Myocarditis is an inflammatory disease of the myocardium caused by infectious or noninfectious etiologies, presenting classically with chest pain, arrhythmia, and/or heart failure/cardiogenic shock. [1-2] It predominantly affects young males (median age 30–45 years; 60–80% male) and is most commonly viral in etiology in Western countries. [2-3]
The following figure illustrates the broad etiologic categories of myocarditis:
1. History
- Key HPI: Acute onset chest pain (82–95%), dyspnea (19–49%), fever (58–65%), palpitations, syncope (5–7%) [2]
- Antecedent illness: URI or GI viral prodrome 1–4 weeks prior is classic — ask specifically about recent febrile illness [1]
- Timing: Symptom onset relative to viral illness, vaccination (mRNA COVID-19, smallpox), or new medication (immune checkpoint inhibitors, clozapine) [1-2]
- Severity/progression: Rapidly worsening dyspnea, exercise intolerance, orthopnea, or exertional presyncope suggest complicated myocarditis [3]
- Important negatives: Absence of exertional angina pattern, no prior CAD, no pleuritic component (though myopericarditis may have pleurisy)
2. Alarm Features
- Cardiogenic shock (3–9% of acute myocarditis = fulminant myocarditis) [2]
- Syncope or presyncope — suggests hemodynamically significant arrhythmia or high-degree AV block [3]
- Sustained ventricular tachycardia or ventricular fibrillation [2]
- New advanced AV block (Mobitz II or third-degree) [5]
- Rapidly declining LVEF — cardiac function may deteriorate rapidly in the initial days [2]
- Hemodynamic instability: hypotension, tachycardia, signs of low cardiac output
- Peripheral eosinophilia — raises concern for eosinophilic myocarditis requiring targeted therapy [3]
3. Medications
Relevant medication contributors
- Immune checkpoint inhibitors (anti-PD-1, anti-CTLA-4): rare but potentially fatal myocarditis [1-2]
- Clozapine: well-recognized cause of drug-induced myocarditis
- Anthracyclines (doxorubicin), trastuzumab: cardiotoxicity with inflammatory component [1]
- Illicit substances: cocaine, methamphetamine [1]
Common treatments
- Uncomplicated (preserved LVEF, chest pain only): NSAIDs (aspirin or ibuprofen) ± colchicine for pericardial-type pain [1]
- HF with reduced EF: ACEi/ARB/ARNI, beta-blocker, MRA, SGLT2i per GDMT [2]
- Arrhythmia: amiodarone for VT; temporary pacing for high-degree AV block [2]
- Fulminant: inotropes (norepinephrine, milrinone), mechanical circulatory support (IABP, VA-ECMO) [2]
- Etiology-specific immunosuppression: high-dose IV methylprednisolone for giant cell myocarditis, ICI-associated myocarditis, eosinophilic myocarditis, and cardiac sarcoidosis [2-3]
Contraindications/cautions
- Avoid NSAIDs in patients with symptomatic HF or shock [1]
- Beta-blockers can precipitate cardiogenic shock in patients with severely compromised cardiac function — use cautiously [6]
4. Diet
- Sodium restriction if heart failure is present
- Fluid restriction in decompensated HF
- Avoid alcohol — direct myocardial toxin that can worsen inflammation
- Avoid stimulants (caffeine in excess, energy drinks) given arrhythmia risk
5. Review of Systems
- Cardiovascular: chest pain, dyspnea, orthopnea, PND, palpitations, syncope, edema
- Constitutional: fever, malaise, fatigue (viral prodrome)
- Respiratory: cough, URI symptoms preceding presentation
- GI: nausea, vomiting, diarrhea (viral prodrome or right heart failure)
- Musculoskeletal: myalgias, arthralgias (systemic autoimmune disease)
- Dermatologic: rash (lupus, drug hypersensitivity, eosinophilic syndromes)
- Neurologic: weakness (associated myasthenia gravis with thymoma) [1]
6. Collateral History and Family History
- Family history of cardiomyopathy or unexplained sudden death — pathogenic variants in DSP and TTN are consistently associated with myocarditis [1]
- Family history of myocarditis — defines Stage A at-risk [1]
- Personal history of autoimmune disease (SLE, sarcoidosis, rheumatoid arthritis) [1]
- Recent travel to endemic areas (Chagas disease, dengue) [2][5]
- Medication/substance use history: ICI therapy, recreational drug use
- Vaccination history: mRNA COVID-19 (especially young males, 3–5 days after second dose), smallpox vaccine [2]
7. Risk Factors
- Male sex, age 30–45 years [2]
- Viral infections: enteroviruses, parvovirus B19, HHV-6, adenovirus, influenza, SARS-CoV-2 [3]
- Genetic predisposition: pathogenic variants in DSP, TTN genes (found in 8–16% of myocarditis patients) [1-2]
- Immune checkpoint inhibitor therapy [1]
- Systemic autoimmune/inflammatory disease: sarcoidosis, SLE, vasculitis [1]
- Cardiotoxic drugs: cocaine, methamphetamine, clozapine, anthracyclines [1]
- mRNA COVID-19 vaccination: ~2.1/100,000 persons; higher in males 16–29 years (~10.7/100,000) [2]
- Hypereosinophilia [1]
8. Differential Diagnosis
- Acute coronary syndrome — the primary alternative diagnosis to rule out; coronary angiography/CTA performed in 46–95% of suspected myocarditis cases [2]
- Takotsubo (stress) cardiomyopathy — apical ballooning, emotional/physical trigger, typically postmenopausal women
- Acute pericarditis — may overlap as myopericarditis; diffuse ST elevation, PR depression
- Pulmonary embolism — troponin elevation, RV strain, dyspnea
- Desmoplakin cardiomyopathy "hot phase" — mimics myocarditis with arrhythmias and inflammation; genetic testing critical [7]
- Cardiac sarcoidosis — may present as myocarditis with conduction disease; FDG-PET helpful [2]
- Giant cell myocarditis — fulminant course, unresolving inflammation; requires EMB for diagnosis [7]
- Spontaneous coronary artery dissection (SCAD) — especially in young women, peripartum [2]
9. Past Medical History
- Prior myocarditis — recurrence risk; defines Stage A [1]
- Autoimmune diseases: SLE, sarcoidosis, inflammatory myopathies
- Cancer and ICI therapy history
- Substance use disorder: cocaine, methamphetamine
- Known cardiomyopathy or genetic cardiac disease
- HIV status — both direct viral myocarditis and opportunistic infections [3]
- Recent organ transplant or immunosuppression
10. Physical Exam
Vital signs
- Tachycardia (most common), hypotension (fulminant), fever
- Tachypnea if HF present
Focused exam
- Cardiac: S3 gallop (ventricular dysfunction), new murmur (mitral regurgitation from LV dilation), muffled heart sounds (pericardial effusion), pericardial friction rub (myopericarditis)
- Lungs: crackles/rales (pulmonary edema)
- JVP: elevated in right heart failure
- Extremities: peripheral edema, cool extremities (low cardiac output)
- Skin: rash (drug hypersensitivity, lupus), track marks (IVDU)
- Lymphadenopathy: sarcoidosis, lymphoma
11. Lab Studies
Recommended labs
- High-sensitivity troponin I or T: elevated in 64–100% of patients; serial measurements recommended [2]
- CRP: elevated in 54–99% [2]
- BNP/NT-proBNP: elevated with ventricular dysfunction
- CBC with differential: leukocytosis; eosinophilia raises concern for eosinophilic myocarditis [1]
- BMP/CMP: renal function, electrolytes (arrhythmia risk)
Targeted labs based on clinical context
- Lyme serology (Borrelia antibodies) if endemic area or conduction disease [2]
- HIV testing [2]
- ANA, ESR if autoimmune etiology suspected
- Peripheral eosinophil count — if elevated, consider eosinophilic myocarditis [3]
Monitoring
- Serial troponin to assess trajectory
- Serial BNP for HF management
12. Imaging
First-line
Gold standard
Rule out ACS
- Coronary angiography or coronary CTA[2]
When imaging is unnecessary
13. Special Tests
- Endomyocardial biopsy (EMB) — the other pivotal diagnostic test; indicated for: [2-3][5]
- Cardiogenic shock or acute HF requiring inotropes/MCS
- Sustained VT or Mobitz II/third-degree AV block
- Failure to respond to GDMT within 1–2 weeks
- Suspected giant cell myocarditis, ICI-associated myocarditis, eosinophilic myocarditis
- Peripheral eosinophilia
- Dallas criteria (histologic): myocardial immune infiltration + nonischemic myocyte death + immune cells adjacent to dead myocytes [2]
- FDG-PET: useful for cardiac sarcoidosis (tracer uptake in myocardium, lungs, lymph nodes) [2]
- Genetic testing: recommended for all consenting patients given increasing recognition of genetic predisposition (DSP, TTN variants); cascade screening of family members if pathogenic variant found [1]
14. ECG
Abnormal in 62–96% of patients: [2]
- ST-segment elevation (58–70%) — mimics STEMI, typically in inferior and lateral leads [2]
- T-wave inversions
- Low voltage, reduced R-wave height
- PR depression (pericardial involvement)
- AV block: first- through third-degree [1]
- Bundle branch block
- Ventricular arrhythmias: PVCs, NSVT, sustained VT/VF [1]
- Sinus tachycardia — most common rhythm abnormality
- Atrial fibrillation [1]
Dangerous patterns
- New high-degree AV block (Mobitz II, complete heart block) — consider Lyme, sarcoidosis, giant cell myocarditis [2]
- Polymorphic VT in active myocarditis vs. monomorphic VT in chronic myocarditis [3]
15. Assessment
Severity stratification (2024 ACC 4-Stage Classification): [1]
- Stage A: At-risk (risk factors present, no evidence of disease)
- Stage B: Asymptomatic with evidence of myocardial inflammation
- Stage C: Symptomatic myocarditis
- Stage D: Advanced myocarditis (hemodynamic or electrical instability requiring intervention)
Prognosis
- ~50% of biopsy-proven cases resolve in 2–4 weeks [1]
- ~25% develop persistent cardiac dysfunction [1]
- 12–25% may deteriorate to end-stage DCM, death, or transplant [1]
- Sudden cardiac death incidence in young adults: ~6–10% [2]
- Key adverse prognostic factors: biventricular reduced EF, symptomatic HF, cardiogenic shock, recurrent ventricular arrhythmias, advanced AV block, presence of LGE on CMR, giant cell histology [1]
The following Kaplan-Meier curves demonstrate the strong prognostic significance of late gadolinium enhancement on CMR — patients without LGE had no sudden cardiac death events during long-term follow-up:
16. Treatment Plan
Uncomplicated myocarditis (preserved LVEF, chest pain only):
- NSAIDs (aspirin or ibuprofen) ± weight-adjusted colchicine for pericardial-type chest pain [1]
- Beta-blocker may be considered [2]
- Activity restriction: no competitive sports or intense exercise for 3–6 months [2][5]
Complicated myocarditis (reduced LVEF, HF, arrhythmia)
- GDMT for HFrEF: ACEi/ARB/ARNI + beta-blocker + MRA + SGLT2i [2]
- Amiodarone for sustained VT; temporary pacing for high-degree AV block [2]
- Avoid NSAIDs in symptomatic HF [1]
Fulminant myocarditis (cardiogenic shock)
- Inotropes: norepinephrine, epinephrine, milrinone [2]
- Mechanical circulatory support: IABP, VA-ECMO, Impella [2]
- Transplant-free survival with MCS: 66–76% [2]
- If no weaning from MCS after 2–3 weeks → consider LVAD or urgent transplant [2]
Etiology-directed immunosuppression: [2-3]
- Giant cell myocarditis: antithymocyte globulin + cyclosporine + high-dose IV methylprednisolone
- ICI-associated: stop ICI + high-dose IV corticosteroids ± abatacept, alemtuzumab
- Eosinophilic myocarditis: corticosteroids (in-hospital mortality 9.9% with steroids vs. 65.7% without)
- Cardiac sarcoidosis: corticosteroids; methotrexate or azathioprine as second-line
- Virus-negative chronic inflammatory cardiomyopathy: prednisone + azathioprine may improve LVEF [3]
Important: Empirical immunosuppression should generally be guided by EMB to exclude active viral infection before initiation. The ESC recommends viral genome analysis on biopsy samples before immunosuppressive therapy. [3]
17. Disposition
Admit (hospitalization recommended): [6]
- Elevated troponin with abnormal ECG/echo/CMR findings
- Any degree of LV systolic dysfunction
- Concerning arrhythmias (VT, high-degree AV block)
- Hemodynamic instability
- Definite myocarditis of any severity (mild or moderate) — ideally at an advanced HF center
Transfer to advanced HF center: [1]
- Severely reduced ventricular function
- Cardiogenic shock
- Electrical instability (sustained VT, advanced AV block)
- Need for MCS or transplant evaluation
Outpatient management may be considered: [6]
- Chest pain as only symptom
- Preserved LVEF
- No ventricular arrhythmias
- Stable hemodynamics
- Close follow-up arranged
ICD consideration: May be considered in patients at high risk for ventricular arrhythmias (initial VT presentation, biopsy-proven sarcoidosis or giant cell myocarditis), but generally deferred during the acute phase given potential for recovery [2]
18. Follow Up / Return Precautions
Follow-up timeline (per 2024 ACC Consensus): [1]
- 2–4 weeks: Repeat echocardiogram to detect progressive LV dysfunction (may unmask giant cell myocarditis)
- 6 months: Follow-up imaging — echocardiogram (low-risk) or CMR (medium/high-risk or Stage D) to assess for residual edema, LGE, and ventricular function
- 6 months: Troponin, ECG, ambulatory rhythm monitoring, exercise testing before return to activity [2]
- Persistent LGE without edema on follow-up CMR is the strongest independent predictor of adverse cardiac events (HR 4.5) [1]
Return precautions — instruct patients to seek immediate care for:
- New or worsening chest pain
- Shortness of breath at rest or with minimal exertion
- Syncope or presyncope
- Palpitations or irregular heartbeat
- New lower extremity swelling
Activity restriction
- No competitive sports or strenuous exercise for 3–6 months [2][5]
- Return to play guided by follow-up CMR, 24-hour Holter, and exercise testing at ~6 months [1]
Genetic counseling
Expected recovery
- Most patients with uncomplicated myocarditis (chest pain, preserved LVEF, no LGE) have excellent prognosis — no deaths or transplants at 5 years in one registry [3]
- ~20% of myocarditis patients may develop dilated cardiomyopathy after 1 year [9]
References
1. 2024 ACC Expert Consensus Decision Pathway on Strategies and Criteria for the Diagnosis and Management Of Myocarditis: A Report of the American College of Cardiology Solution Set Oversight Committee. — Drazner MH, Bozkurt B, Cooper LT, et al. Journal of the American College of Cardiology. 2025.
2. Diagnosis and Treatment of Acute Myocarditis: A Review. — Ammirati E, Moslehi JJ. The Journal of the American Medical Association. 2023.
3. Myocarditis. — Basso C. The New England Journal of Medicine. 2022.
4. Immune Mechanisms of Viral, Autoimmune, and Immune Checkpoint Inhibitor‐Associated Myocarditis. — Jo W, Sun V, Čiháková D. Immunological Reviews. 2026.
5. Current Diagnostic and Treatment Strategies for Specific Dilated Cardiomyopathies: A Scientific Statement From the American Heart Association. — Bozkurt B, Colvin M, Cook J, et al. Circulation. 2016.
6. 2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19 in Adults: Myocarditis and Other Myocardial Involvement, Post-Acute Sequelae of SARS-CoV-2 Infection, and Return to Play: A Report of the American College of Cardiology Solution Set Oversight Committee. — Gluckman TJ, Bhave NM, Allen LA, et al. Journal of the American College of Cardiology. 2022.
7. Myocarditis and Look-Alikes: When the Diagnosis Matters. — Marchetta M, Weber BN, Gasperetti A, et al. Heart. 2026.
8. Long-Term Follow-Up of Biopsy-Proven Viral Myocarditis: Predictors of Mortality and Incomplete Recovery. — Grün S, Schumm J, Greulich S, et al. Journal of the American College of Cardiology. 2012.
9. Dilated Cardiomyopathy: Causes, Mechanisms, and Current and Future Treatment Approaches. — Heymans S, Lakdawala NK, Tschöpe C, Klingel K. Lancet. 2023.