RISTRAD · Risk Stratification for Sudden Cardiac Death

Risk Stratification for Sudden Cardiac Death

Sudden cardiac death (SCD) is a leading cause of total and cardiovascular mortality with about 400 000 death per year in Western Europe. Ventricular fibrillation (VF) is the most common arrhythmia causing SCD. However as of today, the large gap in our knowledge concerning the determinants of VF at the genetic and molecular level hinders developing preventive strategies. In young individuals, SCD occurs primarily in the setting of rare cardiac disorders generally considered as Mendelian diseases. Among these are the primary electrical disorders associating lethal arrhythmias such as VF. These disorders are highly amenable to genetic studies since they manifest clinically with specific features on the electrocardiogram. They constitute then a powerful vector of genes and pathways discoveries allowing breakthroughs in the development of risk stratification and preventive strategies. As a model of a primary rhythm disorder, Brugada syndrome (BrS) may be considered as 'sensitized model' for SCD and be relevant to the broad problem of SCD in the setting of common cardiac pathologies. The aim of RISTRAD was to propose a translational study, combining genome wide association studies in the largest biobank of patients with cardiac arrhythmia ever collected, genotype-phenotype studies for clinical relevance/use and functional characterization for novel genes uncovered. The overarching aim of the study was identifying novel genetic factors associated with rare cardiac arrhythmia disorders and impacts much broader in the field by highlighting mechanisms underlying VF/SCD.In a previous genome wide association study (GWAS) led on 312 BrS cases only and we uncovered a large effect on the development of the disease by the accumulation within the genome of common genetic variants. The cumulative effect of the 3 loci on disease susceptibility was unexpectedly large with an odds ratio of 21.5 in the presence of more than 4 risk alleles versus less than 2.

Data: CORDIS, © European Union