Author + information
- Received June 25, 2017
- Revision received October 21, 2017
- Accepted October 23, 2017
- Published online January 30, 2018.
- Ambarish Pandey, MDa,
- Rohan Khera, MDa,
- Bryan Park, MDa,
- Mark Haykowsky, PhDb,
- Barry A. Borlaug, MDc,
- Gregory D. Lewis, MDd,
- Dalane W. Kitzman, MDe,
- Javed Butler, MDf and
- Jarett D. Berry, MD, MSa,∗ ()
- aDivision of Cardiology, Department of Internal Medicine, University of Texas Southwest Medical Center, Dallas, Texas
- bCollege of Nursing and Health Innovation, University of Texas at Arlington, Arlington, Texas
- cDivision of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
- dDivision of Cardiology, Department of Internal Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
- eDepartment of Internal Medicine, Sections on Cardiovascular Medicine and Geriatrics, Wake Forest School of Medicine, Winston-Salem, North Carolina
- fDivision of Cardiology, Department of Internal Medicine, Stony Brook University School of Medicine, New York, New York
- ↵∗Address for correspondence:
Dr. Jarett D. Berry, Division of Cardiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9047.
Objectives The aim of this study was to compare the relative impairment in different exercise hemodynamic reserve parameters in patients with heart failure with preserved ejection fraction (HFpEF) and control patients using a study-level meta-analysis.
Background A cardinal manifestation of chronic HFpEF is severely decreased exercise capacity. Developing effective therapies for exercise intolerance in HFpEF requires optimal understanding of the factors underlying exercise intolerance.
Methods Data were included from 17 unique cohorts that measured peak oxygen uptake and hemodynamic or echocardiographic parameters during exercise in patients with HFpEF and control subjects in this meta-analysis. Standardized mean differences (SMDs) in the exercise reserve (exercise − resting) measures of hemodynamic or echocardiographic parameters between the HFpEF and control groups were pooled in a random-effects meta-analysis.
Results The pooled analysis included 910 patients with HFpEF and 476 control subjects. In pooled analysis, patients with HFpEF had significantly lower peak oxygen uptake (SMD: −2.13; 95% confidence interval [CI]: −2.68 to −1.57). Among hemodynamic exercise reserve parameters, the largest impairment was observed in chronotropic response reserve (change in heart rate from rest to peak exercise; SMD: −1.87; 95% CI: −2.44 to −1.29), followed by exaggerated increase in pulmonary capillary wedge pressure with exercise (SMD: 1.78; 95% CI: 1.46 to 2.09). Significant abnormalities were also observed in the arteriovenous oxygen difference reserve and stroke volume reserve between the HFpEF and control groups.
Conclusions The most consistent and severe hemodynamic reserve abnormalities observed in patients with HFpEF were impairment in chronotropic reserve and exaggerated increase in pulmonary capillary wedge pressure with exercise. These may be important targets for therapeutic strategies to improve exercise tolerance in patients with HFpEF.
This project was funded by the Strategically Focused Research Network Grant for Prevention from the American Heart Association to the University of Texas Southwestern Medical Center, Dallas, Texas, and Northwestern University School of Medicine, Chicago, Illinois. Dr. Berry has received funding from the Dedman Family Scholar in Clinical Care endowment at the University of Texas Southwestern Medical Center and grant 14SFRN20740000 from the American Heart Association prevention network. Dr. Kitzman has received funding from National Institutes of Health grants R01AG18915, R01AG045551, R01HL107257, and P30AG021332 and The Kermit Glenn Phillips II Chair in Cardiovascular Medicine, Wake Forest School of Medicine. Dr. Khera is supported by the National Heart, Lung, and Blood Institute (grant 5T32HL125247-02) and the National Center for Advancing Translational Sciences (grant UL1TR001105) of the National Institutes of Health. Dr. Kitzman is a consultant for Abbvie, Relypsa, Corvia Medical, and Bayer; has received research grant funding from Novartis, Bayer, and St. Luke’s Hospital of Kansas City; and owns stock in Gilead Science. Dr. Butler has received research support from the NIH, European Union, and Patient Centered Outcomes Research Institute; and is consultant to Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb (BMS), CVRx, Janssen, Luitpold, Medtronic, Novartis, Relypsa, Vifor, and ZS Pharma. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Pandey and Khera contributed equally to this work.
- Received June 25, 2017.
- Revision received October 21, 2017.
- Accepted October 23, 2017.
- 2018 American College of Cardiology Foundation
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