Increased Heart Rate Is Associated With Higher Mortality in Patients With Atrial Fibrillation (AF): Results From the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF)

Abstract

Background: Most patients with atrial fibrillation (AF) require rate control; however, the optimal target heart rate remains under debate. We aimed to assess rate control and subsequent outcomes among patients with permanent AF.

Methods and results: We studied 2812 US outpatients with permanent AF in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation. Resting heart rate was measured longitudinally and used as a time-dependent covariate in multivariable Cox models of all-cause and cause-specific mortality during a median follow-up of 24 months. At baseline, 7.4% (n=207) had resting heart rate <60 beats per minute (bpm), 62% (n=1755) 60 to 79 bpm, 29% (n=817) 80 to 109 bpm, and 1.2% (n=33) ≥110 bpm. Groups did not differ by age, previous cerebrovascular disease, heart failure status, CHA2DS2-VASc scores, renal function, or left ventricular function. There were significant differences in race (P=0.001), sinus node dysfunction (P=0.004), and treatment with calcium-channel blockers (P=0.006) and anticoagulation (P=0.009). In analyses of continuous heart rates, lower heart rate ≤65 bpm was associated with higher all-cause mortality (adjusted hazard ratio [HR], 1.15 per 5-bpm decrease; 95% CI, 1.01 to 1.32; P=0.04). Similarly, increasing heart rate >65 bpm was associated with higher all-cause mortality (adjusted HR, 1.10 per 5-bpm increase; 95% CI, 1.05 to 1.15; P<0.0001). This relationship was consistent across endpoints and in a broader sensitivity analysis of permanent and nonpermanent AF patients.

Conclusions: Among patients with permanent AF, there is a J-shaped relationship between heart rate and mortality. These data support current guideline recommendations, and clinical trials are warranted to determine optimal rate control.

Clinical trial registration: URL: https://ichgcp.net/clinical-trials-registry/NCT01165710" title="See in ClinicalTrials.gov">NCT01165710.

Keywords: atrial fibrillation; heart rate; outcomes; rate control.

© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Figures

Figure 1

Distribution of 12 299 observations of resting heart rate versus concomitant EHRA symptom score in 2812 patients with permanent AF. owing to multiple follow-up visits, individual patients may contribute multiple observations of heart rate and EHRA score. Diamonds represent the means; horizontal lights reflect median and interquartile ranges. The P value is derived by testing for the overall significance of EHRA score levels from the correlated errors model, which yielded a coefficient of 1.11 for mild EHRA (vs. no symptoms), 2.06 for severe EHRA (vs no symptoms), and 2.36 for disabling EHRA (vs. no symptoms). AF indicates atrial fibrillation; bpm, beats per minute; EHRA, European Heart Rhythm Association; IQR, interquartile range.

Figure 2

Relationship between time-dependent resting heart rate and clinical outcome among 2812 patients with permanent AF. Adjusted hazard ratios (with 95% CIs) of increasing heart rate (using the mean heart rate of 73 bpm as the referent) for (A) all-cause mortality, (B) cardiovascular death, and (C) noncardiovascular death. Details of the adjustment covariates for each outcome are provided in Table S2. AF indicates atrial fibrillation; bpm, beats per minute; CI, confidence interval.