Ambarish Pandey1, Rohan Khera1, Bryan Park1, Mark Haykowsky2, Barry A Borlaug3, Gregory D Lewis4, Dalane W Kitzman5, Javed Butler6, Jarett D Berry7. 1. Division of Cardiology, Department of Internal Medicine, University of Texas Southwest Medical Center, Dallas, Texas. 2. College of Nursing and Health Innovation, University of Texas at Arlington, Arlington, Texas. 3. Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota. 4. Division of Cardiology, Department of Internal Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. 5. Department of Internal Medicine, Sections on Cardiovascular Medicine and Geriatrics, Wake Forest School of Medicine, Winston-Salem, North Carolina. 6. Division of Cardiology, Department of Internal Medicine, Stony Brook University School of Medicine, New York, New York. 7. Division of Cardiology, Department of Internal Medicine, University of Texas Southwest Medical Center, Dallas, Texas. Electronic address: jarett.berry@utsouthwestern.edu.
Abstract
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.
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 arteriovenousoxygen 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.
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