Effects of sacubitril/valsartan on atrial function and structure as treatment response indicators in patients with heart failure with reduced ejection fraction: an observational prospective study

Abstract

Abstract Funding Acknowledgements Type of funding sources: None. Background Sacubitril/valsartan (Sac/Val) has been shown to improve mortality and reduce hospitalizations in patients with heart failure with reduced ejection fraction (HFrEF), also through reverse cardiac remodeling. However, temporal changes of functional and structural left atrial parameters, including speckle tracking (ST) analysis, have not been comprehensively characterized yet. Purpose This prospective study sought to: (1) evaluate the impact of Sac/Val on echo parameters, focusing on left atrial function and structure metrics, at two timepoints, 6 and 12 months, after treatment initiation; (2) assess the predictive role of these factors on Sac/Val response at 12 months, including LVEF and biomarker outcomes. Methods From January 2020 to September 2021, HFrEF patients from Policlinico Universitario Agostino Gemelli IRCSS outpatient HF service with indication to Sac/Val treatment were prospectively enrolled; subjects with history of atrial fibrillation and more than moderate mitral regurgitation were excluded. Echocardiographic evaluation was performed before Sac/Val, at 6 and 12 months after treatment initiation. Patients with improvement in left ventricular ejection fraction (LVEF) ≥ 35% and with N-terminal pro-b-type natriuretic peptide (NT pro-BNP) reduction below 1000 pg/mL were considered responders. Results Sixty-six patients (50 males, 16 females) with an age of 64 ± 12 years were finally enrolled, of which 41% were affected by chronic ischemic heart disease. At enrollment, 19 subjects were in New York Heart Association class III-IV, median NT-proBNP was 3063.00 pg/mL and mean LVEF was 30.3±7.7%. LA-EF was 27.8±12.8%, while Left Atrio-ventricular coupling index (LACi) was 0,30±0,12. At ST echocardiography, LV GLS was -8,2±3,0% and LA reservoir strain (LARS) 11,60%. All structural and functional LA parameters significantly improved at T1 and T2: at T2, LARS was 22,51%, LA-EF 37,4±15,8% and LACi 0,28±0,12 (respectively p <0,001, p = 0,05, p = 0,018 compared to baseline). No differences were detected according to dysfunction etiology. Improvements were larger among patients who achieved the pre-specified outcome. LA reservoir strain was the best predictor of positive changes in LVEF and NT-proBNP. Conclusions Precise characterization of LA structural and functional parameters, including ST analysis, may help identifying patients experiencing the highest benefit from Sac/Val, therefore guiding treatment in the HFrEF population.