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

被引：5

作者：

Nagyova, Emilia ^{[1
,2
]}

Hoorntje, Edgar T. ^{[3
,4
]}

te Rijdt, Wouter P. ^{[3
,4
]}

Bosman, Laurens P. ^{[1
]}

Syrris, Petros ^{[5
]}

Protonotarios, Alexandros ^{[5
,6
]}

Elliott, Perry M. ^{[5
]}

Tsatsopoulou, Adalena ^{[6
]}

Mestroni, Luisa ^{[7
]}

Taylor, Matthew R. G. ^{[7
]}

Sinagra, Gianfranco ^{[8
]}

Merlo, Marco ^{[8
]}

Wada, Yuko ^{[9
,10
]}

Horie, Minoru ^{[10
]}

Mogensen, Jens ^{[11
]}

Christensen, Alex H. ^{[12
,13
]}

Gerull, Brenda ^{[14
,15
,16
]}

Song, Lei ^{[17
,18
]}

Yao, Yan ^{[17
,18
]}

Fan, Siyang ^{[17
,18
]}

Saguner, Ardan M. ^{[19
]}

Duru, Firat ^{[19
]}

Koskenvuo, Juha W. ^{[20
]}

Marino, Tania Cruz ^{[21
]}

Tichnell, Crystal ^{[22
]}

Judge, Daniel P. ^{[23
]}

Dooijes, Dennis ^{[24
]}

Deprez, Ronald Lekanne H. ^{[25
]}

Basso, Cristina ^{[26
]}

Pilichou, Kalliopi ^{[26
]}

Bauce, Barbara ^{[26
]}

Wilde, Arthur A. M. ^{[27
]}

Charron, Philippe ^{[28
]}

Fressart, Veronique ^{[28
]}

van der Heijden, Jeroen F. ^{[1
]}

van den Berg, Maarten P. ^{[29
]}

Asselbergs, Folkert W. ^{[1
,30
,31
,32
]}

James, Cynthia A. ^{[22
]}

Jongbloed, Jan D. H. ^{[3
]}

Harakalova, Magdalena ^{[1
,4
,33
]}

van Tintelen, J. Peter ^{[4
,24
,25
]}

机构：

[1] Univ Utrecht, Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands

[2] Comenius Univ, Fac Nat Sci, Dept Mol Biol, Bratislava, Slovakia

[3] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands

[4] Netherlands Heart Inst, Utrecht, Netherlands

[5] UCL, Inst Cardiovasc Sci, Ctr Heart Muscle Dis, London, England

[6] Nikos Protonotarios Med Ctr, Naxos 84300, Greece

[7] Univ Colorado, Cardiovasc Inst, Anschutz Med Campus, Aurora, CO USA

[8] Azienda Sanitaria Univ Giuliano Isontina ASUGI, Cardiothoracovasc Dept, Trieste, Italy

[9] Vanderbilt Univ, Dept Med, Med Ctr, Nashville, TN USA

[10] Shiga Univ Med Sci, Dept Cardiovasc Med, Otsu, Japan

[11] Aalborg Univ Hosp, Dept Cardiol, Aalborg, Denmark

[12] Dept Cardiol, Herlev Gentofte, Denmark

[13] Copenhagen Univ Hosp, Rigshosp, Copenhagen, Denmark

[14] Libin Cardiovasc Inst Alberta, Dept Cardiac Sci, Calgary, AB, Canada

[15] Univ Hosp Wurzburg, Comprehens Heart Failure Ctr CHFC, Wurzburg, Germany

[16] Univ Hosp Wurzburg, Dept Internal Med 1, Wurzburg, Germany

[17] Peking Union Med Coll Chinese Acad Med Sci, Fuwai Hosp, Natl Ctr Cardiovasc Dis, Arrhythmia Ctr, Beijing, Peoples R China

[18] Peking Union Med Coll Chinese Acad Med Sci, Fuwai Hosp, Natl Ctr Cardiovasc Dis, Clin EP Lab,State Key Lab Cardiovasc Dis, Beijing, Peoples R China

[19] Univ Heart Ctr, Dept Cardiol, Zurich, Switzerland

[20] Blueprint Genet, Helsinki, Finland

[21] CIUSSS Saguenay Lac St Jean, Dept Med Biol, Chicoutimi, PQ, Canada

[22] Johns Hopkins Univ, Dept Med, Div Cardiol, Sch Med, Baltimore, MD USA

[23] Med Univ South Carolina, Dept Med, Div Cardiol, Charleston, SC USA

[24] Univ Utrecht, Univ Med Ctr Utrecht, Dept Genet, Utrecht, Netherlands

[25] Univ Amsterdam, Amsterdam Univ Med Ctr, Dept Human Genet, Amsterdam, Netherlands

[26] Univ Padua, Dept Cardiac Thorac Vasc Sci & Publ Hlth, Padua, Italy

[27] Univ Amsterdam, Amsterdam Univ Med Ctr, Heart Ctr, Dept Clin & Expt Cardiol, Amsterdam, Netherlands

[28] Sorbonne Univ, Pitie Salpetriere Hosp, AP HP, Referral Ctr Cardiac Hereditary Dis, Paris, France

[29] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands

[30] UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England

[31] UCL, Hlth Data Res UK, London, England

[32] UCL, Inst Hlth Informat, London, England

[33] Univ Utrecht, Univ Med Ctr Utrecht, Regenerat Med Utrecht RMU, Utrecht, Netherlands

来源：

JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH | 2023年 / 16卷 / 06期

基金：

瑞士国家科学基金会;

关键词：

ARVC; Multiple variants; Desmosomal genes; Composite endpoint; Arrhythmia; Genetics; MUTATION; RISK; DIAGNOSIS; COMPOUND;

D O I：

10.1007/s12265-023-10403-8

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：1276 / 1286

页数：11

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