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 Towbin, G. Michael Vincent, Li Zhang, Ilan Goldenberg

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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 1 2011

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Long QT Syndrome
Heart Rate
Genotype
Romano-Ward Syndrome
Inborn Genetic Diseases
Sudden Cardiac Death
Heart Arrest
Proportional Hazards Models
Multivariate Analysis

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Barsheshet, A., Peterson, D. R., Moss, A. J., Schwartz, P. J., Kaufman, E. S., McNitt, S., ... 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

Genotype-specific QT correction for heart rate and the risk of life-threatening cardiac events in adolescents with congenital long-QT syndrome. / Barsheshet, Alon; Peterson, Derick R.; Moss, Arthur J.; Schwartz, Peter J.; Kaufman, Elizabeth S.; McNitt, Scott; Polonsky, Slava; Buber, Jonathan; Zareba, Wojciech; Robinson, Jennifer L.; Ackerman, Michael J.; Benhorin, Jesaia; Towbin, Jeffrey; Vincent, G. Michael; Zhang, Li; Goldenberg, Ilan.

In: Heart Rhythm, Vol. 8, No. 8, 01.08.2011, p. 1207-1213.

Research output: Contribution to journalArticle

Barsheshet, A, Peterson, DR, Moss, AJ, Schwartz, PJ, Kaufman, ES, McNitt, S, Polonsky, S, Buber, J, Zareba, W, Robinson, JL, Ackerman, MJ, Benhorin, J, Towbin, J, Vincent, GM, 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, vol. 8, no. 8, pp. 1207-1213. https://doi.org/10.1016/j.hrthm.2011.03.009
Barsheshet, Alon ; Peterson, Derick R. ; Moss, Arthur J. ; Schwartz, Peter J. ; Kaufman, Elizabeth S. ; McNitt, Scott ; Polonsky, Slava ; Buber, Jonathan ; Zareba, Wojciech ; Robinson, Jennifer L. ; Ackerman, Michael J. ; Benhorin, Jesaia ; Towbin, Jeffrey ; Vincent, G. Michael ; Zhang, Li ; Goldenberg, Ilan. / Genotype-specific QT correction for heart rate and the risk of life-threatening cardiac events in adolescents with congenital long-QT syndrome. In: Heart Rhythm. 2011 ; Vol. 8, No. 8. pp. 1207-1213.
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AU - Peterson, Derick R.

AU - Moss, Arthur J.

AU - Schwartz, Peter J.

AU - Kaufman, Elizabeth S.

AU - McNitt, Scott

AU - Polonsky, Slava

AU - Buber, Jonathan

AU - Zareba, Wojciech

AU - Robinson, Jennifer L.

AU - Ackerman, Michael J.

AU - Benhorin, Jesaia

AU - Towbin, Jeffrey

AU - Vincent, G. Michael

AU - Zhang, Li

AU - Goldenberg, Ilan

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N2 - 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.

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