title: 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.
  
  
  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.
  
  
  BACKGROUND
  URL: http://clinicaltrials.gov/. Unique identifier: NCT01165710.
authors.affiliation: Duke University Medical Center, Durham, NC (B.A.S., E.D.P., J.P.P.) Duke Clinical Research Institute, Durham, NC (B.A.S., S.K., L.T., F.H., E.D.P., J.P.P.).
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Steinberg
authors.affiliation: Duke Clinical Research Institute, Durham, NC (B.A.S., S.K., L.T., F.H., E.D.P., J.P.P.).
authors.forename: Sunghee
authors.initials: S
authors.lastname: Kim
authors.affiliation: Duke Clinical Research Institute, Durham, NC (B.A.S., S.K., L.T., F.H., E.D.P., J.P.P.).
authors.forename: Laine
authors.initials: L
authors.lastname: Thomas
authors.affiliation: UCLA Division of Cardiology, Los Angeles, CA (G.C.F.).
authors.forename: Gregg C
authors.initials: GC
authors.lastname: Fonarow
authors.affiliation: Mayo Clinic, Rochester, MN (B.J.G.).
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Gersh
authors.affiliation: Duke Clinical Research Institute, Durham, NC (B.A.S., S.K., L.T., F.H., E.D.P., J.P.P.).
authors.forename: Fredrik
authors.initials: F
authors.lastname: Holmqvist
authors.affiliation: Boston University School of Medicine, Boston, MA (E.H.).
authors.forename: Elaine
authors.initials: E
authors.lastname: Hylek
authors.affiliation: Lankenau Institute for Medical Research, Wynnewood, PA (P.R.K.).
authors.forename: Peter R
authors.initials: PR
authors.lastname: Kowey
authors.affiliation: Stanford University School of Medicine, Palo Alto, CA (K.W.M.).
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: Penn State University School of Medicine, Hershey, PA (G.N.).
authors.forename: Gerald
authors.initials: G
authors.lastname: Naccarelli
authors.affiliation: Columbia University College of Physicians and Surgeons, New York, NY (J.A.R.).
authors.forename: James A
authors.initials: JA
authors.lastname: Reiffel
authors.affiliation: Janssen Pharmaceuticals, Inc., Raritan, NJ (P.C.).
authors.forename: Paul
authors.initials: P
authors.lastname: Chang
authors.affiliation: Duke University Medical Center, Durham, NC (B.A.S., E.D.P., J.P.P.) Duke Clinical Research Institute, Durham, NC (B.A.S., S.K., L.T., F.H., E.D.P., J.P.P.).
authors.forename: Eric D
authors.initials: ED
authors.lastname: Peterson
authors.affiliation: Duke University Medical Center, Durham, NC (B.A.S., E.D.P., J.P.P.) Duke Clinical Research Institute, Durham, NC (B.A.S., S.K., L.T., F.H., E.D.P., J.P.P.).
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Piccini
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology; D016009:Chi-Square Distribution; D006339:Heart Rate / Q000187:drug effects; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D000889:Anti-Arrhythmia Agents
keywords: atrial fibrillation; heart rate; outcomes; rate control