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Myocarditis

Dept. Cardiology , Fac. of Medicine


USU
Adam Malik Hospital

Background
Myocarditis is collection of diseases of infectious,
toxic, and autoimmune etiologies characterized
by inflammation of the heart. Subsequent
myocardial destruction can lead to dilated
cardiomyopathy.
Myocarditis is an elusive illness to study,
diagnose, and treat because the clinical
presentation may range from nearly
asymptomatic to overt heart failure requiring
transplantation; a myriad of causes exist, and it is
occasionally the unrecognized culprit in cases of
sudden death.

Pathophysiology (1)
Myocarditis is defined as inflammatory
changes in the heart muscle and is
characterized by myocyte necrosis.
Animal models of viral myocarditis have
lead to a much greater understanding of the
pathophysiology of acute, severe
myocarditis and correlate with the findings
in susceptible patients who apparently
uptake viral RNA and develop a cytotoxic
necrosis and rapid (1-2 d) cell death without
the appearance of the interstitial infiltrate
usually associated with myocarditis.

Pathophysiology (2)

Over 4-14 days, those cells that survive the initial


insult, in response to macrophage activation and
cytokine expression, develop the classic,
histologically apparent infiltration of mononuclear
cells.
In this subacute viral-clearing phase:

Natural killer cells target myocardium expressing viral RNA


and continue myocyte necrosis.
Tumor necrosis factor is also involved in rapidly clearing
virus, but its involvement results in the further recruitment
of inflammatory cells, activates endothelial cells, and has
negative inotropic effects.
In the latter stages of the subacute process, cytotoxic T
lymphocytes infiltrate the myocardium and direct lysis of
cardiocytes, which present virus fragments via the
histocompatibility complex on the surface of myocyte
membrane. Neutralizing antiviral antibodies also develop to
assist in the clearing of virus.

Pathophysiology (3)
In the chronic phases,
the deleterious effects of either inadequate or
inappropriately abundant immune response can
lead to the unfortunate long-term sequelae of
dilated cardiomyopathy and heart failure.
In animal models of insufficient immune
response, viral replication can continue and
cause chronic destruction of myocytes. Biopsy
results of patients with acute myocarditis who
develop dilated cardiomyopathy demonstrate
changes consistent with those seen in
polymerase chain reaction (PCR) amplifying
RNA from enteroviruses.
On the opposite spectrum of immune activity,
overabundant T cells may continue activity into
the chronic phase and also may cause tissue
destruction and heart failure.

The pathogenesis of
myocarditis.

Frequency
United States
The true incidence of myocarditis is unknown because
many cases are asymptomatic, and some symptoms
related to significant morbidity may not be appropriately
credited.
One major urban US medical examiners office attributed
1.3% of sudden and unexpected deaths to myocarditis1,
consistent with other autopsy studies that demonstrate
evidence of myocardial inflammation in 1-1.5% of deaths.
In the United States, viral and medication-related cases
are the most commonly identified causes.
International
Internationally other etiologies (ie, Chagas disease,
diphtheria) play a greater role than in the United States,
and true frequency of disease is even more difficult to
appreciate.

Mortality/Morbidity

Because of its difficulty in diagnosis, the large number


of cases that likely never come to medical attention, and
its previously underappreciated role in sudden
dysrhythmic death, morbidity and mortality data are
difficult to construct.

Rarely, acute myocarditis is fulminant and leads rapidly to death.


Mortality for clinically significant and biopsy proven myocarditis
varies widely. Recent studies have demonstrated death to be as
low as 4% of cases for patients without heart failure and with no
persistent viral genome expression. On the opposite end of the
spectrum, in patients with persistent viral genome expression,
myocarditis related mortality may be as high as 25%.
The appropriate delicate balance of the immune response to viral
invasion of myocytes indicates that a certain number of
individuals, perhaps with genetic predispositions, will advance to
dilated cardiomyopathy and heart failure, the most common
long-term sequelae in those patients who do not recover
completely.

Sex and Age


Sex
The male-to-female ratio is 1.5:1.
Age
The average age of patients with
myocarditis is 42 years. It is a
prominent cause of sudden cardiac
death in young adults, accounting
for 8-12% of such deaths.

History (1)

Many patients present with a nonspecific illness


characterized by fatigue, mild dyspnea, and myalgias. A
few patients present acutely with fulminant congestive
heart failure (CHF) secondary to widespread myocardial
involvement. Small and focal areas of inflammation in
electrically sensitive areas may be the etiology in
patients whose initial presentation is sudden death.
Most cases of myocarditis are subclinical; therefore, the
patient rarely seeks medical attention during acute
illness. These subclinical cases may have transient ECG
abnormalities.
An antecedent viral syndrome is present in more than
one half of patients with myocarditis. The appearance of
cardiac-specific symptoms occurs primarily in the
subacute virus-clearing phase; therefore, patients
commonly present 2 weeks after the acute viremia.

History (2)

Fever is present in 20% of patients.


Other symptoms include fatigue, myalgias
and arthralgias, and malaise.
Chest pain
Chest discomfort is reported in 35% of
patients.
The pain is most commonly described as a
pleuritic, sharp, stabbing precordial pain.
It may be substernal and squeezing and,
therefore, difficult to distinguish from that
typical of ischemic pain.
Dyspnea on exertion is common.

History (3)

Orthopnea and shortness of breath at rest may be


noted if CHF is present.
Palpitations are common. Syncope in a patient with a
presentation consistent with myocarditis should be
carefully approached because it may signal high-grade
atrioventricular (AV) block or risk for sudden death.
Pediatric patients, particularly infants, present with
nonspecific symptoms, including the following:
Fever
Respiratory distress
Poor feeding or, in cases with CHF, sweating while
feeding
Cyanosis in severe cases

Physical (1)

Physical findings can range from nearly


normal examination findings to signs of
fulminant CHF.
Patients with mild cases of myocarditis have a
nontoxic appearance and simply may appear
to have a viral syndrome.
Tachypnea and tachycardia are common.
Tachycardia is often out of proportion to fever.
More acutely ill patients have signs of
circulatory impairment due to left ventricular
failure.

Physical (2)

A widely inflamed heart shows the classic


signs of ventricular dysfunction including
the following:

Jugular venous distention


Bibasilar crackles
Ascites
Peripheral edema

S3 or a summation gallop may be noted with


significant biventricular involvement.
Intensity of S1 may be diminished.
Cyanosis may occur.

Physical (3)

Hypotension caused by left ventricular


dysfunction is uncommon in the acute setting
and indicates a poor prognosis when present.
Murmurs of mitral or tricuspid regurgitation
may be present due to ventricular dilation.
In cases where a dilated cardiomyopathy has
developed, signs of peripheral or pulmonary
thromboembolism may be found.
Diffuse inflammation may develop leading to
pericardial effusion, without tamponade, and
pericardial and pleural friction rub as the
inflammatory process involves surrounding
structures.

Causes (1)

The causes of myocarditis are


numerous and can be roughly
divided into:
infectious,
toxic, and
immunologic etiologies, with viral
etiologies.

Causes (2)

Amongst the infectious causes, viral acute myocarditis is


by far the most common.

Identification of the coxsackie-adenovirus receptor protein


explains the prevalence of these viruses as a frequent cause. The
receptor is the common target of coxsackievirus B of the
enterovirus family and serotypes 2 and 5 of the adenovirus
family.
Other viruses implicated in myocarditis include influenza virus,
echovirus, herpes simplex virus, varicella-zoster virus, hepatitis,
Epstein-Barr virus, and cytomegalovirus. Hepatitis C, in particular,
is becoming a major focus of research.
Human immunodeficiency virus (HIV) deserves special mention
because it seems to function differently than other viruses.
Although some evidence indicates that HIV directly invades
myocytes, HIV genomes can be amplified from patients without
histologic signs of inflammation. In addition, in patients who are
infected with HIV, T-cell mediated immune suppression increases
the risk of contracting myocarditis due to other infectious causes.

Causes (3)

Toxic myocarditis has a number of etiologies


including both medical agents and environmental
agents.

Among the most common drugs that cause


hypersensitivity reactions are clozapine, penicillin,
ampicillin, hydrochlorothiazide, methyldopa, and
sulfonamide drugs.
Numerous medications (eg, lithium, doxorubicin,
cocaine, numerous catecholamines, acetaminophen) may
exert a direct cytotoxic effect on the heart. Zidovudine
(AZT) has been associated with myocarditis .
Environmental toxins include lead, arsenic, and carbon
monoxide. Cases have been attributed to Chinese sumac.
Wasp, scorpion, and spider stings
Radiation therapy may cause a myocarditis with the
development of a dilated cardiomyopathy.

Causes (4)

Immunologic etiologies of myocarditis


encompass a number of clinical
syndromes and include the following:
Connective tissue disorders such as
systemic lupus erythematosus (SLE),
rheumatoid arthritis, scleroderma, and
dermatomyositis that can often result in a
dismal prognosis
Idiopathic inflammatory and infiltrative
disorders such as Kawasaki disease,
sarcoidosis, and giant cell arteritis

Lab Studies

Cardiac enzyme levels

These levels are only elevated in a minority of patients.


Normally, a characteristic pattern of slow elevation
and fall over a period of days occurs; however, a more
abrupt rise is observed in patients with acute
myocardial infarction.

Cardiac troponin I may be more sensitive


because it is present for longer periods after
myocardial damage from any cause.2
Erythrocyte sedimentation rate (ESR) is elevated
in 60% of patients with acute myocarditis.
Leukocytosis is present in 25% of cases.

Imaging Studies (1)

Chest radiography
A chest radiograph often reveals a
normal cardiac silhouette, but
pericarditis or overt clinical CHF is
associated with cardiomegaly.
Vascular redistribution
Interstitial and alveolar edema
Pleural effusion

Myocarditis Infectious/Inflammatory

Imaging Studies (2)

Echocardiography
Impairment of left ventricular systolic and
diastolic function
Segmental wall motion abnormalities
Impaired ejection fraction
A pericardial effusion may be present,
although findings of tamponade are rare.
Ventricular thrombus has been identified in
15% of patients studied with
echocardiography.

Imaging Studies (3)

MRI is capable of showing abnormal signal


intensity in the affected myocardium.

Cardiac MRI is an emerging field in general, and


contrast-enhanced T1- weighted MRI has been
shown to have sensitivities and specificities
approaching 100% for diagnosis.3
MRI can demonstrate nodular and patchy areas of
inflammation, often seen first in the lateral and
inferior wall and can be used to guide later biopsy.
MRI is also one of the modalities used in the
evaluation of young patients with apparently
idiopathic dysrhythmias, and this imaging study
can differentiate focal and diffuse inflammation
from the rare electrically significant myocardial
tumor.

Other Test (1)

Electrocardiography

Sinus tachycardia is the most frequent finding.


ST-segment elevation without reciprocal depression,
particularly when diffuse, is helpful in differentiating
myocarditis from acute myocardial infarction.
Decreased QRS amplitude and transitory Q-wave
development is very suggestive of myocarditis.
As many as 20% of patients will have a conduction
delay, including Mobitz I, Mobitz II, or complete
heart block.
Left or right bundle-branch block is observed in
approximately 20% of abnormal ECG findings and
may persist for months.

Example

Other Test (2)

Viral isolation from other body sites may be


supportive of the diagnosis.
Polymerase chain reaction (PCR) identification of
a viral infection from myocardial tissue,
pericardial fluid, or other body fluid sites can be
helpful. Persistent viral genome, as detected by
PCR, has been identified as one marker of
increased incidence of dilated cardiomyopathy
and mortality.
If a systemic disorder (eg, SLE) is suspected,
antinuclear antibody (ANA) and other collagen
vascular disorder laboratory investigations may be
useful.

Procedures

Cardiac catheterization usually reveals normal coronary


vessels and regional wall motion abnormalities with
diminished ejection fraction. It has no benefit over
noninvasive echocardiography.
Endomyocardial biopsy continues to be of use in diagnosing
myocarditis
The Dallas criteria, the classic histological criteria required
for diagnosis of myocarditis, are no longer broadly
accepted due to stated biopsy sample errors, problems
with inter-rater reliability, and the identification of
alternate patterns of inflammation besides the previously
defined lymphocytic infiltrate with myocyte necrosis.4
The use of MRI to target biopsy, immunohistochemical
staining, and the ability to identify viral genome by PCR
has allowed endomyocardial biopsy to remain a powerful
tool. In one study of nearly 900 patients, biopsy altered
diagnosis in 21% of patients.

Emergency Department
Care (1)

Because many cases of myocarditis are not


clinically obvious, a high degree of suspicion is
required to identify acute myocarditis.
Fortunately, most patients have mild symptoms
consistent with viral syndromes, and they
recover with simple supportive care on an
outpatient basis.

Standard treatment of clinically significant disease


includes the detection of dysrhythmia with cardiac
monitoring, supplemental oxygen, and managing fluid
status.
Left ventricular dysfunction developing from
myocarditis should be approached in much the same
manner as other causes of CHF with some exceptions
(see Medication).

Emergency Department
Care (2)

In general, sympathomimetic drugs should be avoided


because they increase the extent of myocardial
necrosis and mortality.
Beta-blockers should be avoided in the acutely
decompensating phase of illness, but studies that have
used carvedilol have shown decreases in the
expression of several different histochemicals,
subsequent inflammatory myocyte infiltrate, and
mortality.
Patients who present with Mobitz II or complete heart
block require pacemaker placement. Some authors
also suggest the placement of automatic implantable
cardioverter-defibrillators (AICDs) in patients with
significant, persistent decreases in left ventricular (LV)
function.

Consultations

Patients who require emergency


room treatment for new-onset CHF,
dysrhythmia, or cardiogenic shock
should be admitted to the hospital
with continuous cardiac monitoring
and cardiology consultation.

Medication

Medical therapy for myocarditis is an area


of avid research interest but with little
success in human trials.
Treatment primarily involves managing the
complications of myocarditis, chiefly
thromboembolism, dysrhythmia, and CHF,
and is addressed in detail in the
corresponding eMedicine Journal articles;
little is specific to myocarditis except for a
few specific aspects of the treatment of
myocarditis-related CHF.

Drug Category

Angiotensin converting enzyme inhibitors.


Ex. : Captopril (Capoten).
Calcium channel blockers. Ex. : Amlodipine
(Norvasc).
Loop diuretics. Ex. : Furosemide (Lasix).
Cardiac glycosides. Ex. : Digoxin (Digitek,
Lanoxicaps, Lanoxin)
Beta-adrenergic blockers. Ex. : Carvedilol
(Coreg)

Further Inpatient Care


(1)

Patients admitted to the hospital are treated for the


complications of myocarditis.
The increased use of MRI for targeting biopsy, novel
immunohistochemical staining, and PCR for viral
genome detection have lead to improved accuracy
of the technique of endomyocardial biopsy and have
secured its continued place in the evaluation and
treatment of patients with suspected myocarditis.
Although temporary pacemaker placement for
advanced degrees of heart block is indicated, in the
setting of myocarditis, these conduction
disturbances are usually transitory. Therefore,
permanent pacemaker placement usually is not
necessary.

Further Inpatient Care


(2)

Bedrest with restriction of activity and


sodium intake is beneficial.
Mechanical assist devices and
extracorporeal membrane oxygenation are
growing in use as bridges to recovery or
heart transplant.
Patients with fulminant heart failure may
require transplantation, which can be life
saving. Unfortunately, these patients have
a higher rate of rejection than patients
whose underlying cause of heart failure is
not myocarditis.

Further Outpatient Care

The clinician may consider the placement of a


Holter monitor to recognize dysrhythmias on an
outpatient basis.
This may be undertaken after the initial ED
evaluation of a patient who shows no sign of acute
dysrhythmia, CHF, or other complication.
A Holter monitor may also be placed after the
initial inpatient treatment.
Upon discharge from the hospital, all patients with
myocarditis should have follow-up visits with a
cardiologist.
Recovered patients should have restricted activity
for 6 months because rapid return to activity has
provoked recurrent inflammation in animal models.

In/Out Patient Meds

Treatment of pain with a narcotic analgesic


(eg, acetaminophen with codeine) is
appropriate.
Avoid nonsteroidal anti-inflammatory
drugs (NSAIDs), which are relatively
contraindicated in this condition.
Other outpatient medications are
associated with managing the resultant
CHF and are discussed in Medication.

Complications

Congestive heart failure


Pulmonary edema
Cardiogenic shock
Cardiac failure

Dilated cardiomyopathy
Dysrhythmias
Recurrent myositis

Prognosis (1)

Most cases are believed to be clinically


silent and resolve spontaneously without
sequelae; therefore, making accurate
statements concerning the prognosis of
myocarditis is difficult.
Patients who present with CHF experience
morbidity and mortality based on the
degree of left ventricular dysfunction.
Of patients who present with cardiogenic
shock, elderly patients and patients with
giant cell arteritis have a poor prognosis.

Prognosis (2)

Patients with HIV and persistent viral genome


expression from myocytes have dismal outcomes.
One half of patients who present with new-onset
CHF experience considerable improvement of
cardiac function with treatment. One fourth of
patients who present with CHF stabilize with
compromised cardiac function. The conditions of
the remaining one fourth of patients continue to
deteriorate.
Patients who require transplantation have an
increased risk of recurrent myocarditis and graft
rejection.

Patient Education

Patients are advised to restrict


activity since studies have shown
that increased activity promotes
progression of inflammation.

Medical/Legal Pitfalls

Myocarditis may present subtly, but it


should be considered in the patient who
presents with dyspnea and chest
discomfort, particularly if the history
includes a recent viral illness.

Careful physical examination looking for signs


of CHF and pericarditis is helpful.
Electrocardiography, ESR, and cardiac enzyme
levels are useful screening tools.
Patients with evidence of dysrhythmia, CHF, or
thromboembolism must be admitted.

Thank you

References

This 12th edition of Hursts The Heart


http://www.emedicine.com/emerg/top
ic326.htm
http://www.nature.com