Angiotensin receptor/Neprilysin inhibitor effects in CRTd non-responders: From epigenetic to clinical beside.
Angiotensin Receptor Antagonists
/ therapeutic use
Antihypertensive Agents
/ therapeutic use
Cardiac Resynchronization Therapy
Drug Combinations
Epigenesis, Genetic
Heart Failure
/ drug therapy
Humans
MicroRNAs
/ genetics
Neprilysin
/ therapeutic use
Receptors, Angiotensin
/ therapeutic use
Stroke Volume
Treatment Outcome
Ventricular Remodeling
CRTd non-responders
Clinical outcomes
HFrEF
MiRs regulation
Journal
Pharmacological research
ISSN: 1096-1186
Titre abrégé: Pharmacol Res
Pays: Netherlands
ID NLM: 8907422
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
13
05
2022
revised:
07
06
2022
accepted:
07
06
2022
pubmed:
14
6
2022
medline:
10
8
2022
entrez:
13
6
2022
Statut:
ppublish
Résumé
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 in adverse cardiac remodeling. adverse cardiac remodeling characterized by left ventricle ejection fraction (LVEF) reduction, left ventricular end-systolic volume (LVESv) increase, and the 6-minute walking test (6MWT) reduction are relevant pathological mechanisms in CRTd non-responders and could be linked to changes in miRNAs (miRs), regulating cardiac fibrosis, apoptosis, and hypertrophy. miRs levels and clinical outcomes (LVEF, cardiac deaths, and 6MWT) were evaluated at baseline and one year of follow-up in CRTd non-responders divided into ARNI-users and Non-ARNI users. At baseline, there were no differences in levels of inflammatory markers, miR-18, miR-145, and miR-181 (p > 0.05) between Non-ARNI users (n 106) and ARNI-users (n 312). At one year of follow-up, ARNI-users vs. Non-ARNI users showed lowest inflammatory markers (p < 0.01) and miR-181 levels (p < 0.01) and higher values of miR-18 (p < 0.01)and miR-145 (p < 0.01). At one year of follow-up, ARNI-users had a higher increase of LVEF (p < 0.01) and 6MWT (p < 0.01) along with a more significant reduction of LVESv (p < 0.01) compared to Non-ARNI users. Cox regression analysis evidenced that ARNI-based therapies increase the probability of anti-remodeling effects of CRTd. Based on symptomatic improvements, echocardiographic and functional classification improvements, 37 (34.9%) patients among ARNI-users became responders, while only twenty (6.4%) patients became responders among Non-ARNi-users. ARNI might influence epigenetic mechanisms modulating miRs implicated in the adverse cardiac remodeling responses to CRTd.
Sections du résumé
OBJECTIVES
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 in adverse cardiac remodeling.
BACKGROUND
adverse cardiac remodeling characterized by left ventricle ejection fraction (LVEF) reduction, left ventricular end-systolic volume (LVESv) increase, and the 6-minute walking test (6MWT) reduction are relevant pathological mechanisms in CRTd non-responders and could be linked to changes in miRNAs (miRs), regulating cardiac fibrosis, apoptosis, and hypertrophy.
METHODS
miRs levels and clinical outcomes (LVEF, cardiac deaths, and 6MWT) were evaluated at baseline and one year of follow-up in CRTd non-responders divided into ARNI-users and Non-ARNI users.
RESULTS
At baseline, there were no differences in levels of inflammatory markers, miR-18, miR-145, and miR-181 (p > 0.05) between Non-ARNI users (n 106) and ARNI-users (n 312). At one year of follow-up, ARNI-users vs. Non-ARNI users showed lowest inflammatory markers (p < 0.01) and miR-181 levels (p < 0.01) and higher values of miR-18 (p < 0.01)and miR-145 (p < 0.01). At one year of follow-up, ARNI-users had a higher increase of LVEF (p < 0.01) and 6MWT (p < 0.01) along with a more significant reduction of LVESv (p < 0.01) compared to Non-ARNI users. Cox regression analysis evidenced that ARNI-based therapies increase the probability of anti-remodeling effects of CRTd. Based on symptomatic improvements, echocardiographic and functional classification improvements, 37 (34.9%) patients among ARNI-users became responders, while only twenty (6.4%) patients became responders among Non-ARNi-users.
CONCLUSIONS
ARNI might influence epigenetic mechanisms modulating miRs implicated in the adverse cardiac remodeling responses to CRTd.
Identifiants
pubmed: 35697289
pii: S1043-6618(22)00248-1
doi: 10.1016/j.phrs.2022.106303
pii:
doi:
Substances chimiques
Angiotensin Receptor Antagonists
0
Antihypertensive Agents
0
Drug Combinations
0
MIRN145 microRNA, human
0
MicroRNAs
0
Receptors, Angiotensin
0
Neprilysin
EC 3.4.24.11
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
106303Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.