Genetics in Probands With Idiopathic Ventricular Fibrillation: A Multicenter Study

Luigi Pannone; Anaïs Gauthey; Giulio Conte; Randy Osei; Daniela Campanale; Enrico Baldi; Paola Berne; Alessandro Vicentini; Pasquale Vergara; Antonio Sorgente; Christine Rootwelt-Norberg; Domenico Giovanni Della Rocca; Cinzia Monaco; Antonio Bisignani; Vincenzo Miraglia; Marcello Spolverini; Gaetano Paparella; Ingrid Overeinder; Gezim Bala; Alexandre Almorad; Erwin Ströker; Thomy de Ravel; Argelia Medeiros-Domingo; Juan Sieira; Kristina H Haugaa; Pedro Brugada; Mark La Meir; Angelo Auricchio; Gian-Battista Chierchia; Sonia Van Dooren; Carlo de Asmundis

doi:10.1016/j.jacep.2023.03.008

Genetics in Probands With Idiopathic Ventricular Fibrillation: A Multicenter Study

Luigi Pannone, Anaïs Gauthey, Giulio Conte, Randy Osei, Daniela Campanale, Enrico Baldi, Paola Berne, Alessandro Vicentini, Pasquale Vergara, Antonio Sorgente, Christine Rootwelt-Norberg, Domenico Giovanni Della Rocca, Cinzia Monaco, Antonio Bisignani, Vincenzo Miraglia, Marcello Spolverini, Gaetano Paparella, Ingrid Overeinder, Gezim Bala, Alexandre AlmoradErwin Ströker, Thomy de Ravel, Argelia Medeiros-Domingo, Juan Sieira, Kristina H Haugaa, Pedro Brugada, Mark La Meir, Angelo Auricchio, Gian-Battista Chierchia, Sonia Van Dooren, Carlo de Asmundis

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

BACKGROUND: Different genes have been associated with idiopathic ventricular fibrillation (IVF); however, there are no studies correlating genotype with phenotype.

OBJECTIVES: The aim of this study was to define the genetic background of probands with IVF using large gene panel analysis and to correlate genetics with long-term clinical outcomes.

METHODS: All consecutive probands with a diagnosis of IVF were included in a multicenter retrospective study. All patients had: 1) IVF diagnosis throughout the follow-up; and 2) genetic analysis with a broad gene panel. All genetic variants were classified as pathogenic/likely pathogenic (P+), variants of unknown significance (VUS) or no variants (NO-V), following current guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. The primary endpoint was occurrence of ventricular arrhythmias (VA).

RESULTS: Forty-five consecutive patients were included. A variant was found in 12 patients, 3 P+ and 9 VUS carriers. After a mean follow-up time of 105.0 months, there were no deaths and 16 patients (35.6%) experienced a VA. NO-V patients had higher VA free survival during the follow-up, compared with both VUS (72.7% vs 55.6%, log-rank P < 0.001) and P+ (72.7% vs 0%, log-rank P = 0.013). At Cox analysis, P+ or VUS carrier status was a predictor of VA occurrence.

CONCLUSIONS: In probands with IVF, undergoing genetic analysis with a broad panel, the diagnostic yield for P+ is 6.7%. P+ or VUS carrier status is a predictor of VA occurrence.

Original language	English
Pages (from-to)	1296-1306
Number of pages	11
Journal	JACC. Clinical electrophysiology
Volume	9
Issue number	8
Early online date	2023
DOIs	https://doi.org/10.1016/j.jacep.2023.03.008
Publication status	Published - Aug 2023

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10.1016/j.jacep.2023.03.008

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Pannone, L., Gauthey, A., Conte, G., Osei, R., Campanale, D., Baldi, E., Berne, P., Vicentini, A., Vergara, P., Sorgente, A., Rootwelt-Norberg, C., Della Rocca, D. G., Monaco, C., Bisignani, A., Miraglia, V., Spolverini, M., Paparella, G., Overeinder, I., Bala, G., ... de Asmundis, C. (2023). Genetics in Probands With Idiopathic Ventricular Fibrillation: A Multicenter Study. JACC. Clinical electrophysiology, 9(8), 1296-1306. https://doi.org/10.1016/j.jacep.2023.03.008

Pannone, Luigi ; Gauthey, Anaïs ; Conte, Giulio ; Osei, Randy ; Campanale, Daniela ; Baldi, Enrico ; Berne, Paola ; Vicentini, Alessandro ; Vergara, Pasquale ; Sorgente, Antonio ; Rootwelt-Norberg, Christine ; Della Rocca, Domenico Giovanni ; Monaco, Cinzia ; Bisignani, Antonio ; Miraglia, Vincenzo ; Spolverini, Marcello ; Paparella, Gaetano ; Overeinder, Ingrid ; Bala, Gezim ; Almorad, Alexandre ; Ströker, Erwin ; de Ravel, Thomy ; Medeiros-Domingo, Argelia ; Sieira, Juan ; Haugaa, Kristina H ; Brugada, Pedro ; La Meir, Mark ; Auricchio, Angelo ; Chierchia, Gian-Battista ; Van Dooren, Sonia ; de Asmundis, Carlo. / Genetics in Probands With Idiopathic Ventricular Fibrillation : A Multicenter Study. In: JACC. Clinical electrophysiology. 2023 ; Vol. 9, No. 8. pp. 1296-1306.

@article{8c311bcb101a40ee9a0c10a7589c18ad,

title = "Genetics in Probands With Idiopathic Ventricular Fibrillation: A Multicenter Study",

abstract = "BACKGROUND: Different genes have been associated with idiopathic ventricular fibrillation (IVF); however, there are no studies correlating genotype with phenotype.OBJECTIVES: The aim of this study was to define the genetic background of probands with IVF using large gene panel analysis and to correlate genetics with long-term clinical outcomes.METHODS: All consecutive probands with a diagnosis of IVF were included in a multicenter retrospective study. All patients had: 1) IVF diagnosis throughout the follow-up; and 2) genetic analysis with a broad gene panel. All genetic variants were classified as pathogenic/likely pathogenic (P+), variants of unknown significance (VUS) or no variants (NO-V), following current guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. The primary endpoint was occurrence of ventricular arrhythmias (VA).RESULTS: Forty-five consecutive patients were included. A variant was found in 12 patients, 3 P+ and 9 VUS carriers. After a mean follow-up time of 105.0 months, there were no deaths and 16 patients (35.6%) experienced a VA. NO-V patients had higher VA free survival during the follow-up, compared with both VUS (72.7% vs 55.6%, log-rank P < 0.001) and P+ (72.7% vs 0%, log-rank P = 0.013). At Cox analysis, P+ or VUS carrier status was a predictor of VA occurrence.CONCLUSIONS: In probands with IVF, undergoing genetic analysis with a broad panel, the diagnostic yield for P+ is 6.7%. P+ or VUS carrier status is a predictor of VA occurrence.",

author = "Luigi Pannone and Ana{\"i}s Gauthey and Giulio Conte and Randy Osei and Daniela Campanale and Enrico Baldi and Paola Berne and Alessandro Vicentini and Pasquale Vergara and Antonio Sorgente and Christine Rootwelt-Norberg and {Della Rocca}, {Domenico Giovanni} and Cinzia Monaco and Antonio Bisignani and Vincenzo Miraglia and Marcello Spolverini and Gaetano Paparella and Ingrid Overeinder and Gezim Bala and Alexandre Almorad and Erwin Str{\"o}ker and {de Ravel}, Thomy and Argelia Medeiros-Domingo and Juan Sieira and Haugaa, {Kristina H} and Pedro Brugada and {La Meir}, Mark and Angelo Auricchio and Gian-Battista Chierchia and {Van Dooren}, Sonia and {de Asmundis}, Carlo",

year = "2023",

month = aug,

doi = "10.1016/j.jacep.2023.03.008",

language = "English",

volume = "9",

pages = "1296--1306",

journal = "JACC. Clinical electrophysiology",

issn = "2405-500X",

publisher = "Elsevier",

number = "8",

}

Pannone, L, Gauthey, A, Conte, G , Osei, R, Campanale, D, Baldi, E, Berne, P, Vicentini, A, Vergara, P , Sorgente, A, Rootwelt-Norberg, C, Della Rocca, DG , Monaco, C, Bisignani, A, Miraglia, V, Spolverini, M, Paparella, G , Overeinder, I , Bala, G , Almorad, A , Ströker, E , de Ravel, T, Medeiros-Domingo, A, Sieira, J, Haugaa, KH, Brugada, P , La Meir, M, Auricchio, A, Chierchia, G-B , Van Dooren, S & de Asmundis, C 2023, 'Genetics in Probands With Idiopathic Ventricular Fibrillation: A Multicenter Study', JACC. Clinical electrophysiology, vol. 9, no. 8, pp. 1296-1306. https://doi.org/10.1016/j.jacep.2023.03.008

Genetics in Probands With Idiopathic Ventricular Fibrillation : A Multicenter Study. / Pannone, Luigi; Gauthey, Anaïs; Conte, Giulio ; Osei, Randy; Campanale, Daniela; Baldi, Enrico; Berne, Paola; Vicentini, Alessandro; Vergara, Pasquale ; Sorgente, Antonio; Rootwelt-Norberg, Christine; Della Rocca, Domenico Giovanni ; Monaco, Cinzia; Bisignani, Antonio; Miraglia, Vincenzo; Spolverini, Marcello; Paparella, Gaetano ; Overeinder, Ingrid ; Bala, Gezim ; Almorad, Alexandre ; Ströker, Erwin ; de Ravel, Thomy; Medeiros-Domingo, Argelia; Sieira, Juan; Haugaa, Kristina H; Brugada, Pedro ; La Meir, Mark; Auricchio, Angelo; Chierchia, Gian-Battista ; Van Dooren, Sonia ; de Asmundis, Carlo.

In: JACC. Clinical electrophysiology, Vol. 9, No. 8, 08.2023, p. 1296-1306.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Genetics in Probands With Idiopathic Ventricular Fibrillation

T2 - A Multicenter Study

AU - Pannone, Luigi

AU - Gauthey, Anaïs

AU - Conte, Giulio

AU - Osei, Randy

AU - Campanale, Daniela

AU - Baldi, Enrico

AU - Berne, Paola

AU - Vicentini, Alessandro

AU - Vergara, Pasquale

AU - Sorgente, Antonio

AU - Rootwelt-Norberg, Christine

AU - Della Rocca, Domenico Giovanni

AU - Monaco, Cinzia

AU - Bisignani, Antonio

AU - Miraglia, Vincenzo

AU - Spolverini, Marcello

AU - Paparella, Gaetano

AU - Overeinder, Ingrid

AU - Bala, Gezim

AU - Almorad, Alexandre

AU - Ströker, Erwin

AU - de Ravel, Thomy

AU - Medeiros-Domingo, Argelia

AU - Sieira, Juan

AU - Haugaa, Kristina H

AU - Brugada, Pedro

AU - La Meir, Mark

AU - Auricchio, Angelo

AU - Chierchia, Gian-Battista

AU - Van Dooren, Sonia

AU - de Asmundis, Carlo

PY - 2023/8

Y1 - 2023/8

N2 - BACKGROUND: Different genes have been associated with idiopathic ventricular fibrillation (IVF); however, there are no studies correlating genotype with phenotype.OBJECTIVES: The aim of this study was to define the genetic background of probands with IVF using large gene panel analysis and to correlate genetics with long-term clinical outcomes.METHODS: All consecutive probands with a diagnosis of IVF were included in a multicenter retrospective study. All patients had: 1) IVF diagnosis throughout the follow-up; and 2) genetic analysis with a broad gene panel. All genetic variants were classified as pathogenic/likely pathogenic (P+), variants of unknown significance (VUS) or no variants (NO-V), following current guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. The primary endpoint was occurrence of ventricular arrhythmias (VA).RESULTS: Forty-five consecutive patients were included. A variant was found in 12 patients, 3 P+ and 9 VUS carriers. After a mean follow-up time of 105.0 months, there were no deaths and 16 patients (35.6%) experienced a VA. NO-V patients had higher VA free survival during the follow-up, compared with both VUS (72.7% vs 55.6%, log-rank P < 0.001) and P+ (72.7% vs 0%, log-rank P = 0.013). At Cox analysis, P+ or VUS carrier status was a predictor of VA occurrence.CONCLUSIONS: In probands with IVF, undergoing genetic analysis with a broad panel, the diagnostic yield for P+ is 6.7%. P+ or VUS carrier status is a predictor of VA occurrence.

AB - BACKGROUND: Different genes have been associated with idiopathic ventricular fibrillation (IVF); however, there are no studies correlating genotype with phenotype.OBJECTIVES: The aim of this study was to define the genetic background of probands with IVF using large gene panel analysis and to correlate genetics with long-term clinical outcomes.METHODS: All consecutive probands with a diagnosis of IVF were included in a multicenter retrospective study. All patients had: 1) IVF diagnosis throughout the follow-up; and 2) genetic analysis with a broad gene panel. All genetic variants were classified as pathogenic/likely pathogenic (P+), variants of unknown significance (VUS) or no variants (NO-V), following current guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. The primary endpoint was occurrence of ventricular arrhythmias (VA).RESULTS: Forty-five consecutive patients were included. A variant was found in 12 patients, 3 P+ and 9 VUS carriers. After a mean follow-up time of 105.0 months, there were no deaths and 16 patients (35.6%) experienced a VA. NO-V patients had higher VA free survival during the follow-up, compared with both VUS (72.7% vs 55.6%, log-rank P < 0.001) and P+ (72.7% vs 0%, log-rank P = 0.013). At Cox analysis, P+ or VUS carrier status was a predictor of VA occurrence.CONCLUSIONS: In probands with IVF, undergoing genetic analysis with a broad panel, the diagnostic yield for P+ is 6.7%. P+ or VUS carrier status is a predictor of VA occurrence.

UR - http://www.scopus.com/inward/record.url?scp=85164580341&partnerID=8YFLogxK

U2 - 10.1016/j.jacep.2023.03.008

DO - 10.1016/j.jacep.2023.03.008

M3 - Article

C2 - 37227348

VL - 9

SP - 1296

EP - 1306

JO - JACC. Clinical electrophysiology

JF - JACC. Clinical electrophysiology

SN - 2405-500X

IS - 8

ER -

Genetics in Probands With Idiopathic Ventricular Fibrillation: A Multicenter Study

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