BACKGROUND:The morbidity and mortality rates of patients with heart failure (HF) and functional mitral regurgitation (MR) remain substantial despite guideline-directed medical therapy for HF. We evaluated the efficacy of ertugliflozin for reduction of functional MR associated with HF with mild to moderately reduced ejection fraction.METHODS:The EFFORT trial (Ertugliflozin for Functional Mitral Regurgitation) was a multicenter, double-blind, randomized trial to examine the hypothesis that the sodium-glucose cotransporter 2 inhibitor ertugliflozin is effective for improving MR in patients with HF with New York Heart Association functional class II or III, 35%≤ejection fraction<50%, and effective regurgitant orifice area of chronic functional MR >0.1 cm² on baseline echocardiography. We randomly assigned 128 patients to receive either ertugliflozin or placebo in addition to guideline-directed medical therapy for HF. The primary end point was change in effective regurgitant orifice area of functional MR from baseline to the 12-month follow-up. Secondary end points included changes in regurgitant volume, left ventricular (LV) volume indices, left atrial volume index, LV global longitudinal strain, and NT-proBNP (N-terminal pro-B-type natriuretic peptide).RESULTS:The treatment groups were generally well-balanced with regard to baseline characteristics: mean age, 66±11 years; 61% men; 13% diabetes; 51% atrial fibrillation; 43% use of angiotensin receptor-neprilysin inhibitor; ejection fraction, 42±8%; and effective regurgitant orifice area, 0.20±0.12 cm². The decrease in effective regurgitant orifice area was significantly greater in the ertugliflozin group than in the placebo group (−0.05±0.06 versus 0.03±0.12 cm²; P<0.001). Compared with placebo, ertugliflozin significantly reduced regurgitant volume by 11.2 mL (95% CI, −16.1 to −6.3; P=0.009), left atrial volume index by 6.0 mL/m² (95% CI, −12.16 to 0.15; P=0.005), and LV global longitudinal strain by 1.44% (95% CI, −2.42% to −0.46%; P=0.004). There were no significant between-group differences regarding changes in LV volume indices, ejection fraction, or NT-proBNP levels. Serious adverse events occurred in one patient (1.6%) in the ertugliflozin group and 6 (9.2%) in the placebo group (P=0.12).CONCLUSIONS:Among patients with functional MR associated with HF, ertugliflozin significantly improved LV global longitudinal strain and left atrial remodeling, and reduced functional MR. Sodium-glucose cotransporter 2 inhibitors may be considered for patients with functional MR.REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT04231331.

中文翻译：

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艾图格列净治疗与心力衰竭相关的功能性二尖瓣反流：EFFORT 试验

背景：尽管针对心力衰竭（HF）进行了指南指导的药物治疗，但心力衰竭（HF）和功能性二尖瓣反流（MR）患者的发病率和死亡率仍然很高。我们评估了艾格列净减少与射血分数轻度至中度降低的心力衰竭相关的功能性 MR 的功效。 方法：EFFORT 试验（艾格列净治疗功能性二尖瓣反流）是一项多中心、双盲、随机试验，旨在检验以下假设：钠-葡萄糖协同转运蛋白2抑制剂艾图格列净可有效改善纽约心脏协会功能分级II或III级、35%≤射血分数<50%、慢性功能性MR有效返流口面积>0.1 cm ²的心力衰竭患者的MR基线超声心动图。我们随机分配 128 名患者除了接受指南指导的心力衰竭药物治疗外，还接受厄图格列净或安慰剂治疗。主要终点是功能性 MR 有效返流口面积从基线到 12 个月随访的变化。次要终点包括反流容积、左心室 (LV) 容积指数、左心房容积指数、LV 整体纵向应变和 NT-proBNP（N 末端 B 型利尿钠肽原）的变化。 结果：治疗组为基线特征总体上很平衡：平均年龄，66±11岁； 61% 男性； 13% 患有糖尿病； 51% 心房颤动； 43%使用血管紧张素受体脑啡肽酶抑制剂；射血分数，42±8%；有效回流口面积0.20±0.12cm ²。埃尔格列净组有效回流口面积的减少显着大于安慰剂组（-0.05±0.06 vs 0.03±0.12 cm ²；P <0.001）。与安慰剂相比，ertugliflozin 显着减少反流容积 11.2 mL（95% CI，-16.1 至 -6.3；P = 0.009），左心房容积指数显着减少 6.0 mL/m ²（95% CI，-12.16 至 0.15；P = 0.005），左室整体纵向应变增加 1.44%（95% CI，-2.42% 至 -0.46%；P =0.004）。左心室容积指数、射血分数或 NT-proBNP 水平的变化没有显着的组间差异。 ertugliflozin 组有 1 名患者（1.6%）发生严重不良事件，安慰剂组有 6 名患者（9.2%）发生严重不良事件（P = 0.12）。结论：在伴有 HF 的功能性 MR 患者中，ertugliflozin 显着改善了 LV 整体纵向应变和左心房重构，功能性 MR 降低。对于功能性 MR 患者，可考虑使用钠-葡萄糖协同转运蛋白 2 抑制剂。注册：URL：https://www.clinicaltrials.gov；唯一标识符：NCT04231331。