Fig. 18.1
The Coherex FlatStent
Following completion of the Coherex EU Study, the FlatStent received CE Mark approval in 2009 and initiated a limited commercial launch with its corporate partner Abbott Vascular [15–17]. The Abbott distribution deal was signed shortly before the CLOSURE I Trial demonstrated a lack of efficacy. Faced with a contracting OUS market, the FlatStent gained only modest sales traction.
The Coherex US Regulatory plan focused on chronic migraine. Coherex recognized the enrollment failures of MIST, ESCAPE, and PREMIUM but nevertheless felt migraine to represent a tremendous unmet clinical need with compelling bedside observations of diminished migraine symptoms following PFO closure. Coherex engaged numerous migraine neurology key opinion leaders who suggested that the chronic migraine population would be more appropriate for evaluation than the episodic migraine population of the failed PFO trials. Coherex received conditional IDE approval to initiate the RESPONDER Trial for chronic migraine in 2010. However, in light of the numerous failures in the migraine space, Coherex was unable to secure funding to initiate the RESPONDER Trial. Coherex stopped manufacturing and supporting the FlatStent and turned its attention to the WaveCrest Left Atrial Appendage Occluder.
Nitinol Devices and Components (NDC): SeptRx IPO
The SeptRx IPO (intrapocket occluder) PFO closure device has a self-expanding Nitinol frame that is designed to be contained within the PFO tunnel. Two flexible anchor struts originate from the distal aspect of the device and are designed to uncoil from their curved shape to anchor along the left atrial PFO opening while adapting to a variety of PFO tunnel lengths. Additional anchors at the base of the device are designed to expand on the right atrial side of the PFO. The anchors are wrapped with tantalum for radiopacity. The device is delivered over a wire. The initial feasibility data demonstrated excellent closure, procedural and long-term safety [18]. NDC initially received funding from Cordis/Johnson and Johnson (JNJ) to develop the SeptRx device. As the PFO market collapsed, SeptRx along with the others lost its financial backing including from JNJ. The SeptRx management reorganized SeptRX independent from NDC and recently completed the InterSEPT Trial. While published results of InterSEPT are anticipated soon, SeptRx is no longer funding device development or commercial sales.
Cierra (Pfx Closure System)
The PFx Closure System developed by Cierra (Redwood City, CA) is a unique device designed to close a PFO without leaving a permanent implant behind. The device uses monopolar radio frequency energy to “weld” the septum primum to the septum secundum. The device is passed over a wire, opened in the right atrium and pushed until it contacts the right atrial wall. Suction is applied to hold the right atrial surface of the PFO against the energy delivery face. The company demonstrated clinical success, particularly in smaller PFOs [19]. However, faced with a contracting market outside the United States and without a clear US regulatory strategy, Cierra halted development and clinical testing of the Pfx closure system prior to obtaining CE Mark and beginning commercialization.
Coaptus: The Coaptus Radiofrequency PFO Closure System
Coaptus was created with the goal of closing PFOs through radiofrequency energy. The initial RF system applied suction to the right atrial wall of the PFO and then applied RF energy to weld the septum primum to the septum secundum with promising results in animals [20]. However, the results in humans with this initial system were less consistent. Coaptus designed a second generation system that punctured the septum primum and septum secundum in a plane perpendicular to the PFO tunnel. A rivet-like device was then deployed with dual functions of riveting the PFO closed and serving as a means of delivering bipolar energy. With this novel device, energy delivery both welded tissue and induced rapid device endothelialization. Coaptus halted development of clinical testing prior to obtaining CE Mark and commercializing their radiofrequency PFO closure system.
Sutura: HeartStitch/NobleStitch
Sutura (Fountain Valley, CA) initially developed the SuperStitch vascular suturing system to for use during open surgery and catheter-based procedures. They received CE Mark approval with an indication for vascular stitching in general surgery, including endoscopic procedures. The system was adapted for closure of the PFO first as the HeartStitch and then as the NobleStitch, leaving only standard surgical 4-0 polypropolene sutures in the interatrial septum. The first human implants, performed in 2007 demonstrated the device and technique to be safe and effective in smaller PFOs [21]. The device received an expanded CE Mark indication for cardiovascular suturing and PFO closure in 2012. The Sutura/HeartStitch technology has more recently been applied to closure of the left ventricular apex following transapical aortic valve replacement and is being investigated as a means of performing mitral valve edge to edge repair.
Conclusion
The potential markets of PFO closure including migraine, stroke, and sleep apnea induced the medical device industry to investigate PFO specific device alternatives to the ASD indicated devices. The medical device community further recognized the unique PFO anatomy consisting of two overlapping walls as an opportunity for a minimally invasive solution. Many of the novel PFO specific devices developed during the brief period of PFO enthusiasm demonstrated clinical efficacy, albeit in relatively small, nonrandomized series of patients. Each of these novel devices ultimately failed, primarily due to the lack of a regulatory pathway in the United States and the contracting market for PFO closure outside of the United States. The ease of use and clinical efficacy of the double disk devices proved to provide stiff competition. The clinical utility of PFO closure with the novel devices as well as the relative safety and efficacy compared with the double disk devices was never tested and remains unknown. Should the RESPECT Trial lead to a US indication for PFO closure or should the PREMIUM Trial demonstrate efficacy in the reduction of migraine following PFO closure, there may be a resurgent interest in the PFO specific devices.
