Phenotype and Clinical Outcomes in Desmin-Related Arrhythmogenic Cardiomyopathy.
arrhythmogenic cardiomyopathy
desmin
desminopathy
genetics
Journal
JACC. Clinical electrophysiology
ISSN: 2405-5018
Titre abrégé: JACC Clin Electrophysiol
Pays: United States
ID NLM: 101656995
Informations de publication
Date de publication:
23 Apr 2024
23 Apr 2024
Historique:
received:
02
11
2023
revised:
22
02
2024
accepted:
27
02
2024
medline:
10
5
2024
pubmed:
10
5
2024
entrez:
10
5
2024
Statut:
aheadofprint
Résumé
Desmin (DES) pathogenic variants cause a small proportion of arrhythmogenic cardiomyopathy (ACM). Outcomes data on DES-related ACM are scarce. This study sought to provide information on the clinical phenotype and outcomes of patients with ACM caused by pathogenic variants of the DES gene in a multicenter cohort. We collected phenotypic and outcomes data from 16 families with DES-related ACM from 10 European centers. We assessed in vitro DES aggregates. Major cardiac events were compared to historical controls with lamin A/C truncating variant (LMNA-tv) and filament C truncating variant (FLNC-tv) ACM. Of 82 patients (54% males, median age: 36 years), 11 experienced sudden cardiac death (SCD) (n = 7) or heart failure death (HFd)/heart transplantation (HTx) (n = 4) before clinical evaluation. Among 68 survivors, 59 (86%) presented signs of cardiomyopathy, with left ventricular (LV) dominant (50%) or biventricular (34%) disease. Mean LV ejection fraction was 51% ± 13%; 36 of 53 had late gadolinium enhancement (ring-like pattern in 49%). During a median of 6.73 years (Q1-Q3: 3.55-9.52 years), the composite endpoint (sustained ventricular tachycardia, aborted SCD, implantable cardioverter-defibrillator therapy, SCD, HFd, and HTx) was achieved in 15 additional patients with HFd/HTx (n = 5) and SCD/aborted SCD/implantable cardioverter-defibrillator therapy/sustained ventricular tachycardia (n = 10). Male sex (P = 0.004), nonsustained ventricular tachycardia (P = 0.017) and LV ejection fraction ≤50% (P = 0.012) were associated with the composite endpoint. Males with DES variants had similar outcomes to historical FLNC-tv and LMNA-tv controls. However, females showed better outcomes than those with LMNA-tv. In vitro experiments showed the characteristic finding of DES aggregates in 7 of 12 variants. DES ACM is associated with poor outcomes which can be predicted with potentially successful treatments, underscoring the importance of familial evaluation and genetic studies to identify at risk individuals.
Sections du résumé
BACKGROUND
BACKGROUND
Desmin (DES) pathogenic variants cause a small proportion of arrhythmogenic cardiomyopathy (ACM). Outcomes data on DES-related ACM are scarce.
OBJECTIVES
OBJECTIVE
This study sought to provide information on the clinical phenotype and outcomes of patients with ACM caused by pathogenic variants of the DES gene in a multicenter cohort.
METHODS
METHODS
We collected phenotypic and outcomes data from 16 families with DES-related ACM from 10 European centers. We assessed in vitro DES aggregates. Major cardiac events were compared to historical controls with lamin A/C truncating variant (LMNA-tv) and filament C truncating variant (FLNC-tv) ACM.
RESULTS
RESULTS
Of 82 patients (54% males, median age: 36 years), 11 experienced sudden cardiac death (SCD) (n = 7) or heart failure death (HFd)/heart transplantation (HTx) (n = 4) before clinical evaluation. Among 68 survivors, 59 (86%) presented signs of cardiomyopathy, with left ventricular (LV) dominant (50%) or biventricular (34%) disease. Mean LV ejection fraction was 51% ± 13%; 36 of 53 had late gadolinium enhancement (ring-like pattern in 49%). During a median of 6.73 years (Q1-Q3: 3.55-9.52 years), the composite endpoint (sustained ventricular tachycardia, aborted SCD, implantable cardioverter-defibrillator therapy, SCD, HFd, and HTx) was achieved in 15 additional patients with HFd/HTx (n = 5) and SCD/aborted SCD/implantable cardioverter-defibrillator therapy/sustained ventricular tachycardia (n = 10). Male sex (P = 0.004), nonsustained ventricular tachycardia (P = 0.017) and LV ejection fraction ≤50% (P = 0.012) were associated with the composite endpoint. Males with DES variants had similar outcomes to historical FLNC-tv and LMNA-tv controls. However, females showed better outcomes than those with LMNA-tv. In vitro experiments showed the characteristic finding of DES aggregates in 7 of 12 variants.
CONCLUSIONS
CONCLUSIONS
DES ACM is associated with poor outcomes which can be predicted with potentially successful treatments, underscoring the importance of familial evaluation and genetic studies to identify at risk individuals.
Identifiants
pubmed: 38727660
pii: S2405-500X(24)00177-4
doi: 10.1016/j.jacep.2024.02.031
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Funding Support and Author Disclosures Dr Bermudez-Jimenez has received grants from Instituto de Salud Carlos III (ISCIII) through the project JR21/00031 (cofounded by European Regional Development Fund). Dr Zorio has received grants from the Instituto de Salud Carlos III through the projects PI18/01582 and PI21/01282 (co-funded by European Regional Development Fund “A way to make Europe”). Dr Brodehl has received grants from the Medical Faculty of the Ruhr-University Bochum (FoRUM, F1074-2023) and the ‘Deutsche Herzstiftung e.V. (Frankfurt a.M., Germany); and is a shareholder with Tenaya Therapeutics. Dr Lopes has received grants from a Medical Research Council (MRC) Clinical Academic Research Partnership (CARP) award (MR/T005181/1). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.