Blunted cyclic variation of heart rate predicts mortality risk in post-myocardial infarction, end-stage renal disease, and chronic heart failure patients

Aims Cyclic variation of heart rate (CVHR) associated with sleep-disordered breathing is thought to reflect cardiac autonomic responses to apnoeic/hypoxic stress.We examined whether blunted CVHR observed in ambulatory ECG could predict the mortality risk. Methods and results CVHR in night-time Holter ECG was detected by an automated algorithm, and the prognostic relationships of the frequency (F_CV) and amplitude (A_CV) of CVHR were examined in 717 patients after myocardial infarction (post-MI 1, 6% mortality, median follow-up 25 months). The predictive power was prospectively validated in three independent cohorts: a second group of 220 post-MI patients (post-MI 2, 25.5% mortality, follow-up 45 months); 299 patients with endstage renal disease on chronic haemodialysis (ESRD, 28.1% mortality, follow-up 85 months); and 100 patients with chronic heart failure (CHF, 35% mortality, follow-up 38 months). Although CVHR was observed in ≥96% of the patients in all cohorts, F_CV did not predict mortality in any cohort. In contrast, decreased ACV was a powerful predictor of mortality in the post-MI 1 cohort (hazard ratio [95% CI] per 1 ln [ms] decrement, 2.9 [2.2-3.7], P < 0.001). This prognostic relationship was validated in the post-MI 2 (1.8 [1.4-2.2], P < 0.001), ESRD (1.5 [1.3-1.8], P < 0.001), and CHF (1.4 [1.1-1.8], P = 0.02) cohorts. The prognostic value of A_CV was independent of age, gender, diabetes, b-blocker therapy, left ventricular ejection fraction, sleep-time mean R-R interval, and F_CV. Conclusion Blunted CVHR detected by decreased A_CV in a night-time Holter ECG predicts increased mortality risk in post-MI, ESRD, and CHF patients.