Heart Rhythm
Volume 8, Issue 8 , Pages 1207-1213, August 2011

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

  • Alon Barsheshet, MD

      Affiliations

    • Cardiology Division, University of Rochester Medical Center, Rochester, New York
    • Corresponding Author InformationAddress reprint requests and correspondence: Dr. Alon Barsheshet, Heart Research Follow-up Program, Box 653, University of Rochester Medical Center, Rochester, NY 14642
    • ,
  • Derick R. Peterson, PhD

      Affiliations

    • Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, New York
    • ,
  • Arthur J. Moss, MD

      Affiliations

    • Cardiology Division, University of Rochester Medical Center, Rochester, New York
    • ,
  • Peter J. Schwartz, MD

      Affiliations

    • Department of Lung, Blood, and Heart, University of Pavia, Pavia, Italy; Department of Cardiology, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy; Laboratory of Cardiovascular Genetics, IRCCS Istituto Auxologico Italiano, Milan, Italy; Department of Family and Community Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
    • ,
  • Elizabeth S. Kaufman, MD

      Affiliations

    • Heart and Vascular Research Center, MetroHealth Campus of Case Western Reserve University, Cleveland, Ohio
    • ,
  • Scott McNitt, MS

      Affiliations

    • Cardiology Division, University of Rochester Medical Center, Rochester, New York
    • ,
  • Slava Polonsky, MS

      Affiliations

    • Cardiology Division, University of Rochester Medical Center, Rochester, New York
    • ,
  • Jonathan Buber, MD

      Affiliations

    • Cardiology Division, University of Rochester Medical Center, Rochester, New York
    • ,
  • Wojciech Zareba, MD, PhD

      Affiliations

    • Cardiology Division, University of Rochester Medical Center, Rochester, New York
    • ,
  • Jennifer L. Robinson, MS

      Affiliations

    • Cardiology Division, University of Rochester Medical Center, Rochester, New York
    • ,
  • Michael J. Ackerman, MD

      Affiliations

    • Department of Pediatrics, Division of Pediatric Cardiology, Mayo Clinic, Rochester, Minnesota
    • ,
  • Jesaia Benhorin, MD

      Affiliations

    • Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
    • ,
  • Jeffrey A. Towbin, MD

      Affiliations

    • Department of Pediatrics, University of Cincinnati Children's Hospital, Cincinnati, Ohio
    • ,
  • G. Michael Vincent, MD

      Affiliations

    • LDS Hospital, Salt Lake City, Utah
    • ,
  • Li Zhang, MD

      Affiliations

    • LDS Hospital, Salt Lake City, Utah
    • ,
  • Ilan Goldenberg, MD

      Affiliations

    • Cardiology Division, University of Rochester Medical Center, Rochester, New York

Received 11 November 2010; accepted 3 March 2011. published online 11 March 2011.

Background

A prolonged QT interval corrected for heart rate (QTc) is a major risk factor in patients with long QT syndrome (LQTS). However, heart rate–related 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/RR0.8) than LQTS type 2 patients (improved QTc = QT/RR0.2).

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.

Keywords: Aborted cardiac arrest, Heart rate, Long QT syndrome, QT correction, Risk factor, Sudden cardiac death

Abbreviations: ACA, aborted cardiac arrest, ECG, electrocardiogram, HR, hazard ratio, LQTS, long QT syndrome, LQT1, long QT syndrome type 1, LQT2, long QT syndrome type 2, QTc, corrected QT interval, SCD, sudden cardiac death

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 This work was supported in part by research grants HL-33843 and HL-51618 to the University of Rochester Medical Center from the National Institutes of Health, Bethesda, Maryland. Dr. Moss reports receiving a research grant from GeneDx; Dr. Kaufman received research grants from CardioDx and St. Jude Medical. Dr. Ackerman has a consulting relationship and license agreement/royalty arrangement with PGxHealth and received consultant fees from Medtronic, Biotronik, Boston Scientific, and St Jude Medical. This research was carried out while Dr. Alon Barsheshet was a Mirowski-Moss Career Development Awardee at the University of Rochester Medical Center, Rochester, New York.

PII: S1547-5271(11)00276-1

doi:10.1016/j.hrthm.2011.03.009

Heart Rhythm
Volume 8, Issue 8 , Pages 1207-1213, August 2011

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