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© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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.

Details

Title
Evaluation of the Effects of the Sodium–Glucose Cotransporter 2 Inhibitors and Sacubitril/Valsartan Combined Therapy in Patients with HFrEF: An Echocardiographic Study
Author
Fumarulo Isabella 1   VIAFID ORCID Logo  ; Pasquini Annalisa 1   VIAFID ORCID Logo  ; La Vecchia Giulia 2   VIAFID ORCID Logo  ; Pellizzeri Bianca 3 ; Sten Andriy 4 ; Garramone, Barbara 1 ; Vaccarella Marcello 1   VIAFID ORCID Logo  ; Ravenna, Salvatore Emanuele 5 ; Lombardo Antonella 1   VIAFID ORCID Logo  ; Burzotta Francesco 1 ; Pitocco Dario 6 ; Aspromonte Nadia 1 

 Department of Cardiovascular Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; [email protected] (I.F.);, Department of Cardiovascular Sciences, Catholic University of the Sacred Heart, 00168 Rome, Italy 
 Department of Cardiovascular Sciences, Catholic University of the Sacred Heart, 00168 Rome, Italy, Operative Unit of Diagnostic Interventional Cardiology, Isola Tiberina-Gemelli Isola, 00186 Rome, Italy 
 Division of Cardiology, Azienda Ospedaliero Universitaria Policlinico “G. Rodolico-San Marco”, University of Catania, 95100 Catania, Italy 
 Department of Cardiovascular Sciences, Catholic University of the Sacred Heart, 00168 Rome, Italy 
 Department of Life Science, Health and Health Professions, Università degli Studi Link, 00165 Rome, Italy 
 Diabetes Care Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy 
First page
5651
Publication year
2025
Publication date
2025
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3223913549
Copyright
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.