Cardiac autonomic dysfunction in survivors of acute lymphoblastic leukemia in childhood

The purpose of this study was to investigate autonomic regulation of neurocardiac function in survivors of acute lymphoblastic leukemia (ALL) in childhood, through power spectral and time domain analyses of the heart rate variability signal. Studies were conducted on 34 unselected patients and 34 age matched controls. Patients were in remission, off therapy for at least 20 months and from high risk (HR, n=21) and standard risk (SR, n=13) groups as described by Dana-Farber Cancer Institute protocols 87-01 and 91-01. Twenty-nine patients had received cranial irradiation, 7 on a hyperfractionated schedule. Power spectral analysis of the heart rate (PS/HRV) was performed on 30 min heart rate time series and time domain statistics were computed from 24 h Holter recordings. Left ventricular function was assessed by measuring ejection and shortening fractions on echocardiography. All such measures were normal. Analysis of PS/HRV revealed that the supine low frequency: high frequency (LF:HF) area ratio was elevated in patients compared to controls. Changes in the LF and HF power on standing were attenuated in the patients compared to controls. Circadian analysis revealed a depressed diurnal rhythm of heart rate in the patients. Those from the SR group showed greater reduction of the LF power response to orthostatic stress and a reduced circadian rhythm of the heart rate compared to those with HR ALL. Patients from the HR group showed reductions in both HF and LF power responses to orthostasis compared to controls. Elevated supine LF power and depressed circadian variation in the HF power band were evident only in female subjects. Patients who received standard cranial irradiation had higher LF:HF area ratio and diminished LF and HF power responses to orthostatic stress than did subjects in the hyperfractionated group. These findings suggest that the autonomic nervous regulation of the heart is compromised in patients treated for ALL in childhood even when resting echocardiographic measures provide no evidence of cardiac decompensation. The extent of neurocardiac dysfunction is influenced by risk status, gender and schedule of cranial irradiation.