The Genetic Basis of Sudden Cardiac Death: From Diagnosis to Emerging Genetic Therapies

Annu Rev Med. 2025 Jan;76(1):283-299. doi: 10.1146/annurev-med-042423-042903. Epub 2025 Jan 16.

Abstract

Sudden cardiac death (SCD) is an abrupt, tragic manifestation of a number of cardiovascular diseases, primarily ion channelopathies and heritable cardiomyopathies. Because these diseases are heritable, genetics play a key role in the diagnosis and management of SCD-predisposing diseases. Historically, genetics have been used to confirm a diagnosis and identify at-risk family members, but a deeper understanding of the genetic causes of SCD could pave the way for individualized therapy, early risk detection, and a transformative shift toward genetically informed therapies. This review focuses on the evolving genetic landscape of SCD-predisposing diseases, the current state of gene therapy and therapeutic development, and the promise of using predictive genetics to identify individuals at risk of SCD.

Keywords: cardiomyopathy; channelopathy; gene therapy; genetics; sudden cardiac death; therapeutics.

Publication types

  • Review

MeSH terms

  • Brugada Syndrome / diagnosis
  • Brugada Syndrome / genetics
  • Brugada Syndrome / therapy
  • Cardiomyopathies / complications
  • Cardiomyopathies / diagnosis
  • Cardiomyopathies / genetics
  • Cardiomyopathies / therapy
  • Channelopathies / genetics
  • Death, Sudden, Cardiac* / etiology
  • Death, Sudden, Cardiac* / prevention & control
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Genetic Therapy* / methods
  • Humans
  • Long QT Syndrome / diagnosis
  • Long QT Syndrome / genetics
  • Long QT Syndrome / therapy