Polymorphisms associated with ventricular tachyarrhythmias: rationale, design, and endpoints of the 'diagnostic data influence on disease management and relation of genomics to ventricular tachyarrhythmias in implantable cardioverter/defibrillator patients (DISCOVERY)' study.
Implantable cardioverter-defibrillator (ICD) therapy is effective in primary and secondary prevention for patients who are at high risk of sudden cardiac death. However, the current risk stratification of patients who may benefit from this therapy is unsatisfactory. Single nucleotide polymorphisms (SNPs) are DNA sequence variations occurring when a single nucleotide in the genome differs among members of a species. A novel concept has emerged being that these common genetic variations might modify the susceptibility of a certain population to specific diseases. Thus, genetic factors may also modulate the risk for arrhythmias and sudden cardiac death, and identification of common variants could help to better identify patients at risk. The DISCOVERY study is an interventional, longitudinal, prospective, multi-centre diagnostic study that will enrol 1287 patients in approximately 80 European centres. In the genetic part of the DISCOVERY study, candidate gene polymorphisms involved in coding of the G-protein subunits will be correlated with the occurrence of ventricular arrhythmias in patients receiving an ICD for primary prevention. Furthermore, in order to search for additional sequence variants contributing to ventricular arrhythmias, a genome-wide association study will be conducted if sufficient a priori evidence can be gathered. In the second part of the study, associations of SNPs with ventricular arrhythmias will be sought and a search for potential new biological arrhythmic pathways will be investigated. As it is a diagnostic study, DISCOVERY will also investigate the impact of long-term device diagnostic data on the management of patients suffering from chronic cardiac disease as well as medical decisions made regarding their treatment.
Wieneke
Heinrich
H
Department of Cardiology, Elisabeth-Krankenhaus Essen, Klara-Kopp-Weg 1, 45138 Essen, Germany. heinrich.wieneke@t-online.de
Spencker
Sebastian
S
Svendsen
Jesper Hastrup
JH
Martinez
Juan Gabriel
JG
Strohmer
Bernhard
B
Toivonen
Lauri
L
Le Marec
Hervé
H
Garcia
Javier
J
Kaup
Bernd
B
Soykan
Orhan
O
Corrado
Domenico
D
Siffert
Winfried
W
D002864:Chromogranins; D017147:Defibrillators, Implantable; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005820:Genetic Testing; D055106:Genome-Wide Association Study; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics; D006801:Humans; D008137:Longitudinal Studies; D015337:Multicenter Studies as Topic; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D017180:Tachycardia, Ventricular / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy
D002864:Chromogranins; C454420:G-protein beta3 subunit; D005819:Genetic Markers; C406732:GNAS protein, human; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D019205:GTP-Binding Protein alpha Subunits, Gs; D020962:Heterotrimeric GTP-Binding Proteins