Role of Cardiorespiratory Fitness in Modulating Cardiotoxicity in Long-Term Cancer Survivors Exposed to Anthracycline Therapy

Background Childhood cancer survivors (CCS) often experience cardiotoxicity due to cancer treatment. Furthermore, low cardiorespiratory fitness (CRF) is a strong predictor of mortality. Objective This study investigates the effects of a 16-week supervised aerobic exercise intervention on CRF changes, as measured by VO 2peak and parameters of cardiac structure and function via cardiac magnetic resonance imaging (CMR). Methods CCS were enrolled >2 years post-treatment and underwent cardiotoxicity risk stratification, cardiopulmonary stress test to determine CRF, and CMR before and after exercise intervention. Subclinical myocardial dysfunction was assessed by segmental strain abnormality, with specific focus on the number of segments showing peak circumferential strain magnitude (εcc) ≤10% and εcc ≤17%. Results Forty-seven subjects (10-25 years, median 22.0 years, IQR 9.0), 57.4% male, and 76% white were enrolled. Thirty-one patients completed the exercise intervention. VO 2peak increased > 1 mL/kg/min in 16/31 (51.6%) of subjects. These subjects were labeled “responders”, demonstrated a median increase in VO 2peak of 3.8 mL/kg/min. Responders showed significant increase in left (p=0.0348) and right (p=0.0390) ventricular end diastolic volume and stroke volume index (p=0.0141). Left ventricular ejection fraction continued to decline in non-responders with a net difference of 2.45% favoring responders (p=0.007). At baseline, 11 subjects met high-risk definition based on segmental strain abnormalities (i.e. ≥2 segments with peak circumferential strain magnitude (εcc) ≤10% or ≥9 segments ≤17%). High risk subjects showed significant improvement in εcc with a post-intervention reduction in number of segments ≤17% from 8.9 to 5.9 (p=0.014) and ≤10% from 1.8 to 0.3 (p=0.022). Conclusions CCS demonstrated increase in post-intervention VO 2peak and improvement in CMR parameters of structure and function. Those classified as high-risk based on εcc abnormalities benefited the most. Trial registration NCT, NCT04036032 . Unique Protocol ID: 14-110. Registered 25 July 2019 - Retrospectively registered, https://classic.clinicaltrials.gov/ct2/show/NCT04036032