Left and right ventricular systolic and diastolic functional reserves are impaired in anthracycline-treated long-term survivors of childhood cancers

Abstract

Background: Little is known about cardiac functional reserves in childhood cancer survivors. We assessed the left (LV) and right ventricular (RV) functional reserve in anthracycline-treated long-term survivors of childhood cancers. Methods: 103 survivors (57 males) aged 25.0±5.8 years at 15.2±5.8 years after anthracycline therapy and 61 healthy controls (29 males) were studied. Tissue Doppler echocardiography was performed at rest and during supine bicycle exercise to assess mitral and tricuspid annular systolic (s) and early diastolic (e) velocities, and LV myocardial isovolumic acceleration (IVA). The slope of LV force-frequency relationship (FFR) was derived from the changes in IVA with heart rates during exercise (ΔIVA/Δheart rate). The LV and RV functional reserves were further assessed by the systolic (SFRI) and diastolic (DRFI) functional reserve indices, calculated respectively as Δs x [1-1/s at baseline] and Δe x [1-1/e at baseline]. Results: At baseline, mitral annular tissue Doppler indices were similar between survivors and controls (all p>0.05), while tricuspid s and e velocities were significantly lower in survivors (both p<0.05). The FFR slope (p<0.001), LV SFRI (p<0.001), and RV SFRI (p=0.001) were significantly lower in survivors than controls. For diastolic functional reserve, LV but not RV DFRI was significantly lower in survivors than controls (p<0.001). The LV SRFI and RV SRFI (r=0.28, p<0.001) were significantly associated. In patients, LV FFR and LV and RV functional reserve indices did not correlate with age, gender, follow-up duration, and cumulative dose of anthracycline received (all p>0.05) Conclusions: LV and RV functional reserves during exercise are impaired and interrelated in anthracycline-treated long-term survivors of childhood cancers.