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QJM. 2007 Oct;100(10):609-15. Epub 2007 Sep 19.

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

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  • 1School of Pharmacy, University of Queensland, Brisbane, Australia.

Abstract

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.

PMID:
17881416
[PubMed - indexed for MEDLINE]
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