TY - JOUR
T1 - A Systematic Analysis of the Clinical Outcome Associated with Multiple Reclassified Desmosomal Gene Variants in Arrhythmogenic Right Ventricular Cardiomyopathy Patients
AU - Nagyova, Emilia
AU - Hoorntje, Edgar T
AU - Rijdt, Wouter P Te
AU - Bosman, Laurens P
AU - Syrris, Petros
AU - Protonotarios, Alexandros
AU - Elliott, Perry M
AU - Tsatsopoulou, Adalena
AU - Mestroni, Luisa
AU - Taylor, Matthew R G
AU - Sinagra, Gianfranco
AU - Merlo, Marco
AU - Wada, Yuko
AU - Horie, Minoru
AU - Mogensen, Jens
AU - Christensen, Alex H
AU - Gerull, Brenda
AU - Song, Lei
AU - Yao, Yan
AU - Fan, Siyang
AU - Saguner, Ardan M
AU - Duru, Firat
AU - Koskenvuo, Juha W
AU - Cruz Marino, Tania
AU - Tichnell, Crystal
AU - Judge, Daniel P
AU - Dooijes, Dennis
AU - Lekanne Deprez, Ronald H
AU - Basso, Cristina
AU - Pilichou, Kalliopi
AU - Bauce, Barbara
AU - Wilde, Arthur A M
AU - Charron, Philippe
AU - Fressart, Véronique
AU - van der Heijden, Jeroen F
AU - van den Berg, Maarten P
AU - Asselbergs, Folkert W
AU - James, Cynthia A
AU - Jongbloed, Jan D H
AU - Harakalova, Magdalena
AU - van Tintelen, J Peter
N1 - © 2023. The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
U2 - 10.1007/s12265-023-10403-8
DO - 10.1007/s12265-023-10403-8
M3 - Article
C2 - 37418234
SN - 1937-5387
VL - 16
SP - 1276
EP - 1286
JO - Journal of cardiovascular translational research
JF - Journal of cardiovascular translational research
ER -