The medical device development ecosystem: Current regulatory state and challenges for future development: A review.

BACKGROUND/PURPOSE: There has been increasing emphasis on the development of new technology to mitigate unmet clinical needs in cardiovascular disease. This emphasis results in part from recognition that many devices, although being initially developed in the United States, were studied, and then eventually approved abroad before being returned to the U.S. for clinical application. The FDA (Food and Drug Administration) guidance document on Early Feasibility Studies (EFS) and then the 21st Century Cures Act from 2013 to 2016 focused on these issues. MATERIALS/METHODS: There are multiple components of medical device translational pathways to be considered in continuing to reach the goal of providing early access to safe and effective products to the U.S. POPULATION: This review article documents the various stages from early idea innovation to device design and iteration to clinical testing and then potential approval and application in the wide clinical practice of cardiovascular health care. RESULTS: The CDRH (Centers for Devices and Radiological Health) has focused on key components including EFS, Breakthrough Devices Program, Total Product Life Cycle, the Unique Device Identification Program, the establishment of a Digital Health Center of Excellence, and leveraging Collaborative Communities. Each of these initiatives focuses on improving the Medical Device Development Ecosystem. CONCLUSIONS: Major changes in device translational research have improved the device research climate in the United States. Goals remain including increased training and education for constituencies aspiring to work in the field of device development and regulation as part of a continuous health care learning system.

Transapical endovascular implantation of neochordae using a suction and suture device.

OBJECTIVE: Neochordae implantation is a standard method for treatment of mitral valve prolapse. We describe a transcatheter technology enabling transapical endovascular chordal implantation. METHODS: Six adult pigs were anesthetized. Two 10F sheaths were introduced in the femoral vessels for monitoring and intracardiac echo. After midline sternotomy, the pericardium was opened, the apex was punctured inside two 2-0 polypropylene purse strings. A 0.035 in J tipped guidewire was introduced in the left ventricle and an ultra stiff 14F sheath (guide catheter) inserted through the apex. A suction-and-suture device was introduced in the left ventricle. The mitral valve was crossed under echo guidance. Using suction, either the anterior (two cases) or posterior (four cases) leaflet was captured and a loop of 4-0 polypropylene was thrown at the edge of the leaflet. The loop, with a pledget, was exteriorized through the introducer. The introducer was removed and the purse-string tied. Under echo guidance, the neochordae suture was pulled and tied over a pledget to evoke leaflet tethering. The animals were sacrificed and gross anatomy reviewed. RESULTS: Leaflet capture was feasible in the intended location in all cases. Following suture tethering, variable degrees of MR were obtained. At gross anatomy, the neochordae were positioned at 1-4mm from the leaflet free edge, and were firmly attached to the leaflets. CONCLUSIONS: Transcatheter endovascular neochordae implantation is feasible. A prolapse model is needed to further demonstrate feasibility under pathologic conditions. The apical approach allows easy and direct route to transcatheter beating heart minimally invasive mitral repair.

Evolving strategies for the treatment of valvular heart disease: Preclinical and clinical pathways for percutaneous aortic valve replacement.

To decrease the morbidity associated with conventional surgery for calcific aortic stenosis, there has been increasing interest in catheter-based treatment using a stent or frame mounted bioprosthetic valve. Critical to its success is knowledge of pathoanatomy, risk of embolization of calcific debris, and issues associated with device anchoring and paravalvular leaks. In the absence of a chronic animal model of aortic stenosis, development of a catheter-based device has been an iterative process based on experimental and early clinical data gathered abroad, where marketing may be permitted with less clinical data than required in the United States. This process has persuaded many companies to circumvent the time delays occasioned by the FDA regulatory validation of iterative design changes by performing initial studies outside the United States. Because percutaneous aortic valve replacement is considered a Class III device, premarket approval, including defining the patient population, inclusion and exclusion criteria, control population, and interpretable clinical endpoints, is required. In the early clinical experience, percutaneous aortic valve replacement has been directed at high-risk patients who were considered "very poor" or "non-surgical" candidates. Defining and identifying patients for the clinical trial may be challenging, in part because of the difficult selection of an appropriate control group, e.g., conventional aortic valve replacement, best medical management, and/or balloon valvuloplasty.