Genetic Testing in the Evaluation of Unexplained Cardiac Arrest From the CASPER (Cardiac Arrest Survivors With Preserved Ejection Fraction Registry)

被引：82

作者：

Mellor, Greg ^{[1
]}

Laksman, Zachary W. M. ^{[1
]}

Tadros, Rafik ^{[3
]}

Roberts, Jason D. ^{[4
]}

Gerull, Brenda ^{[5
]}

Simpson, Christopher S. ^{[6
]}

Klein, George J. ^{[4
]}

Champagne, Jean ^{[7
]}

Talajic, Mario ^{[3
]}

Gardner, Martin ^{[8
]}

Steinberg, Christian ^{[7
]}

Arbour, Laura ^{[2
]}

Birnie, David H. ^{[9
]}

Angaran, Paul ^{[10
]}

Leather, Richard ^{[2
]}

Sanatani, Shubhayan ^{[11
]}

Chauhan, Vijay S. ^{[12
]}

Seifer, Colette ^{[13
]}

Healey, Jeffrey S. ^{[14
]}

Krahn, Andrew D. ^{[1
]}

机构：

[1] Univ British Columbia, Heart Rhythm Serv, Div Cardiol, Vancouver, BC, Canada

[2] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada

[3] Univ Montreal, Montreal Heart Inst, Dept Med, Cardiovasc Genet Ctr, Montreal, PQ, Canada

[4] Western Univ, Div Cardiol, Dept Med, Sect Cardiac Electrophysiol, London, ON, Canada

[5] Univ Calgary, Libin Cardiovasc Inst, Calgary, AB, Canada

[6] Queens Univ, Dept Cardiol, Kingston, ON, Canada

[7] Quebec Heart & Lung Inst, Quebec City, PQ, Canada

[8] QEII Hlth Sci Ctr, Halifax, NS, Canada

[9] Univ Ottawa, Heart Inst, Ottawa, ON, Canada

[10] Univ Toronto, St Michaels Hosp, Div Cardiol, Toronto, ON, Canada

[11] BC Childrens Hosp, Childrens Heart Ctr, Vancouver, BC, Canada

[12] Univ Hlth Network, Toronto, ON, Canada

[13] St Boniface Gen Hosp, WHRA Cardiac Sci Program, Winnipeg, MB, Canada

[14] Populat Hlth Res Inst, Hamilton, ON, Canada

来源：

CIRCULATION-CARDIOVASCULAR GENETICS | 2017年 / 10卷 / 03期

关键词：

arrhythmia; cardiac arrest; diagnosis; electrocardiography; genetics; MUTATIONS; VARIANTS; DEATH; CHANNELOPATHIES; DIAGNOSIS;

D O I：

10.1161/CIRCGENETICS.116.001686

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background-Unexplained cardiac arrest may be because of an inherited arrhythmia syndrome. The role of genetic testing in cardiac arrest survivors without a definite clinical phenotype is unclear. Methods and Results-The CASPER (Cardiac Arrest Survivors with Preserved Ejection Fraction Registry) is a large registry of cardiac arrest survivors where initial assessment reveals normal coronary arteries, left ventricular function, and resting ECG. Of 375 cardiac arrest survivors in CASPER from 2006 to 2015, 174 underwent genetic testing. Patients were classified as phenotype-positive (n=72) or phenotype-negative (n=102). Genetic testing was performed at treating physicians' discretion in line with contemporary guidelines and availability. All genetic variants identified from original laboratory reports were reassessed by the investigators in line with modern criteria. Pathogenic variants were identified in 29 (17%) patients (60% channelopathy-associated and 40% cardiomyopathy-associated genes) and 70 variants of unknown significance were identified in 32 (18%) patients. Prior syncope (odds ratio, 4.0; 95% confidence interval, 1.6-9.7) and a family history of sudden death (odds ratio, 3.2; 95% confidence interval, 1.1-9.4) were independently associated with the presence of a pathogenic variant. In phenotype-negative patients, broad multiphenotype genetic testing led to higher yields (21% versus 8%; P=0.04) but was associated with more variants of unknown significance (55% versus 5%; P<0.01). Conclusions-Genetic testing identifies a pathogenic variant in a significant proportion of unexplained cardiac arrest survivors. Prior syncope and family history of sudden death are predictors of a positive genetic test. Both arrhythmia and cardiomyopathy genes are implicated. Broad, multiphenotype testing revealed the highest frequency of pathogenic variants in phenotype-negative patients.

引用

页数：13

共 23 条

[11] Diagnosis of unexplained cardiac arrest - Role of adrenaline and procainamide infusion [J].

Krahn, AD ;

Gollob, M ;

Yee, R ;

Gula, LJ ;

Skanes, AC ;

Walker, BD ;

Klein, GJ .

CIRCULATION, 2005, 112 (15) :2228-2234

[12] Epinephrine Infusion in the Evaluation of Unexplained Cardiac Arrest and Familial Sudden Death From the Cardiac Arrest Survivors With Preserved Ejection Fraction Registry [J].

Krahn, Andrew D. ;

Healey, Jeffrey S. ;

Chauhan, Vijay S. ;

Birnie, David H. ;

Champagne, Jean ;

Sanatani, Shubhayan ;

Ahmad, Kamran ;

Ballantyne, Emily ;

Gerull, Brenda ;

Yee, Raymond ;

Skanes, Allan C. ;

Gula, Lorne J. ;

Leong-Sit, Peter ;

Klein, George J. ;

Gollob, Michael H. ;

Simpson, Christopher S. ;

Talajic, Mario ;

Gardner, Martin .

CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY, 2012, 5 (05) :933-940

[13] Systematic Assessment of Patients With Unexplained Cardiac Arrest Cardiac Arrest Survivors With Preserved Ejection Fraction Registry (CASPER) [J].

Krahn, Andrew D. ;

Healey, Jeffrey S. ;

Chauhan, Vijay ;

Birnie, David H. ;

Simpson, Christopher S. ;

Champagne, Jean ;

Gardner, Martin ;

Sanatani, Shubhayan ;

Exner, Derek V. ;

Klein, George J. ;

Yee, Raymond ;

Skanes, Allan C. ;

Gula, Lorne J. ;

Gollob, Michael H. .

CIRCULATION, 2009, 120 (04) :278-285

[14] ClinVar: public archive of interpretations of clinically relevant variants [J].

Landrum, Melissa J. ;

Lee, Jennifer M. ;

Benson, Mark ;

Brown, Garth ;

Chao, Chen ;

Chitipiralla, Shanmuga ;

Gu, Baoshan ;

Hart, Jennifer ;

Hoffman, Douglas ;

Hoover, Jeffrey ;

Jang, Wonhee ;

Katz, Kenneth ;

Ovetsky, Michael ;

Riley, George ;

Sethi, Amanjeev ;

Tully, Ray ;

Villamarin-Salomon, Ricardo ;

Rubinstein, Wendy ;

Maglott, Donna R. .

NUCLEIC ACIDS RESEARCH, 2016, 44 (D1) :D862-D868

[15] Diagnostic yield of molecular autopsy in patients with sudden arrhythmic death syndrome using targeted exome sequencing [J].

Nunn, Laurence M. ;

Lopes, Luis R. ;

Syrris, Petros ;

Murphy, Cian ;

Plagnol, Vincent ;

Firman, Eileen ;

Dalageorgou, Chrysoula ;

Zorio, Esther ;

Domingo, Diana ;

Murday, Victoria ;

Findlay, Iain ;

Duncan, Alexis ;

Carr-White, Gerry ;

Robert, Leema ;

Bueser, Teofila ;

Langman, Caroline ;

Fynn, Simon P. ;

Goddard, Martin ;

White, Anne ;

Bundgaard, Henning ;

Ferrero-Miliani, Laura ;

Wheeldon, Nigel ;

Suvarna, Simon K. ;

O'Beirne, Aliceson ;

Lowe, Martin D. ;

McKenna, William J. ;

Elliott, Perry M. ;

Lambiase, Pier D. .

EUROPACE, 2016, 18 (06) :888-896

[16] Founder mutations in the Netherlands: familial idiopathic ventricular fibrillation and DPP6 [J].

Postema, P. G. ;

Christiaans, I. ;

Hofman, N. ;

Alders, M. ;

Koopmann, T. T. ;

Bezzina, C. R. ;

Loh, P. ;

Zeppenfeld, K. ;

Volders, P. G. A. ;

Wilde, A. A. M. .

NETHERLANDS HEART JOURNAL, 2011, 19 (06) :290-296

[17] PEST sequences and regulation by proteolysis [J].

Rechsteiner, M ;

Rogers, SW .

TRENDS IN BIOCHEMICAL SCIENCES, 1996, 21 (07) :267-271

[18] Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology [J].

Richards, Sue ;

Aziz, Nazneen ;

Bale, Sherri ;

Bick, David ;

Das, Soma ;

Gastier-Foster, Julie ;

Grody, Wayne W. ;

Hegde, Madhuri ;

Lyon, Elaine ;

Spector, Elaine ;

Voelkerding, Karl ;

Rehm, Heidi L. .

GENETICS IN MEDICINE, 2015, 17 (05) :405-424

[19] DIAGNOSTIC-CRITERIA FOR THE LONG QT SYNDROME - AN UPDATE [J].

SCHWARTZ, PJ ;

MOSS, AJ ;

VINCENT, GM ;

CRAMPTON, RS .

CIRCULATION, 1993, 88 (02) :782-784

[20] A Genetic Variants Database for Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy [J].

van der Zwaag, Paul A. ;

Jongbloed, Jan D. H. ;

van den Berg, Maarten P. ;

van der Smagt, Jasper J. ;

Jongbloed, Roselie ;

Bikker, Hennie ;

Hofstra, Robert M. W. ;

van Tintelen, J. Peter .

HUMAN MUTATION, 2009, 30 (09) :1278-1283

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