Risk-guided disease management to prevent heart failure in adult cancer survivors of previous cardiotoxic cancer treatments (REDEEM) trial

Background Long-term adult cancer survivors are at increased risk of heart failure (HF) due to cardiotoxic therapy and conventional cardiovascular risk factors. However, the optimal selection for, and efficacy of cardioprotection is unclear among survivors. Objectives To determine whether a structured cardio-oncology disease management program (CO-DMP) improves functional capacity and myocardial function in long-term survivors identified as having subclinical/Stage B HF (SBHF). Methods REDEEM was a multicenter, RCT of adult cancer survivors ≥5 years after cardiotoxic therapy with ≥1 HF risk factor. SBHF was defined by asymptomatic echocardiographic abnormalities: left ventricular ejection fraction (LVEF; <51% [women] or <50% [men]), impaired global longitudinal shortening (GLS<16%), left ventricular hypertrophy, or diastolic dysfunction. Participants were randomized to a 6-month CO-DMP (angiotensin inhibition/blockade and beta-blockade; exercise training) or usual care (UC). Primary endpoint was change in peak oxygen uptake (VO₂peak). Secondary endpoints included changes in LVEF, GLS and SBHF resolution. Results Of 604 screened survivors, 144 (24%) met criteria for SBHF and were randomized (CO-DMP n=74; UC n=70). Mean duration since cancer diagnosis was 17 years. At 6 months, VO₂peak did not differ between groups (CO-DMP ΔVO₂peak +0.35±2.49 vs UC -0.19±1.98mL/kg/min; p=0.24). In contrast, CO-DMP was associated with significant between group differences in myocardial function, including greater improvements in LVEF (4.26±5.66% vs 1.13±6.94%; p=0.001), GLS (1.76±2.29% vs 1.30±2.08%; p=0.047) and higher SBHF resolution (74% vs 47%; p=0.045). Conclusions In long-term cancer survivors with SBHF, a structured CO-DMP did not improve functional capacity, but did improve myocardial structure and function. Myocardial function in SBHF represents a modifiable therapeutic target. Longer-term follow-up is required to determine effects on clinical HF outcomes.