genome-wide association study with the aim of implantable cardioverter defibrillator implantation genophenotypic risk stratification

Conditions: ICD; Arrythmia; Sudden Cardiac Death

Summary: this clinical study will be conducted with funding from european innovation council(eic) after approval of the fund grant and is part of our organization's european pathfinder project(ref: horizon-eic-2022-pathfinderchallenges-01). the clinical study step of this project will be started in a retrospective time prospective manner by gathering the phenotypic(clinical measuring factors) data from patients who underwent icd implantation therapy. the study will be done as a case-control type in which patients who did not get any shocks in 6 months post-implantation will be allocated to the control group. a customized and highly specific cardiogenomics panel will be designed and ordered to be specially manufactured as a standard kit by illumina® (san diego, california, u.s.) following an exhaustive investigation for collecting genetic variants which correlated to cardiovascular development. mentioned kit bears the standard and validated technology which is part of the genetic tests routine and is being produced by illumina® incorporate. however, as an option manufacturer is designing custom kits for research purposes by getting the desired variant lists using the same technology. accordingly, enrolled patients in the study will be prospectively sampled ( non-invasive saliva sampling) for getting genetically analysed by illumina®'s infinium assay microarray platform with fully customized 700,000 single nucleotide polymorphism kits. the result of this sampling will be data and statistically analysed in a genome-wide association study(gwas) manner by considering the 5x10-8 p.value and will be associated with each phenotypic parameter. accordingly, the study will assess the genetic risk stratification in icd patients in a much more detailed fashion. following this assessment genophenotypic statistical analysed will be done to combine both parameters and generate a formula for scoring the indicator factors based on each odds ratio. correspondingly, this new scaling formula will be analysed, verified and validated further by a randomized sampling of the population in our study before being stated. additionally, this study will not only help to improve current genetic polymorphism clinal significant status (pathogenicity and significance of variant) but also can associate new markers with high significance that can be directly used in clinical screening, diagnosis or clinical approaches.


Eligibility criteria:
inclusion criteria: * icd-implanted patients (both for primary and secondary intervention) * being a volunteer for the study * adequacy in understanding the study risks and accepting the informed consent form * official acceptance of the legal and official parents (both father and mother), if younger than 18 years old exclusion criteria: * the patient who does not volunteer to involve to the study. * diagnosis of underlying arrhythmogenic disease (structural heart disease, brugada, arrhythmogenic right ventricular dysplasia, etc.) * development of electric shock due to acute coronary syndrome * atrial fibrillation (afib) with rapid ventricular response * electric shock in patients with electrolyte imbalance-induced vt/vf * electric shock in a patient with acute myocarditis-induced ventricular arrhythmias * patients that had an electric shock because of pacing / atp ramp-induced vt (rv/crt pacing)

Keywords: implantable cardioverter defibrillators ventricular arrhythmia sudden cardiac death cardiogenomics cardiogenetics gwas genetic polymorphism