{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T14:17:54Z","timestamp":1793197074663,"version":"4.5.0"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,4,6]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Mitral regurgitation (MR) is a major contributor for heart failure (HF) and atrial fibrillation. Despite the advancement of MR surgeries, an effective medical therapy to mitigate MR progression is lacking. Sodium glucose cotransporter 2 inhibitors, a new class of antidiabetic drugs, has shown measurable benefits in reduction of HF hospitalization and cardiovascular mortality but the mechanism is unclear. We hypothesized that dapagliflozin (DAPA), a sodium glucose cotransporter 2 inhibitor, can improve cardiac hemodynamics in MR\u2010induced HF.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">Using a novel, mini\u2010invasive technique, we established a MR model in rats, in which MR induced left heart dilatation and functional decline. Half of the rats were randomized to be administered with DAPA at 10\u00a0mg\/kg per day for 6\u00a0weeks. After evaluation of electrocardiography and echocardiography, hemodynamic studies were performed, followed by postmortem tissue analyses. Results showed that DAPA partially rescued MR\u2010induced impairment including partial restoration of left ventricular ejection fraction and end\u2010systolic pressure volume relationship. Despite no significant changes in electrocardiography at rest, rats treated with DAPA exhibited lower inducibility and decreased duration of pacing\u2010induced atrial fibrillation. DAPA also significantly attenuated cardiac fibrosis, cardiac expression of apoptosis, and endoplasmic reticulum stress\u2010associated proteins.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">DAPA was able to suppress cardiac fibrosis and endoplasmic reticulum stress and improve hemodynamics in an MR\u2010induced HF rat model. The demonstrated DAPA effect on the heart and its association with key molecular contributors in eliciting its cardio\u2010protective function, provides a plausible point of DAPA as a potential strategy for MR\u2010induced HF.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.120.019274","type":"journal-article","created":{"date-parts":[[2021,3,20]],"date-time":"2021-03-20T10:22:42Z","timestamp":1616235762000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":48,"title":["Dapagliflozin Improves Cardiac Hemodynamics and Mitigates Arrhythmogenesis in Mitral Regurgitation\u2010Induced Myocardial Dysfunction"],"prefix":"10.1161","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5332-9841","authenticated-orcid":false,"given":"Yu\u2010Wen","family":"Lin","sequence":"first","affiliation":[{"name":"Division of Cardiology Department of Internal Medicine Chi\u2010Mei Medical Center Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin\u2010Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiology Chi\u2010Mei Medical Center Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jhih\u2010Yuan","family":"Shih","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Internal Medicine Chi\u2010Mei Medical Center Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bor\u2010Chih","family":"Cheng","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Surgery Chi\u2010Mei Medical Center Tainan Taiwan"},{"name":"Department of Biotechnology Southern Taiwan University of Science and Technology Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0890-9414","authenticated-orcid":false,"given":"Ching\u2010Ping","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Medical Research Chi Mei Medical Center Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao\u2010Tsun","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medical Research Chi Mei Medical Center Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5925-8477","authenticated-orcid":false,"given":"Chung\u2010Han","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Hospital and Health Care Administration Chi\u2010Mei Medical Center Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhih\u2010Cherng","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Internal Medicine Chi\u2010Mei Medical Center Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudeshna","family":"Fisch","sequence":"additional","affiliation":[{"name":"Department of Medicine Brigham and Women's HospitalHarvard Medical School Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9525-2144","authenticated-orcid":false,"given":"Wei\u2010Ting","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Internal Medicine Chi\u2010Mei Medical Center Tainan Taiwan"},{"name":"Department of Biotechnology Southern Taiwan University of Science and Technology Tainan Taiwan"},{"name":"Institute of Clinical Medicine College of Medicine National Cheng Kung University Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000485"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehq222"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.semtcvs.2007.04.002"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2014.08.118"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3976"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0117567"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/jce.12191"},{"key":"e_1_3_2_9_2","first-page":"1652","article-title":"Endoplasmic reticulum stress associated apoptosis implicated in atrial fibrillation","volume":"9","author":"Chen JZ","year":"2016","unstructured":"Chen JZ, Xie J, Li GN, He GX, Tan W, Zhu SH, Chen QH, Wu H, Zhang XL, Wang L, et al. 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