The Genomic basis of Unexplained Cardiac Arrest: The GenUCA Investigators (joint funding with DZHK and DHF)

Unexplained cardiac arrest (UCA) accounts for 5-7% of out-of-hospital cardiac arrests.

There are three sub-phenotypes currently recognised: Early Repolarisation Syndrome; Short-Coupled Torsades de Pointes/Ventricular Fibrillation (VF); and idiopathic VF.

Underlying arrhythmia mechanisms are diverse and include delayed depolarisation, premature repolarisation; and/or triggered activity, the causes of which are unknown although there is genetic susceptibility.

We will leverage existing international collaborations to gather the largest single cohort of UCA survivors for whole genome sequencing and association studies to identify underlying rare and common variation.

We will correlate genetic findings with dynamic heart rate related and autonomic ECG parameters on 12 lead 24-hour ambulatory ECG monitoring to clarify underlying mechanisms.

We will study novel genetic associations in mouse and human induced pluripotent stem cell derived cardiomyocyte models to understand their molecular basis and identify druggable targets for future research. We aim to improve patient categorisation, risk prediction management and therapeutics.