CARDIAC AUTONOMIC DYSFUNCTION IN SURVIVORS OF ACUTE LYMPHOBLASTIC-LEUKEMIA IN CHILDHOOD

The purpose of this study was to investigate autonomic regulation of n eurocardiac 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 unselecte d patients and 34 age matched controls. Patients were in remission, of f therapy for at least 20 months and from high risk (HR, n=21) and sta ndard risk (SR, n=13) groups as described by Dana-Farber Cancer Instit ute protocols 87-01 and 91-01. Twenty-nine patients had received crani al irradiation, 7 on a hyperfractionated schedule. Power spectral anal ysis of the heart rate (PS/HRV) was performed on 30 min heart rate tim e series and time domain statistics were computed from 24 h Holter rec ordings. Left ventricular function was assessed by measuring ejection and shortening fractions on echocardiography. All such measures were n ormal. Analysis of PS/HRV revealed that the supine low frequency: high frequency (LF:HF) area ratio was elevated in patients compared to con trols. Changes in the LF and HF power on standing were attenuated in t he patients compared to controls. Circadian analysis revealed a depres sed diurnal rhythm of heart rate in the patients. Those from the SR gr oup showed greater reduction of the LF power response to orthostatic s tress and a reduced circadian rhythm of the heart rate compared to tho se with HR ALL. Patients from the HR group showed reductions in both H F and LF power responses to orthostasis compared to controls. Elevated supine LF power and depressed circadian variation in the HF power ban d 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 hyp erfractionated group. These findings suggest that the autonomic nervou s regulation of the heart is compromised in patients treated for ALL i n childhood even when resting echocardiographic measures provide no ev idence of cardiac decompensation. The extent of neurocardiac dysfuncti on is influenced by risk status, gender and schedule of cranial irradi ation.