Implantable Unpinning Termination Therapy for Cardiac Arrhythmias

Project Summary/Abstract We propose the development and evaluation of a novel implantable low-energy device, using an innovative low-energy multi-pulse therapy, to achieve well-tolerated treatment of ventricular and atrial tachyarrhythmias. Ventricular arrhythmias (VAs) including ventricular tachycardia (VT) and ventricular fibrillation (VF) are responsible for 75-80% of Sudden Cardiac Death (SCD) cases. Sudden cardiac death kills nearly 450,000 Americans yearly. In the majority of these patients, the most common initial arrhythmia is sustained VT which can degrade into VF. A high-energy biphasic shock delivered by an implantable cardiac defibrillator (ICD) is the only existing therapy to terminate VA when low-energy anti-tachycardia pacing fails. These high energy shocks are associated with increased mortality and severe pain. Similarly, atrial fibrillation (AF), an atrial tachyarrhythmia, is a global epidemic. Approximately 33.5 million individuals are affected worldwide and close to 5 million new cases occur each year costing the US healthcare system between $6 and $26 billion annually. AF is a progressive disease with many patients first developing paroxysmal atrial fibrillation (PAF). Left untreated, PAF can progress to persistent or permanent AF. Because of rapid changes in the atria after AF onset, a therapy to treat AF soon after onset may slow the progressive nature of AF. There exists great enthusiasm in the medical community for AF interventions due to the limited efficacy of current treatments and risks to the patients. An effective atrial defibrillator was previously developed; however, it was abandoned due to pain associated with shocks and rapid battery depletion as a high number of high-energy shocks had to be delivered. A well-tolerated, low-energy, device-based VA and AF therapy without high-energy shocks would address a major unmet medical need. Prior canine and early stage acute human studies with a non- implantable version of the proposed system have observed that the proposed therapy approach significantly lowers the energy required for effective VT and AF therapy into ranges that have been reported as tolerated by patients. The goal of this proposed phase IIB project is to develop and test a fully implantable prototype low- energy therapy device for use in future chronic human studies under IDE exemption involving treatment of VT and AF.