A Systematic Analysis of the Clinical Outcome Associated with Multiple Reclassified Desmosomal Gene Variants in Arrhythmogenic Right Ventricular Cardiomyopathy Patients

Emilia Nagyova, Edgar T Hoorntje, Wouter P Te Rijdt, Laurens P Bosman, Petros Syrris, Alexandros Protonotarios, Perry M Elliott, Adalena Tsatsopoulou, Luisa Mestroni, Matthew R G Taylor, Gianfranco Sinagra, Marco Merlo, Yuko Wada, Minoru Horie, Jens Mogensen, Alex H Christensen, Brenda Gerull, Lei Song, Yan Yao, Siyang FanArdan M Saguner, Firat Duru, Juha W Koskenvuo, Tania Cruz Marino, Crystal Tichnell, Daniel P Judge, Dennis Dooijes, Ronald H Lekanne Deprez, Cristina Basso, Kalliopi Pilichou, Barbara Bauce, Arthur A M Wilde, Philippe Charron, Véronique Fressart, Jeroen F van der Heijden, Maarten P van den Berg, Folkert W Asselbergs, Cynthia A James, Jan D H Jongbloed, Magdalena Harakalova*, J Peter van Tintelen

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

2 Citaten (Scopus)
22 Downloads (Pure)

Samenvatting

The presence of multiple pathogenic variants in desmosomal genes (DSC2, DSG2, DSP, JUP, and PKP2) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been linked to a severe phenotype. However, the pathogenicity of variants is reclassified frequently, which may result in a changed clinical risk prediction. Here, we present the collection, reclassification, and clinical outcome correlation for the largest series of ARVC patients carrying multiple desmosomal pathogenic variants to date (n = 331). After reclassification, only 29% of patients remained carriers of two (likely) pathogenic variants. They reached the composite endpoint (ventricular arrhythmias, heart failure, and death) significantly earlier than patients with one or no remaining reclassified variant (hazard ratios of 1.9 and 1.8, respectively). Periodic reclassification of variants contributes to more accurate risk stratification and subsequent clinical management strategy. Graphical Abstract.

Originele taal-2English
Pagina's (van-tot)1276–1286
Aantal pagina's11
TijdschriftJournal of cardiovascular translational research
Volume16
Vroegere onlinedatum7-jul.-2023
DOI's
StatusPublished - dec.-2023

Vingerafdruk

Duik in de onderzoeksthema's van 'A Systematic Analysis of the Clinical Outcome Associated with Multiple Reclassified Desmosomal Gene Variants in Arrhythmogenic Right Ventricular Cardiomyopathy Patients'. Samen vormen ze een unieke vingerafdruk.

Citeer dit