Our study aims to address the knowledge gap regarding the combined impact of ARNI and iSGLT2 on ventricular remodeling, as assessed by volumetric indices and advanced speckle tracking echocardiography (STE), as well as the long-term effects on heart failure biomarkers (NT-proBNP) and major adverse cardiovascular events (MACVE). This evidence concerns the gene NPPB and heart failure.