Immune checkpoint inhibitor-induced arrhythmias: Mechanistic insights from clinical and preclinical studies

Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, but their efficacy continues to be limited by immune-related adverse events. Among these, ICI-induced cardiac arrhythmias are increasingly recognised as a major adverse reaction, encompassing a broad spectrum of clinical phenotypes, including conduction blocks, atrial fibrillation and ventricular arrhythmias. These electrical disorders are not temporally constrained and can occur in isolation or alongside other cardiac complications. Clinically, ICI-induced arrhythmias are just as significant as myocarditis and often lead to treatment interruption, hospitalisation and sudden death. Despite this, the mechanisms driving ICI-induced electrical disturbances remain poorly understood, in part because of limited integration of clinical and preclinical insights. Here, we review emerging evidence on ICI-induced arrhythmias and present a conceptual framework that outlines key factors in their pathogenesis, including immune-driven injury, immune-independent secondary amplifiers, and patient-related susceptibility factors. Understanding these mechanistic pathways is essential for improving risk stratification, surveillance and management in patients receiving ICI therapy.