Research Funding

Project Summary Valvular heart disease is an important health problem afflicting over 2.5% of the US population and catheter- based therapies to address it have advanced significantly in recent years. While surgical repair remains the gold standard, the reduced risk of catheter-based interventions has provided the ability to intervene earlier in the disease process and in patients too sick for surgery while avoiding the risks of cardiopulmonary bypass. A significant limitation of these procedures, however, is that they do not provide the capability to remove native tissue and previously implanted devices to tailor the anatomy to receive a new prosthetic device. For example, transcatheter valves rely on displacing the diseased valve leaflets rather than removing them. In transcatheter aortic valve replacement, the displaced leaflets can obstruct blood flow to the coronary arteries and prevent access for subsequent coronary interventions. In transcatheter mitral valve replacement, the na

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