Incidence of cardiotoxicity assessed with CZT-ERNA in patients undergoing contemporary cancer therapy: a 12-year real-world experience

Cancer therapy has undergone a remarkable transformation over recent decades with the addition of new therapeutic modalities. Nonetheless, adverse effects remain significant, and contemporary real-world data on the incidence and risk factors for cardiotoxicity, as assessed using cadmium-zinc-telluride (CZT) equilibrium radionuclide nuclear angiography (ERNA), remain limited. We included all adult patients who underwent first-time and follow-up assessment of cardiac function with CZT-ERNA within 6 months in relation to cancer therapy at Copenhagen University Hospital – Herlev between 2012 and 2024. The primary outcome was cardiotoxicity, defined as a ≥ 10% reduction in left ventricular ejection fraction (LVEF) from baseline to < 50% during the first year, and was estimated using cumulative incidence functions. Secondary outcomes were LVEF recovery to ≥ 50%, and risk factors for cardiotoxicity. Risk factors were estimated with multiple logistic regression. Of 6,299 patients examined, 2,345 adult patients (70% females, median age 61 years, Q1-Q3 50–71) had a first-time assessment with CZT-ERNA and ≥ 1 follow-up assessment within 6 months, with a total of 9,135 examinations during the first year. Most patients had breast cancer (46%), sarcoma (19%), and melanoma (15%). The overall incidence of cardiotoxicity was 12.3% (95% CI 10.9%-13.6%) and occurred in 278 patients. Median time to cardiotoxicity was 149 days [Q1-Q3 90–236 days] and reversibility was observed in 185 patients (67%). Baseline LVEF (adjusted OR / 10% increase 0.43; 95% CI 0.37–0.50; p < 0.0001), end-systolic volume (adjusted OR / 10 ml increase 1.51; 95% CI 1.38–1.66; p < 0.0001), end-diastolic volume (adjusted OR / 10 ml increase 1.14; 95% CI 1.07–1.21; p < 0.0001), heart rate (adjusted OR / 10 beats per minute increase 1.25; 95% CI 1.12–1.39; p < 0.0001), and body mass index (BMI) (adjusted OR / unit higher 0.97 (95% CI 0.94-1.00; p = 0.03) were associated with cardiotoxicity, whereas systolic blood pressure was not (adjusted OR / 10 mmHg increase 0.95; 95% CI 0.87–1.04; p = 0.25). Cardiotoxicity occurred in approximately 12% of all cancer patients referred for CZT-ERNA surveillance during cancer therapy. Patients with larger left ventricular volumes, lower LVEF, and higher heart rate at baseline may require specific attention.