{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T22:14:16Z","timestamp":1794003256608,"version":"4.8.0"},"reference-count":66,"publisher":"American Medical Association (AMA)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:sec id=\"ab-hoi230018-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>The pathophysiology of exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF) remains incompletely understood. Multiple lines of evidence suggest that abnormal skeletal muscle metabolism is a key contributor, but the mechanisms underlying metabolic dysfunction remain unresolved.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hoi230018-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the associations of skeletal muscle mitochondrial function using respirometric analysis of biopsied muscle fiber bundles from patients with HFpEF with exercise performance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hoi230018-6\">\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>In this cross-sectional study, muscle fiber bundles prepared from fresh vastus lateralis biopsies were analyzed by high-resolution respirometry to provide detailed analyses of mitochondrial oxidative phosphorylation, including maximal capacity and the individual contributions of complex I\u2013linked and complex II-linked respiration. These bioenergetic data were compared between patients with stable chronic HFpEF older than 60 years and age-matched healthy control (HC) participants and analyzed for intergroup differences and associations with exercise performance. All participants were treated at a university referral center, were clinically stable, and were not undergoing regular exercise or diet programs. Data were collected from March 2016 to December 2017, and data were analyzed from November 2020 to May 2021.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hoi230018-7\">\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>Skeletal muscle mitochondrial function, including maximal capacity and respiration linked to complex I and complex II. Exercise performance was assessed by peak exercise oxygen consumption, 6-minute walk distance, and the Short Physical Performance Battery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hoi230018-8\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 72 included patients, 50 (69%) were women, and the mean (SD) age was 69.6 (6.1) years. Skeletal muscle mitochondrial function measures were all markedly lower in skeletal muscle fibers obtained from patients with HFpEF compared with HCs, even when adjusting for age, sex, and body mass index. Maximal capacity was strongly and significantly correlated with peak exercise oxygen consumption (\n                      <jats:italic>R<\/jats:italic>\n                      \u2009=\u20090.69;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001), 6-minute walk distance (\n                      <jats:italic>R<\/jats:italic>\n                      \u2009=\u20090.70;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001), and Short Physical Performance Battery score (\n                      <jats:italic>R<\/jats:italic>\n                      \u2009=\u20090.46;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hoi230018-9\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>In this study, patients with HFpEF had marked abnormalities in skeletal muscle mitochondrial function. Severely reduced maximal capacity and complex I\u2013linked and complex II\u2013linked respiration were associated with exercise intolerance and represent promising therapeutic targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamacardio.2023.0957","type":"journal-article","created":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T12:06:51Z","timestamp":1683720411000},"page":"575","source":"Crossref","is-referenced-by-count":115,"title":["Skeletal Muscle Mitochondrial Respiration and Exercise Intolerance in Patients With Heart Failure With Preserved Ejection Fraction"],"prefix":"10.1001","volume":"8","author":[{"given":"Lina","family":"Scandalis","sequence":"first","affiliation":[{"name":"Division of Geriatrics, Gerontology, and Palliative Care, UC San Diego School of Medicine, University of California, San Diego"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalane W.","family":"Kitzman","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine Section, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara J.","family":"Nicklas","sequence":"additional","affiliation":[{"name":"Section on Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Lyles","sequence":"additional","affiliation":[{"name":"Section on Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Brubaker","sequence":"additional","affiliation":[{"name":"Department of Health and Exercise Science at Wake Forest University, Winston-Salem, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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