Prevention of life threating arrythmias in relatives of cardiac arrest survivors; results of family cascade screening in a representative cohort in Czech Republic

Cardiac arrest (CA) is often the very first sign of an inherited cardiomyopathy or arrhythmic syndrome. The detailed cardiogenetic work up in CA survivors may contribute to individualized therapy in patients and lead to prevention of life threating arrythmias in their relatives.

To assess the molecular architecture of non-ischemic CA in a representative cohort in Czech Republic and test the effectiveness of a family cascade screening.

Between 2013 and 2023 we ascertained 221 non ischemic SCA survivors (137 M / 84 F), age at cardiac arrest 36±16 years. The initial clinical diagnosis in SCA were mostly idiopathic ventricular fibrillation (iVF 120 – 54%), followed by cardiomyopathy or arrhythmic syndrome. Genetic counselling and next generation sequencing of 100 – 5500 genes (Sophia Genetics, Switzerland) were performed. The family cascade screening was carried out in 514 (2,3 per case) relatives, in order to detect their risk of the disease.

Very likely or certain molecular aetiology (i.e. based on presence of ACMG.net Class 4 to 5 variants) was disclosed in 60/221 (27%) of CASs. Most frequently identified genes were PKP2 (12/60 cases), RYR2 (7/60), KCNH2 (7/60) and SCN5A (7/60). Clinical and/or genetic diagnosis of inherited condition was detected in 134/514 (26%) relatives, where 30/134 were already under medical care for heart failure and/or ventricular arrhythmia of unknown aetiology. ICD was implanted in 3 cases after careful risk stratification.

Relatives of Czech CASs have mostly interest in family cascade screening. It led to identification of potentially lethal condition in 26% of them and allowed so the prevention of cardiac arrest. Our results further underline a role of genetic analysis in diagnostic work up in non-ischemic cardiac arrest and even in iVF as cause of cardiac arrest.