Angiotensin receptor/Neprilysin inhibitor effects in CRTd non-responders: From epigenetic to clinical beside

• DOI: 10.1016/j.phrs.2022.106303
• Publication Date: 2022-06-10T18:33:22Z
• Authors: Celestino Sardu; Massimo Massetti; Lucia Scisciola; Maria Consiglia T...; Matteo Santamaria; Mario Volpicelli; Valentino Ducceschi; Giuseppe Signoriello; Nunzia D’Onofrio; Ludovica Marfella; Flavia Casolaro; Michele D.’ Amico; Antonio Ruocco; Maria Luisa Bales...; Ciro Mauro; Concetta Rafaniello; Annalisa Capuano; Giuseppe Paolisso; Raffaele Marfella
• Keywords: Heart Failure; Receptors, Angiotensin; Ventricular Remodeling; CRTd non-responders; Clinical outcomes; HFrEF; MiRs regulation; MiRs regulation; Stroke Volume; HFrEF; Epigenesis, Genetic; 3. Good health; Cardiac Resynchronization Therapy; Angiotensin Receptor Antagonists; Drug Combinations; MicroRNAs; 03 medical and health sciences; Treatment Outcome; 0302 clinical medicine; Clinical outcomes; Humans; Neprilysin; CRTd non-responders; Antihypertensive Agents

We evaluated whether Angiotensin receptor/Neprilysin inhibitors (ARNI) reduce heart failure (HF) hospitalizations and deaths in cardiac resynchronization therapy with defibrillator (CRTd) non-responders patients at 12 months of follow-up, modulating microRNAs (miRs) implied adverse remodeling.adverse remodeling characterized by left ventricle ejection fraction (LVEF) reduction, ventricular end-systolic volume (LVESv) increase, the 6-minute walking test (6MWT) reduction are relevant pathological mechanisms CRTd could be linked to changes miRNAs (miRs), regulating fibrosis, apoptosis, hypertrophy.miRs levels clinical outcomes (LVEF, deaths, 6MWT) were baseline one year follow-up divided into ARNI-users Non-ARNI users.At baseline, there no differences inflammatory markers, miR-18, miR-145, miR-181 (p > 0.05) between users (n 106) 312). At vs. showed lowest markers < 0.01) higher values miR-18 0.01)and miR-145 0.01). had a increase LVEF 6MWT along more significant LVESv compared users. Cox regression analysis evidenced that ARNI-based therapies probability anti-remodeling effects CRTd. Based on symptomatic improvements, echocardiographic functional classification 37 (34.9%) among became responders, while only twenty (6.4%) responders Non-ARNi-users.ARNI might influence epigenetic miRs implicated responses