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 end-stage 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 A(CV) 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, β-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.