocarditis.

CHF often is precipitated by cardiac ischemia or dysrhythmias, cardiac or extracardiac

infection, pulmonary embolus, physical or environmental stresses, changes or
noncompliance with medical therapy, dietary indiscretion, or iatrogenic volume overload.
One also must consider systemic processes such as pregnancy and hyperthyroidism as
precipitants of CHF.

WORKUP
Lab Studies:
Beta-natriuretic peptide
o Until recently, differentiating asthma and other pulmonary disease has been
difficult in the acute setting, particularly because of the poor sensitivities and
specificities of most elements of history and physical examination. The standard
of care has been shotgun therapy, namely treating patients for both CHF and an
acute pulmonary process such as asthma, with both diuretics and beta-agonists.
o The Breathing Not Properly Study has suggested that serum levels of betanatriuretic peptide (BNP) and the BNP precursor, Pro-BNP, can help identify CHF
as the origin of acute dyspnea. This study found sensitivities of 90% with
specificities of 76%. Positive predictive value was 79% with a negative predictive
value of 89%. Mueller found a reduction in hospital length of stay of 3 days when
BNP levels were utilized. However, this study assumed an average length of stay
of 11 days. The average length of stay in the United States for CHF
exacerbations is approximately 4 days. In addition, although the time to initiation
of therapy was reduced in this study from 90 to 60 minutes, the general practice
in the United States is immediate initiation of shotgun therapy.
o In the primary care setting, Wright identified 305 patients with heart failure and
then reevaluated them with or without the Pro-BNP result. Diagnostic accuracy
improved from 52% to 60% without Pro-BNP and from 49% to 70% with ProBNP.
o Maisel identified in the Breathing Not Properly Study a 20% increase in patients
with CHF who presented with dyspnea and a history of asthma or COPD but no
prior history of CHF.
o Mueller found that BNP reduced time to discharge from 12 to 3 days and reduced
costs of hospitalization by 15%
o BNP is available as a point-of-care test, with results available within 15 minutes;
however, only Pro-BNP can be utilized concomitantly with nesiritide.
o Serum levels of BNP of <100 pg/mL are unlikely to be from CHF. In the Breathing
Not Properly Study, BNP of 50 pg/mL increased sensitivity from 90% to 97% at a
cost of reducing specificity. Levels of 100-500 pg/mL may be CHF. However,
other conditions that also elevate right filling pressures, such as pulmonary
embolus, primary pulmonary hypertension, end-stage renal failure, cirrhosis, and
hormone replacement therapy, may also cause elevated BNP levels in this range.
BNP levels of >500 pg/mL are most consistent with CHF.
Serum lab values may identify prerenal azotemia or elevated alanine aminotransferase
(ALT), aspartate aminotransferase (AST), or bilirubin, suggestive of a congestive
hepatopathy. Cardiac enzymes and other serum markers for ischemia or infarction may
be useful as well.
Arterial blood gas (ABG) may be of benefit in evaluation of hypoxemia,
ventilation/perfusion (V/Q) mismatch, hypercapnia, and acidosis.
Mild azotemia, decreased erythrocyte sedimentation rate (ESR), and proteinuria are
observed in early and mild-to-moderate disease.
Increased creatinine, hyperbilirubinemia, and dilutional hyponatremia are observed in
severe cases.
Imaging Studies:

Chest radiography
o Although diagnostic tests are of limited benefit in acute CHF, chest radiography is
the most useful tool. A recent study showed that 1 out 5 patients admitted to the
hospital with CHF lacked signs of congestion on chest radiograph.
o Cardiomegaly may be observed with a cardiothoracic ratio greater than 50%.
Pleural effusions may be present bilaterally or if they are unilateral more
commonly observed on the right.
o Early CHF may manifest as cephalization of pulmonary vessels, generally
reflecting a pulmonary capillary wedge pressure (PCWP) of 12-18 mm Hg. As the
interstitial fluid accumulates, more advanced CHF may be demonstrated by
Kerley B lines (PCWP: 18-25 mm Hg).
o Pulmonary edema is observed as perihilar infiltrates often in the classic butterfly
pattern reflecting a PCWP greater than 25 mm Hg.
o Several limitations exist to the use of chest radiographs when attempting to
diagnose CHF. Classic radiographic progression often is not found, and as much
as a 12-hour radiographic lag from onset of symptoms may occur. In addition,
radiographic findings frequently persist for several days despite clinical recovery.
Emergency transthoracic echocardiography
o Emergency transthoracic echocardiography (ECHO) may help identify regional
wall motion abnormalities as well as globally depressed or myopathic left
ventricular function.
o ECHO may help identify cardiac tamponade, pericardial constriction, and
pulmonary embolus.
o ECHO is also useful in identifying valvular heart disease, such as mitral or aortic
stenosis or regurgitation.
Other Tests:
Electrocardiogram (ECG) is a nonspecific tool but may be useful in diagnosing
concomitant cardiac ischemia, prior myocardial infarction (MI), cardiac dysrhythmias,
chronic hypertension, and other causes of left ventricular hypertrophy.
Procedures:
No defined role exists for invasive monitoring devices such as central venous placement
(CVP) lines. Time-consuming placement of pulmonary artery catheters has not been
shown to prolong survival, even in the coronary care unit and, thus far, has not been well
studied in the emergency department (ED) setting.
Cardiac catheterization may be necessary for a complete evaluation and assessment of
prognosis.
TREATMENT
Prehospital Care:
Prehospital notification by emergency medical services (EMS) personnel should alert ED
staff of a patient presenting with signs and symptoms of CHF and pulmonary edema.
They should receive on-line medical advice for patients with high-risk presentations.
Begin treatment with the ABCs. Administer supplemental oxygen, initially 100%
nonrebreather facemask.
Utilize cardiac monitoring and continuous pulse oximetry.
Obtain intravenous access, as well as a prehospital ECG, if available.
Provide nitroglycerin sublingual or spray for active chest pain in the patient without
severe hypotension and IV furosemide.
Emergency Department Care:
Begin ED treatment of a patient presenting with signs and symptoms of CHF and
pulmonary edema with the ABCs. Administer supplemental oxygen, initially 100%
nonrebreather facemask. Utilize cardiac monitoring and continuous pulse oximetry.
Obtain IV access.

To reduce venous return, elevate the head of the bed. Patients may be most comfortable
in a sitting position with their legs dangling over the side of the bed, which allows for
reduced venous return and decreased preload.
Therapy generally starts with nitrates and diuretics if patients are hemodynamically
stable. Many other treatment modalities may play some role in acute management.
If possible, treat the underlying cause as well, if identified. This is particularly necessary
for patients with known diastolic dysfunction who respond best to reductions in blood
pressure, rather than to diuretics, nitrates, and inotropic agents. Serum BNP levels may
be very useful in the setting of undifferentiated dyspnea, or in the future may be useful to
gauge therapeutic success.
Eliminate contributing factors when possible.
Restrict fluid and sodium.
Consider other treatment modalities, including nesiritide. Nesiritide may be useful in lieu
of nitroglycerin in patients with moderate respiratory distress, particularly if the patient will
not tolerate noninvasive ventilation or in the patient who cannot have nitroglycerin by
protocol (ie, in an observation unit).
o Continuous positive airway pressure (CPAP) and bilevel positive airway pressure
(BiPAP)Recent data comparing nasal CPAP therapy and facemask ventilation
therapy have demonstrated decreased need for intubation rates when these
modalities are used. In patients with severe CHF treated with CPAP, however, no
significant difference was found in short-term mortality rates and length of
hospital stay. Although BiPAP therapy may improve ventilation and vital signs
more rapidly then CPAP, a higher incidence of MI associated with BiPAP has
been reported. BiPAP and CPAP are contraindicated in the presence of acute
facial trauma, the absence of an intact airway, and in patients with an altered
mental status or who are uncooperative.
o Alternating tourniquets, formerly a mainstay of therapy, have been used to
decrease preload. Their use has been supplanted by newer therapies such as
intravenous nitroglycerin and nitroprusside.
o Phlebotomy with removal of 500 mL of blood or via plasmapheresis is another
former mainstay of therapy used to decrease preload. Its use has been
supplanted by newer therapies such as intravenous nitroglycerin and
nitroprusside.
Consultations:
Cardiology
Critical care services
Cardiothoracic surgery for possible heart valve surgery or transplantation
MEDICATION
The goal of pharmacotherapy is to achieve a PCWP of 15-18 mm Hg and a cardiac index >2.2
L/min/m2, while maintaining adequate blood pressure and perfusion to essential organs. These
goals may need to be modified for some patients.
Use of diuretics, nitrates, analgesics, and inotropic agents are indicated for the treatment of CHF
and pulmonary edema. Calcium channel blockers, such as nifedipine and nondihydropyridines,
increase mortality and increase prevalence of recurrent CHF with chronic use. Conflicting
evidence currently exists both in favor of and against the use of calcium channel blockers in the
acute setting; at this time limit their acute use to patients with diastolic dysfunction and heart
failure, a condition not easily determined in the emergency department.
Angiotensin converting enzyme (ACE) inhibitors, such as SL captopril or IV enalapril, may rapidly
reverse hemodynamic instability and symptoms, possibly avoiding an otherwise imminent
intubation. Haude compared 25 mg of SL captopril with 0.8 mg of sublingual nitroglycerin in 24
patients with class III and class IV CHF and found that captopril induces a more sustained and
more pronounced improvement in hemodynamics. Annane gave 1 mg of IV enalapril to 20
patients presenting with acute class III and class IV CHF over 2 hours and demonstrated rapid

hemodynamic improvement with no significant adverse effects on cardiac output or

hepatosplanchnic measurements.
Captopril may play a unique role in sustaining patients with renal failure and concomitant acute
CHF while awaiting definitive therapy with dialysis. Since the information on this subject is still
controversial and limited to small studies, the routine use of ACE inhibitors cannot be
recommended at this time. ACE inhibitors remain a promising area in need of further study.
Beta-blockers, possibly by restoring beta-1 receptor activity or via prevention of catecholamine
activity, appear to be cardioprotective in patients with depressed left ventricular function. The US
Carvedilol Heart Failure study group demonstrated a two-thirds decrease in mortality in patients
taking carvedilol with left ventricular ejection fractions of 35% or less. Beta-blockers, particularly
carvedilol, have been shown to improve symptoms in patients with moderate-to-severe heart
failure. The role of beta-blockers in the acute setting, however, is currently unclear; limit use until
hemodynamic studies indicate that further deterioration will not occur.
Because differentiating CHF and asthma exacerbations is often difficult, treating both with the
shotgun approach is often used, particularly as both may cause bronchospasm. Aerosolized beta2 agonists, which are the more selective of beta-agonists, decrease tachycardia, dysrhythmias,
and cardiac work while transiently enhancing cardiac function. Terbutaline has been shown to be
successful in this setting, as well as albuterol, isoetharine, and bitolterol.
Limit roles of theophylline and aminophylline in the acute setting. They are positive inotropic
agents mediated by an increase in catecholamines, and they dilate coronaries and exert mild
diuretic effects. Nevertheless, they can exacerbate dysrhythmias (eg, multifocal atrial tachycardia
[MAT], ischemia) by increasing cardiac work.
Steroids, IV or PO, have been shown to worsen preexisting heart failure due to systemic sodium
retention and volume expansion, hypokalemia, and occasional hypertension. Inhaled steroids,
because of their lack of systemic side effects, may be a reasonable option in this confusing
patient presentation; however, given their delayed onset of action, they remain an area in need of
further study.
Please see the chapter on Asthma for dosing schedules.
Drug Category: Diuretics -- First-line therapy generally includes a loop diuretic such as
furosemide, which will inhibit sodium chloride reabsorption in the ascending loop of Henle.
Drug Name

Furosemide (Lasix) -- Administer loop diuretics IV, since this allows for both superior
potency and higher peak concentration despite increased incidence of side effects,
particularly ototoxicity.

Adult Dose

A reasonable approach for furosemide might be as follows:

10-20 mg IV for patients symptomatic with CHF not already using diuretics
40-80 mg IV for patients already using diuretics
80-120 mg IV for patients whose symptoms are refractory to the initial dose after 1 h
of its administration
Higher doses and more rapid redosing may be appropriate for the patient in severe
distress

Pediatric Dose
Contraindications

Interactions

Not established
Documented hypersensitivity, hepatic coma, anuria, severe electrolyte depletion
Metformin decreases concentrations; interferes with hypoglycemic effect of
antidiabetic agents and antagonizes muscle relaxing effect of tubocurarine; auditory
toxicity appears to be increased with coadministration of aminoglycosides; hearing
loss of varying degrees may occur; anticoagulant activity of warfarin may be
enhanced when taken concurrently; increased plasma lithium levels and toxicity are
possible when taken concurrently

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Perform frequent serum electrolyte, carbon dioxide, glucose, creatinine, uric acid,
calcium, and BUN determinations during first few months of therapy and periodically
thereafter

Drug Name

Metolazone (Mykrox, Zaroxolyn) -- Both chlorothiazide and metolazone have been

used as adjunctive therapy in patients initially refractory to furosemide.
Chlorothiazide, however, at doses of 250-500 mg IV, decreases GFR with CHF and,
thus, is less potent and causes a greater loss of potassium. Conversely, metolazone
has been demonstrated to be synergistic with loop diuretics in treating refractory
patients.

Adult Dose

5-10 mg PO before redosing with furosemide

Pediatric Dose
Contraindications

Not established
Documented hypersensitivity, hepatic coma, encephalopathy, anuria

Interactions

Thiazides may decrease effect of anticoagulants, sulfonylureas, and gout treatments;

anticholinergics and amphotericin B may increase toxicity of thiazides; effects of
thiazides may decrease when used concurrently with bile acid sequestrants, NSAIDs,
or methenamine; when administered concurrently, thiazides increase toxicity of
anesthetics, diazoxide, digitoxin, lithium, loop diuretics, antineoplastics, allopurinol,
calcium salts, vitamin D, and nondepolarizing muscle relaxants

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Caution in hepatic or renal disease, diabetes mellitus, gout, or lupus erythematosus

Drug Category: Nitrates -- Reduce myocardial oxygen demand by lowering preload and afterload.
In severely hypertensive patients, nitroprusside causes more arterial dilatation than nitroglycerin.
Nevertheless, due to thiocyanate toxicity and the coronary steal phenomenon associated with
nitroprusside, IV nitroglycerin is still the therapy of choice for afterload reduction.

Drug Name

Nitroglycerin (Nitro-Bid, Nitrol, Nitrostat) -- SL nitroglycerin and nitrospray are

particularly useful in the patient who presents with acute pulmonary edema with a
systolic blood pressure of at least 100 mm Hg.
Similar to SL, nitrospray's onset is 1-3 min with a half-life of 5 min. Applicability of
nitrospray may be easier, and storage is up to 4 y. One study demonstrated significant
and rapid hemodynamic improvement in 20 patients given nitrospray with pulmonary
edema in an ICU setting.
Topical nitrate therapy is reasonable in a patient presenting with class I to II CHF.
However, in patients with more severe signs of heart failure or pulmonary edema, IV
nitroglycerin is preferred since it is easier to monitor hemodynamics and absorption,
particularly in the diaphoretic patient.
Oral nitrates, due to delayed absorption, have little role in the acute presentations of
CHF.

Adult Dose

Nitrospray: single spray (0.4 mg) equivalent to a single 1/150 SL; may repeat q3-5min
as hemodynamics permit, up to a maximum of 1.2 mg
Ointment: Apply 1-2 inches of nitropaste to chest wall
Injection: start at 20 mcg/min IV and rate to effect in 5-10 mcg increments q3-5min

Pediatric Dose
Contraindications

Not established
Documented hypersensitivity, severe anemia, shock, postural hypotension, head
trauma, closed-angle glaucoma, cerebral hemorrhage

Interactions

Aspirin may increase nitrate serum concentrations; marked symptomatic orthostatic

hypotension may occur with coadministration of calcium channel blockers (dose
adjustment of either agent may be necessary)

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Exercise caution with coronary artery disease and low systolic blood pressure.

Drug Name

Nitroprusside sodium (Nitropress) -- Produces vasodilation and increases inotropic

activity of the heart. At higher dosages may exacerbate myocardial ischemia by

increasing heart rate. Easily titratable.

Adult Dose
Pediatric Dose
Contraindications

10-15 mcg/min IV and titrate to effective dose range of 30-50 mcg/min and a systolic
blood pressure of at least 90 mm Hg
Not established
Documented hypersensitivity, subaortic stenosis, optic atrophy, tobacco amblyopia,
idiopathic hypertrophic, atrial fibrillation or flutter

Interactions

Patients receiving other hypertensive therapy may be more sensitive to sodium

nitroprusside

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Caution in increased intracranial pressure, hepatic failure, severe renal impairment,

and hypothyroidism; in renal or hepatic insufficiency, nitroprusside levels may
increase and can cause cyanide toxicity; sodium nitroprusside has the ability to lower
blood pressure and thus should be used only in those patients with mean arterial
pressures >70 mm Hg

Drug Category: Analgesics -- Morphine IV is an excellent adjunct in acute therapy. In addition to

being both an anxiolytic and an analgesic, its most important effect is venodilation, which reduces
preload. Also causes arterial dilatation, which reduces systemic vascular resistance (SVR) and
increases cardiac output. Narcan also can reverse the effects of morphine. However, some
evidence indicates that morphine use in acute pulmonary edema may increase the intubation
rate.

Drug Name

Morphine sulfate (Duramorph, Astramorph, MS Contin) -- DOC for narcotic analgesia

due to reliable and predictable effects, safety profile, and ease of reversibility with
naloxone.
Morphine sulfate administered IV may be dosed in a number of ways and commonly
is titrated until desired effect is obtained.

Adult Dose

2-5 mg IV and repeated q10-15min unless respiratory rate is <20 breaths/min or

systolic blood pressure is <100 mm Hg

Pediatric Dose

Not established

Contraindications

Documented hypersensitivity, hypotension, potentially compromised airway with

uncertain rapid airway control, respiratory depression, nausea, emesis, constipation,
urinary retention

Interactions

Phenothiazines may antagonize analgesic effects of opiate agonists; tricyclic

antidepressants, MAOIs, and other CNS depressants may potentiate adverse effects
of morphine

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Caution in atrial flutter and other supraventricular tachycardias; has vagolytic action
and may increase ventricular response rate

Drug Category: Inotropic agents -- Principal inotropic agents include dopamine, dobutamine,
inamrinone (formerly amrinone), milrinone, dopexamine, and digoxin. In the hypotensive patient
presenting with CHF, dopamine and dobutamine are agents usually used. Inamrinone or
milrinone inhibits phosphodiesterase, resulting in an increase of intracellular cyclic AMP and
alteration in calcium transport. As a result, they increase cardiac contractility and reduce vascular
tone by vasodilatation.
Dopexamine is a new synthetic catecholamine with beta-2 and dopaminergic properties causing
vasodilation and increased inotropism but with tachycardia as well. Ultimately may have a role as
an emergent inotropic agent, but dobutamine is probably the current agent of choice.
Digoxin has no role in the emergency management of CHF due to delayed absorption and
diminished efficacy at times of increased sympathetic tone. Thus, has little, if any, benefit in the

patient presenting concomitantly with atrial fibrillation and rapid ventricular response. Limit use of
digoxin to chronic CHF in which its role has been well established.
These agents augment both coronary and renal blood flow.

Drug Name

Dopamine (Intropin) -- Stimulates both adrenergic and dopaminergic receptors.

Hemodynamic effects depend on the dose. Lower doses stimulate mainly
dopaminergic receptors that produce renal and mesenteric vasodilation. Cardiac
stimulation and renal vasodilation is produced by higher doses.
Positive inotropic agent at 2-10 mcg that can lead to tachycardia, ischemia, and
dysrhythmias. Doses >10 mcg cause vasoconstriction, which increases afterload.

Adult Dose

5 mcg/kg/min IV and increase at 5 mcg/kg/min increments to a 20 mcg/kg/min dose

Pediatric Dose
Contraindications

Not established
Documented hypersensitivity, pheochromocytoma, ventricular fibrillation

Interactions

Phenytoin, alpha- and beta-adrenergic blockers, general anesthesia, and MAOIs

increase and prolong effects of dopamine

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Monitor closely urine flow, cardiac output, pulmonary wedge pressure, and blood
pressure during the infusion; prior to infusion, correct hypovolemia with either whole
blood or plasma, as indicated; monitoring central venous pressure or left ventricular
filling pressure may be helpful in detecting and treating hypovolemia

Drug Name

Dobutamine (Dobutrex) -- Produces vasodilation and increases inotropic state. At

higher dosages may cause increased heart rate, thus exacerbating myocardial
ischemia. Strong inotropic agent with minimal chronotropic effect and no
vasoconstriction.

Adult Dose

Starting dose: 2.5 mcg/kg/min IV; generally therapeutic in the range of 10-40
mcg/kg/min

Pediatric Dose
Contraindications

Not established
Documented hypersensitivity; idiopathic hypertrophic subaortic stenosis; atrial
fibrillation or flutter

Interactions

Beta-adrenergic blockers antagonize effects of dobutamine; general anesthetics may

increase toxicity

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Following a myocardial infarction use with extreme caution; hypovolemic state should
be corrected before using this drug

Drug Category: Human B-type natriuretic peptides -- Growing data suggest that Human B-type
natriuretic peptides such as Nesiritide may be effective in reducing pulmonary capillary wedge
pressure and improving dyspnea in patients with acutely decompensated congestive heart failure.
Nesiritide serves as a second messenger to dilate veins and arteries.

Drug Name

Nesiritide (Natrecor) -- Recombinant DNA form of human B-type natriuretic peptides

(hBNP), which dilate veins and arteries.
Human BNP binds to particulate guanylate cyclase receptor of vascular smooth
muscle and endothelial cells. Binding to receptor causes increase in cyclic GMP,
which serves as second messenger to dilate veins and arteries. Reduces pulmonary
capillary wedge pressure and improves dyspnea in patients with acutely
decompensated congestive heart failure.

Adult Dose

2 mcg/kg IV bolus over 60 s; follow by 0.01 mcg/kg/min continuous infusion; bolus

volume (mL) = 0.33 X patient weight (kg); infusion flow rate of bolus (mL/h) = 0.1 X
patient wt (kg)

Pediatric Dose
Contraindications

Not established
Documented hypersensitivity; systolic blood pressure <90 mm Hg; patients suspected
of having, or known to have, low cardiac filling pressures, significant valvular stenosis,
restrictive or obstructive cardiomyopathy, constrictive pericarditis, pericardial
tamponade, conditions in which cardiac output is dependent upon venous return

Interactions

Concurrent administration with ACE inhibitors and other vasodilators may cause
hypotension

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Do not initiate at dose higher than recommended; may affect renal function in patients
whose renal function may depend on activity of renin-angiotensin-aldosterone system;
may cause hypotension (administer in settings where blood pressure can be
monitored closely); discontinue drug if hypotension develops; ventricular tachycardia,
non-sustained VT, headache, abdominal pain, back pain, insomnia, anxiety, angina
pectoris, nausea, and vomiting may occur

FOLLOW-UP
Further Inpatient Care:
Depending on the response to initial ED therapy, disposition decisions vary.
o With few exceptions, patients presenting with acute symptoms of CHF or
pulmonary edema require hospital admission. Many patients, however, who
respond rapidly to early therapy may require only standard hospital ward
admission with telemetry monitoring if ischemic etiologies are being considered.
o Some criteria for discharge from the ED would include gradual onset of shortness
of breath, rapid response to therapy, oxygen saturation greater than 90%, and
acute coronary syndromes and MI unlikely as the precipitating event.
o Those patients who require intubation or remain with significant respiratory,
hemodynamic, and/or cardiovascular compromise often require ICU or CCU
admission.
o If left ventricular function has not been well established previously, obtain either a
multigated nuclear imaging (MUGA) scan or an echocardiogram, which enable
assessment of valvular function and wall motion abnormalities as well as ejection
fraction.
o In patients refractory to medical therapy or with evidence of cardiogenic shock,
cardiac catheterization, angioplasty, coronary bypass, or intraaortic balloon pump
(IABP) may be helpful.
Further Outpatient Care:
Center outpatient care around patient education with specific instructions regarding
dietary restrictions and compliance with medical therapy.
In/Out Patient Meds:
ACE inhibitors are indicated in patients with ejection fractions of 35% or less.
Digoxin also may be helpful in patients with ejection fractions of 35% or less.
Diuretics, such as furosemide, may be helpful regardless of ejection fraction.
Beta-blockers appear to be cardioprotective in patients with depressed left ventricular
function. The US carvedilol heart failure study group demonstrated a two-thirds decrease
in mortality in patients taking carvedilol with left ventricular ejection fractions of 35%.
Beta-blockers are indicated as therapy for patients with diastolic dysfunction or for
patients with coronary insufficiency.
Calcium channel blockers, such as nifedipine and nondihydropyridines, increase mortality
rates and incidence of recurrent CHF with chronic use in patients with depressed LV
function. Amlodipine is the exception to this rule. Calcium channel blockers are useful in
patients with diastolic dysfunction and heart failure.
Transfer:

Consider transfer for unstable patients being evaluated in a center without access to
cardiac catheterization or IABP. These patients may include the following:
o Those who are refractory to medical therapy
o Those in cardiogenic shock
o Those with significant aortic stenosis or other valvular abnormalities possibly
requiring surgical intervention or valvuloplasty
Deterrence/Prevention:
Emphasize patient education with intense instruction regarding compliance with dietary
restrictions and medical therapy.
Emphasize close monitoring of blood pressure, particularly in patients with diastolic
dysfunction.
Patient should modify diet as follows:
o Sodium restriction (initially 4 g/d)
o Weight reduction (if appropriate)
o Appropriate fluid restriction
Patient should modify activity as follows:
o During severe stage, bed rest with elevation of head of bed and anti-embolism
stockings to help control leg edema
o Gradual increase in activity with walking to help increase strength
Complications:
Acute MI
Cardiogenic shock
Arrhythmias (most commonly atrial fibrillation)
Ventricular arrhythmias, such as ventricular tachycardia, often are seen in patients with
significantly depressed left ventricular function.
Electrolyte disturbances
Mesenteric insufficiency
Protein enteropathy
Digitalis intoxication
Prognosis:
Based on data from 4606 patients hospitalized with CHF between 1992-1993, the total inhospital mortality rate was 19%, with 30% of deaths occurring from noncardiac causes.
These patients, however, were noted to have had suboptimal use of proven efficacious
therapy, compared with those who survived hospitalizations, particularly among women
and the elderly. Thirty-year data from the Framingham heart study demonstrated a
median survival of 3.2 years for males and 5.4 years for females.
Results of initial treatment are usually good, regardless of cause.
Long-term prognosis is variable. Mortality rates range from 10% in patients with mild
symptoms to 50% with advanced, progressive symptoms.
Patient Education:
Provide instructions to patients discharged home to return to the ED for recurrence or
changes in severity of symptoms.
Provide specific instructions to patients discharged regarding dietary restrictions and
compliance with medical therapy.
Require patients to promptly follow up with their primary care physician or cardiologist.
Advise patients that printed information is available from the following organizations:
o American Heart Association, 1615 Stemmons Freeway, Dallas, TX 75207, (214)
748-7212
o American College of Cardiology, 9111 Old Georgetown Rd, Bethesda, MD 20814,
(301) 897-5400
For excellent patient education resources, visit eMedicine's Heart Center. Also, see
eMedicine's patient education article Congestive Heart Failure.

MISCELLANEOUS
Medical/Legal Pitfalls:
Failure to recognize and initiate early management of a patient presenting with signs and
symptoms of CHF and pulmonary edema is a pitfall because therapy must begin with the
ABCs, and early treatment should include nitrates and diuretics, if hemodynamics are
stable.
Failure to obtain an ECG early is a pitfall because this may be useful in diagnosing
dysrhythmias, concomitant cardiac ischemia, or prior MI; early ECG also is helpful in
differentiating CHF from other etiologies. Remember, the most common cause of CHF is
coronary artery disease.
Failure to consider use of both CPAP and BiPAP early in therapy as a means to decrease
need for intubation and improve acute respiratory status
Failure to consider and evaluate for diseases with similar presentations
Failure to educate patients concerning changes or noncompliance with medical therapy
and dietary restrictions to help prevent further recurrence
Discharging patients who may have had acute MI as a cause of CHF

Frank-Starling law of the heart

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The Frank-Starling law of the heart (also known as Starling's law or the FrankStarling mechanism) states that the more the ventricle is filled with blood during
diastole (end-diastolic volume), the greater the volume of ejected blood will be during the
resulting systolic contraction (stroke volume).
This means that the force of contractions will increase as the heart is filled with more
blood and is a direct consequence of the effect of an increasing load on a single muscle
fiber. In particular, such increased load stretches further the myocardium and enhances
the affinity of troponin C for Calcium, hence increasing the contractile force. The force
that any single muscle fiber generates is proportional to the initial sarcomere length
(known as preload), and the stretch on the individual fibers is related to the end-diastolic
volume of the ventricle. In the human heart, maximal force is generated with an initial
sarcomere length of 2.2 micrometers, a length which is rarely exceeded in the normal
heart. Initial lengths larger or smaller than this optimal value will decrease the force the
muscle can achieve. For larger sarcomere lengths, this is the result of less overlap of the
thin and thick filaments; for smaller sarcomere lengths, the cause is the decreased
sensitivity for calcium by the myofilaments.
This can be seen most dramatically in the case of premature ventricular contraction. The
premature ventricular contraction causes early emptying of the left ventricle (LV) into the
aorta. Since the next ventricular contraction will come at its regular time, the filling time
for the LV increases, causing an increased LV end-diastolic volume. Because of the
Frank-Starling law, the next ventricular contraction will be more forceful, causing the
ejection of the larger than normal volume of blood, and bringing the LV end-systolic
volume back to baseline.
For example, during vasoconstriction the end diastolic volume increases; since this
increases preload, stroke volume will increase. A simplified way of thinking about this
relationship is that "the heart will pump what it receives."[citation needed]
The above is true of healthy myocardium. In the failing heart, the more the myocardium
is dilated, the weaker it can pump, as it then reverts to Laplace's law.

[edit] History
The law is named after the two physiologists, Otto Frank and Ernest Starling who first
described it.
Long before the development of the sliding filament hypothesis and our understanding
that active tension depends on the sarcomere's length, in 1914 Ernest Starling
hypothesized that "the mechanical energy set free in the passage from the resting to the
active state is a function of the length of the fiber." Therefore, the initial length of
myocardial fibers determines the work done during the cardiac cycle.
http://www.cvphysiology.com/Cardiac%20Function/CF003.htm

Cardiovascular Physiology Concepts

Richard E. Klabunde, Ph.D.

Frank-Starling Mechanism
As described elsewhere, cardiac output increases or decreases in response to
changes in heart rate or stroke volume. When a person stands up, for example,
cardiac output falls because of a fall in central venous pressure, which leads to a
decrease in stroke volume. As another example, limb movement (muscle pump)
during exercise enhances venous return to the heart, which causes an increase in
stroke volume. What is the mechanism by which changes in venous return alters
stroke volume?
In the late19th century, Otto Frank found using isolated frog hearts that the strength
of ventricular contraction was increased when the ventricle was stretched prior to
contraction. This observation was extended by the elegant studies of Ernest Starling
and colleagues in the early 20th century who found that increasing venous return,
and therefore the filling pressure of the ventricle, led to increased stroke volume in
dogs. These cardiac responses, which occur in isolated hearts as well as in intact
animals and humans, are independent of neural and humoral influences on the heart.
In honor of these two early pioneers, the ability of the heart to change its force of
contraction and therefore stroke volume in response to changes in venous return is
called the Frank-Starling mechanism (or Starling's Law of the heart).
Increased venous return increases the ventricular filling (end-diastolic volume) and
therefore preload, which is the initial stretching of the cardiac myocytes prior to
contraction. Myocyte stretching increases the sarcomere length, which causes an
increase in force generation. This mechanism enables the heart to eject the
additional venous return, thereby increasing stroke volume.
This phenomenon is described in mechanical terms by the length-tension and forcevelocity relationships for cardiac muscle. Increasing preload increases the active
tension developed by the muscle fiber and increases the velocity of fiber shortening
at a given afterload and inotropic state.
One mechanism to explain how preload influences contractile force is that
increasing the sarcomere length increases troponin C calcium sensitivity, which
increases the rate of cross-bridge attachment and detachment, and the amount of
tension developed by the muscle fiber (see Excitation-Contraction Coupling). The
effect of increased sarcomere length on the contractile proteins is termed lengthdependent activation.
It has traditionally been taught that the Frank-Starling mechanism is due to changes
in the number of overlapping actin and myosin units within the sarcomere as in
skeletal muscle. According to this view, changes in the force of contraction do not

result from a change in inotropy. Because we now know that changes in preload are
associated with altered calcium handling and troponin C affinity for calcium, a sharp
distinction cannot be made mechanistically between length-dependent (FrankStarling mechanism) and length-independent changes (inotropic mechanisms) in
contractile function.
There is no single Frank-Starling curve on which the ventricle operates. There is
actually a family of curves, each of which is defined by the afterload and inotropic
state of the heart (Figure 2). For example, increasing afterload or decreasing
inotropy shifts the curve down and to the right. Decreasing afterload and increasing
inotropy shifts the curve up and to the left. To summarize, changes in venous return
cause the ventricle to move along a single Frank-Starling curve that is defined by
the existing conditions of afterload and inotropy.
Frank-Starling curves show how changes in ventricular preload lead to changes in
stroke volume. This graphical representation, however, does not show how changes
in venous return affect end-diastolic and end-systolic volume. In order to do this, it
is necessary to describe ventricular function in terms of pressure-volume
diagrams. When venous return is increased, there is increased filling of the ventricle
along its passive pressure curve leading to an increase in end-diastolic volume
(Figure 3). If the ventricle now contracts at this increased preload, and the afterload
is held constant, the ventricle will empty to the same end-systolic volume, thereby
increasing its stroke volume. The increased stroke volume is manifested by an
increase in the width of the pressure-volume loop. The normal ventricle, therefore,
is capable of increasing its stroke volume to match physiological increases in
venous return. This is not, however, the case for ventricles that are in failure.

RK Revised