Multistage Defibrillation Therapy

Cardiac defibrillation through high-energy shocks has remained the most effective life-saving intervention in ventricular arrhythmias. Historically, the pain associated with high-energy shocks has impeded its use in cardioverting atrial fibrillation (AF) through an implantable device in ambulant patients. The advent of optical mapping of arrhythmia mechanisms over the last 30 years has led to a more in-depth understanding of defibrillation mechanisms and to the discovery that low-energy shocks can generate virtual electrode polarizations (VEP) throughout the captured myocardium due to a heterogeneous spread of transmembrane potentials post-shock. VEP have been shown to generate new wavefronts that collide with and extinguish fibrillatory activity. Multiple closely coupled low-energy defibrillation shocks delivered in stages through atrial and coronary sinus defibrillation leads, the so-called multistage defibrillation therapy or multipulse therapy (MPT), have been shown to terminate AF in preclinical animal studies with energies below the pain threshold. MPT generates successive new VEP-induced wavefronts that collide with and eventually extinguishing all fibrillation wavefronts in stages. Multipulse therapy has been shown to be efficacious in reducing AF burden in preclinical animal studies and is now being tested as a potential therapeutic option in reducing AF burden in a clinical study.