Effect of Cardioprotection on the Right Ventricular Function in Breast Cancer Patients Receiving Potentially Cardiotoxic Therapy: A SAFE Trial Substudy

Purpose: To evaluate the effects of cardioprotective therapy (CPT) with neurohormonal inhibitors on cancer therapeutics–related cardiac dysfunction (CTRCD) in breast cancer patients, focusing on right ventricular (RV) function. Methods: This is a secondary analysis of SAFE study, a randomized, phase 3, double-blind, placebo-controlled, four-arm trial, in which the effects of short-term CPT (bisoprolol, ramipril, or both) compared to placebo (P-arm) on subclinical CTRCD were evaluated in 222 women without cardiac risk factors who received intensive anthracycline-based chemotherapy (median isoequivalent doxorubicin dose 288 mg/m2). Among them, 35% received trastuzumab, 98% taxanes, 22% underwent neoadjuvant therapy, 78% adjuvant therapy, and 56% had postoperative radiotherapy. CPT started with chemotherapy and continued for 1 year, or until the completion of trastuzumab therapy. All the patients underwent cardiac surveillance at baseline and 3, 6, 12, and 24 months. Left ventricular CTRCD was assessed following the 2022 ESC guidelines. RV function was evaluated according to established recommendations. RV CTRCD was defined as a greater than 10% reduction in RV fractional area change (FAC). Results: At 24 months, LV CTRCD was observed in 42.9% of P-arm and 3.1% of the CPT arms (p < 0.001). Compared to the CPT arms, there was a significant reduction in RV FAC (−10.5%), S’-wave velocity (−12.2%), and tricuspid annular plane systolic excursion (−9.6%) in the P-arm. Additionally, the RV diameter increased by 7% in the P-arm. RV CTRCD was found in 49.2% of the P-arm and 22% of the CPT arms (p < 0.001). Conclusion: Short-term neurohormonal cardioprotection was effective in reducing RV CTRCD.