RESCUED (REgistry for Sudden Cardiac and UnExpected Death): the German registry for families affected by sudden cardiac death in the young

Abstract

Abstract Background Sudden cardiac death in the young (SCDY) refers to an abrupt and unexpected cardiac arrest at a young age due to an underlying cardiac cause. Previous studies have shown that estimated more than 10% of SCDY victims 1 to 35 years of age suffered from a – previously often undiagnosed – rare genetic cardiac disorder. Due to the inheritability of such sequence variations in disease-causing cardiac genes, blood relatives of the deceased may equally be carriers of the causative genetic variation and therefore have an increased risk for cardiac arrhythmia. Purpose Despite sudden cardiac death (SCD) increasingly gaining global awareness, systematic data collection in form of registries is sparse. The data sets collected in the RESCUED registry allow for the identification of leading causes of SCDY in Germany and offer unique opportunities for further scientific analyses with the aim of revealing unrecognized trends, risk factors and clinical warning signs of SCDY. Methods Our workflows are based on international guidelines for post mortem examination of SCDY victims and clinical assessment of their relatives. Post-mortem assessment of the index patient includes autopsy, histology, toxicology, genetic testing and review of pre-mortem clinical data. Biological relatives within the family of the index patient undergo a cardiogenetic consultation, a set of cardiological examinations and a cascade genetic screening to determine each individual´s cardiac risk profile. Data is recorded in the registry through the web-based interface of the OSSE registry software (Open Source Registry System for Rare Diseases). Results Based on our experience with complex cases of SCD (over 150 SCDY cases and more than 450 relatives) and an in-depth literature research regarding SCD registries, we have developed designated questionnaires for systematic data collection for the deceased index patient and their biological relatives, respectively. We will present insights from the design of this registry, which represents a novel, pedigree-based approach to SCDY as a consequence of a possible underlying genetic cause, and offers a new viewing angle of identifying a possible cause of SCDY. For illustrational purposes, two SCDY cases including clinical data of the family members will be shown. Conclusions RESCUED is Germany´s first registry with a holistic, pedigree-based approach to SCDY. Apart from thoroughly documenting the cardiac deaths of young individuals under the age of 50, the phenotypes of their relatives are equally recorded. Ultimately, insights gained from the RESCUED registry will lead to improved and targeted diagnostic possibilities, risk stratification and, if need be, therapy in susceptible individuals, working towards the prevention of tragic deaths in affected families. The registry will also give insights into possible preceding warning signs and symptoms of SCDY regardless of whether the underlying cause is a rare genetic disease or not.