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.