Huang Zhuoshan, Fan Rui, Zhang Shaozhao, Zhong Junlin, Huang Yiquan, Xie Peihan, Yin Shanshan, Ye Xiaomin, Xu Xinghao, Huang Rihua, Xiong Zhenyu, Guo Yue, Liu Menghui, Lin Yifen, Li Suhua, Qian Xiaoxian, Liu Jinlai, Zhuang Xiaodong, Liao Xinxue
Department of Cardiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Department of Cardiovascular Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
ESC Heart Fail. 2025 Apr 10. doi: 10.1002/ehf2.15296.
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.
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 cm 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/m, 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.
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.
功能性二尖瓣反流（FMR）与心力衰竭患者的不良预后相关，目前的指南指导药物治疗（GDMT）在管理FMR方面疗效有限。本研究旨在评估钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）达格列净对中重度FMR患者的治疗效果。
在这项随机对照试验中，104例中重度FMR患者按1:1比例分配，分别接受每日一次10mg达格列净治疗或在当前FMR的GDMT基础上不接受额外治疗，随访期为3个月。主要终点是二尖瓣反流（MR）的有效反流口面积（EROA）变化。次要终点包括反流容积（RV）、左心室舒张末期容积（LVEDV）、左心室收缩末期容积（LVESV）、左心室质量（LVM）、左心室质量指数（LVMI）、左心室射血分数（LVEF）、E/e'比值和左心房容积指数（LAVI）的变化。还比较了两组间心力衰竭住院或心血管死亡的发生率。结果显示，达格列净显著降低了FMR的EROA（达格列净组为-0.074±0.099cm，对照组为-0.030±0.058cm，P=0.008）。它还显著降低了RV（-9.08±15.27 vs. -2.98±9.28mL，P=0.017）、E/e'比值（-5.88±7.41 vs. -1.98±7.63，P=0.011）和LAVI（-2.50±4.75 vs. -0.43±3.14mL/m，P=0.011），同时改善了LVEF（6.57±10.10 vs. 1.92±9.57%，P=0.017）。两组间LVEDV、LVESV、LVM和LVMI的变化无显著差异（P>0.05）。达格列净组9.6%的患者发生心力衰竭住院，对照组为15.3%（风险比，0.60；95%CI，0.20-1.83；P=0.368）。在3个月的随访期间，达格列净组1.9%的患者发生心血管死亡，对照组为3.8%（风险比，0.49；95%CI，0.04-5.41；P=0.561）。
达格列净在当前GDMT基础上使用时，显示出进一步降低FMR患者MR程度和增强心肌重塑的潜力。这些发现表明SGLT2i在FMR心力衰竭患者中作为对超声心动图参数及可能的预后具有附加积极作用的重要性。
