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Sudden cardiac arrest in young individuals is often caused by ventricular fibrillation (VF). When a cardiac arrest is not treated immediately, it almost always leads to death. In recent years, many causes of cardiac arrest have been identified. In the majority of patients who survive a cardiac arrest, a complete diagnostic work-up can determine the underlying cause of VF. However, in approximately 5% of patients, the cause remains unknown despite extensive diagnostic evaluation. These patients are diagnosed with idiopathic VF.

This thesis focuses on identifying previously unknown or unrecognized substrates in patients with idiopathic VF. Using various approaches, ranging from genetic testing to multiple imaging modalities, potential substrates are investigated. When VF can be explained, targeted treatment becomes possible, potentially preventing recurrences. In addition, family screening can be initiated to assess the risk of sudden cardiac death in relatives. The steps taken to move closer to identifying a substrate and ultimately a possible diagnosis are described in this thesis.