Myocarditis

Refli Hasan, MD, FIHA

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.
 References
This 12th edition of Hursts The Heart
http://www.emedicine.com/emerg/topic326.htm
http://www.nature.com
Thank you