Immune checkpoint inhibitor-induced cardiotoxicity: from immune mechanisms to clinical surveillance and targeted therapies.

Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape across a broad range of malignancies by restoring antitumor immunity through blockade of key inhibitory immune pathways, including programmed death receptor-1 (PD-1), programmed death ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). Yet the same widespread immune activation that drives their therapeutic benefit renders patients susceptible to immune-related adverse events (irAEs). Among these cardiovascular toxicities have emerged as a particularly critical concern, drawing growing attention within the evolving field of cardio-oncology. ICI-associated cardiotoxicity encompasses a broad clinical spectrum, ranging from myocarditis and pericarditis to arrhythmias, heart failure, and vascular complications. Of these, immune-mediated myocarditis is the most severe, carrying a disproportionately high mortality risk despite its relatively low incidence. Its pathophysiology is multifaceted, driven by dysregulated immune activation, myocardial inflammation, T-cell-mediated cytotoxicity, aberrant cytokine release, and molecular mimicry between tumor and cardiac antigens. Additional mechanisms-including B-cell activation, complement cascade signaling, and inflammasome pathway engagement-may further amplify myocardial injury and heighten arrhythmogenic susceptibility. In this review, we summarize current insights into the immunological mechanisms underlying ICI-induced cardiotoxicity and examined the expanding clinical spectrum of cardiovascular irAEs. We further discuss strategies for early detection, risk stratification, and clinical surveillance, encompassing biomarker monitoring and multimodal imaging. Emerging therapeutic strategies targeting implicated immune pathways are also being explored to mitigate cardiovascular complications without compromising anticancer efficacy. A deeper mechanistic understanding will be essential for advancing the prevention, diagnosis, and management of ICI-associated cardiovascular toxicity in oncology practice.