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.

Prognostic Usefulness of Myocardial Work in Patients With Heart Failure and Reduced Ejection Fraction Treated by Sacubitril/Valsartan.

The noninvasive 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 (major adverse cardiovascular events [MACEs]). This study aimed to evaluate the short- and medium-term effect of Sacubitril/Valsartan treatment on MW parameters and the prognostic value of MW in this specific group of patients. Seventy-nine 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. Sacubitril/Valsartan significantly increased myocardial constructive work (CW) (1023 ± 449 vs 1424 ± 484 mm Hg%, p <0.0001) and myocardial work efficiency (WE) [87 (78to 90) vs 90 (86 to 95), p <0.0001]. During FU (2.6 ± 0.9 years), MACEs occurred in 13 (16%) patients. After correction for LV size, LV ejection fraction and WE, global myocardial constructive work (CW) was the only predictor of MACEs [hazard ratio [HR] 0.99 (0.99 to 1.00), p = 0.04]. A CW <910 mm Hg identified patients at particularly increase risk of MACEs [HR 11.09 (1.45 to 98.94), p = 0.002, log-rank test p <0.0001]. In conclusion, 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 allows the prediction of MACEs.

Pharmacoinvasive Strategy Versus Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction in Patients ≥70 Years of Age.

The benefit-risk ratio of a pharmacoinvasive strategy (PI) in patients ≥70 years of age with ST-segment elevation myocardial infarction (STEMI) remains uncertain resulting in its limited use in this population. This study compared efficacy and safety of PI with primary percutaneous coronary intervention (pPCI). Data from 2,841 patients (mean age: 78.1 ± 5.6 years, female: 36.1%) included in a prospective multicenter registry, and who underwent either PI (n = 269) or pPCI (n = 2,572), were analyzed. The primary end point was in-hospital major adverse cardiovascular events (MACE) defined as the composite of all-cause mortality, nonfatal MI, stroke, and definite stent thrombosis. Secondary end points included all-cause death, major bleeding, net adverse clinical events, and the development of in-hospital Killip class III or IV heart failure. Propensity-score matching and conditional logistic regression were used to adjust for confounders. Within the matched cohort, rates of MACE was not statistically different between the PI (n = 247) and pPCI (n = 958) groups, (11.3% vs 9.0%, respectively, odds ratio 1.25, 95% confidence interval 0.81 to 1.94; p = 0.31). Secondary end points were comparable between groups at the exception of a lower rate of development of Killip class III or IV heart failure after PI. The rate of intracranial hemorrhage was significantly higher in the PI group (2.3% vs 0.0%, p = 0.03). In conclusion, the present study demonstrated no difference regarding in-hospital MACE following PI or pPCI in STEMI patients ≥70 years of age. An adequately-powered randomized trial is needed to precisely define the role of PI in this high-risk subgroup.