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Related Experiment Videos

Dynamic analysis of dofetilide-induced changes in ventricular repolarization

G Lande1, P Maison-Blanche, J Fayn

  • 1Department of Cardiology, Lariboisière Hospital, Paris, France.

Clinical Pharmacology and Therapeutics
|October 3, 1998
PubMed
Summary

Dofetilide prolongs QT intervals, with this effect decreasing at faster heart rates but persisting even at rapid heart rates. Dynamic electrocardiographic (ECG) techniques effectively detect these drug-induced repolarization changes.

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Area of Science:

  • Cardiology
  • Pharmacology
  • Electrophysiology

Background:

  • The impact of heart rate on QT prolongation caused by dofetilide, a Class III antiarrhythmic, is debated.
  • Understanding rate-dependent effects is crucial for assessing drug safety and efficacy.

Purpose of the Study:

  • To investigate how heart rate influences dofetilide-induced QT prolongation in healthy volunteers.
  • To evaluate the utility of dynamic electrocardiographic (ECG) techniques in detecting drug-induced repolarization changes.

Main Methods:

  • Ten healthy volunteers underwent 24-hour ECG recordings, with and without dofetilide administration.
  • QT interval versus R-R interval relationships were analyzed during high (Dh) and low (D1) dofetilide concentrations.
  • The slope of the QT-R-R relation served as an index for rate-dependent QT prolongation.

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Main Results:

  • Dofetilide caused a mean 12% increase in ventricular repolarization during high drug concentration (Dh).
  • QT prolongation exhibited reverse rate dependence, increasing with longer R-R cycles (slower heart rates).
  • Significant QT prolongation persisted even at a short R-R cycle of 600 ms.

Conclusions:

  • Dofetilide prolongs the QT interval, and this effect is partially modulated by heart rate.
  • The reverse rate dependence of dofetilide's effect is incomplete, with notable prolongation remaining at rapid heart rates.
  • Dynamic ECG analysis is a valuable tool for identifying subtle, drug-induced alterations in ventricular repolarization.