Ovchinnikov Artem, Potekhina Alexandra, Filatova Anastasiia, Svirida Olga, Zherebchikova Kristina, Ageev Fail, Belyavskiy Evgeny
Laboratory of Myocardial Fibrosis and Heart Failure With Preserved Ejection Fraction, National Medical Research Center of Cardiology Named After Academician E.I. Chazov, Academician Chazov St., 15a, Moscow, 121552, Russia.
Department of Clinical Functional Diagnostics, Russian University of Medicine of the Ministry of Health of the Russian Federation, Dolgorukovskaya St., 4, Moscow, 127006, Russia.
Cardiovasc Diabetol. 2025 May 9;24(1):196. doi: 10.1186/s12933-025-02756-y.
Clinical trials have established the prognostic benefits of sodium‒glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) and heart failure (HF) with preserved ejection fraction (HFpEF), although the underlying mechanisms are not clearly understood. The purpose of this study was to determine the effects of the SGLT2 inhibitor empagliflozin on functional capacity, left ventricular (LV) diastolic function/filling pressure, and cardiac reserves in patients with HFpEF and T2DM.
In the present prospective single-center trial, we enrolled 70 diabetic patients with stable HF according to the New York Heart Association functional class II-III criteria, an LV ejection fraction ≥ 50%, and increased LV filling pressure at rest and/or during exercise (determined by echocardiography). The patients were randomly assigned in an open-label fashion to the empagliflozin group (10 mg a day, n = 35) or the control group (n = 35) for 6 months. Echocardiography (at rest and during exercise), the 6-min walk test distance (6MWD), blood levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), and the profibrotic biomarker sST2 were analysed at baseline and 6 months after randomization. The primary endpoint was the change in the 6MWD, and the secondary endpoints included the change in the left atrial (LA) volume index, early mitral inflow to mitral annulus relaxation velocity (E/e') ratio both at rest and during exercise, key cardiac reserves and biomarkers in the blood from baseline to 6 months.
After 6 months of empagliflozin therapy, the 6MWTD significantly increased, whereas the LA volume index and the E/e' ratio both at rest and during exercise decreased compared with those of the control group (P < 0.05 for all). LV diastolic, LA reservoir and contractile, and chronotropic reserves also improved in the empagliflozin group compared with those in the control group (P < 0.05 for all). Furthermore, treatment with empagliflozin led to improvements in NT-proBNP and ST2 blood levels compared with those in the control group (P < 0.05 for both).
In diabetic patients with HFpEF, empagliflozin treatment improved exercise capacity, which appeared to be the result of favourable effects on LV diastolic dysfunction and key cardiac reserves: LV diastolic, LA reservoir and contractile, and chronotropic. These haemodynamic mechanisms may underline the benefits of SGLT2 inhibitors in large-scale HFpEF trials.
URL: https://www.
gov . Unique Identifier NCT03753087.
临床试验已证实钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂对2型糖尿病（T2DM）合并射血分数保留的心力衰竭（HFpEF）患者具有预后益处，但其潜在机制尚不清楚。本研究旨在确定SGLT2抑制剂恩格列净对HFpEF合并T2DM患者的功能能力、左心室（LV）舒张功能/充盈压和心脏储备的影响。
在本前瞻性单中心试验中，我们根据纽约心脏协会功能分级II-III标准、左心室射血分数≥50%以及静息和/或运动时左心室充盈压升高（通过超声心动图确定），纳入了70例稳定HF的糖尿病患者。患者以开放标签的方式随机分为恩格列净组（每日10 mg，n = 35）或对照组（n = 35），为期6个月。在基线和随机分组后6个月时，分析超声心动图（静息和运动时）、6分钟步行试验距离（6MWD）、N末端脑钠肽前体（NT-proBNP）血水平以及促纤维化生物标志物sST2。主要终点是6MWD的变化，次要终点包括左心房（LA）容积指数的变化、静息和运动时二尖瓣早期血流与二尖瓣环舒张速度（E/e'）比值的变化、关键心脏储备以及从基线到6个月时血液中的生物标志物。
恩格列净治疗6个月后，6MWD显著增加，而与对照组相比，静息和运动时的LA容积指数以及E/e'比值均降低（所有P < 0.05）。与对照组相比，恩格列净组的左心室舒张、左心房储备和收缩以及变时储备也有所改善（所有P < 0.05）。此外，与对照组相比，恩格列净治疗使NT-proBNP和ST2血水平得到改善（两者P < 0.05）。
在HFpEF合并糖尿病患者中，恩格列净治疗改善了运动能力，这似乎是对左心室舒张功能障碍和关键心脏储备（左心室舒张、左心房储备和收缩以及变时）产生有利影响的结果。这些血流动力学机制可能是SGLT2抑制剂在大规模HFpEF试验中获益的基础。
网址：https://www.
gov。唯一标识符NCT03753087。
