Genetic Biomarkers in the Risk Assessment of Sudden Cardiac Events: A Personalized Approach

ABSTRACT Sudden cardiac events are the leading cause of death worldwide. Conventional risk stratification methods, which largely depend on clinical history, imaging, and electrocardiography, are usually inadequate for identifying high‐risk individuals, especially those without visible structural heart disease. Through genetic testing, personalized medicine has been revolutionized by enabling the identification of single‐gene variants, population‐specific polymorphisms, and polygenic risk factors that promote susceptibility to arrhythmia. Inherited channelopathies, such as long QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia, as well as cardiomyopathies, are characterized by strong genotype–phenotype correlations, allowing more accurate prediction of arrhythmia risk. Single‐gene panels, whole‐exome sequencing (WES), whole‐genome sequencing (WGS), and polygenic risk scores (PRS) are not mutually exclusive; rather, they can be used together to enhance diagnostic yield and risk stratification. Screening of relatives of affected individuals enables the early identification of asymptomatic carriers. Moreover, the combination of clinical, imaging, and molecular data supports individualized risk assessment. The next steps emphasize the integration of multiomics, variant interpretation using artificial intelligence, and the creation of ancestry‐specific genetic repositories, which will facilitate predictive and preventive approaches to cardiology. This review describes current genetic testing approaches for sudden cardiac events, their use in personalized risk assessment, and the potential of personalized medicine to lower the risk of sudden cardiac death.