Heart rate variability in arrhythmogenic right ventricular cardiomyopathy correlation with clinical and prognostic features

The identification of subjects with arrhythmogenic right ventricular cardiomyopathy (ARVC) at higher risk for sudden death is an unresolved issue. An influence of the autonomic activity on the genesis of ventricular arrhythmias was postulated. Heart rate variability (HRV) analysis provides a useful method to measure autonomic activity, and is a predictor of increased risk of death after myocardial infarction. For these reasons, the aim of the study was to evaluate HRV and its correlations with ventricular arrhythmias, heart function, and prognostic outcome in patients with ARVC. The study included 46 patients with ARVC who were not taking antiarrhythmic medications. The diagnosis was made by ECG, echocardiography, angiography, and endomyocardial biopsy. Exercise stress test and Holter monitoring were obtained in all patients. Time-domain analysis of HRV was expressed as the standard deviation of all normal to normal NN intervals (SDNN) detected during 24-hour Holter monitoring. Thirty healthy subjects represented a control group for HRV analysis. The mean follow-up was 10.8 +/- 1.86 years. SDNN was reduced in patients with ARVC in comparison with the control group (151 +/- 36 vs 176 +/- 34, P = 0.00042). Moreover, there was a significant correlation of this index with the age of the patients (r = - 0.59, P < 0.001), with the left (r = 0.44, P = 0,002) and right (r = 0.47, P = 0.001) ventricle ejection fraction, with the right ventricular end diastolic volume (r = - 0.62, P < 0.001), and with the ventricular arrhythmias, detected during the same Holter record used for HRV analysis (patients with isolated ventricular ectopic beats < 1,000/24 hours, 184 +/- 34; patients with isolated ventricular ectopic beats > 1,000/24 hours and/or couplets, 156 +/- 25; patients with repetitive ventricular ectopic beats ( 3) and/or ventricular tachycardia, 129 +/- 25; P < 0.001). During follow-up two patients showed a transient but significant reduction of SDNN and a concomitant increase of the arrhythmic events. In eight patients an episode of sustained ventricular tachycardia occurred, but the mean SDNN of this subgroup did not differ from the mean value of the remaining patients (152 +/- 15 vs 150 +/- 39; P = NS). Only one subject died after heart transplantation during follow-up (case censored). Time-domain analysis of HRV seems to be a useful method to assess the autonomic influences in ARVC. A reduction of vagal influences correlates with the extent of the disease. The significant correlation between SDNN and ventricular arrhythmias confirmed the influences of autonomic activity in the modulation of the electrical instability in ARVC patients. However, SDNN was not predictive of spontaneous episodes of sustained ventricular tachycardia.