Electrophysiologic Phenotype Outperforms Left Ventricular Ejection Fraction for Mortality Prediction in Immune Checkpoint Inhibitor Myocarditis

BACKGROUND: Immune checkpoint inhibitor (ICI)-associated myocarditis carries mortality rates approaching 50%. Risk stratification relies heavily on left ventricular ejection fraction (LVEF), yet many fatal cases occur despite preserved systolic function. OBJECTIVES: The study aims to compare the prognostic value of electrophysiologic involvement vs LVEF in ICI-associated myocarditis. METHODS: We systematically searched PubMed for ICI-associated myocarditis cases with extractable patient-level data. Electrophysiologic phenotype (EP) was defined by clinically significant conduction disease or ventricular arrhythmia, including high-grade atrioventricular block, ventricular tachycardia, ventricular fibrillation, or cardiac arrest. LVEF was dichotomized at ≤35%. Cluster-robust logistic regression was used to assess associations with mortality. RESULTS: From 242 publications, 319 cases were extracted; 180 with complete data comprised the analytical cohort (77 deaths; 42.8% mortality). EP involvement (66.7% of cases) was associated with significantly higher mortality vs EP-negative cases (55.0% vs 18.3%; risk ratio: 3.00; 95% CI: 1.72-5.24; P < 0.001). LVEF ≤35% was not significantly associated with mortality (50.7% vs 38.1%; P = 0.125). Among patients with an LVEF >35%, EP involvement was associated with markedly higher mortality (55.1% vs 11.4%; P < 0.001). In adjusted models, EP remained associated with mortality on both the odds-ratio scale (OR: 5.27; 95% CI: 2.29-12.13; P < 0.001) and risk-ratio scale (RR: 2.94; 95% CI: 1.54-5.59; P < 0.001), whereas LVEF ≤35% was not independently associated with mortality. CONCLUSIONS: Electrophysiologic involvement is a dominant prognostic marker in ICI-associated myocarditis, particularly for risk stratification among patients with an LVEF >35%. Risk stratification should prioritize cardiac rhythm monitoring and identification of conduction abnormalities over reliance on LVEF alone.