Left and Right Ventricular Systolic and Diastolic Functional Reserves Are Impaired in Anthracycline-Treated Long-Term Survivors of Childhood Cancers

Background: The aim of this study was to test the hypothesis that left ventricular (LV) and right ventricular (RV) functional reserves are altered in anthracycline-treated long-term survivors of childhood cancers. Methods: One hundred three survivors (55% men) aged 25.0 +/- 5.8 years at 15.2 +/- 5.8 years after chemotherapy and 61 healthy control subjects (52% men) were studied. Tissue Doppler-derived mitral and tricuspid systolic (s) and early diastolic (e) velocities and LV myocardial acceleration during isovolumic contraction (IVA) were determined at rest and during bicycle exercise. The slope of the LV force-frequency relationship was derived from changes in IVA with heart rate during exercise (Delta IVA/Delta[heart rate]). LV and RV functional reserves were further assessed by the systolic functional reserve index (Delta s x [1 - 1/s at baseline]) and diastolic functional reserve index (Delta e x [1 - 1/e at baseline]). Results: At baseline, mitral annular tissue Doppler indices were similar between survivors and control subjects (P >.05 for all), while tricuspid s and e velocities were significantly lower in survivors (P <.05 for both). The force-frequency relationship slope (P <.001), LV systolic functional reserve index (P <.001), and RV systolic functional reserve index (P =.001) were significantly lower in survivors than control subjects. For diastolic functional reserve, LV but not RV diastolic functional reserve index was significantly lower in survivors (P <.001). Multivariate analysis revealed survivor status (beta = -0.39, P <.001) and baseline LV IVA (beta = 0.15, P <.044) as significant determinants of the LV force-frequency relationship. Conclusions: LV and RV functional reserves during exercise are impaired in anthracycline-treated long-term survivors of childhood cancer.