Cardiovascular Testing Detects Underlying Dysfunction in Childhood Leukemia Survivors

PURPOSE: Childhood leukemia survivors commonly develop late-onset cardiovascular disease after treatment with anthracyclines. Resting echocardiogram is the standard procedure for monitoring cardiac health but this method may not be sensitive enough to detect subclinical injury. Exercise echocardiography may provide a viable alternative. METHODS: Nineteen (9 males; age, 19 +/- 3 yr) anthracycline-treated survivors of childhood leukemia and 17 (8 males) healthy individuals of similar age (22 +/- 2 yr) were recruited. All survivors had normal resting echocardiography upon recruitment. Exercise echocardiography was performed using contemporary imaging techniques. Flow-mediated dilation (FMD), body composition, and cardiorespiratory fitness (V O2peak) were assessed to determine predisposition to additional disease. RESULTS: Mitral valve peak flow velocity in late diastole (interaction, P = 0.007) increased from rest in survivors (P = 0.023) and controls (P = 0.020) immediately postexercise but did not recover again in the survivors (exercise-recovery, P = 0.784) after recuperation. Consequently, E/A ratio (interaction, P < 0.001) was lower in the survivors at recovery (P < 0.001). Survivors had reduced FMD (7.88 +/- 1.70 vs 9.65 +/- 2.83; P = 0.030), maximal and recovery HR (P = 0.001; P < 0.001), minute ventilation (P < 0.001), and V O2peak (absolute, 2.64 +/- 0.62 vs 3.14 +/- 0.74 L.min, P = 0.034; relative, 36.78 +/- 11.49 vs 45.14 +/- 6.80 mL.kg.min; P = 0.013) compared with controls. They also had higher total body fat (percentage, P = 0.034; mass, P = 0.024) and fat mass in the central (P = 0.050), peripheral (P = 0.039) and visceral (P < 0.001) regions. Survivors matched controls with regard to height (173.0 +/- 7.8 cm vs 173.8 +/- 9.1 cm; P = 0.796), body mass (76.16 +/- 19.05 kg vs 70.07 +/- 13.96 kg; P = 0.287) and body mass index (25.2 +/- 5.1 vs 22.9 +/- 2.7; P = 0.109). CONCLUSIONS: Exercise echocardiography unmasked subclinical diastolic dysfunction that may indicate late anthracycline toxicity in apparently healthy survivors of childhood leukemia. Presence of secondary risk factors indicates increased predisposition to comorbidities and highlights the importance of assessing cardiovascular health during follow-up.