Master of Sciences, Case Western Reserve University, 2021, Clinical Research

We compared the safety and efficacy of balloon aortic valvuloplasty (BAV) across a range of presentations including critical illness in an intensive care unit (ICU), heart failure hospitalization in a non-ICU ward, and the outpatient setting. We included patients treated with BAV from 1/1/2012-7/31/2019 and compared outcomes and mortality stratified by presentation acuity. 612 patients underwent BAV; 111 (18.1%) ICU, 297 (48.5%) ward, 204 (33.3%) outpatients. Procedural outcomes were similar and complication rates were low. While ICU patients had higher 30-day mortality than ward and outpatients (31.5%, 5.4%, 3.4%; p<0.001), among patients ultimately treated with transcatheter aortic valve replacement (TAVR) there were no differences in long-term mortality (p=0.74). BAV is safe and effective at temporarily improving aortic valve function in patients with aortic stenosis across the spectrum of acuity of illness. Among critically ill patients with shock, BAV may facilitate recovery to discharge and serve as a bridge to TAVR. 

Committee: Grant Reed (Committee Chair) Subjects: Medicine

Master of Science in Mechanical Engineering (MSME), Wright State University, 2018, Mechanical Engineering

Calcific aortic stenosis (CAS) is the most common valvular heart disease and is associated with aortopathy and ventricular dysfunction. Hemodynamic alterations due CAS could affect the aorta lining (endothelium), that is in direct contact with the blood, triggering adverse biological responses that may possibly cause aortic dilation and dissection. Also, CAS could impose excessive ventricular load leading to ventricular wall thickening, thus putting an individual at a higher risk of heart attack or stroke. These pathophysiological effects of CAS are highly dependent on the degree of calcification. However, the impact of CAS development on aorta flow and left ventricular workload remains largely unknown. Hence the objective of this study is to measure experimentally the effect of CAS on aorta hemodynamics using particle image velocimetry; and left ventricular function in terms of left ventricular work, at different stages of calcification. This study will provide insights on aorta flow abnormalities and left ventricular overload, due CAS, which can be linked to aortopathy and heart failure.

Committee: Philippe Sucosky Ph.D., F.A.H.A. (Advisor); George Huang Ph.D. (Committee Member); Zifeng Yang Ph.D. (Committee Member) Subjects: Biomechanics; Fluid Dynamics; Mechanical Engineering; Physiology

Master of Sciences, Case Western Reserve University, 2016, Statistics

Objectives: To determine the feasibility and safety of early discharge strategy following transfemoral transcatheter aortic valve replacement (TAVR) via minimally invasive strategy (MIS). Methods: Two hundred sixty-eight patients who underwent transfemoral TAVR via MIS between 3/2011 and 12/2015 were included. Early discharge was defined as post-procedural length of stay = 3 days. There were 163 patients in the early discharge group and 105 patients in the late discharge group. Propensity score matching yielded 54 pairs of matched patients between the two groups. Thirty-day mortality, thirty-day rehospitalization and long-term survival data were analyzed. Multivariate analysis was used to define predictors of early discharge. Results: Using propensity matched analysis, 30-day mortality was 0% in early discharge vs. 5.5% in late discharge, p=0.08. Thirty-day rehospitalization was 3.7% in early discharge vs. 13 % in late discharge, p=0.16 (OR of 30-day rehospitalization in early discharge was 0.17[95% CI: 0.02-1.38]). Mortality hazard ratio in early discharge was 0.43 [95% CI: 0.11, 1.66]. Survival analysis of the matched sample showed no statistical difference between the groups with Log-rank test p= 0.2. Concerning predictors of early discharge, minor vascular complication, any bleeding, blood transfusion and new pacemaker had lower odds ratios for early discharge. In contrast, discharge to home had a higher odds ratio for early discharge. Conclusion: Early discharge strategy in patients undergoing transfemoral TAVR via MIS is feasible without imposing higher 30-day mortality or rehospitalization. Such a strategy may minimize the functional decline due to longer hospitalization and could lead to lower TAVR costs.

Committee: James Spilsbury Ph.D (Committee Chair) Subjects: Medicine

PHD, Kent State University, 2025, College of Arts and Sciences / School of Biomedical Sciences

Aortic valve stenosis (AS) is a progressive, life-threatening condition characterized by fibro-calcific remodeling of the aortic valve, leading to obstruction of blood flow and impaired cardiac function. Despite its increasing prevalence, no pharmacological therapy currently exists to halt or reverse the disease, highlighting a critical need for novel, non-invasive interventions. This dissertation investigates the therapeutic potential of exosomes derived from NAMPT-overexpressing mesenchymal stem cells (NAMPT-Exo) in mitigating AS and elucidates the underlying mechanisms of action. Using our newly developed endothelial cell-specific CXCR4 knockout (EC CXCR4 KO) induced AS mouse model, we demonstrate the therapeutic potential of NAMPT-Exo in mitigating AS. NAMPT-Exo treatment in EC CXCR4 KO mice significantly attenuated AS progression, reduced valvular calcification and thickening, and improved cardiac function, as shown by echocardiography and histological analyses. Mechanistic studies further revealed that NAMPT-Exo treatment modulates endothelial-to-mesenchymal transition (EndMT), a key contributor to AS pathogenesis. Additionally, we found that miR-146a-3P expression was significantly elevated in cardiac endothelial cells of AS mice, while exosome treatment effectively reduced its levels. These findings provide strong evidence that NAMPT-enriched MSC-derived exosomes represent a novel, cell-free therapeutic strategy for aortic valve stenosis and miR146a-3P may play an essential role in the disease development and progression.

Committee: William Chilian (Committee Member); Feng Dong (Advisor) Subjects: Biomedical Research; Pharmacology

DNP, Otterbein University, 2025, Nursing

Aortic stenosis (AS) is a common valvular disorder that causes left ventricular (LV) outflow obstruction. The prevalence of AS may increase with the aging population and the widespread availability of diagnostic capabilities like echocardiography. With the increasing patient population diagnosed with AS, the chance of encountering these patients during noncardiac surgery (NCS) increases. Performance of anesthesia is challenging in patients with AS due to the pathophysiological consequences of AS and the hemodynamic changes associated with anesthesia. The patient with AS presenting for NCS is at an increased risk of perioperative major adverse cardiac events (MACEs). This project aimed to determine the most up-to-date evidence for the perioperative management of patients with AS undergoing NCS. A literature search was conducted through the EBSCO Discovery Service and Google Scholar to find current evidence. The current evidence was used to create clinical guidelines for the pre and intraoperative management of patients with AS undergoing NCS using the Bayesian approach. The practice question, evidence, translation (PET), part of the Johns Hopkins Evidence-Based Practice Model (JHEBPM), was used as the literature review's framework. An implementation plan to disseminate the guidelines into practice was formed and discussed. The outcome the project team aims to study is the incidence of MACEs in patients with AS undergoing NCS after the implementation of clinical guidelines.

Committee: Brian Garrett (Advisor); Brian Garrett (Committee Chair); Amy Bishop (Committee Member); Regina Prusinski (Committee Member) Subjects: Health Sciences; Nursing

Master of Science, The Ohio State University, 2019, Biomedical Engineering

Coronary flow induces hemodynamic alterations in the aortic sinus region but have previously been studied using non-physiological flows. The objectives of this study are to: (1) investigate the differences among sinus hemodynamics and leaflet wall shear stresses engendered by the left versus right versus non-coronary flow and (2) correlate respective wall shear stresses with leaflet calcification in patients. A left heart simulator flow loop with a tunable coronary circuit provided physiological coronary flow waveforms corresponding to the left coronary case (LCC), right coronary case (RCC), and non-coronary case (NCC). High spatio-temporal resolution particle image velocimetry (PIV) was conducted to quantify leaflet wall shear stress and sinus vorticity fields and to measure aortic leaflet tip kinematics. Thirty-one patients with severe calcific aortic valve disease were segmented from CT data. Calcific volumes in their respective left, right, and non-coronary cusps were correlated with respective quantified leaflet wall shear stress (WSS) probabilities greater than 0.3 Pascal. Leaflet tip position during systole shows the RCC has a wider leaflet opening compared to LCC and NCC. Velocity and vorticity fields combined with leaflet position data show that sinus vorticity is diminished (peak ~43s-1) in the LCC while RCC and NCC maintain high vorticity (1200s-1 and ~950s-1 respectively). WSS magnitudes greater than 0.3 Pa show 20% and 81% greater occurrences in the LCC and RCC respectively compared to NCC. Results from the study conclude that coronary flow differences between LCC, RCC, and NCC show significant impact on leaflet kinematics and sinus flow hemodynamics. Clinical data correlations of the coronary flow cases indicate the left coronary cusp has a higher likelihood of calcification compared to the right. Analysis of the medians of the patient population cusp calcification found significant differences (X2 (2, n = 31) = 7.31, p = 0.0258) between the calcificat (open full item for complete abstract)

Committee: Lakshmi Dasi PhD (Advisor); Samir Ghadiali PhD (Committee Member) Subjects: Biomedical Engineering

Doctor of Philosophy, The Ohio State University, 2005, Veterinary Clinical Sciences

Aortic stenosis (AS) is a common, heritable congenital heart defect affecting Boxer dogs. Veterinarians screen for AS through auscultation. When a typical murmur is auscultated, an echocardiogram identifies the presence and severity of the defect. In the setting of a soft murmur, echocardiographic imaging lesions are often absent, and a noninvasive diagnosis is based on Doppler-identification of high velocity flow across the left ventricular outflow tract (LVOT). However, similar increases in LVOT velocity and cardiac murmurs can occur in normal dogs under sympathetic stimulation. We hypothesized that boxers with ejection murmurs and elevated LVOT velocities have AS. Specific aims were to characterize the relationship between these murmurs and velocities; to evaluate LVOT morphology with echocardiography and angiography; to compare stroke volumes between boxers with and without murmurs; to evaluate pressure gradients across the LVOT for evidence of stenosis under different hemodynamic circumstances; and to identify the site of murmur generation with intracardiac phonocardiography. Of 201 healthy adult boxers, over 50% had left basilar ejection murmurs typical of AS, and 36% demonstrated both a murmur and elevated LVOT velocity. The presence of a murmur predicted a velocity > 2 m/s, with an 87% sensitivity and 66% specificity. Indexed echocardiographic diameters and areas were not different between boxers with ejection murmurs and boxers without murmurs, although they were smaller than in non-boxer dogs. Boxers with murmurs tended to have higher stroke volumes. Angiographically, the LVOT in boxers was diffusely smaller than non-boxers, with substantial narrowing at the sinus of Valsalva Pressure recordings were typical of impulse gradients and significant peak to peak gradients were not found. Intracardiac phonocardiography identified the distal LVOT as the site of murmur generation. The etiology of ejection murmurs and elevated LVOT velocities in boxers is multi-fac (open full item for complete abstract)

Committee: Kathryn Meurs (Advisor) Subjects: