Research Funding

PROJECT SUMMARY Our long-term goal is to specify how patient-specific blood cell activities become altered in transcatheter aortic valve replacement (TAVR) in order to optimize the management of patients with aortic valve diseases. The objective of this application is to determine how patient-specific hematological, physiological and procedural factors promote platelet-driven procoagulant and inflammatory complications in TAVR. Our central hypothesis is that patient-specific biochemical and blood flow features in TAVR support the activation of platelet signaling responses, which promote procoagulant platelet generation and responses underlying transcatheter heart valve (THV) complications and degeneration. This hypothesis is rooted in our preliminary data that: 1) activated platelets adhere to THVs in vivo in a manner related to subclinical leaflet thrombosis (SLT); 2) GPVI-mediated platelet procoagulant signaling responses and fibrin formation are upregulated in TAVR patients; 3) pati

Project Summary/Abstract Approximately 12.4% of patients >75 years of age have aortic stenosis (AS) and 3.4% have severe AS. Transcatheter aortic valve replacement (TAVR) has emerged as a safe and effective therapeutic option for patients with symptomatic severe AS. More than 50,000 TAVRs are now performed annually across >500 hospitals in the United States (US). Despite stringent patient selection criteria and standardized procedural techniques, there remains significant hospital variation in outcomes, including mortality, morbidity, and readmissions, following TAVR in the US. However, the reasons underlying hospital variation in TAVR outcomes remain poorly understood. Identifying organizational practices and processes of care associated with better outcomes is critical to improve the overall outcomes of patients undergoing TAVR. The overarching objective of this proposal is to perform a mixed methods study using a positive deviance approach to understand determinants of hospital vari

DESCRIPTION (provided by applicant): Transcatheter aortic valve implantation (TAVI) is a minimally invasive approach to valve replacement that has had a rapid and profound clinical impact. Less than ten years after the first human use of a TAVI device, nearly 20,000 patients annually receive these novel devices. Today, this clinical population is limited to older, sicker patients who cannot tolerate an open surgical procedure. While commercially available TAVI devices demonstrate excellent survival rates, the large size of these 'first generation' devices drives a high rate (20- 30%) of serious complications. Accordingly, the primary design objective for improved second generation devices is a reduction in device diameter. The majority of the crossing profile (diameter) comes from the cusps themselves, which are comprised of relatively thick pericardium derived from animal sources. Thus a reduction in cusp thickness would have a dramatic impact on patient outcomes (decreased strok