Author + information
- Received December 16, 2015
- Revision received February 9, 2016
- Accepted February 19, 2016
- Published online June 1, 2016.
- Jacob Joseph, MBBS, MDa,b,∗ (, )
- Brian C. Claggett, PhDa,
- Inder S. Anand, MDc,
- Jerome L. Fleg, MDd,
- Thao Huynh, MD, PhDe,
- Akshay S. Desai, MDa,
- Scott D. Solomon, MDa,
- Eileen O’Meara, MDf,
- Sonja Mckinlay, MDg,
- Bertram Pitt, MDh,
- Marc A. Pfeffer, MD, PhDa and
- Eldrin F. Lewis, MDa
- aDepartment of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
- bVeterans’ Affairs Boston Healthcare System, Boston, Massachusetts
- cUniversity of Minnesota, Minneapolis, Minnesota
- dNational Institutes of Health, Bethesda, Maryland
- eMontreal General Hospital, Montreal, Quebec, Canada
- fInstitute de Cardiologie de Montréal, Montreal, Quebec, Canada
- gNew England Research Institute, Watertown, Massachusetts
- hUniversity of Michigan, Ann Arbor, Michigan
- ↵∗Reprint requests and correspondence:
Dr. Jacob Joseph, Department of Medicine, Brigham and Women’s Hospital, 77 Avenue Louis Pasteur, New Research Building, Room 630, Boston, Massachusetts 02115.
Objectives This study examined the relationship between baseline QRS duration and clinical outcomes in subjects enrolled in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial.
Background Heart failure with preserved ejection fraction (HFPEF) is a heterogeneous clinical syndrome. Whether QRS duration identifies HFPEF subjects at an increased risk of adverse outcomes has not been well studied.
Methods QRS duration was analyzed as a dichotomous variable (≥120 ms or <120 ms) and as a continuous variable to determine its relation to the primary outcome (composite of cardiovascular death, aborted cardiac arrest, or HF hospitalization [HFH]) and to each component of the primary outcome. Multivariate analyses were conducted in the entire study cohort as well as in separate analyses for subjects enrolled only from North and South America, or from Russia and Georgia.
Results The QRS duration of ≥120 ms was independently associated with an increased risk of the primary outcome (p = 0.009) and HFH (p = 0.003) in the entire study cohort and in the subset enrolled in the Americas. There was a linear relation of QRS duration with risk of the primary outcome and HFH. No interaction was observed between treatment with spironolactone and QRS duration. The risk of adverse outcomes was increased independently of the type of conduction abnormality underlying prolonged QRS duration.
Conclusions This post hoc analysis demonstrated that prolonged QRS duration identifies HFPEF subjects at a higher risk of adverse clinical outcomes and that spironolactone had a similar effect on outcomes independent of QRS duration. (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function [TOPCAT]; NCT00094302)
This study was supported by National Institutes of Health/National Heart, Lung, and Blood Institute contract HHSN268200425207C. The contents of this paper do not necessarily represent the views of the U.S. Department of Health and Human Services, National Institutes of Health, or National Heart, Lung, and Blood Institute. Dr. Desai is a consultant for and has received research support from Novartis and AtCor Medical; and is a consultant for St. Jude Medical, Relypsa and Merck Sharpe & Dohme. Dr. Pitt is a consultant for Pfizer, Bayer, Relypsa, AstraZeneca, and KBP Biosciences; and holds stock options in Relypsa and KBP Biosciences. Dr. Pfeffer is a consultant for AstraZeneca, Bayer, Boehringer Ingelheim, DalCor, Genzyme, Eli Lilly, Medicines Company, Merck Sharpe & Dohme, Novartis, Relypsa, Salix, Sanderling, Sanofi, Takeda, Teva, Thrasos, and Vericel; and has received research support from Amgen, Celladon, Novartis, and Sanofi. Dr. Pfeffer is co-inventor of inhibitors of a renin-angiotensin system, whose patents are held by Brigham and Women's Hospital, assigned to Novartis Pharmaceuticals. Dr. Lewis has financial relationships with and has received research grants from Novartis, Amgen, and Sanofi; and is a consultant for and serves on the advisory boards of Modest and Novartis. Dr. Solomon has received research support from National Heart, Lung, and Blood Institute; and is a consultant for Novartis and Bayer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received December 16, 2015.
- Revision received February 9, 2016.
- Accepted February 19, 2016.
- American College of Cardiology Foundation