Myocarditis

Refli Hasan, MD, FIHA

Dept. Cardiology, Fac. of Medicine USU
Adam Malik Hospital
 Overview (1)
 Background
 Pathophysiology
 Frequency
 Mortality/Morbidity
 Sex and Age
 History
 Physical
 Causes
 Lab Studies
 Imaging Studies
 Other Test
 Procedures
 Overview (2)
 Emergency Department Care
 Consultations
 Medication
 Drug Category
 Further Inpatient Care
 Further Outpatient Care
 In/Out Patient Meds
 Complications
 Prognosis
 Patient Education
 Medical/Legal Pitfalls
 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
 http://www.emedicine.com/emerg/topic326.htm
 http://www.nature.com
 http://www.texasheartinstitute.org/HIC/Topics/i
mages/myocard.jpg
 http://www.kumc.edu/instruction/medicine/pedc
ard/cardiology/cxrs/dilatedcardiomyopcxrsss.gif
 http://www.panfarma.co.yu/_Panfarma/images/
ekg_bukvar/image63.jpg
Thank you