Drug induced QT prolongation: the measurement and assessment of the QT interval in clinical practice

Abstract

There has been an increasing focus on drug induced QT prolongation including research on drug development and QT prolongation, following the removal of drugs due to torsades de pointes (TdP). Although this has improved our understanding of drug-induced QT prolongation there has been much less research aimed at helping clinicians assess risk in individual patients with drug induced QT prolongation. This review will focus on assessment of drug-induced QT prolongation in clinical practice using a simple risk assessment approach. Accurate measurement of the QT interval is best done manually, and not using the measurement of standard ECG machines. Correction for heart rate (HR) using correction formulae such as Bazett's is often inaccurate. These formulae underestimate and overestimate the duration of cardiac repolarization at low and high heart rates, respectively. Numerous cut-offs have been suggested as an indicator of an abnormal QT, but are problematic in clinical practice. An alternative approach is the QT nomogram which is a plot of QT vs. HR. The nomogram has an 'at risk' line and QT-HR pairs above this line have been shown in a systematic study to be associated with TdP and the line is more sensitive and specific than Bazett's QTc of 440 ms or 500 ms. Plotting the QT-HR pair for patients on drugs suspected or known to cause QT prolongation allows assessment of the QT interval based on normal population QT variability. This risk assessment then allows the safer commencement of drugs therapeutically or management of drug induced effects in overdose.

Figure 1

Standard 12-lead ECG of a valproate overdose showing QT prolongation of 560 ms by manual measurement but the automatic measurement is 422 ms

Figure 2

The QT nomogram developed by Chan et al. The nomogram line separates HR,QT pairs above the line associated with an increased risk of torsades de pointes compared with those below the line

Figure 3

Plots of QT vs. heart rate on the QT nomogram for a control group of patients taking overdoses of drugs that do not affect the QT interval (paracetamol, diazepam, oxazepam and temazepam) (A), 10 patients given intramuscular droperidol for sedation where multiple ECGs were recorded over a period of 6 to 24 h using a 12-lead Holter recorder (B), 83 patients taking an amisulpride overdose including six who developed TdP (crosses) (C) and 260 patients taking a quetiapine overdose (D)

Figure 4

Recommended approach when commencing drugs that are known to prolong the QT interval