Empagliflozin does not change cardiac index nor systemic vascular resistance but rapidly improves left ventricular filling pressure in patients with type 2 diabetes: a randomized controlled study.
Empagliflozin does not change cardiac index nor systemic vascular resistance but rapidly improves left ventricular filling pressure in patients with type 2 diabetes: a randomized controlled study.
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DOI：
10.1186/s12933-020-01175-5
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发表时间：
2021-01-07
影响因子：
9.3
通讯作者：
Lehrke M
中科院分区：
文献类型：
--
作者：
Rau M;Thiele K;Hartmann NK;Schuh A;Altiok E;Möllmann J;Keszei AP;Böhm M;Marx N;Lehrke M
在 EMPA-REG OUTCOME 试验（恩格列净心血管结果事件试验）中，使用钠-葡萄糖协同转运蛋白 2 (SGLT2) 抑制剂恩格列净治疗可显着减少 2 型糖尿病 (T2D) 和已确诊心血管疾病患者的心力衰竭住院率 (HHF)。试验前 3 个月内 HHF 事件曲线的早期分离表明，直接的血流动力学效应可能发挥了作用。然而，迄今为止，尚无关于 SGLT2 抑制剂对血流动力学参数和心脏功能的早期影响的数据。因此，本研究检查了恩格列净治疗对血流动力学参数的早期和延迟影响，包括全身血管阻力指数、心脏指数和每搏输出量指数，以及心功能的超声心动图测量。在这项安慰剂对照、随机、双盲、探索性研究中，2 型糖尿病患者被随机分配服用恩格列净 10 毫克或安慰剂，为期 3 个月。治疗 1 天、3 天和 3 个月后评估血流动力学和超声心动图参数。恩格列净组 (n = 22) 和安慰剂组 (n = 20) 的基线特征没有差异。恩格列净导致尿葡萄糖排泄显着增加（基线：7.3 ± 22.7 g/24 h；第 1 天：48.4± 34.7 g/24 h；p< 0.001）以及尿量（1740 ± 601 mL/24 h）显着增加。与安慰剂相比，一天后已达到 2112 ± 837 mL/24 h；p = 0.011）。恩格列净治疗对全身血管阻力指数的主要终点没有影响，对任何时间点的心脏指数、每搏输出量指数或脉搏率也没有影响。此外，超声心动图显示左心室射血分数和应变分析评估的左心室收缩功能没有差异。然而，通过早期二尖瓣流入速度相对于早期舒张期左心室舒张（E/eʹ）的降低来评估，恩格列净显着改善了左心室充盈压，这在治疗第1天变得显着（基线：9.2±2.6；第1天：8.5±2.2；p=0.005），并且在整个研究过程中保持明显。这主要归因于早期二尖瓣流入速度 E 降低（基线：0.8±0.2 m/s；第 1 天：0.73±0.2 m/s；p=0.003）。恩格列净治疗 T2D 患者 1 或 3 天后以及 3 个月后对血流动力学参数没有显着影响，但会导致舒张功能快速且持续的显着改善。试用注册EudraCT编号：2016-000172-19；注册日期：2017-02-20（clinicaltrialregister.eu）
In the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial) treatment with the sodium-glucose cotransporter-2 (SGLT2) inhibitor empagliflozin significantly reduced heart failure hospitalization (HHF) in patients with type 2 diabetes mellitus (T2D) and established cardiovascular disease. The early separation of the HHF event curves within the first 3 months of the trial suggest that immediate hemodynamic effects may play a role. However, hitherto no data exist on early effects of SGLT2 inhibitors on hemodynamic parameters and cardiac function. Thus, this study examined early and delayed effects of empagliflozin treatment on hemodynamic parameters including systemic vascular resistance index, cardiac index, and stroke volume index, as well as echocardiographic measures of cardiac function. In this placebo-controlled, randomized, double blind, exploratory study patients with T2D were randomized to empagliflozin 10 mg or placebo for a period of 3 months. Hemodynamic and echocardiographic parameters were assessed after 1 day, 3 days and 3 months of treatment. Baseline characteristics were not different in the empagliflozin (n = 22) and placebo (n = 20) group. Empagliflozin led to a significant increase in urinary glucose excretion (baseline: 7.3 ± 22.7 g/24 h; day 1: 48.4 ± 34.7 g/24 h; p < 0.001) as well as urinary volume (1740 ± 601 mL/24 h to 2112 ± 837 mL/24 h; p = 0.011) already after one day compared to placebo. Treatment with empagliflozin had no effect on the primary endpoint of systemic vascular resistance index, nor on cardiac index, stroke volume index or pulse rate at any time point. In addition, echocardiography showed no difference in left ventricular systolic function as assessed by left ventricular ejections fraction and strain analysis. However, empagliflozin significantly improved left ventricular filling pressure as assessed by a reduction of early mitral inflow velocity relative to early diastolic left ventricular relaxation (E/eʹ) which became significant at day 1 of treatment (baseline: 9.2 ± 2.6; day 1: 8.5 ± 2.2; p = 0.005) and remained apparent throughout the study. This was primarily attributable to reduced early mitral inflow velocity E (baseline: 0.8 ± 0.2 m/s; day 1: 0.73 ± 0.2 m/sec; p = 0.003). Empagliflozin treatment of patients with T2D has no significant effect on hemodynamic parameters after 1 or 3 days, nor after 3 months, but leads to rapid and sustained significant improvement of diastolic function. Trial registration EudraCT Number: 2016-000172-19; date of registration: 2017-02-20 (clinicaltrialregister.eu)
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