CARDIAC REMODELING IN PATIENTS WITH HFrEF TREATED WITH SACUBITRIL/VALSARTAN: ECHOCARDIOGRAPHIC ANALYSIS

Aim of the study: The aim of the present study was to assess reverse remodelling in patients with HFrEF after six months of treatment with sacubitril/valsartan through 3D echocardiography and two-dimensional Speckle Tracking echocardiography, which are known to allow automatic and reproducible assessment of ventricular volumes, ejection fraction, left atrium volume and global longitudinal strain of the left ventricle and left atrium, and other additional echocardiographic parameters. Regarding right heart, size and function were assessed, with PAPS, TAPSE and S'TDI estimated. A further aim of the study was to analyse the clinical and echocardiographic baseline characteristics of the patients in order to identify the presence of factors predictive of significant reverse remodelling, and, thus, of response to sacubitril/valsartan therapy. Finally, the variation in atrial natriuretic peptides plasmatic levels after sacubitril/valsartan therapy was also evaluated. Material and Methods: In this prospective longitudinal study, patients with HFrEF treated with sacubitril/valsartan were enrolled. The following were inclusion criteria: age over 18, EF ≤ 35%, NYHA class ≥ II, treatment with the maximum tolerated dosage of ACEi or ARB or patients naïve to ACEi or ARB, undergoing pre-treatment with one of theese drugs. Exclusion criteria were: symptomatic hypotension, systolic blood pressure <100mmHg, eGFR <30 ml/min/1.73 m2, serum potassium levels >5.2 mmol/L, history of angioedema, adverse reactions during ACEi/ARB therapy, concomitant initiation of therapy that may induce reverse remodelling (for example, CRT implantation or coronary revascularization during follow-up or in the six months prior to enrolment), non-sinus rhythm, suboptimal acoustic window. Patients have been undergoing a clinical examination, 12-lead electrocardiogram, transthoracic echocardiogram (2D/3D parameters and 2D-Speckle Tracking), and dosage of natriuretic peptides before the start of therapy with sacubitril/valsartan and in follow-up at 6 months. Functional assessment was performed using the NYHA classification. Results: The final study population consisted of 32 patients. At the time of the follow up several echocardiographic parameters improved significantly in the entire study population. 13 (41%) of the patients in the study population were classified 'responders' and 19 (59%) were 'super responders'. In the 'responders' group more severe left ventricular remodelling before treatment was documented, in particular greater VTDi values and higher indexed atrial volumes. An improvement in global ventricular and atrial strain was also observed in 'responders', although less marked than the other group. Conclusions: Sacubitril/valsartan significantly improves reverse remodeling in patients with HFrEF. This result tends to occur in patients with a ventricular dilation of lesser severity. In accordance with these considerations, the drug should be used early and independently of the apparent clinical "stability" to avoid further progression of ventricular remodelling. Further studies may lead to an indication of sacubitril/valsartan since an earlier stage of the disease.