Impact of sacubitril/valsartan on systolic heart failure: Right heart location and clustering analysis

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) is a heterogeneous syndrome. In heart failure (HF) classifications, right ventricle (RV) function was for a long time unrecognized in favor of left ventricular ejection fraction (LVEF). The response to sacubitril/valsartan might differ according to phenotypes and the impact of right ventricular characteristics on this response remains controversial. OBJECTIVES: First, we applied clustering analysis in a HFrEF population undergoing sacubitril/valsartan treatment according to guidelines, to identify phenotypes and their associated clinical outcomes. Secondly, we evaluated RV-remodeling. MATERIAL AND METHODS: It is a prospective, observational, single-center study conducted on 108 symptomatic patients (mean age 66 ±12.8 years, 22.2% women). First, the clustering analysis was applied in a HFrEF population undergoing sacubitril/valsartan treatment, according to the guidelines, in order to identify phenotypes and clinical outcomes associated with them. Secondly, we evaluated RV-remodeling. RESULTS: Two distinct clusters were identified. Among the differences between phenotypes, RV (tricuspid annular plane systolic excursion (TAPSE) 16 ±4 mm compared to 19 ±4 mm, p < 0.001; RV free wall strain -19 ±5% compared to -21 ±4%, p = 0.046; RV fraction area change (FAC) 31 ±9% compared to 38 ±9%, p < 0.001), LV-filling pressure (E-wave deceleration time 138 (median: 41) ms compared to 180 (median: 94) ms, p < 0.001; E/e' 16.7 (median: 8.0) ms compared to 13.0 (median: 9.7) ms, p = 0.02) and creatinine level (106 ±34 μmol/L compared to 90 ±19 μmol/L, p = 0.002) were substantially different at the initiation of therapy. Major adverse cardiac events (MACEs) or death occurred in 38 out of 107 patients: 51.1% in cluster 1 compared to 24.2% in cluster 2 (p = 0.0074). A significant improvement in RV-functional parameters was observed under treatment. The TAPSE improved and correlated with the change in left ventricular (LV) function. Yet, it did not correlate with systolic pulmonary artery pressure (sPAP) and LV end-diastolic diameter. CONCLUSIONS: The HFrEF phenotype characterized by more severe RV dysfunction has a worse prognosis during sacubitril/valsartan therapy. Both RVand LV functions significantly improve when the patient is treated with sacubitril/valsartan.