The Best ECG Lead for Predicting the Risk of Drug-Induced Torsade De Pointes Using Corrected QT Interval: A Comparative Prognostic Study.

Abstract

Introduction: Torsade de pointes (TdP) is a deadly complication from drug-induced QT prolongation. Each of the 12 lead of an electrocardiogram (ECG) has a different length of QT interval, and thus might have a different performance in TdP prediction. This study aimed to determine the best ECG lead or set of leads in this regard.

Methods: This is a comparative prognostic accuracy study using a two-gate data gathering design. The population in this study was from two sources, a case group (Patients who had drug-induced TdP, which were identified through a systematic Medline search) and a control group (those who overdosed on QT-prolonging drugs, which included patients who were under the consultation of Medical Toxicology Services). The areas under the receiver operating characteristic curve (AUROC) of heart rate-corrected QT (QTc) in each single ECG lead and of a mean/median QTc from a set of ECG leads (17 index test) in predicting the risk of TdP were calculated and compared with each other, trying to find the best lead for this propose. QTc Interval measurements were done by four investigators (Interrater reliabilities 0.95).

Results: Finally, we included 136 and 148 ECGs from TdP cases and controls, respectively. V3 lead had the highest frequency of longest QTc interval, among the leads. The lead having the longest QTc yielded the greatest AUROC in predicting TdP regardless of QT correction formulas (QTcFRA=0.9915, QTcRTH=0.9893, QTcBZT=0.9904). The mean QTc of 3 leads (lead II, plus any two of leads V2-V4), and a median QTc of 6 leads (I, II, aVF, V2, V4, V6) provided similar overall performance for TdP prediction (regardless of the type of QTc formula).

Conclusion: The longest QTc provided the greatest AUROC in predicting drug-induced TdP, however, the longest QTc is not located in a fixed individual lead in any patient. A less time-consuming method with comparable performance to that of the longest QTc was to use a mean QTc from 3 leads (lead II, plus any two of leads V2-V4). The potential clinical impact of this finding needs to be verified in a prospective cohort study.