Real-world incidence of cancer therapy–related cardiac dysfunction in a large, diverse, and contemporary cohort

BACKGROUND AND AIMS: Cancer therapy-related cardiac dysfunction (CTRCD) is a complication of contemporary oncologic treatment and a contributor to incident heart failure (HF) in cancer survivors. Although certain potentially cardiotoxic cancer therapies are known to increase risk, 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 within an integrated US health system. METHODS AND RESULTS: We conducted a retrospective cohort study of adult Kaiser Permanente Northern California (KPNC) members diagnosed with malignant tumours between 2012 and 2022 who received anthracyclines, human epidermal growth factor receptor (HER2) inhibitors, immune checkpoint inhibitors (ICIs), or tyrosine kinase inhibitors. CTRCD was defined as a >10% decline in left ventricular ejection fraction to 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% confidence interval 7.7-9.1). Incidence was highest with HER2 inhibitors (10.7%) and lowest with ICIs (5.2%) (P < .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 risk prediction models and targeted surveillance strategies to reduce downstream HF risk.