Author + information
- Received September 18, 2019
- Revision received December 27, 2019
- Accepted January 2, 2020
- Published online March 23, 2020.
- Payman Zamani, MD, MTRa,∗ (, )
- Elizabeth A. Proto, BAa,
- Jeremy A. Mazurek, MDa,
- Stuart B. Prenner, MDa,
- Kenneth B. Margulies, MDa,
- Raymond R. Townsend, MDb,
- Daniel P. Kelly, MDa,
- Zoltan Arany, MD, PhDa,
- David C. Poole, PhD, DScc,
- Peter D. Wagner, MDd and
- Julio A. Chirinos, MD, PhDa
- aDivision of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
- bDivision of Nephrology/Hypertension, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
- cDepartments of Kinesiology, Anatomy, and Physiology, Kansas State University, Manhattan, Kansas
- dDivision of Pulmonary Medicine, University of California-San Diego, San Diego, California
- ↵∗Address for correspondence:
Dr. Payman Zamani, Hospital of the University of Pennsylvania, 3400 Civic Center Boulevard, South Pavilion, 11-176, Philadelphia, Pennsylvania 19104.
• ΔAVo2 during exercise is a complex metric that incorporates into its calculation skeletal muscle blood flow and DmO2 across the skeletal muscle capillary membrane.
• Although ΔAVo2 was reduced in patients with HFpEF during both systemic and local (forearm) exercise, there was no difference in forearm DmO2 among subjects with HFpEF, those with hypertension, and healthy control subjects; therefore, abnormalities in forearm DmO2 cannot explain the reduced forearm ΔAVo2 seen in subjects with HFpEF.
• Local forearm exercise performance predicted about one-third of the variability in systemic aerobic capacity, demonstrating that peripheral factors are important in determining whole-body exercise tolerance.
• Degree of adiposity strongly correlated with ΔAVo2 during both local and whole-body exercise, suggesting that adipose tissue may play an active role in limiting exercise capacity in subjects with HFpEF.
The aim of this study was to determine the arteriovenous oxygen content difference (ΔAVo2) in adult subjects with and without heart failure with preserved ejection fraction (HFpEF) during systemic and forearm exercise. Subjects with HFpEF had reduced ΔAVo2. Forearm diffusional conductance for oxygen, a lumped conductance parameter that incorporates all impediments to the movement of oxygen from red blood cells in skeletal muscle capillaries into the mitochondria within myocytes, was estimated. Forearm diffusional conductance for oxygen was not different among adults with HFpEF, those with hypertension, and healthy control subjects; therefore, diffusional conductance cannot explain the reduced forearm ΔAVo2. Instead, adiposity was strongly associated with ΔAVo2, suggesting an active role for adipose tissue in reducing exercise capacity in patients with HFpEF.
The project described was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health (NIH), through grant UL1TR001878. Dr. Zamani is supported by NIH grant 5-K23-HL130551; and has consulted for Vyaire (modest). Dr. Mazurek has received advisory board honoraria from Actelion Pharmaceuticals (modest) and United Therapeutics (modest). Dr. Margulies is supported by NIH grants U10-HL110338, R01HL121510, and R01HL133080; and receives research funding from Sanofi (significant), Merck (significant), and GlaxoSmithKline (significant). Dr. Kelly is supported by NIH grants R01 DK045416, R01 HL058493, and R01 HL128349; and has received advisory board honoraria from Pfizer (significant) and Amgen (modest). Dr. Poole is supported by NIH grant HL-2-108328. Dr. Wagner is serving as an expert witness in a legal case of scientific misconduct. Dr. Chirinos is supported by NIH grants R01-HL 121510-01A1, R61-HL-146390, R01-AG058969, 1R01-HL104106, P01-HL094307, R03-HL146874-01, and R56-HL136730. Gregory Lewis, MD, served as guest editor for this paper.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received September 18, 2019.
- Revision received December 27, 2019.
- Accepted January 2, 2020.
- 2020 The Authors