Impact of DCM-Causing Genetic Background on Long-Term Response to Cardiac Resynchronization Therapy.

LBBB LBBBICMP LV remodeling cardiac resynchronization therapy dilated cardiomyopathy genetic background super responder

Journal

JACC. Clinical electrophysiology
ISSN: 2405-5018
Titre abrégé: JACC Clin Electrophysiol
Pays: United States
ID NLM: 101656995

Informations de publication

Date de publication:
08 May 2024
Historique:
received: 15 11 2023
revised: 20 02 2024
accepted: 22 03 2024
medline: 25 5 2024
pubmed: 25 5 2024
entrez: 25 5 2024
Statut: aheadofprint

Résumé

Patients with nonischemic dilated cardiomyopathy (DCM), severe left ventricular (LV) dysfunction, and complete left bundle branch block benefit from cardiac resynchronization therapy (CRT). However, a large heterogeneity of response to CRT is described. Several predictors of response to CRT have been identified, but the role of the underlying genetic background is still poorly explored. In the present study, the authors sought to define differences in LV remodeling and outcome prediction after CRT when stratifying patients according to the presence or absence of DCM-causing genetic background. From our center, 74 patients with DCM subjected to CRT and available genetic testing were retrospectively enrolled. Carriers of causative monogenic variants in validated DCM-causing genes, and/or with documented family history of DCM, were classified as affected by genetically determined disease (GEN+DCM) (n = 25). Alternatively, by idiopathic dilated cardiomyopathy (idDCM) (n = 49). The primary outcome was long-term LV remodeling and prevalence of super response to CRT (evaluated at 24-48 months after CRT); the secondary outcome was heart failure-related death/heart transplant/LV assist device. GEN+DCM and idDCM patients were homogeneous at baseline with the exception of QRS duration, longer in idDCM. The median follow-up was 55 months. Long-term LV reverse remodeling and the prevalence of super response were significantly higher in the idDCM group (27% in idDCM vs 5% in GEN+DCM; P = 0.025). The heart failure-related death/heart transplant/LV assist device outcome occurred more frequently in patients with GEN+DCM (53% vs 24% in idDCM; P = 0.028). Genotyping contributes to the risk stratification of patients with DCM undergoing CRT implantation in terms of LV remodeling and outcomes.

Sections du résumé

BACKGROUND BACKGROUND
Patients with nonischemic dilated cardiomyopathy (DCM), severe left ventricular (LV) dysfunction, and complete left bundle branch block benefit from cardiac resynchronization therapy (CRT). However, a large heterogeneity of response to CRT is described. Several predictors of response to CRT have been identified, but the role of the underlying genetic background is still poorly explored.
OBJECTIVES OBJECTIVE
In the present study, the authors sought to define differences in LV remodeling and outcome prediction after CRT when stratifying patients according to the presence or absence of DCM-causing genetic background.
METHODS METHODS
From our center, 74 patients with DCM subjected to CRT and available genetic testing were retrospectively enrolled. Carriers of causative monogenic variants in validated DCM-causing genes, and/or with documented family history of DCM, were classified as affected by genetically determined disease (GEN+DCM) (n = 25). Alternatively, by idiopathic dilated cardiomyopathy (idDCM) (n = 49). The primary outcome was long-term LV remodeling and prevalence of super response to CRT (evaluated at 24-48 months after CRT); the secondary outcome was heart failure-related death/heart transplant/LV assist device.
RESULTS RESULTS
GEN+DCM and idDCM patients were homogeneous at baseline with the exception of QRS duration, longer in idDCM. The median follow-up was 55 months. Long-term LV reverse remodeling and the prevalence of super response were significantly higher in the idDCM group (27% in idDCM vs 5% in GEN+DCM; P = 0.025). The heart failure-related death/heart transplant/LV assist device outcome occurred more frequently in patients with GEN+DCM (53% vs 24% in idDCM; P = 0.028).
CONCLUSIONS CONCLUSIONS
Genotyping contributes to the risk stratification of patients with DCM undergoing CRT implantation in terms of LV remodeling and outcomes.

Identifiants

DOI: 10.1016/j.jacep.2024.03.019 PMID: 38795101
pubmed: 38795101
pii: S2405-500X(24)00253-6
doi: 10.1016/j.jacep.2024.03.019
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Funding Support and Author Disclosures This study was supported by CRTrieste Foundation and Cassa di Risparmio di Gorizia Foundation to Dr Sinagra. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Auteurs

Matteo Dal Ferro (M)

Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, Trieste, Italy. Member of the European Reference Network for rare, low-prevalence, or complex diseases of the Heart (ERN GUARD-Heart). Electronic address: matteo.dalferro@asugi.sanita.fvg.it.

Alessia Paldino (A)

Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, Trieste, Italy. Member of the European Reference Network for rare, low-prevalence, or complex diseases of the Heart (ERN GUARD-Heart).

Caterina Gregorio (C)

Biostatistics Unit, University of Trieste, Trieste, Italy; Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden.

Riccardo Bessi (R)

Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, Trieste, Italy. Member of the European Reference Network for rare, low-prevalence, or complex diseases of the Heart (ERN GUARD-Heart).

Denise Zaffalon (D)

Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, Trieste, Italy. Member of the European Reference Network for rare, low-prevalence, or complex diseases of the Heart (ERN GUARD-Heart).

Giulia De Angelis (G)

Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden; Cardiology Department, Azienda Sanitaria Universitaria Friuli Occidentale (ASFO), Pordenone, Italy.

Giovanni Maria Severini (GM)

Institute for Maternal and Child Health-IRCCS, Burlo Garofolo, Trieste, Italy.

Davide Stolfo (D)

Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, Trieste, Italy. Member of the European Reference Network for rare, low-prevalence, or complex diseases of the Heart (ERN GUARD-Heart).

Marta Gigli (M)

Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, Trieste, Italy. Member of the European Reference Network for rare, low-prevalence, or complex diseases of the Heart (ERN GUARD-Heart).

Francesca Brun (F)

Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, Trieste, Italy. Member of the European Reference Network for rare, low-prevalence, or complex diseases of the Heart (ERN GUARD-Heart).

Laura Massa (L)

Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, Trieste, Italy. Member of the European Reference Network for rare, low-prevalence, or complex diseases of the Heart (ERN GUARD-Heart).

Renata Korcova (R)

Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, Trieste, Italy. Member of the European Reference Network for rare, low-prevalence, or complex diseases of the Heart (ERN GUARD-Heart).

Luca Salvatore (L)

Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, Trieste, Italy. Member of the European Reference Network for rare, low-prevalence, or complex diseases of the Heart (ERN GUARD-Heart).

Elisabetta Bianco (E)

Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, Trieste, Italy. Member of the European Reference Network for rare, low-prevalence, or complex diseases of the Heart (ERN GUARD-Heart).

Luisa Mestroni (L)

Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, Trieste, Italy. Member of the European Reference Network for rare, low-prevalence, or complex diseases of the Heart (ERN GUARD-Heart); Cardiovascular Institute and Adult Medical Genetics Program, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.

Marco Merlo (M)

Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, Trieste, Italy. Member of the European Reference Network for rare, low-prevalence, or complex diseases of the Heart (ERN GUARD-Heart); Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.

Massimo Zecchin (M)

Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, Trieste, Italy. Member of the European Reference Network for rare, low-prevalence, or complex diseases of the Heart (ERN GUARD-Heart).

Gianfranco Sinagra (G)

Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, Trieste, Italy. Member of the European Reference Network for rare, low-prevalence, or complex diseases of the Heart (ERN GUARD-Heart); Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.

Classifications MeSH