Electrocardiographic measures of repolarization heterogeneity are not predictive for Torsades de Pointes among undifferentiated patients with prolonged QTc: A case control study

Abstract

Introduction Torsades de Pointes (TdP) is a potentially lethal polymorphic ventricular tachydysrhythmia associated with and caused by prolonged myocardial repolarization. However, prediction of TdP is challenging. We sought to determine if electrocardiographic myocardial repolarization heterogeneity is necessary and predictive of TdP. Methods We performed a case control study of TdP at a large urban hospital. We identified cases based on a hospital center electrocardiogram (ECG) database search for tracings from 1/2005 to 6/2019 with heart rate corrected QT (QTc) > 500, QRS < 120, and heart rate (HR) < 60, and a subsequent natural language search of electronic health records for the terms: TdP, polymorphic ventricular tachycardia, sudden cardiac death, and relevant variants. Controls were drawn in a 2:1 ratio to cases from a similar pool of ECGs, and matching for QTc, heart rate, sex, and age. We abstracted historical, laboratory, and ECG data using detailed written instructions and an electronic database. We included a second blinded data abstractor to test data abstraction and manual ECG measurement reliability. We used General Electric (GE) QT Guard software for automated repolarization measurements. We compared groups using unpaired statistics. Results We included 75 cases and 150 controls. The number of current QTc prolonging medications and serum electrolytes were substantially the same between the two groups. We found no significant difference in measures of QT or T wave repolarization heterogeneity. Conclusion Electrocardiographic repolarization heterogeneity is not greater in otherwise unselected patients with QTc prolongation who suffer TdP and does not appear predictive of TdP. However, previous observations suggest specific repolarization characteristics may be useful for defined patient subgroups at risk for TdP.

Long QT begets long QT

“…Lessons to be learned from the present study . The important take‐home message from the present study 8 is that once a definitely long QT is identified, telling apart patients who will develop torsade‐de‐pointes, from those who will not, is difficult. This is in agreement with observations made in the large azimilide‐studies alluded before 12 : Although the risk of torsade‐de‐pointes increased significantly once the QTc increased above 500 ms and augmented sharply once the QTc reached 580 ms, the majority of patients with torsade had QTc below these values whereas a significant proportion of patients without torsade developed QTc values above those limits 12 …”

“…The authors then focused on ECG parameters, like T peak – T end , the interval from the peak to the end of the T‐wave (an accepted surrogate from increased dispersion of repolarization), 11 focusing also on T‐wave morphology. None of these ECG parameters were useful for telling apart patients with torsade‐de‐pointes from patients with comparable, yet uneventful, severe QT‐prolongation 8 . The number of patients studied was small (75 patients vs. 150 controls); accordingly, the absence of predictive value for the ECG parameters tested, may reflect insufficient statistical power.…”

“…Finally, Marril et al observed that as many as 1:3 of all patients with torsade‐de‐pointes received amiodarone as treatment for this arrhythmia. Since amiodarone is contraindicated in the LQTS, this finding suggests that the correct diagnosis was initially missed 8 . As recently reviewed elsewhere, 18 numerous forms of “look‐alike” polymorphic ventricular tachyarrhythmias exist.…”

“…Even today, telling apart LQTS‐patients who will develop QT‐related arrhythmias (torsade‐de‐pointes), from those who will remain asymptomatic, remains challenging. In this issue of the Journal, Marril et al demonstrate that some of the electrocardiographic (ECG) parameters accepted as high‐risk markers for imminent torsade‐de‐pointes, are not as reliable as expected 8 …”

“…In contrast to previous studies looking at potential predictors of torsades, 9,10 patients and controls in the present study were matched for age, gender, and heart rate. Importantly, they were also purposedly matched by their QT‐interval duration 8 . The authors then focused on ECG parameters, like T peak – T end , the interval from the peak to the end of the T‐wave (an accepted surrogate from increased dispersion of repolarization), 11 focusing also on T‐wave morphology.…”