Advancing precision cardio-oncology: multimodal surveillance and stratified management of immunotherapy-induced cardiovascular toxicity

Abstract

The advent of immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell (CAR-T) therapies has revolutionized oncology but is increasingly associated with severe cardiovascular immune-related adverse events (irAEs). This narrative review comprehensively examines the epidemiology, pathophysiologic mechanisms, biomarkers, advanced imaging, and management strategies for immunotherapy-associated cardiovascular toxicities. ICI-associated myocarditis is a rare but potentially fatal complication occurring early in therapy, particularly with combination regimens, while the broader cardiovascular spectrum also encompasses pericarditis, arrhythmias, heart failure, and accelerated atherosclerosis. Mechanistically, preclinical data suggest that ICI-associated myocarditis is hypothesized to be mediated by autoreactive CD8+ T-cell cross-reactivity against shared cardiac antigens, macrophage expansion, and inflammatory cytokine signaling, whereas CAR-T cardiovascular toxicity appears to contribute primarily secondary to systemic cytokine release syndrome (CRS). For early detection and risk stratification, high-sensitivity cardiac troponin remains the foundational biomarker, complemented by advanced multimodal imaging such as global longitudinal strain (GLS) echocardiography, cardiac magnetic resonance (CMR), and emerging molecular positron emission tomography (PET). High-dose systemic corticosteroids remain the first-line intervention for symptomatic ICI-associated myocarditis, with targeted therapies like abatacept and ruxolitinib showing promise for steroid-refractory cases. Ultimately, proactive risk factor assessment and multidisciplinary cardio-oncology surveillance are imperative to mitigate acute toxicities and long-term atherosclerotic risks, ensuring optimal patient outcomes.