is a new treatment for heart failure with reduced ejection fraction which has a spectacular effect on survival  The effect of this drug on myocardial work are unknown  Sacubitril-Valsartan increases myocardial constructive work and work efficiency  Pressure-strain loops are a recently introduced tool for the non invasive estimation of myocardial work.  Constructive work a prognostic of major adverse cardiac events in patients with heart failure receiving Sacubitril-Valsartan

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. Materials 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 RV-and LV functions significantly improve when the patient is treated with sacubitril/valsartan.

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Funding Acknowledgements Type of funding sources: None. Background the non-invasive assessment of myocardial work (MW) by pressure-strain loops analysis (PSL) is a relative new tool for the evaluation of myocardial performance. Sacubitril/Valsartan is a treatment for heart failure with reduced ejection fraction (HFrEF) which has a spectacular effect on the reduction of cardiovascular events (MACEs). Purposes of this study were to evaluate 1) the short and medium term effect of Sacubitril/Valsartan treatment on MW parameters; 2) the prognostic value of MW in this specific group of patients. Methods 79 patients with HFrEF (mean age: 66 ± 12 years; LV ejection fraction: 28 ± 9%) were prospectively included in the study and treated with Sacubitril/Valsartan. Echocardiographic examination was performed at baseline, and after 6- and 12-month of therapy with Sacubitril/Valsartan. Results Sacubitril/Valsartan significantly increased myocardial constructive work (CW) (1023 ± 449 vs 1424 ± 484 mmHg%, p &lt; 0.0001) and myocardial work efficiency (WE) [87 (78-90) vs 90 (86-95), p &lt; 0.0001]. During FU (2.6 ± 0.9 years), MACEs occurred in 13 (16%) patients. After correction for LV size, LVEF and WE, global myocardial constructive work (CW) was the only predictor of MACEs [HR 0.99 (0.99-1.00), p = 0.05]. (Table 1). A CW &lt; 910 mmHg (AUC = 0.81, p &lt; 0.0001, Figure 1, left panel) identified patients at particularly increase risk of MACEs [HR 11.09 (1.45-98.94), p = 0.002, log-rank test p &lt; 0.0001] (Figure 2, Right panel). Conclusions in patients with HFrEF who receive a comprehensive background beta-blocker and mineral-corticoid receptor antagonist therapy, Sacubitril/Valsartan induces a significant improvement of myocardial CW and WE. In this population, the estimation of CW before the initiation of Sacubitril/Valsartan therapy allows the prediction of MACEs. Univariable analysis Multivariable analysis HR (95% CI) p-value HR (95% CI) p-value Age, per year 0.99 (0.95-1.04) 0.81 Ischemic cardiomyopathy 1.07 (0.36-3.21) 0.89 LVEDVi*, per ml/m2 1.01 (1.00-1.03) 0.03 LVESVi, per ml/m2 1.01 (1.00-1.03) 0.009 1.01 (0.99-1.02) 0.35 LVEF, per % 0.91 (0.85-0.98) 0.01 1.02 (0.93-1.12) 0.71 CW, per mmHg% 0.99 (0.99-1.00) 0.002 0.99 (0.99-1.00) 0.04 WE, per mmHg% 0.91 (0.86-0.96) 0.001 0.95 (0.88-1.02) 0.16 Predictors of MACEs at univariable and multivariable analysis Abstract Figure 1 A and B