Genotype-specific QT correction for heart rate and the risk of life-threatening cardiac events in adolescents with congenital long-QT syndrome

Alon Barsheshet, Derick R. Peterson, Arthur J. Moss, Peter J. Schwartz, Elizabeth S. Kaufman, Scott McNitt, Slava Polonsky, Jonathan Buber, Wojciech Zareba, Jennifer L. Robinson, Michael J. Ackerman, Jesaia Benhorin, Jeffrey A. Towbin, G. Michael Vincent, Li Zhang, Ilan Goldenberg

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Background: A prolonged QT interval corrected for heart rate (QTc) is a major risk factor in patients with long QT syndrome (LQTS). However, heart raterelated risk in this genetic disorder differs among genotypes. Objective: This study hypothesized that risk assessment in LQTS patients should incorporate genotype-specific QT correction for heart rate. Methods: The independent contribution of 4 repolarization measures (the absolute QT interval, and Bazett's, Fridericia's, and Framingham's correction formulas) to the risk of aborted cardiac arrest or sudden cardiac death during adolescence, before and after further adjustment for the RR interval, was assessed in 727 LQTS type 1 and 582 LQTS type 2 patients. Improved QT/RR correction was calculated using a Cox model, dividing the coefficient on log(RR) by that on log(QT). Results: Multivariate analysis demonstrated that in LQTS type 1 patients 100-ms increments in the absolute QT interval were associated with a 3.3-fold increase in the risk of life-threatening cardiac events (P =.020), and 100-ms decrements in the RR interval were associated with a further 1.9-fold increase in the risk (P =.007), whereas in LQTS type 2 patients, resting heart rate was not a significant risk factor (hazard ratio 1.11; P =.51; P value for heart rate × genotype interaction =.036). Accordingly, analysis of an improved QT correction formula showed that patients with the LQTS type 1 genotype required a greater degree of QT correction for heart rate (improved QTc = QT/RR 0.8) than LQTS type 2 patients (improved QTc = QT/RR 0.2). Conclusion: Our findings suggest that risk stratification for life-threatening cardiac events in LQTS patients can be improved by incorporating genotype-specific QT correction for heart rate.

Original languageEnglish (US)
Pages (from-to)1207-1213
Number of pages7
JournalHeart rhythm
Volume8
Issue number8
DOIs
StatePublished - Aug 2011

Keywords

  • Aborted cardiac arrest
  • Heart rate
  • Long QT syndrome
  • QT correction
  • Risk factor
  • Sudden cardiac death

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Genotype-specific QT correction for heart rate and the risk of life-threatening cardiac events in adolescents with congenital long-QT syndrome'. Together they form a unique fingerprint.

  • Cite this

    Barsheshet, A., Peterson, D. R., Moss, A. J., Schwartz, P. J., Kaufman, E. S., McNitt, S., Polonsky, S., Buber, J., Zareba, W., Robinson, J. L., Ackerman, M. J., Benhorin, J., Towbin, J. A., Vincent, G. M., Zhang, L., & Goldenberg, I. (2011). Genotype-specific QT correction for heart rate and the risk of life-threatening cardiac events in adolescents with congenital long-QT syndrome. Heart rhythm, 8(8), 1207-1213. https://doi.org/10.1016/j.hrthm.2011.03.009