Burn it, stitch it, plug it… there are many ways to close a PFO: Insights into the challenges of medical device development

Our understanding of patent foramen ovale (PFO) closure in the prevention of recurrent stroke and in the treatment of migraine and decompression illness continues to evolve. The potential markets associated with stroke and migraine prevention have attracted interest in PFO closure by the medical device manufacturers and venture capitalists. The focus of their efforts have been primarily to provide devices that are safe and easy to deliver. Established medical device companies with experience with ASD closure devices (NMT Medical, Boston, MA and AGA Medical Corporation, Plymouth, MN) and more recently with abdominal aorta stent grafts (W.L. Gore & Associates, Flagstaff, AZ) as well as venture backed ‘‘start-up’’ companies (Velocimed/St. Jude Medical, St. Paul, MN, Coherex Medical, Salt Lake City, UT, and Cierra, Redwood City, CA) have taken on this challenge. In the vanguard of these efforts is Cierra, Inc., a venture backed start-up company founded to develop technology to close PFOs without the use of a permanent implant. As a practicing interventional cardiologist and a medical device entrepreneur, I have followed the development of these devices closely. The case of Cierra and its PFx RF PFO closure system illustrates many of the challenges encountered in the development of novel medical devices for new (and unproven) indications. Cierra emanated from The Foundry, a silicon valley incubator, managed by preeminent entrepreneurs and engineers, and backed by leading silicon valley venture capital firms [1]. Conceptually, the ability to ‘‘weld’’ the PFO shut is most appealing, in that it allows for PFO closure without leaving a permanent intracardiac implant behind. The Paradigm II Study, the results of which are reported in this edition of Catheterization and Cardiovascular Interventions is the culmination of these efforts [2]. The Paradigm II Study is a multicenter prospective series evaluating the PFx Device in 144 patients undergoing PFO closure for primarily stroke prevention as well as migraine prevention and decompression illness. Though not stated, it appears that this study was performed to support CE mark approval required for selling the PFx device in EU countries. The Cierra PFx is a novel and cleverly designed device, which is tracked over a guide wire placed across the PFO. The device is positioned in the right atrium, after which the interatrial septum is engaged by the use of suction. RF energy is then delivered via a predetermined algorithm, heating the tissue to close the PFO. The study demonstrated that the procedure could be performed with relative ease, engaging the interatrial septum and delivering energy with an acceptable safety profile. Unfortunately, at 6 months, closure was achieved in only 55% of cases. Further review indicates that when a second generation device was used to treat patients with smaller tunnels, a more acceptable closure rate of 73% was achieved. This rate, however, was still below published rates for leading closure devices [3]. The closure rate observed at 6 months indicates that further device development would be required for the Cierra PFx device to become a mainstay for PFO closure. As a start-up company without revenue, the Cierra would be required to raise additional funds to further refine and clinically validate a next generation device. Scanning the internet indicates that Cierra was not successful and has been forced to close down after 5 years of effort by an experienced team having 28 million dollars invested [4]. This case illustrates the challenges and risks associated with medical device development in general and highlights issues specific to the development of PFO closure devices. A reasonable question to ask is why