Unpinning Termination Therapy for Ventricular Tachyarrhythmias

Project Summary Abstract Sudden cardiac death is a major cause of death around the worldwith nearlysudden deaths per year in the United StatesVentricular fibrillationVFis the most frequent direct causeThe most common strategy for terminating VF is with a singlelargebiphasic high energyHEelectric shock by an implantable cardiac defibrillatorICDDespite their effectivenessthere have been increasing concerns with current ICD highenergy therapydue to cardiac tissue damage likely a result of high voltage shocks and pain caused by inappropriate shocksRedesign and optimization of shock waveforms is critical for developing a low energy defibrillator that will be more acceptable to patients and cliniciansWe aim to develop implantable low energy defibrillators to address unmet needs for treating cardiac rhythm disordersThevirtual electrode polarizationVEPconcept has been proposed as a mechanism responsible for termination of atrial fibrillationAFand demonstrated in experimental optical mapping studies in vitro and in vivoRecent canine studies and human results have revealed that Unpinning TerminationUPTtherapy for atrial fibrillation significantly lowers the energy required for atrial defibrillationMechanistically it is explained asunpinning of reentrant wave fronts that maintain AFpreventing re pinning of wave fronts to tissue heterogeneitiessuch as scarsandannihilating remaining wave fronts not self extinguishedThe unpinning stage uses multiple pulses to unpin the reentry from the stabilizing resistive heterogeneityThe applied electric field creates stronger VEP at tissue heterogeneitieswhich causes excitation and then unpinning of the reentryMore recent animal findings from Cardialen s Phase I STTR project indicate that UPT therapy is also highly effective as ventricular tachycardiaVTtherapyTo deliver and test this novel method clinicallyan efficient cardioverter system is proposed in this Phase II SBIR projectFollowing development of this systemthis Phase II SBIR project aims to confirm that UPT therapy can terminate ATP refractory VT and VF with low energy in humansIt is anticipated that the proposed new study in humans will confirm fundamentally important insights into the hypothesis that multiple phased low energy shocks can safely terminate ventricular tachycardia and ventricular fibrillationWe expect the study will be a big step forward from theVEP and unpinningtheory to ventricular defibrillator clinical developmentIf the enhanced research UPT therapy system is proven effective and safe for terminating ventricular tachyarrhythmiasit should advance commercial product development of low energy multiple pulse implantable defibrillator devices and will also encourage a higher percentage of eligible patients to consider this life saving treatment