Myocarditis

Risk factors

• Recent viral illness (parvovirus B19, HHV-6, coxsackievirus, adenovirus, influenza, SARS-CoV-2)
• Immune checkpoint inhibitor therapy (pembrolizumab, nivolumab, ipilimumab) — can cause fulminant myocarditis
• Bacterial (Lyme, diphtheria), protozoal (Trypanosoma cruzi → Chagas disease), parasitic infections
• Autoimmune disease (SLE, sarcoidosis, giant cell myocarditis, eosinophilic disorders)
• Cardiotoxic drug or toxin exposure (anthracyclines, clozapine, cocaine, heavy alcohol)
• Hypersensitivity reactions (sulfonamides, penicillins, certain antiepileptics)

Pathophysiology

Viral or other antigen-driven injury triggers a multi-phase response: (1) initial viral replication and direct myocyte damage; (2) innate and adaptive immune activation with infiltration of lymphocytes, macrophages, and sometimes eosinophils, often producing maximal myocardial injury; (3) variable outcomes — recovery, dilated cardiomyopathy, or chronic inflammatory cardiomyopathy. Giant cell myocarditis and eosinophilic myocarditis represent particularly aggressive subtypes.

Clinical presentation

Differential diagnosis

• Acute coronary syndrome — Older patient, atherosclerotic risk factors, regional wall motion abnormality matching a coronary distribution; coronary angiography distinguishes
• Stress (Takotsubo) cardiomyopathy — Postmenopausal women after major stressor; apical ballooning, transient LV dysfunction with normal coronaries
• Acute pericarditis — Sharp pleuritic pain, friction rub, diffuse concave ST elevation with PR depression; troponin only mildly elevated unless myopericarditis
• Dilated cardiomyopathy (other etiology) — Chronic insidious presentation; family history may suggest genetic cause
• Sepsis-related cardiomyopathy — Critically ill patient with systemic infection; reversible LV dysfunction tracks with sepsis resolution
• Tachycardia-induced cardiomyopathy — Persistent tachyarrhythmia (e.g., AFib with RVR); EF improves with rate/rhythm control
• Cardiac sarcoidosis — Conduction disease (AV block), VT in younger patient, extracardiac sarcoid (lung, lymph node); FDG-PET and cardiac MRI characteristic

Diagnostic workup

Diagnostic algorithm

flowchart TD
  A[Suspected myocarditis<br/>new HF / chest pain / arrhythmia<br/>+ recent viral prodrome] --> B[ECG, troponin, BNP<br/>echocardiogram]
  B --> C{Obstructive CAD<br/>excluded?}
  C -->|No| D[Coronary angio or CTA]
  C -->|Yes| E[Cardiac MRI<br/>Lake Louise criteria]
  E --> F{Hemodynamically<br/>stable?}
  F -->|Yes| G[Supportive care<br/>GDMT for HFrEF<br/>exercise restriction]
  F -->|No / arrhythmia<br/>or refractory| H[Endomyocardial biopsy]
  H --> I{Specific<br/>histology?}
  I -->|Giant cell / eosinophilic /<br/>sarcoid / ICI| J[Immunosuppression<br/>± advanced support]
  I -->|Lymphocytic| G
  H --> K[MCS bridge:<br/>IABP / Impella / VA-ECMO]

Treatment

Complications

• Cardiogenic shock and death (fulminant myocarditis)
• Progression to chronic dilated cardiomyopathy
• Sustained ventricular tachyarrhythmias and sudden cardiac death
• AV block requiring permanent pacing (especially in Lyme, sarcoid, giant cell forms)
• Mural thrombus and systemic embolization in dilated, akinetic LV

PANCE pearls

• Suspect myocarditis in any young patient with new-onset heart failure or unexplained ventricular arrhythmia, especially after a viral illness.
• Cardiac MRI with Lake Louise criteria (edema + late gadolinium enhancement) is the noninvasive diagnostic standard; biopsy is reserved for aggressive, refractory, or specific-treatment-changing cases.
• Giant cell myocarditis: rapidly progressive HF and VT in young/middle-aged adults — requires aggressive immunosuppression and often urgent transplant evaluation.
• Checkpoint inhibitor myocarditis: rare but high mortality — stop the offending agent and give high-dose steroids; consult cardio-oncology early.
• Return-to-play guidance: avoid competitive exercise for at least 3-6 months after presumed viral myocarditis; resume only after normalization of EF, troponin, and absence of arrhythmia on testing.

References

• AHA 2020 — AHA Scientific Statement: Recognition and Initial Management of Fulminant Myocarditis (Kociol et al., Circulation 2020)
• ESC 2013 — ESC Working Group on Myocardial and Pericardial Diseases — Position Statement on Myocarditis (Caforio et al., Eur Heart J 2013)
• Lake Louise Criteria 2018 — Cardiovascular Magnetic Resonance in Nonischemic Myocardial Inflammation: Expert Recommendations (Ferreira et al., JACC 2018)
• AHA/ACC/HFSA 2022 — 2022 Guideline for the Management of Heart Failure (Heidenreich et al., JACC 2022)