Heart Rate Variability Triangular Index as a Predictor of Cardiovascular Mortality in Patients With Atrial Fibrillation

Abstract

Background Impaired heart rate variability (HRV) is associated with increased mortality in sinus rhythm. However, HRV has not been systematically assessed in patients with atrial fibrillation (AF). We hypothesized that parameters of HRV may be predictive of cardiovascular death in patients with AF. Methods and Results From the multicenter prospective Swiss-AF (Swiss Atrial Fibrillation) Cohort Study, we enrolled 1922 patients who were in sinus rhythm or AF. Resting ECG recordings of 5-minute duration were obtained at baseline. Standard parameters of HRV (HRV triangular index, SD of the normal-to-normal intervals, square root of the mean squared differences of successive normal-to-normal intervals and mean heart rate) were calculated. During follow-up, an end point committee adjudicated each cause of death. During a mean follow-up time of 2.6±1.0 years, 143 (7.4%) patients died; 92 deaths were attributable to cardiovascular reasons. In a Cox regression model including multiple covariates (age, sex, body mass index, smoking status, history of diabetes mellitus, history of hypertension, history of stroke/transient ischemic attack, history of myocardial infarction, antiarrhythmic drugs including β blockers, oral anticoagulation), a decreased HRV index ≤ median (14.29), but not other HRV parameters, was associated with an increase in the risk of cardiovascular death (hazard ratio, 1.7; 95% CI, 1.1-2.6; P=0.01) and all-cause death (hazard ratio, 1.42; 95% CI, 1.02-1.98; P=0.04). Conclusions The HRV index measured in a single 5-minute ECG recording in a cohort of patients with AF is an independent predictor of cardiovascular mortality. HRV analysis in patients with AF might be a valuable tool for further risk stratification to guide patient management. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02105844.

Keywords: atrial fibrillation; heart rate variability; morbidity/mortality.

Conflict of interest statement

Dr Zuern reports a research grant from Medtronic and speaker fees from Vifor Pharma and Novartis. Dr Conen has received speaker fees from Servier, Canada. Dr Kühne has received grants from the Swiss National Science Foundation and the Swiss Heart Foundation, and lecture/consulting fees from Daiichi‐Sankyo, Boehringer Ingelheim, Bayer, Pfizer‐BMS, AstraZeneca, Sanofi‐Aventis, Novartis, MSD, Medtronic, Boston Scientific, St. Jude Medical, Biotronik, Sorin, Zoll, and Biosense Webster. Dr Kobza received institutional grants from Abbott, Biosense‐Webster, Biotronik, Boston‐Scientific, Medtronic, and Sis‐Medical. Dr Bonati has received an unrestricted research grant from AstraZeneca, and consultancy or advisory board fees or speaker’s honoraria from Amgen, Bayer, Bristol‐Myers Squibb, Claret Medical, and InnovHeart, and travel grants from AstraZeneca and Bayer. The remaining authors have no disclosures to report.

Figures

Figure 1. Flow chart of patient selection from the Swiss Atrial Fibrillation (Swiss‐AF) Cohort Study.

HRVI indicates heart rate variability triangular index.

Figure 2. Calculation of heart rate variability triangular index (HRVI).

Left upper figure: Standard resting ECG recording. Left lower figure: Corresponding tachogram of the RR intervals. Right figure: Calculation of HRVI. First, all normal‐to‐normal (NN) intervals are divided according to their length in bins of 8 ms. Second, the number of NN intervals in the modal bin (ie, the maximum of the density distribution) is sought. Finally, the HRVI is defined as the total number of NN intervals divided by the number of NN intervals in the modal bin. X indicates the modal bin; and Y, the number of NN intervals in the modal bin.

Figure 3. Prognostic impact of heart rate variability triangular index (HRVI) in the entire study cohort.

Kaplan–Meier curves of cardiovascular and all‐cause mortality stratified by the median heart rate variability triangular index. Mortality probabilities were significantly different (P=0.005 and P=0.008, respectively). Pts indicates patients.

Figure 4. Estimated cardiovascular mortality hazard ratios of heart rate variability triangular index ≤ median (14.29) vs > median by different grouping variables.

The interaction tests whether the hazard ratio depends on the grouping variable; a small P‐value supports that the effect of the heart rate variability triangular index differs between groups.