{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:52:16Z","timestamp":1791237136416,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Echocardiography"],"published-print":{"date-parts":[[2026,2]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Heart failure (HF) with reduced ejection fraction (HFrEF) is characterized by progressive left ventricular (LV) remodeling and is often complicated by secondary (functional) mitral regurgitation (MR). Sacubitril\u2013valsartan (S\/V), an angiotensin receptor\u2013neprilysin inhibitor (ARNI), has demonstrated superiority over enalapril in reducing morbidity and mortality in HFrEF. Its mechanism of action includes promoting LV reverse remodeling (LVRR), but the comprehensive effect on both LVRR and secondary MR, particularly using advanced three\u2010dimensional (3D) echocardiography, requires further elucidation.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n To evaluate the effect of 1\u2010year S\/V therapy on LVRR and the severity of secondary MR in patients with HFrEF, utilizing both two\u2010dimensional (2D) and 3D echocardiographic parameters.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This prospective, single\u2010center study included 80 patients with HFrEF (LVEF \u2264 40%) initiated on S\/V. Comprehensive 2D and 3D transthoracic echocardiography was performed at baseline 6 months, and 1 year of treatment. LVRR was assessed by changes in LV volumes (EDVI, ESVI), LVEF, and LV mass index (LVMI). MR severity was quantified using the effective regurgitant orifice area (EROA). Paired statistical tests (\n t<\/jats:italic>\n \u2010test or Wilcoxon signed\u2010rank test) were used for pre\u2010 and posttreatment comparisons. Correlation and multivariable linear regression analyses were performed to identify predictors of LVRR.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n After 1 year of S\/V therapy, patients with HFrEF demonstrated marked and consistent improvements in both MR and (LV) structure and function. EROA decreased from 0.36 \u00b1 0.08 cm\n 2<\/jats:sup>\n to 0.24 \u00b1 0.09 cm\n 2<\/jats:sup>\n (\u221234.6%,\n p<\/jats:italic>\n < 0.001), accompanied by reductions in regurgitant volume (RV) (\u221232.6%,\n p<\/jats:italic>\n < 0.001) and regurgitant fraction (\u221230.8%,\n p<\/jats:italic>\n < 0.001). LVRR was evidenced by significant increases in LVEF (3D: +42.1%,\n p<\/jats:italic>\n < 0.001, Cohen's\n d<\/jats:italic>\n = 2.63) and reductions in LVEDV (\u221218.0%,\n p<\/jats:italic>\n < 0.001) and LVESV (\u221231.8%,\n p<\/jats:italic>\n < 0.001), as well as a 14.7% decrease in LVMI (\n p<\/jats:italic>\n < 0.001). Correlation analysis revealed that MR improvement closely paralleled LV remodeling, with \u0394EROA strongly associated with reductions in LVESVI (\n r<\/jats:italic>\n = 0.774,\n p<\/jats:italic>\n < 0.001), LVEDVI (\n r<\/jats:italic>\n = 0.558,\n p<\/jats:italic>\n < 0.001), and LVEF improvement (\n r<\/jats:italic>\n = \u22120.781,\n p<\/jats:italic>\n < 0.001). Multivariable regression identified lower baseline LVEF (3D) as the strongest independent predictor of LVRR (\n \u03b2<\/jats:italic>\n = \u22122.304,\n p<\/jats:italic>\n < 0.001)\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n S\/V therapy induces significant and comprehensive LVRR and a marked reduction in secondary MR severity in HFrEF patients. The strong correlation between these two effects suggests that MR improvement is primarily driven by LVRR. Lower baseline LVEF is a powerful predictor of the magnitude of LVRR.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/echo.70413","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T16:48:07Z","timestamp":1772988487000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effect of Sacubitril\u2013Valsartan on Secondary Mitral Regurgitation and Left Ventricular Reverse Remodeling in Patients With Heart Failure With Reduced Ejection Fraction: A 2D and 3D Echocardiographic Study"],"prefix":"10.1111","volume":"43","author":[{"given":"Mohammed Ali Mohammed","family":"Hammad","sequence":"first","affiliation":[{"name":"Department of Cardiology Faculty of Medicine Kafr Elsheikh University Kafr Elsheikh Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismael","family":"Elbarky","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Alexandria University Kafr Elsheikh Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reda","family":"Biomy","sequence":"additional","affiliation":[{"name":"Department of Cardiology Faculty of Medicine Kafr Elsheikh University Kafr Elsheikh Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wael Anwar Elshahat","family":"Hassib","sequence":"additional","affiliation":[{"name":"Department of Cardiology Faculty of Medicine Kafr Elsheikh University Kafr Elsheikh Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled","family":"Abouelmagd","sequence":"additional","affiliation":[{"name":"Department of Cardiology Faculty of Medicine\u2010Al Azhar University New Damietta Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Kamal Ibrahim","family":"Salama","sequence":"additional","affiliation":[{"name":"Department of Cardiology Faculty of Medicine Kafr Elsheikh University Kafr Elsheikh 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