Phenotype and Clinical Outcomes in Desmin-Related Arrhythmogenic Cardiomyopathy.

Fecha de publicación: 01/06/2024 Fecha Ahead of Print: 23/04/2024

Autores de IIS La Fe

Esther Zorio Grima

Autor

Participantes ajenos a IIS La Fe

Bermudez-Jimenez FJ
Protonotarios A
García-Hernández S
Pérez Asensio A
Rampazzo A
Brodehl A
Arias MA
Macías-Ruiz R
Fernández-Armenta J
Remior Perez P
Muñoz-Esparza C
Pilichou K
Bauce B
Merino JL
Moliner-Abós C
Ochoa JP
Barriales-Villa R
Garcia-Pavia P
Lopes LR
Syrris P
Corrado D
Elliott PM
McKenna WJ
Jimenez-Jaimez J

Grupos

Cardiopatías familiares, muerte súbita y mecanismos de enfermedad (CAFAMUSME)

Investigador Principal

Aitana Braza Boils

Abstract

BACKGROUND: Desmin (DES) pathogenic variants cause a small proportion of arrhythmogenic cardiomyopathy (ACM). Outcomes data on DES-related ACM are scarce. OBJECTIVES: 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: 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: 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: 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.

Datos de la publicación

ISSN/ISSNe:: 2405-500X, 2405-5018
Tipo:: Article
Páginas:: 1178-1190
DOI:: 10.1016/j.jacep.2024.02.031
Factor de Impacto:: 2,115 SCImago ℠
Cuartil:: Q1 SCImago ℠

Documentos

No hay documentos

Métricas

Filiaciones

Bermudez-Jimenez FJ:: Department of Cardiology, Virgen de las Nieves University Hospital, Granada, Spain

Instituto de Investigación Biosanitaria. ibs.GRANADA, Granada, Spain
Protonotarios A:: Inherited Cardiovascular Diseases Unit, St Bartholomew's Hospital, London, United Kingdom

Centre for Heart Muscle Disease, Institute of Cardiovascular Science, University College London, London, United Kingdom
García-Hernández S:: Instituto de Investigación Biomédica de A Coruña (INIBIC, CIBERCV), A Coruña, Spain

Health in Code SL, Cardiología, A Coruña, Spain
Pérez Asensio A:: Department of Cardiology, Puerta del Mar University Hospital, Cádiz, Spain

Biomedical Research and Innovation Institute of Cadiz (INiBICA), Cádiz, Spain
Rampazzo A:: Departments of Biology and Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, Padua, Italy
Zorio E:: Inherited Cardiac Diseases Unit, Cardiology Department at Hospital Universitario y Politécnico La Fe and Research Group on Inherited Heart Diseases, Sudden Death and Mechanisms of Disease (CaFaMuSMe), Barcelona, Spain

Instituto de Investigación. Instituto de Investigación Sanitaria La Fe, Valencia, Spain

Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
Brodehl A:: Erich and Hanna Klessmann Institute for Cardiovascular Research & Development, Heart and Diabetes Centre NRW, Ruhr-University Bochum, Bad Oeynhausen, Germany
Arias MA:: Arrhythmia Unit, Hospital Universitario de Toledo, Toledo, Spain
Macías-Ruiz R:: Department of Cardiology, Virgen de las Nieves University Hospital, Granada, Spain

Instituto de Investigación Biosanitaria. ibs.GRANADA, Granada, Spain
Fernández-Armenta J:: Department of Cardiology, Puerta del Mar University Hospital, Cádiz, Spain

Biomedical Research and Innovation Institute of Cadiz (INiBICA), Cádiz, Spain
Remior Perez P:: Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain

Inherited Cardiac Disease Unit, Hospital Universitario Virgen Arrixaca, Murcia, Spain
Muñoz-Esparza C:: Inherited Cardiac Disease Unit, Hospital Universitario Virgen Arrixaca, Murcia, Spain
Pilichou K:: Departments of Biology and Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, Padua, Italy
Bauce B:: Departments of Biology and Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, Padua, Italy
Merino JL:: Viamed Santa Elena and La Paz University Hospitals, Idipaz, Madrid, Spain
Moliner-Abós C:: Cardiology department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

IIB-SantPau, CIBERCV, Universidad Autónoma de Barcelona, Barcelona, Spain
Ochoa JP:: Instituto de Investigación Biomédica de A Coruña (INIBIC, CIBERCV), A Coruña, Spain

Health in Code SL, Cardiología, A Coruña, Spain
Barriales-Villa R:: Instituto de Investigación Biomédica de A Coruña (INIBIC, CIBERCV), A Coruña, Spain

Department of Cardiology, Complexo Hospitalario Universitario A Coruña, Spain
Garcia-Pavia P:: Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain

Inherited Cardiac Disease Unit, Hospital Universitario Virgen Arrixaca, Murcia, Spain

Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain
Lopes LR:: Inherited Cardiovascular Diseases Unit, St Bartholomew's Hospital, London, United Kingdom

Centre for Heart Muscle Disease, Institute of Cardiovascular Science, University College London, London, United Kingdom
Syrris P:: Centre for Heart Muscle Disease, Institute of Cardiovascular Science, University College London, London, United Kingdom
Corrado D:: Departments of Biology and Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, Padua, Italy
Elliott PM:: Inherited Cardiovascular Diseases Unit, St Bartholomew's Hospital, London, United Kingdom

Centre for Heart Muscle Disease, Institute of Cardiovascular Science, University College London, London, United Kingdom
McKenna WJ:: Centre for Heart Muscle Disease, Institute of Cardiovascular Science, University College London, London, United Kingdom

Instituto de Investigación Biomédica de A Coruña (INIBIC, CIBERCV), A Coruña, Spain
Jimenez-Jaimez J:: Department of Cardiology, Virgen de las Nieves University Hospital, Granada, Spain

Instituto de Investigación Biosanitaria. ibs.GRANADA, Granada, Spain

Keywords

arrhythmogenic cardiomyopathy; desmin; desminopathy; genetics

Campos de estudio

Proyectos asociados

RED INVESTIGACION (RECAVA)

RD06/0014/0004 . INSTITUTO DE SALUD CARLOS III; FUNDACION PARA LA INV BIOMEDICA- HOSPITAL GREGORIO MARAÑON; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2006