Electrophysiological Phenotype-Genotype Study of Sustained Monomorphic Ventricular Tachycardia in Inherited, High Arrhythmic Risk, Left Ventricular Cardiomyopathy.

Fecha de publicación: 01/12/2024

Autores de IIS La Fe

Esther Zorio Grima

Autor
Julia Martínez Solé

Autor

Participantes ajenos a IIS La Fe

Cabrera-Borrego, Eva
Bermudez-Jimenez, Francisco J
Gasperetti, Alessio
Tandri, Harikrishna
Sanchez-Millan, Pablo J
Molina-Lerma, Manuel
Roca-Luque, Ivo
Vazquez-Calvo, Sara
Compagnucci, Paolo
Casella, Michela
Tondo, Claudio
Peichl, Petr
Peretto, Giovani
Paiotti, Elena
Saguner, Ardan M
Castro-Urda, Victor
Mora-Ayestaran, Nerea
Larranaga-Moreira, Jose M
Fernandez de-Aspe, Pablo
Barriales-Villa, Roberto
Munoz-Esparza, Carmen
Lopes, Luis R
Tonko, Johanna B
Lambiase, Pier D
Elliott, Perry M
Rodriguez-Manero, Moises
Canadas-Godoy, Victoria
Giacoman, Sebastian
Alvarez-Lopez, Miguel
Macias-Ruiz, Rosa
McKenna, William J
Tercedor-Sanchez, Luis
Jimenez-Jaimez, Juan

Grupos

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

Investigador Principal

Aitana Braza Boils

Abstract

BACKGROUND: Among inherited cardiomyopathies involving the left ventricle, whether dilated or not, certain genotypes carry a well-established arrhythmic risk, notably manifested as sustained monomorphic ventricular tachycardia (SMVT). Nonetheless, the precise localization and electrophysiological profile of this substrate remain undisclosed across different genotypes. METHODS: Patients diagnosed with cardiomyopathy and left ventricle involvement due to high-risk genetic variants and SMVT treated by electrophysiological study were recruited from 18 European/US centers. Electrophysiological study, imaging, and outcomes data after ablation were assessed in relation to genotype. RESULTS: Seventy-one patients were included (49.6 Q1-Q3 [40-60] years, 76% men). They were divided into 4 groups according to the affected protein: desmosomal (DSP, PKP2, DSG2, and DSC2), nuclear membrane (LMNA and TMEM43), cytoskeleton (FLNC and DES), and sarcoplasmic reticulum (PLN). Desmosomal genes, TMEM43, and PLN were associated with biventricular disease, while variants in LMNA and cytoskeleton genes had predominant left ventricle involvement (P=0.001). The location of the clinical-SMVT substrate was significantly different based on genotype (P=0.005). DSP and cytoskeleton genes presented SMVTs with right bundle branch block morphology, which origin was identified in the inferolateral segments of the left ventricle. The other desmosomal genes (PKP2 and DSG2), along with TMEM43, showed SMVTs with left bundle branch block morphology and predominantly right ventricular substrate. In contrast, LMNA substrate was mainly observed in the interventricular septum. During a median of 26 Q1-Q3 (10.6-65) months, 27% of patients experienced recurrences of clinical SMVT with differences between genotypes (log-rank 0.016). Nuclear membrane genes demonstrated the highest recurrence rate compared with desmosomal genes (hazard ratio, 4.56 [95% CI, 1.5-13.8]). CONCLUSIONS: The anatomic substrate of SMVTs shows a strong correlation with the underlying genotype, electrocardiographic morphology, and recurrence rate. Particularly, patients with nuclear membrane gene variants have a significantly higher recurrence rate compared with those with desmosomal gene variants.

Datos de la publicación

ISSN/ISSNe:: 1941-3149, 1941-3084
Tipo:: Article
Páginas:: 13145-13145
DOI:: 10.1161/CIRCEP.124.013145
Factor de Impacto:: 2,471 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Métricas

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Keywords

cytoskeleton; desmosome; electrophysiology; sarcoplasmic reticulum; ventricular tachycardiagenotype

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