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Electrocardiogram-based index for the assessment of drug-induced hERG potassium channel block

Laura Burattini1, Agnese Sbrollini1, Laura Scinocca1

  • 1Department of Information Engineering, Università Politecnica delle Marche, Ancona, Italy.

Journal of Electrocardiology
|November 5, 2021
PubMed

Insights

A new electrocardiogram (ECG) index, BECG(%), reliably assesses drug-induced hERG channel block. This non-invasive method evaluates cardiac repolarization changes, aiding in predicting potential drug risks.

Area of Science:

  • Cardiology
  • Pharmacology
  • Biophysics

Background:

  • Drug-induced block of the hERG potassium channel can lead to dangerous heart rhythm abnormalities like torsade de pointes.
  • Assessing this block non-invasively is crucial for drug safety and patient monitoring.

Purpose of the Study:

  • To develop and validate a novel, reliable index for non-invasive assessment of drug-induced hERG potassium channel block.
  • To utilize electrocardiographic T-wave features for this assessment.

Main Methods:

  • Measured early repolarization duration (ERD30%) and T-wave slope to amplitude ratio (TS/A) in 22 healthy subjects receiving hERG blockers.
  • Developed a regression model (BECG(%) = a·ERD30% + b·TS/A + c·ERD30%·TS/A + d) to predict hERG block.
  • Compared ECG-derived BECG(%) with plasma-based reference measurements (BREF(%)).

Main Results:

  • The regression model yielded specific coefficients (a=-561.0 s-1, b=-9.7 s, c=77.2, d=138.9).
  • In the testing dataset, a strong correlation (r=0.67, p < 10-81) was found between BECG(%) and BREF(%).
  • The estimation error was -11.5 ± 16.7%.

Conclusions:

  • The developed BECG(%) index is a reliable non-invasive tool for assessing drug-induced hERG potassium channel block.
  • This index is effective independently of concomitant blocks in other ion channels.
  • The findings support the use of ECG T-wave features for predicting drug-induced cardiac repolarization abnormalities.
Abstract

Keywords:
Cardiac repolarizationDrug safetyElectrocardiogramIon channel blockPredictionT wave

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