Genetic and Phenotypic Characterization of Community Hospital Patients With QT Prolongation

J Am Heart Assoc. 2018 Aug 21;7(16):e009706. doi: 10.1161/JAHA.118.009706.

Abstract

Background Congenital long- QT syndrome ( LQTS ) is a genetic disorder characterized by prolongation of the corrected QT interval ( QT c) on an ECG . The aim of the present study was to estimate the prevalence of pathogenic and likely pathogenic sequence variants in patients who had at least 1 ECG with a QT c ≥500 ms. Methods and Results Telemark Hospital Trust is a community hospital within the Norwegian national health system, serving ≈173 000 inhabitants. We searched the ECG database at Telemark Hospital Trust, Norway, from January 2004 to December 2014, and identified 1531 patients with at least 1 ECG with a QT c ≥500 ms. At the time of inclusion in this study (2015), 766 patients were alive. A total of 733 patients were invited to participate, and 475 accepted. The 17 genes that have been reported to cause monogenic LQTS were sequenced among the patients. Pro- QT c score was calculated for each patient. A molecular genetic cause of LQTS was detected in 31 (6.5%) of 475 patients. These patients had a lower pro- QT c score than those without pathogenic or likely pathogenic variants (1.7±1.0 versus 2.8±1.6; P<0.001). Conclusions Compared with the general population, hospitalized patients with a QT c ≥500 ms in at least 1 ECG recording had an increased likelihood for pathogenic and likely pathogenic variants in LQTS genes. We recommend increased awareness of the possibility of LQTS in patients with at least 1 ECG with a QT c ≥500 ms.

Keywords: genetic testing; inherited arrhythmia; long‐QT syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cardiac Conduction System Disease / diagnosis
  • Cardiac Conduction System Disease / genetics
  • ERG1 Potassium Channel / genetics*
  • Electrocardiography
  • Female
  • Genotype
  • Hospitalization
  • Hospitals, Community
  • Humans
  • KCNQ1 Potassium Channel / genetics*
  • Long QT Syndrome / diagnosis
  • Long QT Syndrome / epidemiology
  • Long QT Syndrome / genetics*
  • Male
  • Middle Aged
  • NAV1.5 Voltage-Gated Sodium Channel / genetics*
  • Norway
  • Phenotype

Substances

  • ERG1 Potassium Channel
  • KCNH2 protein, human
  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human
  • NAV1.5 Voltage-Gated Sodium Channel
  • SCN5A protein, human