Quick Recap
Cardiovascular System, Protocol 10/12.
1. Definition
Myocarditis = inflammation of the myocardium, typically from infectious (usually viral), autoimmune, toxin/drug, or immune-checkpoint-inhibitor-related causes, ranging from subclinical/self-limited disease to fulminant myocarditis — an abrupt, severe presentation with hemodynamic compromise/cardiogenic shock requiring ICU-level hemodynamic support, distinguished from non-fulminant ("acute") myocarditis by the abruptness and severity of onset rather than by histology alone.
Myocarditis is a recognized cause of both LV-predominant and RV-predominant cardiogenic shock (see Cardiogenic Shock protocol etiology table) and should be actively considered in any younger patient presenting with new unexplained heart failure/cardiogenic shock without prior cardiac history.
2. Pathophysiology
Viral (most common infectious cause): direct viral cytotoxicity followed by a T-cell-mediated immune response against infected/damaged myocytes; common viral triggers include coxsackievirus/enterovirus, adenovirus, parvovirus B19, human herpesvirus 6, influenza, and (increasingly recognized) SARS-CoV-2 and post-mRNA-vaccine myocarditis (typically mild/self-limited in the latter case).
Giant cell myocarditis: rare, idiopathic, T-cell-mediated with multinucleated giant cells on biopsy — aggressive course, high rate of progression to cardiogenic shock, high mortality without prompt immunosuppression; associated with thymoma and autoimmune disease in some cases.
Immune-checkpoint-inhibitor (ICI) myocarditis: increasingly recognized iatrogenic cause in oncology patients on PD-1/PD-L1 or CTLA-4 inhibitors — can be fulminant, often coexists with ICI-related myositis/myasthenia-like neuromuscular toxicity (screen for concurrent respiratory muscle weakness), requires urgent high-dose immunosuppression and ICI discontinuation.
Other causes: autoimmune/connective tissue disease-associated myocarditis, drug/toxin-induced (anthracyclines, cocaine), hypersensitivity/eosinophilic myocarditis (drug reaction), radiation-associated, sarcoidosis (granulomatous, arrhythmia-prone).
3. Immediate Stabilization (ABCDE)
Follow the Cardiogenic Shock protocol in full for hemodynamic stabilization (SCAI staging, inotrope/vasopressor selection, MCS escalation ladder) — fulminant myocarditis is managed as a cardiogenic shock etiology with the added considerations below.
Key myocarditis-specific considerations:
- Arrhythmia risk is high (both from the inflammatory process itself and from any conduction system involvement) — continuous telemetry is essential; be prepared for VT/VF and high-grade AV block, especially with giant cell myocarditis and cardiac sarcoidosis
- Avoid unnecessary NSAIDs — theoretical concern for worsening myocardial inflammation in the acute phase (extrapolated from post-MI pericarditis literature; direct myocarditis evidence is limited)
- Early recognition that fulminant myocarditis, despite severe initial presentation, often has a BETTER long-term recovery potential than other cardiogenic shock etiologies IF the patient survives the acute phase with adequate hemodynamic support — this shapes an aggressive-support, transplant-avoidance-where-possible strategy in appropriate candidates, in contrast to some other CS etiologies where early transplant/durable device listing may be prioritized sooner
- Low threshold for early MCS (including VA-ECMO) as a bridge to recovery given the potential for myocardial recovery with fulminant myocarditis specifically — early proactive MCS deployment before irreversible end-organ damage is a recognized strategy in this population
Checklist:
4. Focused History
Recent viral prodrome (fever, myalgias, GI symptoms in preceding days-weeks), chest pain (can mimic ACS), palpitations/syncope (arrhythmia), dyspnea/heart failure symptoms, current or recent immune checkpoint inhibitor therapy (and screen for concurrent myositis/ptosis/dysphagia suggesting overlapping ICI neuromuscular toxicity), known autoimmune disease, cocaine/stimulant use, anthracycline chemotherapy exposure, recent mRNA vaccination (typically mild, self-limited course), family history of cardiomyopathy/sudden death (consider genetic cardiomyopathy overlap in some presentations).
5. Examination + POCUS
Signs of heart failure/cardiogenic shock (Section 3, Cardiogenic Shock protocol), pericardial friction rub if concurrent myopericarditis, arrhythmia on exam, signs of the underlying trigger (rash/myopathy in ICI toxicity, stigmata of autoimmune disease).
POCUS/Echo: may show global or regional hypokinesis (can mimic Takotsubo or ACS pattern — wall motion abnormalities in myocarditis do NOT necessarily respect a single coronary territory, which is a useful discriminator from true coronary occlusion), reduced EF, pericardial effusion if myopericarditis, and RV involvement assessment.
6. Syndrome Identification
New unexplained cardiogenic shock/heart failure, particularly in a younger patient without prior cardiac history or significant CAD risk factors, should trigger active consideration of myocarditis — distinguish from ACS (Section 7) and from other cardiogenic shock etiologies via history, biomarker pattern, and imaging.
7. Differential Diagnosis
Tier | Examples |
Must exclude (mimics with overlapping presentation) | ACS/type 1 MI (coronary angiography often performed to exclude), Takotsubo/stress cardiomyopathy, sepsis-induced cardiomyopathy |
Common triggers to identify | Viral infection, ICI therapy, autoimmune disease flare |
Must-not-miss | Giant cell myocarditis (aggressive, needs urgent immunosuppression), cardiac sarcoidosis (arrhythmia risk, granulomatous), eosinophilic/hypersensitivity myocarditis (drug reaction) |
8. Severity Assessment
Apply the SCAI cardiogenic shock staging (see Cardiogenic Shock protocol) as the primary severity/escalation framework once fulminant myocarditis is causing shock. General ICU severity scores (SOFA/APACHE II) for overall prognostication.
9. Investigations
- Bedside: ECG (may show diffuse ST changes mimicking pericarditis/ACS, arrhythmia, conduction block), continuous telemetry, POCUS
- Labs: troponin (often markedly elevated, out of proportion to a discrete coronary territory), BNP/NT-proBNP, inflammatory markers (ESR/CRP), viral serologies/PCR panel as clinically indicated, autoimmune serologies if connective tissue disease suspected, eosinophil count (hypersensitivity myocarditis)
- Coronary angiography: often performed to exclude obstructive CAD/ACS as the cause of new cardiogenic shock, especially when the presentation overlaps with ACS
- Cardiac MRI: key non-invasive diagnostic tool once stable enough to undergo it — identifies myocardial edema, hyperemia, and late gadolinium enhancement (LGE) patterns consistent with myocarditis (typically non-coronary-territory distribution, often subepicardial/mid-wall LGE, distinguishing from the subendocardial-to-transmural pattern of ischemic injury)
- Endomyocardial biopsy (EMB): the diagnostic gold standard, particularly important when giant cell myocarditis or cardiac sarcoidosis is suspected, since these specifically change management (urgent immunosuppression) and prognosis; also relevant for confirming ICI-associated myocarditis when the diagnosis is uncertain. EMB is invasive and has a false-negative rate due to patchy myocardial involvement (sampling error), so a negative biopsy does not fully exclude the diagnosis.
10. Evidence-Based Management
Hemodynamic support: per Cardiogenic Shock protocol in full — inotropes/vasopressors per SCAI stage, early MCS/ECMO consideration given recovery potential (Section 3).
Immunosuppression — etiology-dependent, NOT routine for all myocarditis:
- Giant cell myocarditis: urgent high-dose immunosuppression (typically combination corticosteroids + additional agents such as cyclosporine/antithymocyte globulin per cardiology/EMB-guided protocols) — delay in immunosuppression is associated with worse outcomes; this is the myocarditis subtype where aggressive, EMB-confirmed immunosuppression has the clearest rationale
- ICI-associated myocarditis: immediate discontinuation of the checkpoint inhibitor + high-dose corticosteroids (methylprednisolone, often 500-1000mg/day initially, similar to other severe immune-related adverse event regimens) +/- additional immunosuppression (e.g., infliximab, ATG) for steroid-refractory cases per oncology/cardio-oncology guidance; screen for and treat concurrent ICI myositis/myasthenia given shared mechanism and respiratory muscle involvement risk
- Autoimmune-disease-associated myocarditis (e.g., SLE, sarcoidosis): treat per the underlying disease's immunosuppressive protocol (see relevant Endocrine/Rheumatology-adjacent protocols)
- Viral (non-giant-cell) myocarditis: no proven benefit to routine immunosuppression or antiviral therapy in the general viral myocarditis population — management is supportive; immunosuppression is reserved for biopsy-proven autoimmune/giant cell/eosinophilic subtypes, not applied empirically
Arrhythmia management: per the Arrhythmias protocol; low threshold for temporary pacing if high-grade AV block develops, particularly relevant in giant cell myocarditis and cardiac sarcoidosis.
Avoid/use cautiously: NSAIDs (theoretical inflammation concern), routine anticoagulation (individualize based on EF/thrombus risk, similar to other severe cardiomyopathy presentations — see ACS protocol mural thrombus discussion for the general principle).
11. Organ Support
See Cardiogenic Shock protocol for full inotrope/vasopressor/MCS detail; temporary pacing for high-grade block; standard ICU supportive care; nutrition and mobilization once stabilizing.
12. Consultation Matrix
Consultation | Trigger | Timing |
Cardiology/Advanced Heart Failure | All suspected myocarditis with hemodynamic compromise | Immediate |
Interventional Cardiology | Coronary angiography to exclude ACS | Immediate if diagnostic uncertainty with ACS |
Electrophysiology | High-grade AV block, VT/VF | Immediate |
Oncology/Cardio-oncology | ICI-associated myocarditis | Immediate |
Rheumatology | Autoimmune-disease-associated myocarditis | Urgent |
13. Monitoring Framework
Continuous telemetry (arrhythmia/heart block surveillance), serial troponin/BNP trend, serial echo for EF/recovery trend, hemodynamic monitoring per Cardiogenic Shock protocol, watch for immunosuppression-related complications (infection risk) if treated.
14. Complications
Cardiogenic shock, life-threatening arrhythmia/heart block, progression to dilated cardiomyopathy (in a subset, particularly if inadequately treated giant cell myocarditis or delayed recognition), death (highest in giant cell myocarditis without prompt immunosuppression). Prevention: early recognition, appropriate biopsy-guided immunosuppression for specific subtypes, arrhythmia surveillance. Rescue: MCS/ECMO as bridge to recovery or transplant, temporary pacing for heart block.
15. Escalation & De-escalation
Escalate: worsening SCAI stage despite medical therapy -> MCS/ECMO per Cardiogenic Shock protocol, especially given fulminant myocarditis's relatively favorable recovery potential once bridged through the acute phase.
De-escalate: improving EF/hemodynamics, arrhythmia resolving -> wean inotropes/MCS, transition to standard HF medical therapy (GDMT) as tolerated, continue immunosuppression taper if applicable per the specific etiology's protocol.
16. ICU Discharge Criteria
Hemodynamically stable off/on minimal support, arrhythmia controlled or defined management plan (e.g., ICD candidacy assessment if indicated), immunosuppression regimen (if applicable) established with follow-up plan, cardiology/advanced HF follow-up arranged, EF trend documented for prognostication.
17. Documentation & Medicolegal Checklist
18. Key Guidelines
American Heart Association Scientific Statement on Fulminant Myocarditis (Kociol et al., Circulation 2020, general reference — verify current edition); ESC Position Statement on Myocarditis; ASCO/oncology society guidance on immune-related adverse event (irAE) management for ICI-associated myocarditis.
19. Controversies
Role of routine cardiac MRI vs endomyocardial biopsy in diagnostic workup remains debated — MRI is less invasive and increasingly used as a primary diagnostic tool, but biopsy remains necessary when giant cell myocarditis or sarcoidosis is specifically suspected given the direct management implications and MRI's lower specificity for these subtypes. Immunosuppression for non-giant-cell, non-ICI, non-autoimmune viral myocarditis remains unsupported by evidence despite occasional empiric use in severe cases — this is a genuine area where practice sometimes outpaces evidence. Optimal timing/threshold for MCS/ECMO deployment (early proactive vs reserved for refractory shock) mirrors the same debate as in the general Cardiogenic Shock protocol, but is arguably weighted more toward early/proactive support here given the recognized recovery potential specific to fulminant myocarditis.
20. References
- Cardiogenic Shock etiology table (fulminant myocarditis as LV/RV failure cause). Washington Manual of Critical Care, 4th ed, 2025 (Ch. 4).
- Jennette JC, Falk RJ, Bacon PA, et al. 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides (referenced for autoimmune myocarditis overlap). Arthritis Rheum. 2013;65(1):1-11.
- Kociol RD, Cooper LT, Fang JC, et al. Recognition and initial management of fulminant myocarditis: a scientific statement from the American Heart Association. Circulation. 2020;141(6):e69-e92.
- Caforio ALP, Pankuweit S, Arbustini E, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: ESC position statement. Eur Heart J. 2013;34(33):2636-2648.
- Puzanov I, Diab A, Abdallah K, et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations. J Immunother Cancer. 2017;5:95 (irAE myocarditis management framework).