Chaos and the transition to ventricular fibrillation: A new approach to antiarrhythmic drug evaluation

James N. Weiss, Alan Garfinkel, Hrayr S. Karagueuzian, Zhilin Qu, Peng Sheng Chen

Research output: Contribution to journalReview article

239 Scopus citations

Abstract

Sudden cardiac death resulting from ventricular fibrillation can be separated into 2 components: initiation of tachycardia and degeneration of tachycardia to fibrillation. Clinical drug studies such as CAST and SWORD demonstrated that focusing exclusively on the first component is inadequate as a therapeutic modality. The hope for developing effective pharmacological therapy rests on a comprehensive understanding of the second component, the transition from tachycardia to fibrillation. We summarize evidence that the transition from tachycardia to fibrillation is a transition to spatiotemporal chaos, with similarities to the quasiperiodic transition to chaos seen in fluid turbulence. In this scenario, chaos results from the interaction of multiple causally independent oscillatory motions. Simulations in 2- dimensional cardiac tissue suggest that the destabilizing oscillatory motions during spiral-wave reentry arise from restitution properties of action potential duration and conduction velocity. The process of spiral-wave breakup in simulated cardiac tissue predicts remarkably well the sequence by which tachycardia degenerates to fibrillation in real cardiac tissue. Modifying action potential duration and conduction velocity restitution characteristics can prevent spiral-wave breakup in simulated cardiac tissue, suggesting that drugs with similar effects in real cardiac tissue may have antifibrillatory efficacy (the Restitution Hypothesis). If valid for the real heart, the Restitution Hypothesis will support a new paradigm for antiarrhythmic drug classification, incorporating an antifibrillatory profile based on effects on cardiac restitution and the traditional antitachycardia profile (classes 1 through 4).

Original languageEnglish (US)
Pages (from-to)2819-2826
Number of pages8
JournalCirculation
Volume99
Issue number21
DOIs
StatePublished - Jun 1 1999

Keywords

  • Arrhythmia
  • Death, sudden
  • Drugs
  • Dynamics
  • Fibrillation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Weiss, J. N., Garfinkel, A., Karagueuzian, H. S., Qu, Z., & Chen, P. S. (1999). Chaos and the transition to ventricular fibrillation: A new approach to antiarrhythmic drug evaluation. Circulation, 99(21), 2819-2826. https://doi.org/10.1161/01.CIR.99.21.2819