Author + information
- Received September 16, 2011
- Revision received December 5, 2011
- Accepted December 15, 2011
- Published online May 15, 2012.
- Davide Castagno, MD⁎,†,
- Hicham Skali, MD, MSc⁎,
- Madoka Takeuchi, MS⁎,
- Karl Swedberg, MD, PhD‡,
- Salim Yusuf, MBBS, DPhil§,
- Christopher B. Granger, MD∥,
- Eric L. Michelson, MD¶,
- Marc A. Pfeffer, MD, PhD⁎,
- John J.V. McMurray, MD⁎,#,
- Scott D. Solomon, MD⁎,⁎ (, )
- CHARM Investigators
- ↵⁎Reprint requests and correspondence:
Dr. Scott D. Solomon, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115
Objectives The aim of this study was to explore the relationship between baseline resting heart rate and outcomes in patients with chronic heart failure (HF) according to baseline left ventricular ejection fraction (LVEF) and cardiac rhythm.
Background Elevated resting heart rate is associated with worse outcomes in patients with HF and reduced LVEF. Whether this association is also found in patients with HF and preserved LVEF is uncertain, as is the predictive value of heart rate in patients in atrial fibrillation (AF).
Methods Patients enrolled in the CHARM (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) Program were divided into groups by tertiles of baseline heart rate. Cox proportional hazard models were used to investigate the association between heart rate and pre-specified outcomes in the overall population as well as in subgroups defined according to LVEF (≤40% vs. >40%) and presence (or absence) of AF at baseline.
Results After adjusting for predictors of poor prognosis, patients in the highest heart rate tertile had worse outcomes when compared with those in the lowest heart rate group (e.g., for the composite of cardiovascular death or HF hospital stay hazard ratio: 1.23, 95% confidence interval: 1.11 to 1.36, p < 0.001). The relationship between heart rate and outcomes was similar across LVEF categories and was not influenced by beta-blocker use (p value for interaction >0.10 for both endpoints). However, amongst patients in AF at baseline, heart rate had no predictive value (p value for interaction <0.001).
Conclusions Resting heart rate is an important predictor of outcome in patients with stable chronic HF without AF, regardless of LVEF or beta-blocker use.
The CHARM Program was sponsored by AstraZeneca. No extramural funding was used to support this work. Drs. Swedberg, Yusuf, Pfeffer, and McMurray have received research grants, honoraria for lectures, and/or consulting fees from AstraZeneca. Dr. Swedberg has received research grants, honoraria or consulting fees from Servier. Dr. Granger has relationships with Astellas, AstraZeneca, Pfizer, Sanofi-Aventis, The Medicines Co., Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Hoffmann-LaRoche, Medtronic, Merck & Co., Novartis, and Otsuka. Dr. Pfeffer has received consulting fees from Servier, Daiichi Sankyo, Affectis, Eleven Biotherapeutics, GlaxoSmithKline, Hamilton Health Sciences, Merck, Novartis, Pfizer Japan, Roche, Sanofi-Aventis, Anthera, University of Oxford, AstraZeneca, Boehringer, Boston Scientific, Bristol-Myers Squibb, and Concert; and research grants from Amgen, Novartis, Sanofi-Aventis, AstraZeneca, Baxter, and Celladon. Dr. Michelson is an employee of AstraZeneca, sponsor of the CHARM Program. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received September 16, 2011.
- Revision received December 5, 2011.
- Accepted December 15, 2011.
- American College of Cardiology Foundation