Sinus node function and ventricular repolarization during exercise stress test in long QT syndrome patients with KvLQT1 and HERG potassium channel defects

J Am Coll Cardiol. 1999 Sep;34(3):823-9. doi: 10.1016/s0735-1097(99)00255-7.


Objectives: This study was performed to evaluate the QT interval and heart rate responses to exercise and recovery in gene and mutation type-specific subgroups of long QT syndrome (LQTS) patients.

Background: Reduced heart rate and repolarization abnormalities are encountered among long QT syndrome (LQTS) patients. The most common types of LQTS are LQT1 and LQT2.

Methods: An exercise stress test was performed in 23 patients with a pore region mutation and in 22 patients with a C-terminal end mutation of the cardiac potassium channel gene causing LQT1 type of long QT syndrome (KVLQT1 gene), as well as in 20 patients with mutations of the cardiac potassium channel gene causing LQT2 type of long QT syndrome (HERG gene) and in 33 healthy relatives. The QT intervals were measured on electrocardiograms at rest and during and after exercise. QT intervals were compared at similar heart rates, and rate adaptation of QT was studied as QT/heart rate slopes.

Results: In contrast to the LQT2 patients, achieved maximum heart rate was decreased in both LQT1 patient groups, being only 76 +/- 5% of predicted in patients with pore region mutation of KvLQT1. The QT/heart rate slopes were significantly steeper in LQT2 patients than in controls during exercise. During recovery, the QT/heart rate slopes were steeper in all LQTS groups than in controls, signifying that QT intervals lengthened excessively when heart rate decreased. At heart rates of 110 or 100 beats/min during recovery, all LQT1 patients and 89% of LQT2 patients had QT intervals longer than any of the controls.

Conclusions: LQT1 is associated with diminished chronotropic response and exaggerated prolongation of QT interval after exercise. LQT2 patients differ from LQT1 patients by having marked QT interval shortening and normal heart rate response to exercise. Observing QT duration during recovery enhances the clinical diagnosis of these LQTS types.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cation Transport Proteins*
  • Child
  • DNA-Binding Proteins*
  • ERG1 Potassium Channel
  • Electrocardiography / methods
  • Electrocardiography / statistics & numerical data
  • Ether-A-Go-Go Potassium Channels
  • Exercise / physiology*
  • Exercise Test / methods
  • Exercise Test / statistics & numerical data
  • Female
  • Heart Ventricles / physiopathology
  • Humans
  • KCNQ Potassium Channels
  • KCNQ1 Potassium Channel
  • Long QT Syndrome / diagnosis
  • Long QT Syndrome / genetics
  • Long QT Syndrome / physiopathology*
  • Male
  • Middle Aged
  • Mutation / genetics
  • Mutation / physiology
  • Potassium Channels / genetics
  • Potassium Channels / physiology*
  • Potassium Channels, Voltage-Gated*
  • Sinoatrial Node / physiopathology*
  • Statistics, Nonparametric
  • Trans-Activators*
  • Transcriptional Regulator ERG


  • Cation Transport Proteins
  • DNA-Binding Proteins
  • ERG protein, human
  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels
  • KCNH2 protein, human
  • KCNH6 protein, human
  • KCNQ Potassium Channels
  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Trans-Activators
  • Transcriptional Regulator ERG