Author + information
- Received November 19, 2018
- Revision received January 10, 2019
- Accepted January 14, 2019
- Published online February 25, 2019.
- Anna L. Beale, MBBS, BMedScia,b,c,
- Shane Nanayakkara, MBBSa,b,c,
- Louise Segana,b,
- Justin A. Mariani, MBBS, PhDa,b,c,
- Micha T. Maeder, MD, PhDd,
- Vanessa van Empel, MD, PhDe,
- Donna Vizi, RNa,
- Shona Evans, NZSca,
- Carolyn S.P. Lam, MBBS, PhDf and
- David M. Kaye, MBBS, PhDa,b,c,∗ ()
- aDepartment of Cardiology, Alfred Hospital, Melbourne, Victoria, Australia
- bHeart Failure Research Group, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
- cDepartment of Medicine, Monash University, Clayton, Victoria, Australia
- dCardiology Department, Kantonsspital St. Gallen, St. Gallen, Switzerland
- eDepartment of Cardiology, Maastricht University Medical Centre, Maastricht, the Netherlands
- fDepartment of Cardiology, National Heart Centre, Duke University, National University of Singapore Medical School, Singapore
- ↵∗Address for correspondence:
Prof. David M. Kaye, Department of Cardiology, Alfred Hospital, Commercial Road, Melbourne, Victoria 3004, Australia.
Objectives This study sought to identify sex differences in central and peripheral factors that contribute to the pathophysiology of heart failure with preserved ejection fraction (HFpEF) by using complementary invasive hemodynamic and echocardiographic approaches.
Background Women are overrepresented among patients with HFpEF, and there are established sex differences in myocardial structure and function. Exercise intolerance is a fundamental feature of HFpEF; however, sex differences in the physiological determinants of exercise capacity in HFpEF are yet to be established.
Methods Patients with exertional intolerance with confirmed HFpEF were included in this study. Evaluation of the subjects included resting and exercise hemodynamics, echocardiography, and mixed venous blood gas sampling.
Results A total of 161 subjects included 114 females (71%). Compared to males, females had a higher pulmonary capillary wedge pressure (PCWP) indexed to peak exercise workload (0.8 [0.5 to 1.2] mm Hg/W vs. 0.6 [0.4 to 1] mm Hg/W, respectively; p = 0.001) and lower systemic (1.1 [0.9 to 1.5] ml/mm Hg vs. 1 [0.7 to 1.2] ml/mm Hg, respectively; p = 0.019) and pulmonary (2.9 [2.2 to 4.2] ml/mm Hg vs. 2.4 [1.9 to 3] ml/mm Hg, respectively; p = 0.032) arterial compliance at exercise. Mixed venous blood gas analysis demonstrated a greater rise in lactate indexed to peak workload (0.05 [0.04 to 0.09] mmol/l/W vs. 0.04 [0.03 to 0.06] mmol/l/W, respectively; p = 0.007) in women compared to men. Women had higher mitral inflow velocity to diastolic mitral annular velocity at early filling (E/e′) ratios at rest and peak exercise, along with a higher ejection fraction and smaller ventricular dimensions.
Conclusions Women with HFpEF demonstrate poorer diastolic reserve with higher echocardiographic and invasive measurements of left ventricular filling pressures at exercise, accompanied by lower systemic and pulmonary arterial compliance and poorer peripheral oxygen kinetics.
Dr. Lam has received support from Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, and Vifor Pharma; and serves on the advisory boards of Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, Vifor Pharma, Novartis, Amgen, Merck, Janssen Research and Development, Menarini, Boehringer Ingelheim, Novo Nordisk, Abbott Diagnostics, Corvia, Stealth BioTherapeutics, JanaCare, Biofourmis, and Darma. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received November 19, 2018.
- Revision received January 10, 2019.
- Accepted January 14, 2019.
- 2019 American College of Cardiology Foundation
This article requires a subscription or purchase to view the full text. If you are a subscriber or member, click Login or the Subscribe link (top menu above) to access this article.