Background: Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, but ICI myocarditis (ICI-M) remains a potentially fatal complication. The clinical implications and predictors of left ventricular ejection fraction (LVEF) <50% in ICI-M are not well understood.
Objective: This study aimed to identify factors associated with LVEF <50% versus ≥50% at the time of hospitalization for ICI-M. A secondary objective was to evaluate the relationship between LVEF and 30-day all-cause mortality.
Methods: The International ICI-Myocarditis Registry, a retrospective, international, multicenter database, included 757 patients hospitalized with ICI-M. Patients were stratified by LVEF as reduced LVEF (<50%) or preserved LVEF (≥50%) on admission. Cox proportional hazards models assessed the associations between LVEF and clinical events, and multivariable logistic regression examined factors linked to LVEF.
Results: Of 757 patients, 707 had documented LVEF on admission: 244 (35%) with LVEF <50% and 463 (65%) with LVEF ≥50%. Compared with patients with LVEF ≥50%, those with LVEF <50% were younger (<70 years), had a body mass index of less than 25kg/m2, and were more likely to have received chest radiation (24.2% vs 13.5%; P < 0.001). Multivariable analysis identified predictors of LVEF <50%, including exposure to BRAF/MEK inhibitors, preexisting heart failure, dyspnea at presentation, and at least 40 days from ICI initiation to ICI-M onset. Conversely, myositis symptoms were associated with LVEF ≥50%. LVEF <50% was marginally associated with 30-day all-cause mortality (unadjusted log-rank P = 0.062; adjusted for age, cancer types, and ICI therapy, hazard ratio 1.50; 95% confidence interval: 1.02-2.20).
Conclusions: Dyspnea, time from ICI initiation, a history of heart failure, and prior cardiotoxic therapy may be predictors for an initial LVEF <50% in patients with ICI-M.
JACC CardioOncology Editor-in-Chief and CME Editor
Bonnie Ky, MD, MSCE, FACC
Author
Megan Pelter, MD
Important Dates
Date of Release: April 15, 2025
Term of Approval/Date of CME/MOC Expiration: April 14, 2026