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达格列净对射血分数降低的心力衰竭 2 型糖尿病患者的急性多效作用:一项交叉试验。

Acute pleiotropic effects of dapagliflozin in type 2 diabetic patients with heart failure with reduced ejection fraction: a crossover trial.

机构信息

Flinders Medical Centre, Bedford Park, South Australia, Australia.

Flinders University, Bedford Park, South Australia, Australia.

出版信息

ESC Heart Fail. 2021 Oct;8(5):4346-4352. doi: 10.1002/ehf2.13553. Epub 2021 Aug 11.

Abstract

AIMS

This study aimed to explore the rapid effects of dapagliflozin in heart failure with reduced ejection fraction (HFrEF).

METHODS AND RESULTS

We studied the functional, echocardiographic, electrophysiological, lung ultrasound, ambulatory blood pressure (BP), microvascular and macrovascular function, and biochemical effects of 2 week treatment with dapagliflozin in 19 type 2 diabetic HFrEF patients in a double-blind, crossover, placebo-controlled trial. Dapagliflozin had no significant effect on clinical, functional, or quality of life parameters. Dapagliflozin reduced systolic BP [114 (105, 131) vs. 106 (98, 113) mmHg, P < 0.01] and diastolic BP [71 (61, 78) vs. 62 (55, 70) mmHg, P < 0.01]. There was no effect on cardiac chamber size, ventricular systolic function, lung ultrasound, or arterial wave reflection. Dapagliflozin increased creatinine [117 (92, 129) vs. 122 (107, 135) μmol/L, P < 0.05] and haemoglobin [135 (118, 138) vs. 136 (123, 144) g/L, P < 0.05]. There was a reduction in ventricular ectopy [1.4 (0.1, 2.9) vs. 0.2 (0.1, 1.4) %, P < 0.05] and an increase in standard deviation of normal heart beat intervals [70 (58, 90) vs. 74 (62, 103), P < 0.05]. Unexpectedly, dapagliflozin increased high-sensitivity troponin T [25 (19, 37) vs. 28 (20, 42) ng/L, P < 0.01] and reduced reactive hyperaemia index [1.29 (1.21, 1.56) vs. 1.40 (1.23, 1.84), P < 0.05].

CONCLUSIONS

After 2 weeks, while multiple parameters supported BP reduction and haemoconcentration with dapagliflozin, reduction in cardiac filling pressure, lung water, and functional improvement was not shown. Reduced ventricular ectopic burden suggests an early antiarrhythmic benefit. The small increase in troponin T and the reduction in the reactive hyperaemia index warrant further mechanistic exploration in this treatment of proven mortality benefit in HFrEF.

摘要

目的

本研究旨在探讨达格列净对射血分数降低的心力衰竭(HFrEF)的快速作用。

方法和结果

我们在一项双盲、交叉、安慰剂对照试验中研究了 19 例 2 型糖尿病合并 HFrEF 患者接受 2 周达格列净治疗后的功能、超声心动图、电生理、肺部超声、动态血压(BP)、微血管和大血管功能以及生化作用。达格列净对临床、功能或生活质量参数没有显著影响。达格列净降低收缩压[114(105,131)vs. 106(98,113)mmHg,P<0.01]和舒张压[71(61,78)vs. 62(55,70)mmHg,P<0.01]。对心腔大小、心室收缩功能、肺部超声或动脉波反射无影响。达格列净增加肌酐[117(92,129)vs. 122(107,135)μmol/L,P<0.05]和血红蛋白[135(118,138)vs. 136(123,144)g/L,P<0.05]。室性心律失常减少[1.4(0.1,2.9)vs. 0.2(0.1,1.4)%,P<0.05],正常心跳间期标准差增加[70(58,90)vs. 74(62,103),P<0.05]。出乎意料的是,达格列净增加了高敏肌钙蛋白 T[25(19,37)vs. 28(20,42)ng/L,P<0.01]和降低了反应性充血指数[1.29(1.21,1.56)vs. 1.40(1.23,1.84),P<0.05]。

结论

在 2 周后,虽然多项参数支持达格列净降低血压和血液浓缩,但并未显示心腔充盈压、肺水和功能改善。室性心律失常负担的减少表明早期具有抗心律失常作用。肌钙蛋白 T 的小幅度增加和反应性充血指数的降低需要进一步探讨这种治疗方法对射血分数降低的心力衰竭的潜在益处的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1204/8497349/faff96172d0a/EHF2-8-4346-g001.jpg

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