Dapagliflozin effect on functional mitral regurgitation and myocardial remodelling: The DEFORM trial

Abstract Aims Functional mitral regurgitation (FMR) is associated with adverse outcomes in patients with heart failure, and current guideline‐directed medical therapy (GDMT) offers limited efficacy in managing FMR. This study aims to evaluate the therapeutic impact of the sodium‐glucose cotransporte...

Full description

Saved in:
Bibliographic Details
Main Authors: Zhuoshan Huang, Rui Fan, Shaozhao Zhang, Junlin Zhong, Yiquan Huang, Peihan Xie, Shanshan Yin, Xiaomin Ye, Xinghao Xu, Rihua Huang, Zhenyu Xiong, Yue Guo, Menghui Liu, Yifen Lin, Suhua Li, Xiaoxian Qian, Jinlai Liu, Xiaodong Zhuang, Xinxue Liao
Format: Article
Language:English
Published: Wiley 2025-08-01
Series:ESC Heart Failure
Subjects:
Online Access:https://doi.org/10.1002/ehf2.15296
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850059592653864960
author Zhuoshan Huang
Rui Fan
Shaozhao Zhang
Junlin Zhong
Yiquan Huang
Peihan Xie
Shanshan Yin
Xiaomin Ye
Xinghao Xu
Rihua Huang
Zhenyu Xiong
Yue Guo
Menghui Liu
Yifen Lin
Suhua Li
Xiaoxian Qian
Jinlai Liu
Xiaodong Zhuang
Xinxue Liao
author_facet Zhuoshan Huang
Rui Fan
Shaozhao Zhang
Junlin Zhong
Yiquan Huang
Peihan Xie
Shanshan Yin
Xiaomin Ye
Xinghao Xu
Rihua Huang
Zhenyu Xiong
Yue Guo
Menghui Liu
Yifen Lin
Suhua Li
Xiaoxian Qian
Jinlai Liu
Xiaodong Zhuang
Xinxue Liao
author_sort Zhuoshan Huang
collection DOAJ
description Abstract Aims Functional mitral regurgitation (FMR) is associated with adverse outcomes in patients with heart failure, and current guideline‐directed medical therapy (GDMT) offers limited efficacy in managing FMR. This study aims to evaluate the therapeutic impact of the sodium‐glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin in patients with moderate or severe FMR. Methods and results In this randomized controlled trial, 104 patients with moderate or severe FMR were assigned in a 1:1 ratio to receive either dapagliflozin 10 mg once daily or no additional treatment alongside current GDMT for FMR, with a follow‐up period of 3 months. The primary endpoint was the change in effective regurgitant orifice area (EROA) of mitral regurgitation (MR). Secondary endpoints included changes in regurgitant volume (RV), left ventricular end‐diastolic volume (LVEDV), left ventricular end‐systolic volume (LVESV), left ventricular mass (LVM), left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF), E/e′ ratio, and left atrial volume index (LAVI). The incidence of hospitalization for heart failure or cardiovascular death was also compared between the groups. As a result, dapagliflozin significantly reduced the EROA of FMR (−0.074 ± 0.099 vs. −0.030 ± 0.058 cm2 for dapagliflozin vs. control, P = 0.008). It also significantly decreased RV (−9.08 ± 15.27 vs. −2.98 ± 9.28 mL, P = 0.017), E/e′ ratio (−5.88 ± 7.41 vs. −1.98 ± 7.63, P = 0.011), and LAVI (−2.50 ± 4.75 vs. −0.43 ± 3.14 mL/m2, P = 0.011) while improving LVEF (6.57 ± 10.10 vs. 1.92 ± 9.57%, P = 0.017). No significant differences were observed in changes in LVEDV, LVESV, LVM, and LVMI between groups (P > 0.05). Hospitalization for heart failure occurred in 9.6% of the dapagliflozin group and 15.3% of the control group (hazard ratio, 0.60; 95% CI, 0.20–1.83; P = 0.368). Cardiovascular death occurred in 1.9% of the dapagliflozin group compared to 3.8% of the control group (hazard ratio, 0.49; 95% CI, 0.04–5.41; P = 0.561) during the 3‐month follow‐up. Conclusions Dapagliflozin demonstrates the potential to further reduce the degree of MR and enhance myocardial remodelling in patients with FMR when used in addition to current GDMT. These findings suggest the importance of SGLT2i in heart failure patients with FMR as an additive positive effect on echocardiographic parameter and possibly outcome.
format Article
id doaj-art-48995da5a0404505a03e8635763d492e
institution DOAJ
issn 2055-5822
language English
publishDate 2025-08-01
publisher Wiley
record_format Article
series ESC Heart Failure
spelling doaj-art-48995da5a0404505a03e8635763d492e2025-08-20T02:50:51ZengWileyESC Heart Failure2055-58222025-08-011242866287710.1002/ehf2.15296Dapagliflozin effect on functional mitral regurgitation and myocardial remodelling: The DEFORM trialZhuoshan Huang0Rui Fan1Shaozhao Zhang2Junlin Zhong3Yiquan Huang4Peihan Xie5Shanshan Yin6Xiaomin Ye7Xinghao Xu8Rihua Huang9Zhenyu Xiong10Yue Guo11Menghui Liu12Yifen Lin13Suhua Li14Xiaoxian Qian15Jinlai Liu16Xiaodong Zhuang17Xinxue Liao18Department of Cardiology, The First Affiliated Hospital Sun Yat‐Sen University Guangzhou ChinaDepartment of Medical Ultrasonics, The First Affiliated Hospital Sun Yat‐Sen University Guangzhou ChinaDepartment of Cardiology, The First Affiliated Hospital Sun Yat‐Sen University Guangzhou ChinaDepartment of Ultrasonography, The Third Affiliated Hospital Sun Yat‐Sen University Guangzhou ChinaDepartment of Cardiology, The First Affiliated Hospital Sun Yat‐Sen University Guangzhou ChinaDepartment of Cardiology, The First Affiliated Hospital Sun Yat‐Sen University Guangzhou ChinaDepartment of Ultrasonography, The Third Affiliated Hospital Sun Yat‐Sen University Guangzhou ChinaDepartment of Cardiology, The First Affiliated Hospital Sun Yat‐Sen University Guangzhou ChinaDepartment of Cardiology, The First Affiliated Hospital Sun Yat‐Sen University Guangzhou ChinaDepartment of Cardiology, The First Affiliated Hospital Sun Yat‐Sen University Guangzhou ChinaDepartment of Cardiology, The First Affiliated Hospital Sun Yat‐Sen University Guangzhou ChinaDepartment of Cardiology, The First Affiliated Hospital Sun Yat‐Sen University Guangzhou ChinaDepartment of Cardiology, The First Affiliated Hospital Sun Yat‐Sen University Guangzhou ChinaDepartment of Cardiology, The First Affiliated Hospital Sun Yat‐Sen University Guangzhou ChinaDepartment of Cardiovascular Medicine, The Third Affiliated Hospital Sun Yat‐Sen University Guangzhou ChinaDepartment of Cardiovascular Medicine, The Third Affiliated Hospital Sun Yat‐Sen University Guangzhou ChinaDepartment of Cardiovascular Medicine, The Third Affiliated Hospital Sun Yat‐Sen University Guangzhou ChinaDepartment of Cardiology, The First Affiliated Hospital Sun Yat‐Sen University Guangzhou ChinaDepartment of Cardiology, The First Affiliated Hospital Sun Yat‐Sen University Guangzhou ChinaAbstract Aims Functional mitral regurgitation (FMR) is associated with adverse outcomes in patients with heart failure, and current guideline‐directed medical therapy (GDMT) offers limited efficacy in managing FMR. This study aims to evaluate the therapeutic impact of the sodium‐glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin in patients with moderate or severe FMR. Methods and results In this randomized controlled trial, 104 patients with moderate or severe FMR were assigned in a 1:1 ratio to receive either dapagliflozin 10 mg once daily or no additional treatment alongside current GDMT for FMR, with a follow‐up period of 3 months. The primary endpoint was the change in effective regurgitant orifice area (EROA) of mitral regurgitation (MR). Secondary endpoints included changes in regurgitant volume (RV), left ventricular end‐diastolic volume (LVEDV), left ventricular end‐systolic volume (LVESV), left ventricular mass (LVM), left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF), E/e′ ratio, and left atrial volume index (LAVI). The incidence of hospitalization for heart failure or cardiovascular death was also compared between the groups. As a result, dapagliflozin significantly reduced the EROA of FMR (−0.074 ± 0.099 vs. −0.030 ± 0.058 cm2 for dapagliflozin vs. control, P = 0.008). It also significantly decreased RV (−9.08 ± 15.27 vs. −2.98 ± 9.28 mL, P = 0.017), E/e′ ratio (−5.88 ± 7.41 vs. −1.98 ± 7.63, P = 0.011), and LAVI (−2.50 ± 4.75 vs. −0.43 ± 3.14 mL/m2, P = 0.011) while improving LVEF (6.57 ± 10.10 vs. 1.92 ± 9.57%, P = 0.017). No significant differences were observed in changes in LVEDV, LVESV, LVM, and LVMI between groups (P > 0.05). Hospitalization for heart failure occurred in 9.6% of the dapagliflozin group and 15.3% of the control group (hazard ratio, 0.60; 95% CI, 0.20–1.83; P = 0.368). Cardiovascular death occurred in 1.9% of the dapagliflozin group compared to 3.8% of the control group (hazard ratio, 0.49; 95% CI, 0.04–5.41; P = 0.561) during the 3‐month follow‐up. Conclusions Dapagliflozin demonstrates the potential to further reduce the degree of MR and enhance myocardial remodelling in patients with FMR when used in addition to current GDMT. These findings suggest the importance of SGLT2i in heart failure patients with FMR as an additive positive effect on echocardiographic parameter and possibly outcome.https://doi.org/10.1002/ehf2.15296DapagliflozinFunctional mitral regurgitationMyocardial remodelling
spellingShingle Zhuoshan Huang
Rui Fan
Shaozhao Zhang
Junlin Zhong
Yiquan Huang
Peihan Xie
Shanshan Yin
Xiaomin Ye
Xinghao Xu
Rihua Huang
Zhenyu Xiong
Yue Guo
Menghui Liu
Yifen Lin
Suhua Li
Xiaoxian Qian
Jinlai Liu
Xiaodong Zhuang
Xinxue Liao
Dapagliflozin effect on functional mitral regurgitation and myocardial remodelling: The DEFORM trial
ESC Heart Failure
Dapagliflozin
Functional mitral regurgitation
Myocardial remodelling
title Dapagliflozin effect on functional mitral regurgitation and myocardial remodelling: The DEFORM trial
title_full Dapagliflozin effect on functional mitral regurgitation and myocardial remodelling: The DEFORM trial
title_fullStr Dapagliflozin effect on functional mitral regurgitation and myocardial remodelling: The DEFORM trial
title_full_unstemmed Dapagliflozin effect on functional mitral regurgitation and myocardial remodelling: The DEFORM trial
title_short Dapagliflozin effect on functional mitral regurgitation and myocardial remodelling: The DEFORM trial
title_sort dapagliflozin effect on functional mitral regurgitation and myocardial remodelling the deform trial
topic Dapagliflozin
Functional mitral regurgitation
Myocardial remodelling
url https://doi.org/10.1002/ehf2.15296
work_keys_str_mv AT zhuoshanhuang dapagliflozineffectonfunctionalmitralregurgitationandmyocardialremodellingthedeformtrial
AT ruifan dapagliflozineffectonfunctionalmitralregurgitationandmyocardialremodellingthedeformtrial
AT shaozhaozhang dapagliflozineffectonfunctionalmitralregurgitationandmyocardialremodellingthedeformtrial
AT junlinzhong dapagliflozineffectonfunctionalmitralregurgitationandmyocardialremodellingthedeformtrial
AT yiquanhuang dapagliflozineffectonfunctionalmitralregurgitationandmyocardialremodellingthedeformtrial
AT peihanxie dapagliflozineffectonfunctionalmitralregurgitationandmyocardialremodellingthedeformtrial
AT shanshanyin dapagliflozineffectonfunctionalmitralregurgitationandmyocardialremodellingthedeformtrial
AT xiaominye dapagliflozineffectonfunctionalmitralregurgitationandmyocardialremodellingthedeformtrial
AT xinghaoxu dapagliflozineffectonfunctionalmitralregurgitationandmyocardialremodellingthedeformtrial
AT rihuahuang dapagliflozineffectonfunctionalmitralregurgitationandmyocardialremodellingthedeformtrial
AT zhenyuxiong dapagliflozineffectonfunctionalmitralregurgitationandmyocardialremodellingthedeformtrial
AT yueguo dapagliflozineffectonfunctionalmitralregurgitationandmyocardialremodellingthedeformtrial
AT menghuiliu dapagliflozineffectonfunctionalmitralregurgitationandmyocardialremodellingthedeformtrial
AT yifenlin dapagliflozineffectonfunctionalmitralregurgitationandmyocardialremodellingthedeformtrial
AT suhuali dapagliflozineffectonfunctionalmitralregurgitationandmyocardialremodellingthedeformtrial
AT xiaoxianqian dapagliflozineffectonfunctionalmitralregurgitationandmyocardialremodellingthedeformtrial
AT jinlailiu dapagliflozineffectonfunctionalmitralregurgitationandmyocardialremodellingthedeformtrial
AT xiaodongzhuang dapagliflozineffectonfunctionalmitralregurgitationandmyocardialremodellingthedeformtrial
AT xinxueliao dapagliflozineffectonfunctionalmitralregurgitationandmyocardialremodellingthedeformtrial