Research Unit of Cardiology, Department of Cardiology, Odense University Hospital, Odense, Denmark.
Steno Diabetes Centre Odense, Odense University Hospital, Odense, Denmark.
JAMA Cardiol. 2021 Jul 1;6(7):836-840. doi: 10.1001/jamacardio.2020.6827.
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) improve outcomes in patients with heart failure and a reduced ejection fraction (HFrEF). The association with cardiac remodeling has not been investigated.
To investigate the outcome of the SGLT2i empagliflozin, compared with placebo, on cardiac remodeling in patients with HFrEF.
DESIGN, SETTING, AND PARTICIPANTS: This exploratory post hoc analysis included participants with stable HFrEF and ejection fractions of 40% or less, who were randomly enrolled in an investigator-initiated, multicenter, double-blind, placebo-controlled randomized clinical trial in Denmark. Enrollment commenced on June 29, 2017, and continued through September 10, 2019, with the last participant follow-up on December 20, 2019.
Randomization (1:1) to empagliflozin (10 mg once daily) or matching placebo in addition to recommended heart failure therapy for 12 weeks.
Efficacy measures were changes from baseline to week 12 in left ventricular end-systolic and end-diastolic volume indexes, left atrial volume index, and left ventricular ejection fraction adjusted for age, sex, type 2 diabetes, and atrial fibrillation. Secondary efficacy measures included changes in left ventricular mass index, global longitudinal strain, and relative wall thickness.
A total of 190 patients were randomized (95 each receiving empagliflozin and placebo), with a mean (SD) age of 64 (11) years; 162 were men (85.3%), 97 (51.1%) had ischemic HFrEF, 24 (12.6%) had type 2 diabetes, and the mean (SD) latest recorded left ventricular ejection fraction was 29% (8%). Of the 190, 186 completed the study. Empagliflozin significantly reduced left ventricular end-systolic volume index (-4.3 [95% CI, -8.5 to -0.1] mL/m2; P = .04), left ventricular end-diastolic volume index (-5.5 [95% CI, -10.6 to -0.4] mL/m2; P = .03), and left atrial volume index (-2.5 [95% CI, -4.8 to -0.1] mL/m2; P = .04) compared with placebo at 12 weeks' follow-up, with no change in left ventricular ejection fraction (1.2% [95% CI, -1.2% to 3.6%]; P = .32). These findings were consistent across subgroups. Of secondary efficacy measures, left ventricular mass index was significantly reduced by empagliflozin (-9.0 [95% CI, -17.2 to -0.8] g/m2; P = .03).
In this small, randomized, short-term study, empagliflozin was associated with modest reductions in left ventricular and left atrial volumes with no association with ejection fraction. Effects beyond 12 weeks of SGLT2i use require further study.
ClinicalTrials.gov Identifier: NCT03198585.
重要性：钠-葡萄糖协同转运蛋白 2 抑制剂（SGLT2i）可改善射血分数降低的心力衰竭（HFrEF）患者的预后。但其与心脏重构的关联尚未被研究。
目的：研究 SGLT2i 恩格列净与安慰剂相比，对 HFrEF 患者心脏重构的影响。
设计、地点和参与者：这是一项探索性事后分析，纳入了稳定的 HFrEF 患者，射血分数为 40%或更低，这些患者是在丹麦进行的一项由研究者发起的、多中心、双盲、安慰剂对照的随机临床试验中随机入组的。招募于 2017 年 6 月 29 日开始，2019 年 9 月 10 日结束，最后一次随访是在 2019 年 12 月 20 日。
干预措施：随机（1:1）接受恩格列净（每日 10mg）或匹配的安慰剂，同时接受推荐的心力衰竭治疗 12 周。
主要观察指标：疗效指标是左心室收缩末期和舒张末期容积指数、左心房容积指数和左心室射血分数（根据年龄、性别、2 型糖尿病和心房颤动进行调整）从基线到第 12 周的变化。次要疗效指标包括左心室质量指数、整体纵向应变和相对壁厚度的变化。
结果：共有 190 名患者被随机分配（每组 95 人分别接受恩格列净和安慰剂），平均（标准差）年龄为 64（11）岁；162 名男性（85.3%），97 名（51.1%）患有缺血性 HFrEF，24 名（12.6%）患有 2 型糖尿病，最近记录的左心室射血分数的平均值（标准差）为 29%（8%）。在 190 名患者中，186 名完成了研究。与安慰剂相比，恩格列净显著降低了左心室收缩末期容积指数（-4.3[95%置信区间，-8.5 至 -0.1]ml/m2；P = .04）、左心室舒张末期容积指数（-5.5[95%置信区间，-10.6 至 -0.4]ml/m2；P = .03）和左心房容积指数（-2.5[95%置信区间，-4.8 至 -0.1]ml/m2；P = .04），而左心室射血分数没有变化（1.2%[95%置信区间，-1.2%至 3.6%]；P = .32）。这些发现在各亚组中均一致。在次要疗效指标中，恩格列净显著降低了左心室质量指数（-9.0[95%置信区间，-17.2 至 -0.8]g/m2；P = .03）。
结论：在这项小型、随机、短期研究中，恩格列净与左心室和左心房容积的适度减少相关，与射血分数无关联。SGLT2i 使用超过 12 周的效果需要进一步研究。
试验注册：ClinicalTrials.gov 标识符：NCT03198585。
