What are the etiologies of myocarditis and the recommended diagnostic and therapeutic management?

Myocarditis: Causes and Management

Etiologies of Myocarditis

In North America and Western Europe, viral infections are the predominant cause of myocarditis, with parvovirus B19 and human herpes virus 6 being the most frequently identified pathogens. 1

Infectious Causes

Viral Pathogens (Most Common):

• Parvovirus B19 and human herpes virus 6 are the most frequent viral causes in Western Europe 1
• Coxsackie B and other enteroviruses remain critical pathogens in acute and fulminant myocarditis 1
• Adenoviruses are commonly identified in endomyocardial biopsies 2
• Approximately two dozen viruses have been linked to myocarditis overall 1
• Coinfection with two or more viruses occurs in a substantial minority of cases 1

Regional Infectious Causes:

• Chagas disease, poststreptococcal rheumatic heart disease, and HIV are important causes in specific world regions 1
• Diphtheria-associated myocarditis has been reported from Afghanistan and India 1
• Typhoid fever, rubella, and scorpion bite have been reported from Asian regions 1
• Lyme disease can cause myocarditis with heart block and ventricular tachyarrhythmias 3
• A careful travel and exposure history is essential for evaluating unexplained cardiomyopathy 1

Non-Infectious Causes

Autoimmune and Inflammatory Conditions:

• Giant cell myocarditis is an aggressive, noninfectious autoimmune disorder that is rapidly fatal without advanced heart failure treatment and multidrug immunosuppression 1
• Cardiac sarcoidosis often affects the heart without clinical evidence of extracardiac disease 1
• Kawasaki disease can cause myocarditis in specific demographic groups 1

Other Causes:

• Drug-induced myocarditis 4
• Autoimmune diseases 4

Diagnostic Approach

Initial Evaluation

When myocarditis is suspected, obtain a 12-lead ECG, transthoracic echocardiography, cardiac troponin, erythrocyte sedimentation rate, and C-reactive protein. 3

Request cardiology consultation for any troponin elevation accompanied by ECG or echocardiographic abnormalities suggestive of myocarditis. 3

Clinical Presentations Requiring Evaluation

• Acute chest pain (pericarditic or pseudoischemic) 1
• New onset (days to 3 months) or worsening dyspnea at rest or with exercise, with or without fatigue and signs of left- or right-sided heart failure 1
• Subacute/chronic (>3 months) dyspnea or fatigue with heart failure signs 1
• Palpitations, unexplained arrhythmia symptoms, syncope, or aborted sudden cardiac death 1
• Unexplained cardiogenic shock 1

ECG Findings

Look for new abnormalities including:

• First- to third-degree atrioventricular block or bundle-branch block 1
• ST/T-wave changes or diffuse ST elevation 1, 5
• Sinus arrest 1
• Ventricular tachycardia or fibrillation 1
• Atrial fibrillation 1
• Reduced R-wave height, intraventricular conduction delay (QRS >120 ms), or abnormal Q waves 1, 5
• PR segment depression 5

Cardiac Biomarkers

• Elevated troponin T or I indicates myocardiocytolysis 1
• Persistently elevated or fluctuating cardiac troponin levels signal ongoing myocardial injury and clinical deterioration 3
• Fulminant myocarditis is associated with higher cardiac troponin levels than acute myocarditis 1

Advanced Imaging

Cardiac MRI is a highly sensitive, non-invasive modality for confirming acute myocarditis and should be performed in hemodynamically stable patients. 3

• CMR can detect myocardial edema and late gadolinium enhancement in classic myocarditic patterns 1
• Persistent myocardial inflammatory infiltrates or localized fibrosis on CMR are markers of increased sudden cardiac death risk 3

Endomyocardial Biopsy

Endomyocardial biopsy remains the gold standard for definitive diagnosis, particularly in patients with a life-threatening disease course. 3, 6

Biopsy is specifically indicated when:

• Giant cell myocarditis is suspected (requires definitive diagnosis for aggressive immunosuppression) 6
• Cardiac sarcoidosis is suspected (can confirm diagnosis when pathology yields noncaseating granulomas, though absence does not rule it out) 1
• The patient deteriorates despite supportive treatment 2
• Life-threatening clinical course requires consideration of immunosuppression 6

Management Strategy

Acute Phase Care

Admit all patients with definitive myocarditis to the hospital; transfer fulminant cases to centers equipped for advanced heart failure therapies, mechanical circulatory support, and transplant evaluation. 3

Guideline-Directed Medical Therapy

Initiate neurohormonal blockade with ACE inhibitors (or ARBs) and beta-blockers for patients with reduced left ventricular ejection fraction. 3, 6

• Add diuretics as clinically indicated for volume overload 6
• Continue guideline-directed heart failure therapy indefinitely after discharge as clinically appropriate 3

Arrhythmia Management

Institute continuous ECG monitoring and mandatory inpatient observation for patients presenting with ventricular arrhythmias or high-grade heart block. 3

Implant a temporary pacemaker for symptomatic bradyarrhythmias (heart block or sinus node dysfunction). 3, 6

Administer antiarrhythmic therapy (such as amiodarone) for symptomatic non-sustained or sustained ventricular tachycardia during acute myocarditis. 6

Avoid ICD implantation during the acute phase of myocarditis, as many arrhythmias resolve with recovery. 6

Consider early ICD implantation in giant cell myocarditis or cardiac sarcoidosis complicated by hemodynamically significant sustained ventricular tachycardia or aborted cardiac arrest, due to adverse prognosis. 3

• Delay ICD implantation in other patients who survive the acute phase but have persistent life-threatening ventricular arrhythmias, provided they have reasonable expectation of survival with good functional status for more than 1 year 6

Warning Signs of Clinical Deterioration

Monitor for:

• Progressive wall-motion abnormalities and worsening left ventricular function on echocardiography 3
• Persistently elevated or fluctuating cardiac troponin levels 3
• Widening of QRS complex (>120 ms) and frequent non-sustained ventricular arrhythmias, which often precede sustained, life-threatening arrhythmias 3

Immunosuppressive Therapy

When Immunosuppression IS Indicated

Administer aggressive multidrug immunosuppression for giant cell myocarditis, as this rapidly fatal condition has shown improved survival with immunotherapy. 6

Prescribe corticosteroids as first-line therapy for cardiac sarcoidosis. 6

• Alternative immunosuppressive agents (methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide, pentoxifylline, thalidomide) are reasonable for patients who cannot tolerate corticosteroids or who continue to worsen clinically despite corticosteroid treatment 1
• Collaborate with a pulmonologist or rheumatologist for immune-modulating therapy in sarcoidosis 1

Administer corticosteroids for COVID-19-related myocarditis when the patient has concurrent pneumonia requiring supplemental oxygen or hemodynamic compromise/MIS-A. 3

Consider empiric corticosteroid therapy in fulminant myocarditis when biopsy demonstrates severe myocardial infiltrates, provided the risk of infection is carefully weighed. 3

When Immunosuppression IS NOT Indicated

Do not administer routine immunosuppression for typical viral (lymphocytic) myocarditis, as the Myocarditis Treatment Trial definitively showed no beneficial effect of prednisone combined with either azathioprine or cyclosporine in biopsy-proven lymphocytic myocarditis. 3, 6

This is a critical pitfall: the temptation to use immunosuppression broadly must be resisted, as it provides no benefit in viral myocarditis and may cause harm.

Etiology-Specific Interventions

Administer targeted antimicrobial therapy for Lyme disease- or diphtheria-associated myocarditis, which frequently presents with heart block and may precipitate ventricular tachyarrhythmias. 3

For suspected pericardial involvement accompanying myocarditis, prescribe NSAIDs, colchicine, and/or low-dose prednisone. 3

Exercise Restriction

Restrict exercise during the acute phase to reduce myocardial oxygen demand and prevent worsening inflammation. 6

Return to Activity

Athletes recovering from acute myocarditis must undergo resting echocardiogram, 24-hour Holter monitoring, and exercise ECG 3–6 months after the acute episode before returning to competitive sports. 3

Clearance requires:

• Normal left ventricular systolic function 3
• Normalized injury and inflammation biomarkers 3
• Absence of clinically relevant arrhythmias on Holter monitoring and exercise ECG 3

Mandate a minimum three-month period of exercise abstinence when no arrhythmias are detected on monitoring and stress testing. 3

Prognosis

The majority of myocarditis cases are self-limited with complete recovery of cardiac function. 3, 6

• Fulminant myocarditis, although uncommon, carries a high acute mortality rate 3, 6
• Approximately 21% of patients develop dilated cardiomyopathy during long-term follow-up 3, 5
• Viral persistence after acute disease can be detected from heart biopsy samples in the setting of chronic dilated cardiomyopathy 1