Myocarditis, Infectious

Essentials of Diagnosis

• Often follows an upper respiratory infection

• May present with chest pain (pleuritic or nonspecific) or signs of heart failure

• Echocardiogram documents cardiomegaly and contractile dysfunction

• Myocardial biopsy, though not sensitive, may reveal a characteristic inflammatory pattern; MRI has a role in diagnosis

General Considerations

• Cardiac dysfunction due to primary myocarditis is presumedly caused by either an acute viral infection or a postviral immune response

• Causes include

  • RNA viruses

    • Picornaviruses (coxsackie A and B, echovirus, poliovirus, hepatitis virus)

    • Orthomyxovirus (influenza)

    • Paramyxoviruses (respiratory syncytial virus, mumps)

    • Togaviruses (rubella)

    • Flaviviruses (dengue fever, yellow fever)

    • SARS-CoV-2 (COVID-19)

  • DNA viruses

    • Adenovirus (A1, 2, 3, and 5)

    • Erythrovirus (Bi9V and 2)

    • Herpesviruses (human herpes virus 6 A and B, cytomegalovirus, Epstein-Barr virus, varicella-zoster)

    • Retrovirus (HIV)

  • Bacteria

    • Chlamydia (Chlamydophila pneumoniae, C psittaci)

    • Haemophilus influenzae

    • Legionella

    • Pneumophilia

    • Brucella

    • Clostridium

    • Francisella tularensis

    • Neisseria meningitis

    • Mycobacterium (tuberculosis)

    • Salmonella

    • Staphylococcus

    • Streptococcus A, Streptococcus pneumoniae

    • Tularemia

    • Tetanus

    • Syphilis

    • Vibrio cholera

  • Spirocheta

    • Borrelia recurrentis

    • Leptospira

    • Treponema pallidum

  • Rickettsia

    • Coxiella burnetti

    • R rickettsii, R prowazekii

  • Fungi

    • Actinomyces

    • Aspergillus

    • Candida

    • Cryptococcus

    • Histoplasma

    • Nocardia

  • Protozoa

    • Entamoeba histolytica

    • Plasmodium falciparum

    • Trypanosoma cruzi, T burcei, T gondii

    • Leishmania

  • Helminthic

    • Ascaris

    • Echinococcus granulosus

    • Schistosoma

    • Trichenella spiralis

    • Wuchereria bancrofti

• Patients may present several days to a few weeks after the onset of an acute febrile illness or a respiratory infection or they may present with heart failure without antecedent symptoms

• Onset of heart failure may be gradual or may be abrupt and fulminant

• In acute fulminant myocarditis,

  • Low output and shock may be present with severely depressed LV systolic function

  • The LV chamber size is typically not very enlarged

• A pericardial friction rub may be present

• In the European Study of Epidemiology and Treatment of Inflammatory Heart Disease,

  • 72% of participants had dyspnea

  • 32% had chest pain

  • 18% had arrhythmias

• Pulmonary and systemic emboli may occur

• Pleural-pericardial chest pain is common

• Examination reveals tachycardia, a gallop rhythm, and other evidence of heart failure or conduction defects

• At times, the presentation may mimic an acute myocardial infarction with ST changes, positive cardiac markers, and regional wall motion abnormalities despite normal coronaries

• Microaneurysms may also occur and may be associated with serious ventricular arrhythmias

• Approximately 10% of all dilated cardiomyopathy patients have viral myocarditis as the cause

Laboratory Findings

• No specific laboratory finding

• However, white blood cell count is usually elevated

• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are usually increased

• Troponin I or T levels are elevated in about one-third of patients, but CK-MB is elevated in only 10%

• Other biomarkers, such as B-type natriuretic peptide (BNP and proBNP), are usually elevated

Imaging

• Chest radiograph

  • Nonspecific

  • However, cardiomegaly is frequent, though not universal

• Evidence for pulmonary venous hypertension is common

• Frank pulmonary edema may be present

Diagnostic Studies

• ECG

  • May show sinus tachycardia, other arrhythmias, nonspecific repolarization changes, and intraventricular conduction abnormalities

  • Presence of Q waves or left bundle branch block portends a higher rate of death or cardiac transplantation

  • Ventricular ectopy may be the initial and only clinical finding

• Echocardiography provides the most convenient way of evaluating cardiac function and can exclude many other processes

• MRI with gadolinium enhancement reveals spotty areas of injury throughout the myocardium, but both T2- and T1-weighted images are needed to achieve optimal results; correlation with endomyocardial biopsy results is poor

Endomyocardial Biopsy

• Confirmation of myocarditis requires histologic evidence

• The AHA/ACC/ESC class I recommendations for biopsy are

  • Patients with heart failure, a normal-sized or dilated left ventricle < 2 weeks after onset of symptoms, and hemodynamic compromise

  • Patients with a dilated left ventricle 2 weeks to 3 months after onset of symptoms, new ventricular arrhythmias or atrioventricular nodal block (Mobitz II or complete heart block) or who do not respond to usual care after 1–2 weeks

• Angiotensin-converting enzyme (ACE) inhibitors and beta-blockers are given if left ventricular ejection fraction (LVEF) is < 40%

• Nonsteroidal anti-inflammatory medications should be used if myopericarditis-related chest pain occurs

• Colchicine has been suggested if pericarditis predominates

• Arrhythmias should be suppressed

• Specific antimicrobial therapy is indicated when an infecting agent is identified

• Exercise should be limited during the recovery phase

• Some experts believe digoxin should be avoided, and it likely has little value in this setting anyway

• Immunosuppressive therapy with corticosteroids and intravenous immunoglobulin (IVIG), 2 g/kg over 24 hours, is recommended in some cases

• Patients with fulminant myocarditis require aggressive short-term support, including an IABP or an LV assist device

• If severe pulmonary infiltrates accompany the fulminant myocarditis, extracorporeal membrane oxygenation (ECMO) support may be temporarily required

Prognosis

• Acute myocarditis has been implicated as a cause of sudden death in 5–22% of such cases in athletes younger than 35 years; death rate is high

• Patients with subacute disease have a dilated cardiomyopathy and generally make an incomplete recovery

• Those who present with chronic disease tend to have only mild dilation of the LV and eventually present with a more restrictive cardiomyopathy

When to Refer

• Patients in whom myocarditis is suspected should be seen by a cardiologist at a tertiary care center where facilities are available for diagnosis and therapies available should a fulminant course ensue