Global electrical heterogeneity associated with drug-induced torsades de pointes

Heart Rhythm. 2021 Jan;18(1):57-62. doi: 10.1016/j.hrthm.2020.07.038. Epub 2020 Aug 8.


Background: Drugs belonging to diverse therapeutic classes can prolong myocardial refractoriness or slow conduction. These drugs may be effective and well-tolerated, but the risk of sudden cardiac death from torsades de pointes (TdP) remains a major concern. The corrected QT interval has significant limitations when used for risk stratification. Measurement of global electrical heterogeneity (GEH) could help identify the substrate vulnerable to drug-induced ventricular arrhythmias.

Objective: The purpose of this study was to improve risk stratification for drug-induced TdP by measuring GEH on the electrocardiogram (ECG).

Methods: We analyzed ECG data from a case-control study of patients with a history of drug-induced TdP as well as age- and sex-matched controls. Vectorcardiograms were constructed from ECGs. GEH was measured via the spatial ventricular gradient (SVG) vector (magnitude, azimuth, and elevation). Log odds coefficients for TdP were estimated using multivariable logistic regression.

Results: Among 17 cases (47% male; age 58.9 ± 12.5 years) and 17 controls (29% male; age 61.0 ± 12.2 years), 34 ECGs were analyzed. SVG azimuth was significantly different between cases and controls (3.4 vs 22.0 degrees, respectively; P = 0.02). After adjusting for sex and QTc interval, odds of TdP increased by a factor of 3.2 for each 1 SD change in SVG azimuth from the control group mean (95% confidence interval 1.07-9.14; P = .04). QTc was not significant in the multivariable analysis (P = .20).

Conclusion: SVG azimuth is correlated with a history of drug-induced TdP independent of QTc. GEH measurement may help identify patients at high risk for drug-induced arrhythmias.

Keywords: Antiarrhythmic drugs; Electrical heterogeneity; Electrocardiography; Sudden cardiac death; Torsades de pointes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-Arrhythmia Agents / adverse effects*
  • Case-Control Studies
  • Death, Sudden, Cardiac / epidemiology*
  • Electrocardiography / drug effects*
  • Female
  • Heart Rate / drug effects*
  • Heart Ventricles / physiopathology
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Torsades de Pointes / chemically induced*
  • Torsades de Pointes / complications
  • Torsades de Pointes / physiopathology
  • United States / epidemiology


  • Anti-Arrhythmia Agents