{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T10:09:01Z","timestamp":1792922941195,"version":"4.5.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"24","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2024,6,11]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>The morbidity and mortality rates of patients with heart failure (HF) and functional mitral regurgitation (MR) remain substantial despite guideline-directed medical therapy for HF. We evaluated the efficacy of ertugliflozin for reduction of functional MR associated with HF with mild to moderately reduced ejection fraction.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              The EFFORT trial (Ertugliflozin for Functional Mitral Regurgitation) was a multicenter, double-blind, randomized trial to examine the hypothesis that the sodium-glucose cotransporter 2 inhibitor ertugliflozin is effective for improving MR in patients with HF with New York Heart Association functional class II or III, 35%\u2264ejection fraction&lt;50%, and effective regurgitant orifice area of chronic functional MR &gt;0.1 cm\n              <jats:sup>2<\/jats:sup>\n              on baseline echocardiography. We randomly assigned 128 patients to receive either ertugliflozin or placebo in addition to guideline-directed medical therapy for HF. The primary end point was change in effective regurgitant orifice area of functional MR from baseline to the 12-month follow-up. Secondary end points included changes in regurgitant volume, left ventricular (LV) volume indices, left atrial volume index, LV global longitudinal strain, and NT-proBNP (N-terminal pro-B-type natriuretic peptide).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              The treatment groups were generally well-balanced with regard to baseline characteristics: mean age, 66\u00b111 years; 61% men; 13% diabetes; 51% atrial fibrillation; 43% use of angiotensin receptor-neprilysin inhibitor; ejection fraction, 42\u00b18%; and effective regurgitant orifice area, 0.20\u00b10.12 cm\n              <jats:sup>2<\/jats:sup>\n              . The decrease in effective regurgitant orifice area was significantly greater in the ertugliflozin group than in the placebo group (\u22120.05\u00b10.06 versus 0.03\u00b10.12 cm\n              <jats:sup>2<\/jats:sup>\n              ;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.001). Compared with placebo, ertugliflozin significantly reduced regurgitant volume by 11.2 mL (95% CI, \u221216.1 to \u22126.3;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.009), left atrial volume index by 6.0 mL\/m\n              <jats:sup>2<\/jats:sup>\n              (95% CI, \u221212.16 to 0.15;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.005), and LV global longitudinal strain by 1.44% (95% CI, \u22122.42% to \u22120.46%;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.004). There were no significant between-group differences regarding changes in LV volume indices, ejection fraction, or NT-proBNP levels. Serious adverse events occurred in one patient (1.6%) in the ertugliflozin group and 6 (9.2%) in the placebo group (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.12).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>Among patients with functional MR associated with HF, ertugliflozin significantly improved LV global longitudinal strain and left atrial remodeling, and reduced functional MR. Sodium-glucose cotransporter 2 inhibitors may be considered for patients with functional MR.<\/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: NCT04231331.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.124.069144","type":"journal-article","created":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T18:01:04Z","timestamp":1718042464000},"page":"1865-1874","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":60,"title":["Ertugliflozin for Functional Mitral Regurgitation Associated With Heart Failure: EFFORT Trial"],"prefix":"10.1161","volume":"149","clinical-trial-number":[{"clinical-trial-number":"nct04231331","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4031-8649","authenticated-orcid":true,"given":"Duk-Hyun","family":"Kang","sequence":"first","affiliation":[{"name":"Asan Medical Center (D.-H.K., M.-S.K., J.-M.S.), College of Medicine, University of Ulsan, Seoul, Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7075-847X","authenticated-orcid":true,"given":"Sung-Ji","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (S.-J.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8306-9622","authenticated-orcid":true,"given":"Sung-Hee","family":"Shin","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, College of Medicine, Inha University, Incheon, Korea (S.-H.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4966-3924","authenticated-orcid":true,"given":"In-Chang","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Center, Seoul National University Bundang Hospital, Seongnam, Korea (I.-C.H., Y.E.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8479-9889","authenticated-orcid":true,"given":"Yeonyee Elizabeth","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Center, Seoul National University Bundang Hospital, Seongnam, Korea (I.-C.H., Y.E.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7950-2131","authenticated-orcid":true,"given":"Hyung-Kwan","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Seoul National University Hospital, Seoul, Korea (H.-K.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4329-6016","authenticated-orcid":true,"given":"Mijin","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Pusan National University Hospital, Pusan National University Schollo of Medicine, Pusan, Korea (M.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0860-3650","authenticated-orcid":true,"given":"Min-Seok","family":"Kim","sequence":"additional","affiliation":[{"name":"Asan Medical Center (D.-H.K., M.-S.K., J.-M.S.), College of Medicine, University of Ulsan, Seoul, Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Cheol","family":"Yun","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Clinical Epidemiology and Biostatistics (S.-C.Y.), College of Medicine, University of Ulsan, Seoul, Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6754-8199","authenticated-orcid":true,"given":"Jong-Min","family":"Song","sequence":"additional","affiliation":[{"name":"Asan Medical Center (D.-H.K., M.-S.K., J.-M.S.), College of Medicine, University of Ulsan, Seoul, Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9856-9227","authenticated-orcid":true,"given":"Seok-Min","family":"Kang","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Severance Medical Center, Seoul, Korea 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