Drug-induced QT prolongation and torsades de pointes: evaluation of a QT nomogram

Background: Although QT prolongation is associated with increased risk of torsade de pointes (TdP), the precise relationship is not well defined. Aim: To evaluate the performance of a QT nomogram in assessing the risk of TdP from QT–RR combinations. Design: Systematic review. Methods: We systematically searched MEDLINE/EMBASE for cases of drug-induced TdP. Controls were patients taking non-cardiotoxic drugs in overdose. Inclusion criteria were definite TdP, normal ECG before or after the event, association with a drug/toxin and QT–RR measurements available. The upper bound of a QT–RR cloud diagram developed from human preclinical studies was converted into a QT nomogram [QT vs. heart rate (HR)]. QT–HR combinations for TdP cases and controls were plotted with the QT nomogram, and curves corresponding to a QTc = 440 ms and QTc = 500 ms for comparison (Bazett's correction). Results: We identified 129 cases of TdP. TdP cases occurred at lower HR values with longer QT intervals, with most cases occurring at HR 30–90 bpm. Controls were more evenly distributed, with HR 40–160 bpm. The sensitivity and specificity of the QT nomogram were 96.9% (95%CI 93.9–99.9) and 98.7% (95%CI 96.8–100), respectively. For Bazett QTc = 440 ms, sensitivity and specificity were 98.5% (95%CI 96.3–100) and 66.7% (95%CI 58.6–74.7), respectively, whereas for Bazett QTc =500 ms they were 93.8% (95%CI 89.6–98.0) and 97.2% (95%CI 94.3–100), respectively. Discussion: The QT nomogram is a clinically relevant risk assessment tool that accurately predicts arrhythmogenic risk for drug-induced QT prolongation. Further prospective evaluation of the nomogram is needed.