Sudden cardiac arrest in patients without overt heart disease: a limited value of next generation sequencing

Pol Arch Intern Med. 2018 Dec 21;128(12):721-730. doi: 10.20452/pamw.4366. Epub 2018 Nov 7.

Abstract

INTRODUCTION Unexplained sudden cardiac arrest (SCA), occurs in up to 10% of patients and is often attributed to an inherited arrhythmia syndrome. Family screening and genetic testing may help clarify the cause of unexplained SCA. OBJECTIVES We aimed to assess the usefulness of clinical evaluation and genetic testing in patients after unexplained SCA and in their families. PATIENTS AND METHODS In the years 2014-2017, we studied 44 unrelated patients after unexplained SCA and 96 of their relatives. All patients and relatives underwent comprehensive cardiac evaluation. In 31 patients with SCA, next generation sequencing (NGS) was performed. The Kaplan-Meier survival curve was constructed to compare the event-free survival depending on clinical diagnosis or genotype. An adverse event was defined as an adequate implantable cardioverter-defibrillator discharge. RESULTS Based on the clinical evaluation, diagnosis was established in 39% of probands (long QT syndrome 21%; short QT syndrome 7%; Brugada syndrome 7%; catecholaminergic polymorphic ventricular tachycardia, 2%; and early repolarization syndrome, 2%). Ventricular arrhythmia was identified in the relatives of 19% of probands. In 18 of the 31 probands (54.8%), 23 rare gene variants were identified, of which only 2 were classified as pathogenic. The event-free survival over a median of 4.5 years was similar in patients with or without clinical diagnosis and in carriers and noncarriers of a rare genetic variant. CONCLUSIONS This study shows the significance of an extensive clinical assessment in unexplained SCA victims and their relatives. Routine genetic testing by NGS has low diagnostic and prognostic value.

MeSH terms

  • Adult
  • Aged
  • Arrhythmogenic Right Ventricular Dysplasia / genetics
  • Brugada Syndrome / genetics
  • Death, Sudden, Cardiac / etiology
  • Death, Sudden, Cardiac / pathology*
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Long QT Syndrome / genetics
  • Male
  • Middle Aged
  • Pedigree*
  • Tachycardia, Ventricular / genetics

Supplementary concepts

  • Polymorphic catecholergic ventricular tachycardia