SUBJECT: Ph.D. Dissertation Defense
BY: Immanuel David Madukauwa David
TIME: Friday, March 29, 2019, 9:00 a.m.
TITLE: A Comprehensive Analysis of Potential Factors for Transcatheter Aortic Valve Thrombosis Risk
COMMITTEE: Dr. Ajit P. Yoganathan, Chair (BME)
Dr. Vasilis Babaliaros (Emory University, Medicine)
Dr. Rahul Sharma (Cedars Sinai Medical Center)
Dr. Wei Sun (BME)
Dr. John Oshinski (BME)
Dr. Cyrus Aidun (ME)


Transcatheter aortic valve replacement (TAVR) is indicated for aortic stenosis (AS) patients who are deemed intermediate or greater surgical risk. Recent evidence of leaflet thrombosis and reduced leaflet mobility in TAVR devices has led to concerns of stroke and long-term valve durability. Risk factors for thrombosis in TAVR patients remain poorly defined. While materials and blood chemistry are likely to be contributing factors to thrombosis risk, early clinical evidence and experimental data suggest that the fluid dynamic environment in the specific setting of the transcatheter aortic valve (TAV) is a major factor in the development of leaflet thrombosis. This environment can be altered by anatomical, procedural, and device related parameters. Additionally, it has been demonstrated that the thrombus originates in the “neo-sinus,” which is the pocket formed between the TAV leaflets and the native aortic valve leaflets. This study, organized in three parts, aimed to elucidate the contribution of anatomical, deployment, and fluid dynamic factors to a thrombogenic environment in the neo-sinus region of transcatheter aortic valves via analyses of clinical imaging data and a battery of in vitro experiments on select commercial TAVs and their replicas. The first segment of this study demonstrated that some aortic root anatomical dimensions and TAV deployment characteristics influence neo-sinus thrombus incidence and severity in TAVR patients as determined by an analysis of CT scans. In the second segment of this study, it was demonstrated by laser-induced fluorescence imaging that a higher implantation of the CoreValve improves neo-sinus fluid washout, and slight under-expansion of both the CoreValve and the SAPIEN 3 improve fluid washout of the region. Furthermore, these trends were replicated in a subset of experiments using an aortographic benchtop washout technique at normal and low cardiac outputs. An analysis of retrospective routinely-acquired clinical aortographic data confirmed the trend of TAV expansion yielding improved neo-sinus washout. This established aortography as a potential means of peri-procedurally evaluating TAVR patient flow-related thrombosis risk. The last segment of this study demonstrated that the TAV cusp most proximal to the native LCC has less flow stasis as a result of coronary flow in its vicinity compared to the TAV cusp proximal to the native NCC. This trend was seen in a supra-annular TAV replica and but not the intra-annular replica. This thesis work facilitated an understanding of how certain anatomical and TAV deployment characteristics influence neo-sinus thrombosis risk and severity particularly with respect to the Virchow’s triad factor, flow stasis. These findings may be instrumental in improving patient outcomes as device deployment criteria and device design are finetuned in the near future.