Controlling the complex spatio-temporal dynamics underlying life-threatening cardiac arrhythmias such as fibrillation is extremely difficult due to the nonlinear interaction of excitation waves within a heterogeneous anatomical substrate1–4. Lacking a better strategy, strong, globally resetting electrical shocks remain the only reliable treatment for cardiac fibrillation5–7. Here, we establish the relation between the response of the tissue to an electric field and the spatial distribution of heterogeneities of the scale-free coronary vascular structure. We show that in response to a pulsed electric field E, these heterogeneities serve as nucleation sites for the generation of intramural electrical waves with a source density ρ(E), and a characteristic time τ for tissue depolarization that obeys a power law τ∝Eα. These intramural wave sources permit targeting of electrical turbulence near the cores of the vortices of electrical activity that drive complex fibrillatory dynamics. We show in vitro that simultaneous and direct access to multiple vortex cores results in rapid synchronization of cardiac tissue and therefore efficient termination of fibrillation. Using this novel control strategy, we demonstrate, for the first time, low-energy termination of fibrillation in vivo. Our results give new insights into the mechanisms and dynamics underlying the control of spatio-temporal chaos in heterogeneous excitable media and at the same time provide new research perspectives towards alternative, life-saving low-energy defibrillation techniques.
Background-Electrically based therapies for terminating atrial fibrillation (AF) currently fall into 2 categories:antitachycardia pacing and cardioversion. Antitachycardia pacing uses low-intensity pacing stimuli delivered via a single electrode and is effective for terminating slower tachycardias but is less effective for treating AF. In contrast, cardioversion uses a single high-voltage shock to terminate AF reliably, but the voltages required produce undesirable side effects, including tissue damage and pain. We propose a new method to terminate AF called far-field antifibrillation pacing, which delivers a short train of low-intensity electric pulses at the frequency of antitachycardia pacing but from field electrodes. Prior theoretical work has suggested that this approach can create a large number of activation sites ("virtual" electrodes) that emit propagating waves within the tissue without implanting physical electrodes and thereby may be more effective than point-source stimulation. Methods and Results-Using optical mapping in isolated perfused canine atrial preparations, we show that a series of pulses at low field strength (0.9 to 1.4 V/cm) is sufficient to entrain and subsequently extinguish AF with a success rate of 93% (69 of 74 trials in 8 preparations). We further demonstrate that the mechanism behind far-field antifibrillation pacing success is the generation of wave emission sites within the tissue by the applied electric field, which entrains the tissue as the field is pulsed. Conclusions-AF in our model can be terminated by far-field antifibrillation pacing with only 13% of the energy required for cardioversion. Further studies are needed to determine whether this marked reduction in energy can increase the effectiveness and safety of terminating atrial tachyarrhythmias clinically. Key Words: arrhythmia Ⅲ atrium Ⅲ cardioversion Ⅲ fibrillation Ⅲ mapping A trial fibrillation (AF) is the most common sustained cardiac arrhythmia worldwide, 1 affecting Ͼ2.2 million people in the United States alone. 2 Complications associated with chronic AF include increased risk for both thromboembolism and stroke. 2 Left untreated, paroxysmal AF often progresses to permanent AF, which is resistant to therapy. 3 Although underlying anatomic or pathophysiological factors may fuel this progression, 3 AF itself may lead to its own perpetuation through electric, structural, and metabolic remodeling of atrial tissue. The realization that AF begets AF 4 has led to management strategies that are designed to avoid the progression of AF by reducing the frequency and duration of AF episodes. Clinical Perspective on p 476One such strategy, cardioversion, attempts to reset all electric activity in the atria and requires the use of large (Ͼ5 V/cm) electric field gradients. 5-7 These high energies cause pain and trauma for the patient, damage the myocardium, and reduce battery life in implanted devices. 8 Another strategy, antitachycardia pacing (ATP), seeks to avoid the development of permanent AF by suppressing paroxysmal A...
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