Long-Term Arrhythmic Follow-Up and Risk Stratification of Patients With Desmoplakin-Associated Arrhythmogenic Right Ventricular Cardiomyopathy

Alessio Gasperetti; Richard Carrick; Alexandros Protonotarios; Mikael Laredo; Iris van der Schaaf; Petros Syrris; Brittney Murray; Crystal Tichnell; Chiara Cappelletto; Marta Gigli; Kristen Medo; Peter Crabtree; Ardan M. Saguner; Firat Duru; Robyn Hylind; Dominic Abrams; Neal K. Lakdawala; Charles Massie; Julia Cadrin-Tourigny; Mattia Targetti; Iacopo Olivotto; Maddalena Graziosi; Moniek Cox; Elena Biagini; Philippe Charron; Michela Casella; Claudio Tondo; Momina Yazdani; James S. Ware; Sanjay Prasad; Leonardo Calò; Eric Smith; Adam Helms; Sophie Hespe; Jodie Ingles; Harikrishna Tandri; Flavie Ader; Luisa Mestroni; Arthur Wilde; Marco Merlo; Estelle Gandjbakhch; Hugh Calkins; Anneline S. J. M. te Riele; J. Peter van Tintelen; Perry Elliot; Cynthia A. James

doi:10.1016/j.jacadv.2024.100832

Long-Term Arrhythmic Follow-Up and Risk Stratification of Patients With Desmoplakin-Associated Arrhythmogenic Right Ventricular Cardiomyopathy

Alessio Gasperetti, Richard Carrick, Alexandros Protonotarios, Mikael Laredo, Iris van der Schaaf, Petros Syrris, Brittney Murray, Crystal Tichnell, Chiara Cappelletto, Marta Gigli, Kristen Medo, Peter Crabtree, Ardan M. Saguner, Firat Duru, Robyn Hylind, Dominic Abrams, Neal K. Lakdawala, Charles Massie, Julia Cadrin-Tourigny, Mattia TargettiIacopo Olivotto, Maddalena Graziosi, Moniek Cox, Elena Biagini, Philippe Charron, Michela Casella, Claudio Tondo, Momina Yazdani, James S. Ware, Sanjay Prasad, Leonardo Calò, Eric Smith, Adam Helms, Sophie Hespe, Jodie Ingles, Harikrishna Tandri, Flavie Ader, Luisa Mestroni, Arthur Wilde, Marco Merlo, Estelle Gandjbakhch, Hugh Calkins, Anneline S. J. M. te Riele, J. Peter van Tintelen, Perry Elliot, Cynthia A. James

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

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Abstract

Background: Patients with likely pathogenic/pathogenic desmoplakin (DSP) variants are poorly characterized. Some of them meet diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC), but it is unclear how risk stratification strategies for ARVC perform in this setting. Objectives: The purpose of this study was to characterize arrhythmic outcomes and to test the performance of the recently validated ARVC risk calculator in patients with DSP likely pathogenic/pathogenic variants fulfilling definite 2010 ARVC Task Force Criteria (DSP-TFC+). Methods: DSP-TFC+ patients were enrolled from 20 institutions across 3 continents. Ventricular arrhythmias (VA), defined as a composite of sustained ventricular tachycardia (VT), appropriate implantable cardioverter defibrillator therapies, and ventricular fibrillation/sudden cardiac death events in follow-up, were reported as the primary outcome. We tested the performance of the ARVC risk calculator for VA prediction, reporting c-statistics. Results: Among 252 DSP-TFC+ patients (age 39.6 ± 16.9 years, 35.3% male), 94 (37.3%) experienced VA over 44.5 [IQR: 19.6-78.3] months. Patients with left ventricle involvement (n = 194) were at higher VA risk (log-rank P = 0.0239). History of nonsustained VT (aHR 2.097; P = 0.004) showed the strongest association with VA occurrence during the first 5-year follow-up. Neither age (P = 0.723) nor male sex (P = 0.200) was associated with VAs at follow-up. In 204 patients without VA at diagnosis, incident VA rate was high (32.8%; 7.37%/y). The ARVC risk calculator performed poorly overall (c-statistic 0.604 [0.594-0.614]) and very poorly in patients with left ventricular disease (c-statistic 0.558 [0.556-0.560]). Conclusions: DSP-TFC+ patients are at substantial risk for VAs. The ARVC risk calculator performs poorly in DSP-TFC+ patients suggesting need for a gene-specific risk algorithm. Meanwhile, DSP-TFC+ patients with nonsustained VT should be considered as high-risk.

Original language	English
Article number	100832
Journal	JACC: Advances
Volume	3
Issue number	3
DOIs	https://doi.org/10.1016/j.jacadv.2024.100832
Publication status	Published - 1 Mar 2024

Keywords

ACM
ARVC
desmoplakin
risk stratification

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10.1016/j.jacadv.2024.100832

Cite this

Gasperetti, A., Carrick, R., Protonotarios, A., Laredo, M., van der Schaaf, I., Syrris, P., Murray, B., Tichnell, C., Cappelletto, C., Gigli, M., Medo, K., Crabtree, P., Saguner, A. M., Duru, F., Hylind, R., Abrams, D., Lakdawala, N. K., Massie, C., Cadrin-Tourigny, J., ... James, C. A. (2024). Long-Term Arrhythmic Follow-Up and Risk Stratification of Patients With Desmoplakin-Associated Arrhythmogenic Right Ventricular Cardiomyopathy. JACC: Advances, 3(3), Article 100832. https://doi.org/10.1016/j.jacadv.2024.100832

@article{0c4018725f4f426186b8d33ba84a645c,

title = "Long-Term Arrhythmic Follow-Up and Risk Stratification of Patients With Desmoplakin-Associated Arrhythmogenic Right Ventricular Cardiomyopathy",

abstract = "Background: Patients with likely pathogenic/pathogenic desmoplakin (DSP) variants are poorly characterized. Some of them meet diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC), but it is unclear how risk stratification strategies for ARVC perform in this setting. Objectives: The purpose of this study was to characterize arrhythmic outcomes and to test the performance of the recently validated ARVC risk calculator in patients with DSP likely pathogenic/pathogenic variants fulfilling definite 2010 ARVC Task Force Criteria (DSP-TFC+). Methods: DSP-TFC+ patients were enrolled from 20 institutions across 3 continents. Ventricular arrhythmias (VA), defined as a composite of sustained ventricular tachycardia (VT), appropriate implantable cardioverter defibrillator therapies, and ventricular fibrillation/sudden cardiac death events in follow-up, were reported as the primary outcome. We tested the performance of the ARVC risk calculator for VA prediction, reporting c-statistics. Results: Among 252 DSP-TFC+ patients (age 39.6 ± 16.9 years, 35.3% male), 94 (37.3%) experienced VA over 44.5 [IQR: 19.6-78.3] months. Patients with left ventricle involvement (n = 194) were at higher VA risk (log-rank P = 0.0239). History of nonsustained VT (aHR 2.097; P = 0.004) showed the strongest association with VA occurrence during the first 5-year follow-up. Neither age (P = 0.723) nor male sex (P = 0.200) was associated with VAs at follow-up. In 204 patients without VA at diagnosis, incident VA rate was high (32.8%; 7.37%/y). The ARVC risk calculator performed poorly overall (c-statistic 0.604 [0.594-0.614]) and very poorly in patients with left ventricular disease (c-statistic 0.558 [0.556-0.560]). Conclusions: DSP-TFC+ patients are at substantial risk for VAs. The ARVC risk calculator performs poorly in DSP-TFC+ patients suggesting need for a gene-specific risk algorithm. Meanwhile, DSP-TFC+ patients with nonsustained VT should be considered as high-risk.",

keywords = "ACM, ARVC, desmoplakin, risk stratification",

author = "Alessio Gasperetti and Richard Carrick and Alexandros Protonotarios and Mikael Laredo and {van der Schaaf}, Iris and Petros Syrris and Brittney Murray and Crystal Tichnell and Chiara Cappelletto and Marta Gigli and Kristen Medo and Peter Crabtree and Saguner, {Ardan M.} and Firat Duru and Robyn Hylind and Dominic Abrams and Lakdawala, {Neal K.} and Charles Massie and Julia Cadrin-Tourigny and Mattia Targetti and Iacopo Olivotto and Maddalena Graziosi and Moniek Cox and Elena Biagini and Philippe Charron and Michela Casella and Claudio Tondo and Momina Yazdani and Ware, {James S.} and Sanjay Prasad and Leonardo Cal{\`o} and Eric Smith and Adam Helms and Sophie Hespe and Jodie Ingles and Harikrishna Tandri and Flavie Ader and Luisa Mestroni and Arthur Wilde and Marco Merlo and Estelle Gandjbakhch and Hugh Calkins and {te Riele}, {Anneline S. J. M.} and {Peter van Tintelen}, J. and Perry Elliot and James, {Cynthia A.}",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

month = mar,

day = "1",

doi = "10.1016/j.jacadv.2024.100832",

language = "English",

volume = "3",

journal = "JACC: Advances",

issn = "2772-963X",

number = "3",

}

Gasperetti, A, Carrick, R, Protonotarios, A, Laredo, M, van der Schaaf, I, Syrris, P, Murray, B, Tichnell, C, Cappelletto, C, Gigli, M, Medo, K, Crabtree, P, Saguner, AM, Duru, F, Hylind, R, Abrams, D, Lakdawala, NK, Massie, C, Cadrin-Tourigny, J, Targetti, M, Olivotto, I, Graziosi, M, Cox, M, Biagini, E, Charron, P, Casella, M, Tondo, C, Yazdani, M, Ware, JS, Prasad, S, Calò, L, Smith, E, Helms, A, Hespe, S, Ingles, J, Tandri, H, Ader, F, Mestroni, L, Wilde, A, Merlo, M, Gandjbakhch, E, Calkins, H, te Riele, ASJM, Peter van Tintelen, J, Elliot, P & James, CA 2024, 'Long-Term Arrhythmic Follow-Up and Risk Stratification of Patients With Desmoplakin-Associated Arrhythmogenic Right Ventricular Cardiomyopathy', JACC: Advances, vol. 3, no. 3, 100832. https://doi.org/10.1016/j.jacadv.2024.100832

TY - JOUR

T1 - Long-Term Arrhythmic Follow-Up and Risk Stratification of Patients With Desmoplakin-Associated Arrhythmogenic Right Ventricular Cardiomyopathy

AU - Gasperetti, Alessio

AU - Carrick, Richard

AU - Protonotarios, Alexandros

AU - Laredo, Mikael

AU - van der Schaaf, Iris

AU - Syrris, Petros

AU - Murray, Brittney

AU - Tichnell, Crystal

AU - Cappelletto, Chiara

AU - Gigli, Marta

AU - Medo, Kristen

AU - Crabtree, Peter

AU - Saguner, Ardan M.

AU - Duru, Firat

AU - Hylind, Robyn

AU - Abrams, Dominic

AU - Lakdawala, Neal K.

AU - Massie, Charles

AU - Cadrin-Tourigny, Julia

AU - Targetti, Mattia

AU - Olivotto, Iacopo

AU - Graziosi, Maddalena

AU - Cox, Moniek

AU - Biagini, Elena

AU - Charron, Philippe

AU - Casella, Michela

AU - Tondo, Claudio

AU - Yazdani, Momina

AU - Ware, James S.

AU - Prasad, Sanjay

AU - Calò, Leonardo

AU - Smith, Eric

AU - Helms, Adam

AU - Hespe, Sophie

AU - Ingles, Jodie

AU - Tandri, Harikrishna

AU - Ader, Flavie

AU - Mestroni, Luisa

AU - Wilde, Arthur

AU - Merlo, Marco

AU - Gandjbakhch, Estelle

AU - Calkins, Hugh

AU - te Riele, Anneline S. J. M.

AU - Peter van Tintelen, J.

AU - Elliot, Perry

AU - James, Cynthia A.

PY - 2024/3/1

Y1 - 2024/3/1

N2 - Background: Patients with likely pathogenic/pathogenic desmoplakin (DSP) variants are poorly characterized. Some of them meet diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC), but it is unclear how risk stratification strategies for ARVC perform in this setting. Objectives: The purpose of this study was to characterize arrhythmic outcomes and to test the performance of the recently validated ARVC risk calculator in patients with DSP likely pathogenic/pathogenic variants fulfilling definite 2010 ARVC Task Force Criteria (DSP-TFC+). Methods: DSP-TFC+ patients were enrolled from 20 institutions across 3 continents. Ventricular arrhythmias (VA), defined as a composite of sustained ventricular tachycardia (VT), appropriate implantable cardioverter defibrillator therapies, and ventricular fibrillation/sudden cardiac death events in follow-up, were reported as the primary outcome. We tested the performance of the ARVC risk calculator for VA prediction, reporting c-statistics. Results: Among 252 DSP-TFC+ patients (age 39.6 ± 16.9 years, 35.3% male), 94 (37.3%) experienced VA over 44.5 [IQR: 19.6-78.3] months. Patients with left ventricle involvement (n = 194) were at higher VA risk (log-rank P = 0.0239). History of nonsustained VT (aHR 2.097; P = 0.004) showed the strongest association with VA occurrence during the first 5-year follow-up. Neither age (P = 0.723) nor male sex (P = 0.200) was associated with VAs at follow-up. In 204 patients without VA at diagnosis, incident VA rate was high (32.8%; 7.37%/y). The ARVC risk calculator performed poorly overall (c-statistic 0.604 [0.594-0.614]) and very poorly in patients with left ventricular disease (c-statistic 0.558 [0.556-0.560]). Conclusions: DSP-TFC+ patients are at substantial risk for VAs. The ARVC risk calculator performs poorly in DSP-TFC+ patients suggesting need for a gene-specific risk algorithm. Meanwhile, DSP-TFC+ patients with nonsustained VT should be considered as high-risk.

AB - Background: Patients with likely pathogenic/pathogenic desmoplakin (DSP) variants are poorly characterized. Some of them meet diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC), but it is unclear how risk stratification strategies for ARVC perform in this setting. Objectives: The purpose of this study was to characterize arrhythmic outcomes and to test the performance of the recently validated ARVC risk calculator in patients with DSP likely pathogenic/pathogenic variants fulfilling definite 2010 ARVC Task Force Criteria (DSP-TFC+). Methods: DSP-TFC+ patients were enrolled from 20 institutions across 3 continents. Ventricular arrhythmias (VA), defined as a composite of sustained ventricular tachycardia (VT), appropriate implantable cardioverter defibrillator therapies, and ventricular fibrillation/sudden cardiac death events in follow-up, were reported as the primary outcome. We tested the performance of the ARVC risk calculator for VA prediction, reporting c-statistics. Results: Among 252 DSP-TFC+ patients (age 39.6 ± 16.9 years, 35.3% male), 94 (37.3%) experienced VA over 44.5 [IQR: 19.6-78.3] months. Patients with left ventricle involvement (n = 194) were at higher VA risk (log-rank P = 0.0239). History of nonsustained VT (aHR 2.097; P = 0.004) showed the strongest association with VA occurrence during the first 5-year follow-up. Neither age (P = 0.723) nor male sex (P = 0.200) was associated with VAs at follow-up. In 204 patients without VA at diagnosis, incident VA rate was high (32.8%; 7.37%/y). The ARVC risk calculator performed poorly overall (c-statistic 0.604 [0.594-0.614]) and very poorly in patients with left ventricular disease (c-statistic 0.558 [0.556-0.560]). Conclusions: DSP-TFC+ patients are at substantial risk for VAs. The ARVC risk calculator performs poorly in DSP-TFC+ patients suggesting need for a gene-specific risk algorithm. Meanwhile, DSP-TFC+ patients with nonsustained VT should be considered as high-risk.

KW - ACM

KW - ARVC

KW - desmoplakin

KW - risk stratification

UR - http://www.scopus.com/inward/record.url?scp=85184007517&partnerID=8YFLogxK

U2 - 10.1016/j.jacadv.2024.100832

DO - 10.1016/j.jacadv.2024.100832

M3 - Article

SN - 2772-963X

VL - 3

JO - JACC: Advances

JF - JACC: Advances

IS - 3

M1 - 100832

ER -

Long-Term Arrhythmic Follow-Up and Risk Stratification of Patients With Desmoplakin-Associated Arrhythmogenic Right Ventricular Cardiomyopathy

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Keywords

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