{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T08:28:27Z","timestamp":1793348907944,"version":"4.5.0"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2023,1,31]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Exercise intolerance is a defining characteristic of heart failure with preserved ejection fraction (HFpEF). A marked rise in pulmonary capillary wedge pressure (PCWP) during exertion is pathognomonic for HFpEF and is thought to be a key cause of exercise intolerance. If true, acutely lowering PCWP should improve exercise capacity. To test this hypothesis, we evaluated peak exercise capacity with and without nitroglycerin to acutely lower PCWP during exercise in patients with HFpEF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Thirty patients with HFpEF (70\u00b16 years of age; 63% female) underwent 2 bouts of upright, seated cycle exercise dosed with sublingual nitroglycerin or placebo control every 15 minutes in a single-blind, randomized, crossover design. PCWP (right heart catheterization), oxygen uptake (breath \u00d7 breath gas exchange), and cardiac output (direct Fick) were assessed at rest, 20 Watts (W), and peak exercise during both placebo and nitroglycerin conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      PCWP increased from 8\u00b14 to 35\u00b19 mm\u2009Hg from rest to peak exercise with placebo. With nitroglycerin, there was a graded decrease in PCWP compared with placebo at rest (\u20131\u00b12 mm\u2009Hg), 20W (\u20135\u00b15 mm\u2009Hg), and peak exercise (\u20137\u00b16 mm\u2009Hg; drug \u00d7 exercise stage\n                      <jats:italic>P<\/jats:italic>\n                      =0.004). Nitroglycerin did not affect oxygen uptake at rest, 20W, or peak (placebo, 1.34\u00b10.48 versus nitroglycerin, 1.32\u00b10.46 L\/min; drug \u00d7 exercise\n                      <jats:italic>P<\/jats:italic>\n                      =0.984). Compared with placebo, nitroglycerin lowered stroke volume at rest (\u20138\u00b113 mL) and 20W (\u20137\u00b111 mL), but not peak exercise (0\u00b110 mL).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Sublingual nitroglycerin lowered PCWP during submaximal and maximal exercise. Despite reduction in PCWP, peak oxygen uptake was not changed. These results suggest that acute reductions in PCWP are insufficient to improve exercise capacity, and further argue that high PCWP during exercise is not by itself a limiting factor for exercise performance in patients with HFpEF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Registration:<\/jats:title>\n                    <jats:p>\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique identifier: NCT04068844.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.122.061828","type":"journal-article","created":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T05:00:25Z","timestamp":1671166825000},"page":"378-387","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":63,"title":["Challenging the Hemodynamic Hypothesis in Heart Failure With Preserved Ejection Fraction: Is Exercise Capacity Limited by Elevated Pulmonary Capillary Wedge Pressure?"],"prefix":"10.1161","volume":"147","clinical-trial-number":[{"clinical-trial-number":"nct04068844","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0628-4919","authenticated-orcid":true,"given":"Satyam","family":"Sarma","sequence":"first","affiliation":[{"name":"Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital, Dallas (S.S., J.P.M., B.N.B., C.M.H., D.J.W., A.R.T., T.G.B., B.D.L.)."},{"name":"University of Texas Southwestern Medical Center, Dallas (S.S., J.P.M., B.N.B., C.M.H., D.J.W., A.R.T., T.G.B., B.D.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P.","family":"MacNamara","sequence":"additional","affiliation":[{"name":"Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital, Dallas (S.S., J.P.M., B.N.B., C.M.H., D.J.W., A.R.T., T.G.B., B.D.L.)."},{"name":"University of Texas Southwestern Medical Center, Dallas (S.S., J.P.M., B.N.B., C.M.H., D.J.W., A.R.T., T.G.B., B.D.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2642-7083","authenticated-orcid":true,"given":"Bryce N.","family":"Balmain","sequence":"additional","affiliation":[{"name":"Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital, Dallas (S.S., J.P.M., B.N.B., C.M.H., D.J.W., A.R.T., T.G.B., B.D.L.)."},{"name":"University of Texas Southwestern Medical Center, Dallas (S.S., J.P.M., B.N.B., C.M.H., D.J.W., A.R.T., T.G.B., B.D.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Christopher M.","family":"Hearon","sequence":"additional","affiliation":[{"name":"Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital, Dallas (S.S., J.P.M., B.N.B., C.M.H., D.J.W., A.R.T., T.G.B., B.D.L.)."},{"name":"University of Texas Southwestern Medical Center, Dallas (S.S., J.P.M., B.N.B., C.M.H., D.J.W., A.R.T., T.G.B., B.D.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4200-3790","authenticated-orcid":true,"given":"Denis J.","family":"Wakeham","sequence":"additional","affiliation":[{"name":"Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital, Dallas (S.S., J.P.M., B.N.B., C.M.H., D.J.W., A.R.T., T.G.B., B.D.L.)."},{"name":"University of Texas Southwestern Medical Center, Dallas (S.S., J.P.M., B.N.B., C.M.H., D.J.W., A.R.T., T.G.B., B.D.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9899-0812","authenticated-orcid":true,"given":"Andrew R.","family":"Tomlinson","sequence":"additional","affiliation":[{"name":"Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital, Dallas (S.S., J.P.M., B.N.B., C.M.H., D.J.W., A.R.T., T.G.B., B.D.L.)."},{"name":"University of Texas Southwestern Medical Center, Dallas (S.S., J.P.M., B.N.B., C.M.H., D.J.W., A.R.T., T.G.B., B.D.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4642-7769","authenticated-orcid":true,"given":"Linda S.","family":"Hynan","sequence":"additional","affiliation":[{"name":"Peter O\u2019Donnell Jr School of Public Health and Department of Psychiatry (L.S.H.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony G.","family":"Babb","sequence":"additional","affiliation":[{"name":"Institute for Exercise and 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