Electrocardiographic Predictors of Torsadogenic Risk During Dofetilide or Sotalol Initiation: Utility of a Novel T Wave Analysis Program

Abstract

Introduction: Initiation of class III anti-arrhythmic medications requires telemetric monitoring for ventricular arrhythmias and QT prolongation to reduce the risk of torsades de pointes (TdP). Heart rate-corrected QT interval (QTc) is an indicator of risk, however it is imperfect, and subtle abnormalities of repolarization have been linked with arrhythmogenesis.

Purpose: Identification of electrocardiographic predictors of torsadogenic risk through the application of a novel T wave analysis tool.

Methods: Among all patients admitted to Mayo Clinic for initiation of dofetilide or sotalol, we identified 13 cases who developed drug-induced TdP and 26 age and sex matched controls that did not develop TdP. The immediate pre-TdP ECG of those with TdP was compared to the last ECG performed prior to hospital discharge in controls using a novel T wave program that quantified subtle changes in T wave morphology.

Results: The QTc and 12 T wave parameters successfully distinguished TdP cases from controls. The top performing parameters were the QTc in lead V3 (mean case vs control 480 vs 420 msec, p < 0.001, r = 0.72) and T wave right slope in lead I (mean case vs control -840.29 vs -1668.71 mV/s, p = 0.002, r = 0.45). The addition of T wave right slope to QTc improved prediction accuracy from 79 to 88 %.

Conclusion: Our data demonstrate that, in addition to QTc, the T wave right slope is correlated strongly with TdP risk. This suggests that a computer-based repolarization measurement tool that integrates additional data beyond the QTc may identify patients with the greatest torsadogenic potential.

Keywords: Class III antiarrhythmics; Electrocardiography; Risk stratification; T wave analysis; Torsade de pointes.

Figure 1

ROC classification of the ECG features A. ROC curve for QTc, AUC= 0.8096 B. ROC curve for T wave right slope. AUC =0.6442 C. ROC curve for QTc and T wave right slope. AUC =0.8750 Comparison of mean values of Lead V3 - QTc and Lead I - T wave right slope, cases vs controls. This is data analysed from the ECG closest to the Tdp event (case) or dismissal (control)

Figure 1

ROC classification of the ECG features A. ROC curve for QTc, AUC= 0.8096 B. ROC curve for T wave right slope. AUC =0.6442 C. ROC curve for QTc and T wave right slope. AUC =0.8750 Comparison of mean values of Lead V3 - QTc and Lead I - T wave right slope, cases vs controls. This is data analysed from the ECG closest to the Tdp event (case) or dismissal (control)

Figure 2

ECG average tracings and box plots. Above, QTc (synchronised by Q wave), below T wave right slope (synchronised by T wave)

Figure 3

A - ECG from Tdp case. This highlights a shallow T wave right slope, especially visible in Lead I (when compared to ECG of age and sex match control of Figure 3 B) B - ECG from age and sex matched control. Note the T wave right slope is steeper when compared to Figure 3A (Tdp case).

Figure 3

A - ECG from Tdp case. This highlights a shallow T wave right slope, especially visible in Lead I (when compared to ECG of age and sex match control of Figure 3 B) B - ECG from age and sex matched control. Note the T wave right slope is steeper when compared to Figure 3A (Tdp case).