Real-World Incidence of Cancer Therapy–Related Cardiac Dysfunction in a Large, Diverse, and Contemporary Cohort

AIMS: Cancer therapy-related cardiac dysfunction (CTRCD) is a significant complication of contemporary oncologic treatment and a key contributor to incident heart failure (HF) in cancer survivors. Although certain potentially cardiotoxic cancer therapies are known to increase risk, contemporary population-based estimates in large, diverse, and contemporary cohorts remain limited. The aim of the Kaiser Permanente Cardiovascular Health Enhancement and Monitoring for Oncology (KP CHEMO) study was to determine the incidence, timing, and treatment-specific variation in CTRCD among adults receiving potentially cardiotoxic cancer therapies within an integrated United States (U.S.) health system. METHODS AND RESULTS: We conducted a retrospective cohort study of adult Kaiser Permanente Northern California (KPNC) members diagnosed with malignant tumors between 2012 and 2022 who received anthracyclines, human epidermal growth factor receptor (HER2) inhibitors, immune checkpoint inhibitors (ICIs), or tyrosine kinase inhibitors (TKIs). CTRCD was defined as a >10% decline in left ventricular ejection fraction (LVEF) to <53% or incident HF identified by natural language processing. Crude and cumulative incidence rates were calculated overall and by drug class. Early CTRCD was ≤12 months; late was >12 months. Among 26,646 patients (mean age 62±14 years; 64% women; 57% non-Hispanic White), the cumulative incidence of CTRCD was 8.4% (95% CI 7.7-9.1). Incidence was highest with HER2 inhibitors (10.7%) and lowest with ICIs (5.2%) (P<0.001). Nearly half of all events occurred within the first year. CONCLUSIONS: CTRCD was common and occurred predominantly within the first year after therapy initiation, potentially reflecting both early susceptibility and more intensive early surveillance. Variation across drug classes highlights differing cardiotoxic risk profiles. These findings support early risk prediction models and targeted surveillance strategies to reduce downstream HF risk.