Evaluation of the Effects of the Sodium-Glucose Cotransporter 2 Inhibitors and Sacubitril/Valsartan Combined Therapy in Patients with HFrEF: An Echocardiographic Study

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.

Keywords: echocardiography; gliflozins; global longitudinal strain; heart failure.

Figure 1

Changes in myocardial deformation parameters of LV assessed by STE after 3 months of iSGLT2 therapy. Baseline (t0) on the left; 3 months (t1) on the right. At each time point: (1) Top left: endocardial tracking; (2) bottom left: GCS; (3) bottom right: GLS; (4) top right: evolution over time of endomyocardial deformation (top) and volumes (bottom). GCS: global circumferential strain; GLS: global longitudinal strain; LV: left ventricle; STE: speckle tracking echocardiography.

Figure 2

Changes in left ventricle end diastolic volume index after 3 and 12 months of iSGLT2 therapy.

Figure 3

Changes in left ventricle end diastolic diameter after 3 and 12 months of iSGLT2 therapy.

Figure 4

Changes in left ventricle ejection fraction after 3 and 12 months of iSGLT2 therapy.

Figure 5

Changes in left ventricle global longitudinal strain after 3 and 12 months of iSGLT2 therapy.

Figure 6

Central illustration. Fup: follow-up; HF: heart failure; iSGLT2: Sodium–glucose cotransporter 2 inhibitors; MACVE: major cardiovascular events; MI: myocardial infarction; STE: speckle tracking echocardiography.