Electrophysiologic Phenotype Outperforms Left Ventricular Ejection Fraction for Mortality Prediction in Immune...

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.

The study aims to compare the prognostic value of electrophysiologic involvement vs LVEF in ICI-associated myocarditis.

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.

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.

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.