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It is frequently prescribed to patients with HF who have a suboptimal response or intolerance to beta-blockers. Degenerative mitral regurgitation (MR) is a valvular heart disease often associated with the development of HF and atrial fibrillation (AF). However, studies comparing the effects of ivabradine and beta-blockers on MR are lacking. Therefore, this study aimed to explore the potential therapeutic effects of ivabradine and carvedilol on MR using a rat model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Using a novel echo-guided mini-invasive surgery, MR was created in 12-weeks-old Sprague\u2013Dawley rats. After 2 weeks, the rats were randomized to receive either ivabradine or carvedilol for 4 weeks. Echocardiography was performed at baseline and at two-week intervals. Following haemodynamic studies, postmortem tissues were analysed. Notably, the MR-induced myocardial dysfunction did not improve considerably after treatment with ivabradine or carvedilol. However, in haemodynamic studies, pharmacological therapies, particularly carvedilol, mitigated MR-induced chamber dilatation (end-systolic volume and end-diastolic volume; MR vs. MR + Carvedilol; P &amp;lt; 0.05) and decreased compliance (end-systolic pressure\u2013volume relationship; MR vs. MR + Carvedilol; P &amp;lt; 0.05). Compared with ivabradine, a shorter duration (MR vs. MR + Carvedilol; P &amp;lt; 0.05) and reduced inducibility (MR vs. MR + Carvedilol and MR vs. MR + Ivabradine; P &amp;lt; 0.05) of AF were observed in MR rats treated with carvedilol. Similarly, reduced cardiac fibrosis and apoptosis were observed in the MR rat model in the treatment groups, especially in those treated with carvedilol (MR vs. MR + Carvedilol; P &amp;lt; 0.01).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Although both ivabradine and carvedilol, at least in part, mitigated MR-induced chamber dilatation and decreased compliance, carvedilol had a better effect on reversing MR-induced cardiac fibrosis, apoptosis, and arrhythmogenesis than ivabradine. When compared with Ivabradine, MR rats treated with carvedilol exhibited a shorter duration and reduced inducibility of AF, thus providing more effective suppression of HCN4. Further investigations are required to validate our findings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.14577","type":"journal-article","created":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T18:18:51Z","timestamp":1699985931000},"page":"251-260","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Ivabradine Could Not Decrease Mitral Regurgitation Triggered Atrial Fibrosis and Fibrillation Compared with Carvedilol"],"prefix":"10.1093","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0585-6134","authenticated-orcid":false,"given":"Wei-Chieh","family":"Lee","sequence":"first","affiliation":[{"name":"School of Medicine, College of Medicine, National Sun Yat-sen University , Kaohsiung ,","place":["Taiwan"]},{"name":"Department of Internal Medicine, Division of Cardiology, Chi Mei Medical Center , Tainan ,","place":["Taiwan"]},{"name":"College of Medicine, Institute of Clinical Medicine, National Cheng Kung University , Tainan ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Wen","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiology, Chi Mei Medical Center , Tainan ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jhih-Yuan","family":"Shih","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, National Sun Yat-sen University , Kaohsiung ,","place":["Taiwan"]},{"name":"Department of Internal Medicine, Division of Cardiology, Chi Mei Medical Center , Tainan ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhih-Cherng","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, National Sun Yat-sen University , Kaohsiung ,","place":["Taiwan"]},{"name":"Department of Internal Medicine, Division of Cardiology, Chi Mei Medical Center , Tainan ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan-Chun","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, National Sun Yat-sen University , Kaohsiung ,","place":["Taiwan"]},{"name":"Department of Internal Medicine, Division of Cardiology, Chi Mei Medical Center , Tainan ,","place":["Taiwan"]},{"name":"Department of Surgery, Division of Cardiovascular Surgery, Chi Mei Medical Center , Tainan ,","place":["Taiwan"]},{"name":"Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy and Science , Tainan ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Ting","family":"Chang","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, National Sun Yat-sen University , Kaohsiung ,","place":["Taiwan"]},{"name":"Department of Internal Medicine, Division of Cardiology, Chi 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