AUTHOR=Monosilio Sara , Filomena Domenico , Luongo Federico , Sannino Michele , Cimino Sara , Neccia Matteo , Mariani Marco Valerio , Birtolo Lucia Ilaria , Benedetti Giulia , Tonti Giovanni , Pedrizzetti Gianni , Vizza Carmine Dario , Maestrini Viviana , Agati Luciano 

TITLE=Cardiac and Vascular Remodeling After 6 Months of Therapy With Sacubitril/Valsartan: Mechanistic Insights From Advanced Echocardiographic Analysis

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.883769

DOI=10.3389/fcvm.2022.883769

ISSN=2297-055X

ABSTRACT=<sec><title>Background</title><p>Effects of Sacubitril/Valsartan (S/V) on left ventricular (LV) mechanics and ventricular-arterial coupling in patients with heart failure with reduced ejection fraction (HFrEF) are not completely understood. The aim of this study was to evaluate both cardiac and vascular remodeling in a group of HFrEF patients undergoing S/V therapy.</p></sec><sec><title>Methods</title><p>Fifty HFrEF patients eligible to start a therapy with S/V were enrolled. Echocardiographic evaluation was performed at baseline and after 6 months of follow-up (FU). Beside standard evaluation, including global longitudinal strain (GLS), estimated hemodynamic forces (HDFs) and non-invasive pressure-volume curves (PV loop) were assessed using dedicated softwares. HDFs were evaluated over the entire cardiac cycle, in systole and diastole, both in apex to base (A-B) and latero-septal (L-S) directions. The distribution of LV HDFs was evaluated by L-S over A-B HDFs ratio (L-S/A-B HDFs ratio). Parameters derived from estimated PV loop curves were left ventricular end-systolic elastance (E<sub>es</sub>), arterial elastance (E<sub>a</sub>), and ventricular-arterial coupling (VAC).</p></sec><sec><title>Results</title><p>At 6 months of FU indexed left ventricular end-diastolic and end-systolic volumes decreased (EDVi: 101 ± 28 mL vs. 86 ± 30 mL, <italic>p</italic> &lt; 0.001; ESVi: 72 ± 23 mL vs. 55 ± 24 mL, <italic>p</italic> &lt; 0.001), ejection fraction and GLS significantly improved (EF: 29 ± 6% vs. 37 ± 7%, <italic>p</italic> &lt; 0.001; GLS: −9 ± 3% vs. −13 ± 4%, <italic>p</italic> &lt; 0.001). A reduction of E<sub>a</sub> (2.11 ± 0.91 mmHg/mL vs. 1.72 ± 0.44 mmHg/mL, <italic>p</italic> = 0.008) and an improvement of E<sub>es</sub> (1.01 ± 0.37 mmHg/mL vs. 1.35 ± 0.6 mmHg/mL, <italic>p</italic> &lt; 0.001) and VAC (2.3 ± 1.1 vs. 1.5 ± 0.7, <italic>p</italic> &lt; 0.001) were observed. Re-alignment of HDFs occurred, with a reduction of diastolic L-S/A-B HDFs ratio [23 (20–35)% vs. 20 (11–28) %, <italic>p</italic> &lt; 0.001].</p></sec><sec><title>Conclusion</title><p>S/V therapy leads to a complex phenomenon of reverse remodeling involving increased myocardial contractility, HDFs distribution improvement, and afterload reduction.</p></sec>