Arrhythmic outcomes following immune checkpoint inhibitor (ICI) therapy in patients with non–small cell lung cancer (NSCLC) without heart failure or myocarditis.

Abstract

e24006 Background: Despite the established prognostic benefit, immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs), including cardiovascular complications such as new-onset heart disease and myocarditis. However, data on the occurrence of atrial and ventricular arrhythmias following ICI therapy remain conflicting. We therefore leveraged a large real-world database to evaluate the association between ICI therapy and incident arrhythmias in patients with non–small cell lung cancer (NSCLC). Methods: We conducted a retrospective cohort study using data from the U.S. Collaborative Network, spanning January 2020 through January 2025. Adult patients with NSCLC treated with ICI therapy were included. Patients with a prior history of cardiac arrest, implantable cardioverter-defibrillator implantation, myocarditis, or any atrial or ventricular arrhythmia before the index date were excluded. Additionally, patients who developed myocarditis during follow-up were excluded given its known association with arrhythmic risk. The index date was defined as the date of first ICI administration, and patients were followed for up to 36 months. The primary outcome was the incidence of overall arrhythmia, defined as new-onset atrial fibrillation (AF), atrial flutter, supraventricular tachycardia (SVT), or ventricular tachycardia (VT) after ICI initiation. Secondary outcomes included AF requiring cardioversion or antiarrhythmic therapy, AF or atrial flutter, and VT. Baseline characteristics, including demographics, comorbidities, laboratory values, and medication use, were balanced using propensity score matching to improve comparability between groups. Results: After propensity score matching, 72,498 patients were included in each group, with no significant differences in baseline characteristics or medication use. The mean age was 77 years; 55% were male, 68% were White, and 9.8% were Black. Over a 36-month follow-up period, patients receiving ICI therapy had a higher incidence of overall arrhythmia (HR 1.07, 95% CI 1.05–1.10), AF requiring cardioversion or antiarrhythmic therapy (HR 1.15, 95% CI 1.10–1.20), AF or atrial flutter (HR 1.04, 95% CI 1.01–1.07), and VT (HR 1.12, 95% CI 1.03–1.23). Conclusions: Among patients with NSCLC without prior heart failure, myocarditis, or arrhythmia, ICI therapy was associated with a significantly increased risk of atrial and ventricular arrhythmias. These findings suggest that ICI therapy in NSCLC is associated with clinically meaningful arrhythmic risk even in the absence of myocarditis or heart failure, supporting proactive cardiovascular surveillance during treatment.