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

Sudden cardiac death resulting from ventricular fibrillation can be separat ed into 2 components: initiation of tachycardia and degeneration of tachyca rdia to fibrillation. Clinical drug studies such as CAST and SWORD demonstr ated that focusing exclusively on the first component is inadequate as a th erapeutic modality. The hope for developing effective pharmacological thera py rests on a comprehensive understanding of the second component, the tran sition from tachycardia to fibrillation. We summarize evidence that the tra nsition from tachycardia to fibrillation is a transition to spatiotemporal chaos, with similarities to the quasiperiodic transition to chaos seen in f luid turbulence. In this scenario, chaos results from the interaction of mu ltiple causally independent oscillatory motions. Simulations in 2-dimension al 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 sim ulated cardiac tissue predicts remarkably well the sequence by which tachyc ardia 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 dr ugs with similar effects in real cardiac tissue may have antifibrillatory e fficacy (the Restitution Hypothesis). If valid for the real heart, the Rest itution Hypothesis will support a new paradigm for antiarrhythmic drug clas sification, incorporating an antifibrillatory profile based on effects on c ardiac restitution and the traditional antitachycardia profile (classes 1 t hrough 4).