{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T12:06:42Z","timestamp":1788091602802,"version":"build-2803163510"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"25","funder":[{"name":"FWO","award":["11PGA24N"],"award-info":[{"award-number":["11PGA24N"]}]}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2026,6,23]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Atrial functional mitral regurgitation (AFMR) characterizes a high-risk phenotype in heart failure with preserved ejection fraction (HFpEF). Although sacubitril\/valsartan reduces functional mitral regurgitation (MR) in HF with reduced EF (HFrEF), its impact on exercise hemodynamics and the dynamic burden of AFMR in HFpEF remains to be elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      This multicenter, randomized, open-label trial with blinded primary endpoint assessment assigned 84 patients with symptomatic HFpEF and at least moderate AFMR within the previous year to sacubitril\/valsartan (n=41) or standard-of-care (SOC; n=43). The primary outcome was the 6-month change in the exercise mean pulmonary arterial pressure to cardiac output (mPAP\/CO) slope, assessed using cardiopulmonary exercise testing with simultaneous echocardiography (CPETecho). Secondary outcomes included changes in peak oxygen consumption (peak VO\n                      <jats:sub>2<\/jats:sub>\n                      ), Kansas City Cardiomyopathy Questionnaire (KCCQ), N-terminal pro\u2013B-type natriuretic peptide (NT-proBNP) levels, left atrial (LA) volume and function, and AFMR severity in rest and during stress.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      At 6 months, sacubitril\/valsartan significantly improved the mPAP\/CO slope compared with SOC (adjusted between-group difference in change, \u20130.93 mm Hg\/L\/min; 95% CI, \u20131.80 to \u20130.07;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.035). This hemodynamic benefit was accompanied by improvements in peak VO\n                      <jats:sub>2<\/jats:sub>\n                      (mean change, +0.9 versus \u20130.6mL\/kg\/min;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.002) and KCCQ (median increase, 10 versus 2 points;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.002). Significant reductions in NT-proBNP and LA volume were observed (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001 for both), alongside a significant blunting of the dynamic MR increase during exercise (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.020). Target dose was achieved in 60% of patients, with symptomatic hypotension as the primary titration-limiting factor.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>\n                      In HFpEF and AFMR, sacubitril\/valsartan was associated with improvements in exercise hemodynamics and peak VO\n                      <jats:sub>2<\/jats:sub>\n                      , along with attenuation of the exercise-induced increase in AFMR. These findings suggest a phenotype-specific benefit, warranting confirmation in larger, placebo-controlled, clinical outcome trials.\n                    <\/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: NCT05991284. EudraCT: 2023-506634-70-00\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.126.080833","type":"journal-article","created":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T11:51:06Z","timestamp":1778327466000},"page":"1973-1983","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Angiotensin Receptor Neprilysin Inhibitor in Heart Failure With Preserved Ejection Fraction and Secondary Mitral Regurgitation: The PRAISE-MR Randomized Trial"],"prefix":"10.1161","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5615-3191","authenticated-orcid":true,"given":"Sebastiaan","family":"Dhont","sequence":"first","affiliation":[{"name":"Department of Cardiology, Hospital Oost-Limburg, Genk, Belgium (S.D., P.M., E.M., S.D., W.M., P.B.B.)."},{"name":"Faculty of Medicine and Life Sciences, Limburg Clinical Research Center, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium (S.D., S.M.F., P.K., E.M., K.T., S.D., L.H., W.M., J.V., P.B.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2909-9166","authenticated-orcid":true,"given":"Sara","family":"Moura Ferreira","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Life Sciences, Limburg Clinical Research Center, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium (S.D., S.M.F., P.K., E.M., K.T., S.D., L.H., W.M., J.V., P.B.B.)."},{"name":"Department of Cardiology, Jessa &amp; Science, Jessa Hospital, Hasselt, Belgium (S.M.F, L.H., J.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6294-7668","authenticated-orcid":true,"given":"Xavier","family":"Galloo","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Jette, Belgium (X.G., F.H.V.)."},{"name":"Centre for Cardiovascular Diseases, University Hospital Brussels, Jette, Belgium (X.G., F.H.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6036-2113","authenticated-orcid":true,"given":"Pieter","family":"Martens","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Oost-Limburg, Genk, Belgium (S.D., P.M., E.M., S.D., W.M., P.B.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0204-0132","authenticated-orcid":true,"given":"Evelyne","family":"Meekers","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Oost-Limburg, Genk, Belgium (S.D., P.M., E.M., S.D., W.M., P.B.B.)."},{"name":"Faculty of Medicine and Life Sciences, Limburg Clinical Research Center, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium (S.D., S.M.F., P.K., E.M., K.T., S.D., L.H., W.M., J.V., P.B.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrien","family":"Tartaglia","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Life Sciences, Limburg Clinical Research Center, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium (S.D., S.M.F., P.K., E.M., K.T., S.D., L.H., W.M., J.V., P.B.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2215-8680","authenticated-orcid":true,"given":"S\u00e9bastien","family":"Deferm","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Oost-Limburg, Genk, Belgium (S.D., P.M., E.M., S.D., W.M., P.B.B.)."},{"name":"Faculty of Medicine and Life Sciences, Limburg Clinical Research Center, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium (S.D., S.M.F., P.K., E.M., K.T., S.D., L.H., W.M., J.V., P.B.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7784-3610","authenticated-orcid":true,"given":"Lieven","family":"Herbots","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Life Sciences, Limburg Clinical Research Center, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium (S.D., S.M.F., P.K., E.M., K.T., S.D., L.H., W.M., J.V., P.B.B.)."},{"name":"Department of Cardiology, Jessa &amp; Science, Jessa Hospital, Hasselt, Belgium (S.M.F, L.H., J.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9995-8590","authenticated-orcid":true,"given":"Wilfried","family":"Mullens","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Oost-Limburg, Genk, Belgium (S.D., P.M., E.M., S.D., W.M., P.B.B.)."},{"name":"Faculty of Medicine and Life Sciences, Limburg Clinical Research Center, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium (S.D., S.M.F., P.K., E.M., K.T., S.D., L.H., W.M., J.V., P.B.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0599-9290","authenticated-orcid":true,"given":"Frederik H.","family":"Verbrugge","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Jette, Belgium (X.G., F.H.V.)."},{"name":"Centre for Cardiovascular Diseases, University Hospital Brussels, Jette, Belgium (X.G., F.H.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2697-0825","authenticated-orcid":true,"given":"Jan","family":"Verwerft","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Life Sciences, Limburg Clinical Research Center, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium (S.D., S.M.F., P.K., E.M., K.T., S.D., L.H., W.M., J.V., P.B.B.)."},{"name":"Department of Cardiology, Jessa &amp; 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