Kertai, Miklos DJi, YunqiLi, Yi-JuMathew, Joseph PDaubert, James PPodgoreanu, Mihai VPEGASUS Investigative Team2024-01-112024-01-112016-040832-610X1496-8975https://hdl.handle.net/10161/29746<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>The results suggest a contribution of IL1β in modulating susceptibility to postoperative QTc prolongation after cardiac surgery.PEGASUS Investigative TeamHumansPostoperative ComplicationsElectrocardiographyCardiac Surgical ProceduresRisk FactorsProspective StudiesHaplotypesPolymorphism, Single NucleotideInterleukin-1betaJournal article