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Canadian Journal of Anesthesia/Journal canadien d'anesthésie
Published in: Canadian Journal of Anesthesia/Journal canadien d'anesthésie 4/2016

01-04-2016 | Reports of Original Investigations

Interleukin-1β gene variants are associated with QTc interval prolongation following cardiac surgery: a prospective observational study

Authors: Miklos D. Kertai, MD, PhD, Yunqi Ji, PhD, Yi-Ju Li, PhD, Joseph P. Mathew, MD, James P. Daubert, MD, Mihai V. Podgoreanu, MD, for the PEGASUS Investigative Team

Published in: Canadian Journal of Anesthesia/Journal canadien d'anesthésie | Issue 4/2016

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Abstract

Background

We characterized cardiac surgery-induced dynamic changes of the corrected QT (QTc) interval and tested the hypothesis that genetic factors are associated with perioperative QTc prolongation independent of clinical and procedural factors.

Methods

All study subjects were ascertained from a prospective study of patients who underwent elective cardiac surgery during August 1999 to April 2002. We defined a prolonged QTc interval as > 440 msec, measured from 24-hr pre- and postoperative 12-lead electrocardiograms. The association of 37 single nucleotide polymorphisms (SNPs) in 21 candidate genes –involved in modulating arrhythmia susceptibility pathways with postoperative QTc changes– was investigated in a two-stage design with a stage I cohort (n = 497) nested within a stage II cohort (n = 957). Empirical P values (Pemp) were obtained by permutation tests with 10,000 repeats.

Results

After adjusting for clinical and procedural risk factors, we selected four SNPs (P value range, 0.03-0.1) in stage I, which we then tested in the stage II cohort. Two functional SNPs in the pro-inflammatory cytokine interleukin-1β (IL1β), rs1143633 (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.53 to 0.95; Pemp = 0.02) and rs16944 (OR, 1.31; 95% CI, 1.01 to 1.70; Pemp = 0.04), remained independent predictors of postoperative QTc prolongation. The ability of a clinico-genetic model incorporating the two IL1B polymorphisms to classify patients at risk for developing prolonged postoperative QTc was superior to a clinical model alone, with a net reclassification improvement of 0.308 (P = 0.0003) and an integrated discrimination improvement of 0.02 (P = 0.000024).

Conclusion

The results suggest a contribution of IL1β in modulating susceptibility to postoperative QTc prolongation after cardiac surgery.
Appendix
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Metadata
Title
Interleukin-1β gene variants are associated with QTc interval prolongation following cardiac surgery: a prospective observational study
Authors
Miklos D. Kertai, MD, PhD
Yunqi Ji, PhD
Yi-Ju Li, PhD
Joseph P. Mathew, MD
James P. Daubert, MD
Mihai V. Podgoreanu, MD
for the PEGASUS Investigative Team
Publication date
01-04-2016
Publisher
Springer US
Published in
Canadian Journal of Anesthesia/Journal canadien d'anesthésie / Issue 4/2016
Print ISSN: 0832-610X
Electronic ISSN: 1496-8975
DOI
https://doi.org/10.1007/s12630-015-0576-8

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