Delayed QT Prolongation: Derivation of a Novel Risk Factor for Adverse Cardiovascular Events from Acute Drug Overdose

Introduction: In ED patients with acute drug overdose involving prescription medication and/or substances of abuse, severe QTc prolongation (> 500 ms) is predictive of adverse cardiovascular events (ACVE), defined as myocardial injury, ventricular dysrhythmia, shock, or cardiac arrest. However, it is unclear whether delayed severe QTc prolongation (dsQTp) is a risk factor for ACVE and if specific clinical factors are associated with occurrence of dsQTp. Methods: A secondary analysis of a prospective cohort of consecutive adult ED patients with acute drug overdose was performed on patients with initial QTc < 500 ms. The predictor variable, dsQTp, was defined as initial QTc < 500 ms followed by repeat QTc ≥ 500 ms. The primary outcome was occurrence of ACVE. Multivariable logistic regression was performed to test whether dsQTp was an independent predictor of ACVE and to derive clinical factors associated with dsQTp. Results: Of 2311 patients screened, 1648 patients were included. The dsQTp group (N = 27) was older than the control group (N = 1621) (51.6 vs 40.2, p < 0.001) and had a higher number of drug exposures (2.92 vs 2.16, p = 0.003). Following adjustment for age, sex, race/ethnicity, number of exposures, serum potassium, and opioid exposure, dsQTp remained an independent predictor of ACVE (aOR: 12.44, p < 0.0001). Clinical factors associated with dsQTp were age > 45 years and polydrug (≥ 3) overdoses. Conclusion: In this large secondary analysis of ED patients with acute drug overdose, dsQTp was an independent risk factor for in-hospital occurrence of ACVE.