Plexisyl-AF™: Kit for the Prevention of Post-Operative Atrial Fibrillation

Post-operative atrial fibrillation is the most common and significant complication of more than 1 million annual cardiothoracic surgery procedures such as coronary bypass grafts and aortic heart valve repairs. Post-operative atrial fibrillation occurs in 20-40% of coronary bypass and 60% of heart valve repair patients. Its occurrence is associated with worse morbidity and longer intensive-care hospitalization. To illustrate, according to various studies, the hospitalization time of bypass patients who experience atrial fibrillation is increased by an average of 2-4 days that are not reimbursed to the hospital. The economic impact of this prolongation exceeds $900 million per year in the United States alone. Aside from the economic impact, patients with persistent post-operative atrial fibrillation have significantly higher risk of stroke and other cardiovascular complications.

Post-operative atrial fibrillation is considered a vexing problem and the last, major unresolved complication of cardiothoracic surgeries. The onset of clinically relevant atrial fibrillation cannot be predicted in individual patients; advanced age is the only generally accepted predictor.

Post-operative atrial fibrillation is an abnormal irregular heart rhythm where apparently random electrical signals are generated throughout the upper chambers (atria) of the heart. While the precise mechanisms of this process are not well-defined, the surgical procedure triggers an initial imbalance in the cardiac autonomic nerve system. This initial imbalance causes different areas of the atrial tissue to become uncoordinated in their conductivity; some are excitable and some are refractory. This disturbance then leads to multiple reentrant pathways for the impulses that regulate heart rhythm. Atrial fibrillation ensues.

Watch the Plexisyl-AF™ Videos

Surgical procedure demonstrating 1^st-generation product

Prophylaxis for post-operative atrial fibrillation.

Research conducted by Symphony Medical and its scientific advisors indicates that the trigger of persistent and clinically relevant post-operative atrial fibrillation stems from the vagus nerve which plays a key role in the autonomic nerve system. The vagus innervates the Sinoatrial node, an area located in the right atrium of the heart that functions as the impulse generator or pacemaker for the heart. The company’s technology targets the autonomic nerve network and provides a protective, fully-reversible isolation or parasympathectomy of the vagal input to the heart.

To accomplish this protective isolation, during the cardiothoracic surgical procedure, a biopolymer is injected into two areas of the atrium termed epicardial fat pads. These fat pads are distinct structures that act as critical relays in the highly complex neural network mediated by the vagus and the Sinoatrial node. The biopolymer polymerizes upon injection to neutralize the fat pad conduction pathways but it eventually dissolves and is bioadsorbed within 10 to 14 days, leaving behind no visible effects. However, during the period that it is present, it removes the alleged trigger for persistent atrial fibrillation.

Symphony Medical's kit for the prevention of post-operative atrial fibrillation includes three proprietary components. In addition to the biopolymer mentioned above, the kit includes a disposable two-channel applicator and a disposable hand-held electrical stimulation device used to accurately detect the precise location of the injections. The biopolymer does not include any animal-derived components and is supplied to Symphony Medical under an exclusive licensing arrangement. The biopolymer is currently approved for other surgical uses in numerous countries including the United States and the European Union.

The Kit offers the following advantages:

• Easy to use by the surgeon during the operation because the precise detection of the injection locations and the injections themselves take up only a few minutes.
• Pinpoint efficacy because the mechanism of action targets specifically the parasympathetic nerve input thought to be responsible for clinically relevant and persistent post-operative atrial fibrillation.
• Effective only during the critical period after the operation when clinically relevant and persistent post-operative atrial fibrillation occurs; the biopolymer degrades and adsorbs safely without altering the cardiac tissue.
• Safety backed by the inertness and extensive evaluation of Symphony Medical's biopolymer of choice in this and in other medical applications.

The biopolymer utilized in Symphony Medical's Kit for the prevention of post-operative atrial fibrillation has been evaluated extensively to maximize its conduction-isolating effect before biodegrading quickly and safely. In 2005 and 2006, the Company engaged in two safety clinical trials to establish the feasibility and safety of the procedure using a human plasma-sourced biopolymer that is approved for other surgical uses in numerous countries including the United States and the European Union. This first generation product confirmed the simplicity of use, was exceptionally well tolerated by patients, and showed discernable activity in most patients.

In parallel, however, through extensive additional testing, Symphony Medical identified and continued developing a next-generation biopolymer with significantly enhanced properties as shown in physical and preclinical testing. This inert material does not contain human-sourced materials and is considered a device rather than a biologic-device combination product. The Company is now concluding preclinical testing and expects to initiate the clinical evaluation phase in the U.S. and in Europe in the first quarter of 2008.