Unexplained Sudden Cardiac Arrest and Sudden Cardiac Death in the Young: What is Killing These Young People When Nothing is Found?

Unexplained sudden cardiac arrest (SCA) and sudden cardiac death (SCD) in the young remains a critical issue for clinicians, researchers, patients and their family members. In this review, we explore the current status of SCA and SCD evaluation in the young, including recent monogenic and polygenic disease discoveries, advancements in cardiac imaging and our growing understanding of the role of the Purkinje system in triggering life threatening and even fatal ventricular arrhythmias. Yet, despite these advancements, over a third of SCA and SCD among individuals with seemingly structurally normal hearts remain unexplained. We explore the future role of artificial intelligence, novel biomarkers, multimodality cardiac imaging, genetic discoveries, as well as wearable devices and sensors in closing this current gap. With the overarching framework provided in this review, we envision a future in which collaboration among patients, clinicians, researchers, innovators, and policy makers culminates in our ability to diagnose, predict, and ultimately prevent SCA and SCD in the young.