Author + information
- Received November 17, 2018
- Revision received December 30, 2018
- Accepted January 4, 2019
- Published online March 25, 2019.
- Emil Wolsk, MD, PhDa,∗ (, )
- David Kaye, MD, PhDb,
- Jan Komtebedde, DVMc,
- Sanjiv J. Shah, MDd,
- Barry A. Borlaug, MDe,
- Daniel Burkhoff, MD, PhDf,
- Dalane W. Kitzman, MDg,
- Carolyn S.P. Lam, MBBS, PhDh,i,j,
- Dirk J. van Veldhuisen, MDh,i,
- Piotr Ponikowski, MD, PhDk,
- Mark C. Petrie, MDl,
- Christian Hassager, MD, DMSca,
- Jacob E. Møller, MD, DMScm and
- Finn Gustafsson, MD, DMSca
- aDepartment of Cardiology, Rigshospitalet, Copenhagen, Denmark
- bBaker IDI Heart and Diabetes Research Institute, Melbourne, Australia
- cDC Devices, Boston, Massachusetts
- dDivision of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
- eDivision of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, Minnesota
- fCardiovascular Research Foundation, Orangeburg, New York
- gDepartment of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina
- hNational Heart Centre Singapore, Singapore, Singapore
- iDuke-National University of Singapore, Singapore
- jDepartment of Cardiology, University Medical Center Groningen, the Netherlands
- kDepartment of Heart Diseases, Medical University and Centre for Heart Diseases, Military Hospital, Wrocław, Poland
- lInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom
- mDepartment of Cardiology, Odense University Hospital, Odense, Denmark
- ↵∗Address for correspondence:
Dr. Emil Wolsk, Department of Cardiology, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, Copenhagen, N/A 2100, Denmark.
Objectives This study sought to discern which central (e.g., heart rate, stroke volume [SV], filling pressure) and peripheral factors (e.g., oxygen use by skeletal muscle, body mass index [BMI]) during exercise were most strongly associated with the presence of heart failure and preserved ejection fraction (HFpEF) as compared with healthy control subjects exercising at the same workload.
Background The underlying mechanisms limiting exercise capacity in patients with HFpEF are not fully understood.
Methods In patients with HFpEF (n = 108), the hemodynamic response at peak exercise was measured using right-sided heart catheterization and was compared with that in healthy control subjects (n = 42) at matched workloads to reveal hemodynamic differences that were not attributable to the workload performed. The patients studied were prospectively included in the REDUCE-LAP HF (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) trials and HemReX (Effect of Age on the Hemodynamic Response During Rest and Exercise in Healthy Humans) study. Univariable and multivariable logistic regression models were used to analyze variables associated with HFpEF versus control subjects.
Results Compared with healthy control subjects, pulmonary capillary wedge pressure (PCWP) and SV were the only independent hemodynamic variables that were associated with HFpEF, a finding explaining 66% (p < 0.0001) of the difference between the groups. When relevant baseline characteristics were added to the base model, only BMI emerged as an additional independent variable, in total explaining of 90% of the differences between groups (p < 0.0001): PCWP (47%), BMI (31%), and SV (12%).
Conclusions The study identified 3 key variables (PCWP, BMI, and SV) that independently correlate with the presence of patients with HFpEF compared with healthy control subjects exercising at the same workload. Therapies that decrease left-sided heart filling pressures could improve exercise capacity and possibly prognosis.
- body mass index
- invasive exercise testing
- heart failure with preserved ejection fraction
- pulmonary capillary wedge pressure
Dr. Wolsk has received a speaker fee from Novartis. Dr. Kaye has received research grants from the National Health and Medical Research Council of Australia; has received consulting fees from AstraZeneca, Bayer, and Novartis; and is an unpaid member of the Corvia Medical Scientific Advisory Group. Dr. Komtebedde is Chief Medical Officer of Corvia Medical; and holds equity in Corvia Medical. Dr. Shah has received research funding from Actelion, AstraZeneca, Corvia Medical, and Novartis; has received consulting fees from Actelion, AstraZeneca, Bayer, Ironwood, Merck, Novartis, and Sanofi; and has received National Institutes of Health grants R01 HL127028, R01 HL140731, and R01 HL107577. Dr. Borlaug has received research funding from the National Heart, Lung, and Blood Institute (grants RO1 HL128526 and U10 HL110262), Mast Therapeutics, Medtronic, GlaxoSmithKline, and Teva; and has consulted and served on advisory boards for Actelion, Amgen, AstraZeneca, Merck, and MyoKardia. Dr. Burkhoff has been a consultant for and is the director of Hemodynamic Core Laboratory for Corvia Medical; and is the founder of PVLoops, LLC. Dr. Kitzman has received consulting fees from Corvia Medical, Medtronic, Bayer, Merck, Relypsa, and Abbvie; research funding from Novartis and Bayer; and owns stock in Gilead. Dr. Lam has received research support from Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, and Vifor Pharma; has consulted for Corvia, AstraZeneca, Bayer, Novartis, Amgen, Merck, Janssen Research & Development LLC, Menarini, Boehringer-Ingelheim, Abbott Diagnostics, Stealth BioTherapeutics, and Takeda; and is on the advisory board, steering committee, and/or executive committee for Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, Vifor Pharma, Novartis, Amgen, Merck, Janssen Research & Development LLC, Menarini, Boehringer-Ingelheim, Abbott Diagnostics, Corvia Medical, Stealth BioTherapeutics, JanaCare, Biofourmis, and Darma. Dr. Veldhuisen member of the steering committee of the REDUCE-LAP trial; and has received travel expenses from Corvia Medical. Dr. Ponikowski has received unrestricted research grants from Corvia Medical; and is an unpaid member of the Corvia Medical Scientific Advisory Group. Dr. Petrie has received speaker fees or consulting honoraria from Takeda, Novartis, AstraZeneca, Maquet, Boehringer-Ingelheim, Pfizer, Daiichi Sankyo, Servier, and Eli Lilly; has served on clinical events committees for Roche, Bayer, Stealth BioTherapeutics, AstraZeneca, GlaxoSmithKline, Novo Nordisk, Astellas, Cardiorentis, Reservlogix, and Boehringer-Ingelheim; and is an unpaid member of the Corvia Medical Scientific Advisory Group. Dr. Møller has received a research grant and speaker fees from Abiomed. Dr. Gustafsson has received unrestricted research grants from Corvia Medical; is an unpaid member of the Corvia Medical Scientific Advisory Group; has received speaker fees from Carmat, Abbott, and Orion; and has received a consultant fees from Bayer. Dr. Hassager has reported that he has no relationships relevant to the contents of this paper to disclose.
- Received November 17, 2018.
- Revision received December 30, 2018.
- Accepted January 4, 2019.
- 2019 American College of Cardiology Foundation
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