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 QT c 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.

Citalopram Overdose: a Fatal Case

“…Thus the development of TdP more than 24 h into the overdose is not surprising. Assessment of QT prolongation and TdP risk, however, is complex and controversial, with Bazett's formula, which was applied here, tending to overestimate TdP risk at higher heart rates and to underestimate the risk at low heart rates [15]. A QT interval nomogram to correct for this tendency has been developed [15].…”

“…Assessment of QT prolongation and TdP risk, however, is complex and controversial, with Bazett's formula, which was applied here, tending to overestimate TdP risk at higher heart rates and to underestimate the risk at low heart rates [15]. A QT interval nomogram to correct for this tendency has been developed [15]. Although the TdP risk by this nomogram appears to be less than that by Bazett's formula, it was still increased during the time preceding her arrhythmic event.…”

Risk assessment of drug-induced QT prolongation

“…1 Most of this research has been conducted by the pharmaceutical industry and has arisen following market withdrawals of medicines that caused torsades de pointes arrhythmia, such as cisapride and some non-sedating antihistamines. Little of this information has flowed to clinicians and there remains a paucity of clinically relevant data to guide patient management.…”

“…Methods of measuring the QT interval, correcting for heart rate and determining what is an abnormal interval are outdated and provide a poor risk assessment for patients. 1 Confusion also remains about the safety and level of risk with many drugs that have been associated with QT prolongation. Genetics account for a large amount of the variability in the QT interval in healthy individuals.…”

“…Genetics account for a large amount of the variability in the QT interval in healthy individuals. 1,5 This may explain why some individuals are more predisposed to QT prolongation. Physiological factors also influence the QT interval.…”