Impaired exercise capacity and left ventricular function in long-term adult survivors of childhood acute lymphoblastic leukemia

Abstract

Background: Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for late cardiotoxic effects of cancer treatment, but conflicting evidence exists on the effects of anthracyclines on left ventricular (LV) diastolic function and exercise capacity. Procedure: We performed a cross-sectional study with comprehensive echocardiography in 138 adult survivors of childhood ALL, median 23.4 years after diagnosis. Pulsed tissue Doppler measurements of early diastolic mitral annular velocities (e') were used for the assessment of diastolic function, and compared to 138 matched controls. Of the survivors, 133 also performed ergospirometry measuring peak oxygen uptake (VO2max). Associations between cancer treatment, LV function, and VO2max were analyzed. Results: The survivor group had lower e' values than controls (e' septal 11.0 vs. 12.6cm/s, P<0.001), but the difference was confined to the subgroup of anthracycline treated survivors (median cumulative dose 120mg/m2). Anthracycline exposure was inversely correlated with e' (regression coefficient -1.581, P=0.009). Reduced VO2max/kg occurred in 47% of the survivors, but more often in anthracycline treated survivors (56%) than anthracycline naïve survivors (17%, P<0.001). Anthracycline exposure was inversely correlated with VO2max/kg (regression coefficient -3.084, P=0.05 in multivariate analysis). Furthermore, associations were observed between measures of LV function and VO2max/kg, and e' was the best predictor of VO2max/kg (standardized coefficient 0.355, P<0.001 in multivariate analysis). Conclusions: Adult survivors of childhood ALL have increased risk for impaired LV diastolic function and impaired exercise capacity, both associated with previous anthracycline exposure. Furthermore, there is an association between LV diastolic function and exercise capacity.