Exercise Intolerance Among Survivors Of Childhood Cancer Exposed To Cardiotoxic Therapy: Identification Of Survivors At Increased Risk Through Myocardial Strain And Ejection Fraction.

10565 Background: Exercise intolerance is an established risk factor for heart failure and death in the general population. Exercise capacity and factors associated with intolerance have not been extensively studied in adult survivors of childhood cancer exposed to cardiotoxic therapy. Methods: Survivors exposed to cardiotoxic therapies, without clinical heart failure (N = 577, 52% male, mean age 35.8±8.2 years), and community controls (N = 286, 48% male, mean age 34.4±10.0 years) completed maximal cardiopulmonary exercise testing to determine exercise capacity (pkVO2; intolerance defined as < 20th %tile of age- and sex-specific predicted values) and echocardiography for EF and global longitudinal strain (GLS). EF < 50% and GLS ≥2 SD above age and sex normative values were evaluated for associations with exercise intolerance among survivors in models adjusted for race, pulmonary function, neuropathy, strength, physical activity and smoking. Results: Exercise intolerance (93.7%) and abnormal EF (7.6%) and GLS (27.6%) were common among survivors, differing significantly from controls: lower mean pkVO2 (25.8±8.0 vs. 32.9±9.4, p = 0.001) and EF (57.6±5.5 vs. 60.3±5.5, p < 0.001) and higher GLS (-19.6±2.6 vs. -20.4±3.2, p < 0.001). Conclusions: Survivors exposed to cardiotoxic agents have dose dependent impairment in exercise capacity. Abnormal GLS, but not EF, is associated with exercise intolerance among survivors, and should be considered in screening guidelines for survivors. pkVO2 EF GLS Control 32.9±9.4 60.3±5.5 -20.4±3.2 1-199 mg/m2 anthracyclines 28.7±6.4* 58.4±5.4* -20.2±2.8 200-349 mg/m2 anthracyclines 27.6±6.5* 58.4±5.4* -20.2±2.8 350+ mg/m2 anthracyclines 25.4±6.1* 57.2±4.9* -19.5±2.6* Chest RT, any anthracyclines 27.5±4.8* 57.0±3.9* -19.5±2.0* Chest RT, no anthracyclines 25.4±7.1* 58.2±6.0* -19.1±3.0* *p < 0.05 for comparison with control In adjusted models, EF < 50% was not (OR 2.2, 95% CI 0.4-11.1), but GLS ≥2 SD was (OR 3.0, 95% CI 1.1-8.2) associated with exercise intolerance among survivors. In models limited to survivors with EF > 50% GLS identified survivors with exercise intolerance (OR 3.7, 95% CI 1.1-13.0).