Fumarulo Isabella, Pasquini Annalisa, La Vecchia Giulia, Pellizzeri Bianca, Sten Andriy, Garramone Barbara, Vaccarella Marcello, Ravenna Salvatore Emanuele, Lombardo Antonella, Burzotta Francesco, Pitocco Dario, Aspromonte Nadia
Department of Cardiovascular Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
Department of Cardiovascular Sciences, Catholic University of the Sacred Heart, 00168 Rome, Italy.
Int J Mol Sci. 2025 Jun 12;26(12):5651. doi: 10.3390/ijms26125651.
Sodium-glucose cotransporter 2 inhibitors (iSGLT2) have become the fourth pillar of the medical treatment for heart failure with reduced ejection fraction (HFrEF). However, the mechanisms of action of iSGLT2 remain poorly understood. The effectiveness of combined ARNI and iSGLT2 therapy in left ventricular (LV) remodeling is still under study. We aim to investigate the effects of ARNI + iSGLT2 combination therapy in patients affected by HFrEF in terms of ventricular remodeling using speckle tracking echocardiography (STE). In this observational study, 136 patients with HFrEF taking ARNI were enrolled. All patients were evaluated at baseline (before iSGLT2), at 3 months and at 12 months from the beginning of iSGLT2 therapy. Echocardiographic parameters, including STE analysis and volumetric and LV contractile function indices, were collected at the three timepoints. The objectives were (1) to evaluate the effects of ARNI + iSGLT2 combination therapy on ultrasound (US) measurements; (2) to evaluate the effects on the variation of laboratory data indicative of HF (NT-pro-BNP); and (3) to evaluate the medium-long term impact of the ARNI + iSGLT2 combination therapy in terms of major cardiovascular events (MACVE). After only three months of combined ARNI + iSGLT2 therapy, we reported a significant improvement in ventricular and atrial volumetric indices, systolic function indices and myocardial deformation parameters assessed by STE. We also reported a significant decrease in NTproBNP levels. This trend was confirmed at 12 months follow-up. Furthermore, narrowing down the analysis to patients who were already treated with ARNI when they started taking iSGLT2, we reported similar results in the improvement of US parameters and NTproBNP levels. Our study has shown that the ARNI + iSGLT2 combination therapy leads to a clinical improvement and positive ventricular remodeling. Even the single introduction of additional iSGLT-2 in HFrEF patients on an otherwise optimized therapy resulted in a significant improvement in US and laboratory variables. The results of our study suggest implementing iSGLT-2 therapy as soon as possible, as the structural and functional cardiac improvements achieved by these drugs are achieved in the short term and maintained in the long term.
钠-葡萄糖协同转运蛋白2抑制剂（iSGLT2）已成为射血分数降低的心力衰竭（HFrEF）药物治疗的第四大支柱。然而，iSGLT2的作用机制仍知之甚少。ARNI与iSGLT2联合治疗对左心室（LV）重构的有效性仍在研究中。我们旨在使用斑点追踪超声心动图（STE）研究ARNI+iSGLT2联合治疗对受HFrEF影响患者心室重构的影响。在这项观察性研究中，纳入了136例服用ARNI的HFrEF患者。所有患者在基线时（开始使用iSGLT2之前）、开始使用iSGLT2治疗后的3个月和12个月进行评估。在这三个时间点收集超声心动图参数，包括STE分析以及容积和LV收缩功能指标。目标是：（1）评估ARNI+iSGLT2联合治疗对超声（US）测量的影响；（2）评估对指示HF的实验室数据（NT-pro-BNP）变化的影响；（3）评估ARNI+iSGLT2联合治疗对主要心血管事件（MACVE）的中长期影响。仅在ARNI+iSGLT2联合治疗三个月后，我们就报告了通过STE评估的心室和心房容积指标、收缩功能指标和心肌变形参数有显著改善。我们还报告了NTproBNP水平显著降低。在12个月的随访中这一趋势得到了证实。此外，将分析范围缩小到开始服用iSGLT2时已接受ARNI治疗的患者，我们在US参数和NTproBNP水平的改善方面报告了类似结果。我们的研究表明，ARNI+iSGLT2联合治疗可带来临床改善和积极的心室重构。即使在已接受优化治疗的HFrEF患者中单独加用iSGLT-2也能使US和实验室变量有显著改善。我们的研究结果表明应尽快实施iSGLT-2治疗，因为这些药物实现的心脏结构和功能改善在短期内即可达成并能长期维持。
