Integrating Cardiovascular Engineering and Biofluid Mechanics in High School Science, Technology, Engineering, and Mathematics Education: An Experiential Approach.

Science, technology, engineering, and mathematics (STEM) education workshops and programs play a key role in promoting early exposure to scientific applications and questions. Such early engagement leads to growing not only passion and interest in science, but it also leads to skill development through hands-on learning and critical thinking activities. Integrating physiology and engineering together is necessary especially to promote health technology awareness and introduce the young generation to areas where innovation is needed and where there is no separation between health-related matters and engineering methods and applications. To achieve this, we created a workshop aimed at K-12 (grades 9-11) students as part of the Summer Youth Programs at Michigan Technological University. The aim of this workshop was to expose students to how engineering concepts and methods translate into health- and medicine-related applications and cases. The program consisted of a total of 15 h and was divided into three sections over a period of 2 weeks. It involved a combination of theoretical and hands-on guided activities that we developed. At the end of the workshop, the students were provided a lesson or activity-specific assessment sheet and a whole workshop-specific assessment sheet to complete. They rated the programs along a 1-5 Likert scale and provided comments and feedback on what can be improved in the future. Students rated hands-on activities the highest in comparison with case studies and individual independent research. Conclusively, this STEM summer-youth program was a successful experience with many opportunities that will contribute to the continued improvement of the workshop in the future.

Association of Bovine Arch Anatomy With Incident Stroke After Transcatheter Aortic Valve Replacement.

BACKGROUND: Acute ischemic stroke complicates 2% to 3% of transcatheter aortic valve replacements (TAVRs). This study aimed to identify the aortic anatomic correlates in patients after TAVR stroke. METHODS AND RESULTS: This is a single-center, retrospective study of patients who underwent TAVR at the Mayo Clinic between 2012 and 2022. The aortic arch morphology was determined via a manual review of the pre-TAVR computed tomography images. An "a priori" approach was used to select the covariates for the following: (1) the logistic regression model assessing the association between a bovine arch and periprocedural stroke (defined as stroke within 7 days after TAVR); and (2) the Cox proportional hazards regression model assessing the association between a bovine arch and long-term stroke after TAVR. A total of 2775 patients were included (59.6% men; 97.8% White race; mean±SD age, 79.3±8.4 years), of whom 495 (17.8%) had a bovine arch morphology. Fifty-seven patients (1.7%) experienced a periprocedural stroke. The incidence of acute stroke was significantly higher among patients with a bovine arch compared with those with a nonbovine arch (3.6% versus 1.7%; P=0.01). After adjustment, a bovine arch was independently associated with increased periprocedural strokes (adjusted odds ratio, 2.16 [95% CI, 1.22-3.83]). At a median follow-up of 2.7 years, the overall incidence of post-TAVR stroke was 6.0% and was significantly higher in patients with a bovine arch even after adjusting for potential confounders (10.5% versus 5.0%; adjusted hazard ratio, 2.11 [95% CI, 1.51-2.93]; P<0.001). CONCLUSIONS: A bovine arch anatomy is associated with a significantly higher risk of periprocedural and long-term stroke after TAVR.

Differential Impact of Blood Pressure Control Targets on Epicardial Coronary Flow After Transcatheter Aortic Valve Replacement.

Background: The cause for the association between increased cardiovascular mortality rates and lower blood pressure (BP) after aortic valve replacement (AVR) is unclear. This study aims to assess how the epicardial coronary flow (ECF) after AVR varies as BP levels are changed in the presence of a right coronary lesion. Methods: The hemodynamics of a 3D printed aortic root model with a SAPIEN 3 26 deployed were evaluated in an in vitro left heart simulator under a range of varying systolic blood pressure (SBP) and diastolic blood pressure (DBP). ECF and the flow ratio index were calculated. Flow index value <0.8 was considered a threshold for ischemia. Results: As SBP decreased, the average ECF decreased below the physiological coronary minimum at 120 mmHg. As DBP decreased, the average ECF was still maintained above the physiological minimum. The flow ratio index was >0.9 for SBP ≥130 mmHg. However, at an SBP of 120 mmHg, the flow ratio was 0.63 (p ≤ 0.0055). With decreasing DBP, no BP condition yielded a flow ratio index that was less than 0.91. Conclusions: Reducing BP to the current recommended levels assigned for the general population after AVR in the presence of coronary artery disease may require reconsideration of levels and treatment priority. Additional studies are needed to fully understand the changes in ECF dynamics after AVR in the presence and absence of coronary artery disease.

Effect of Blood Pressure Levels on Sinus Hemodynamics in Relation to Calcification After Bioprosthetic Aortic Valve Replacement.

Coexisting hypertension and aortic stenosis are common. Some studies showed that elevated blood pressures may be associated with progression of calcific aortic valve disease (CAVD) while others showed no correlation. Flow dynamics in the sinuses of Valsalva are considered key factors in the progression of CAVD. While the relationship between hemodynamics and CAVD is not yet fully understood, it has been demonstrated that they are tightly correlated. This study aims to investigate the effect of changing systolic and diastolic blood pressures (SBP and DBP, respectively) on sinus hemodynamics in relation to potential initiation or progression of CAVD after aortic valve replacement (AVR). Evolut R, SAPIEN 3 and Magna valves were deployed in an aortic root under pulsatile conditions. Using particle image velocimetry, the hemodynamics in the sinus were assessed. The velocity, vorticity, circulation ( Γ ) and shear stress were calculated. This study shows that under elevated SBP and DBP, velocity, vorticity, and shear stress nearby the leaflets increased. Additionally, larger fluctuations of Γ and area under the curve throughout the cardiac cycle were observed. Elevated blood pressures are associated with higher velocity, vorticity, and shear stress near the leaflets which may initiate or accelerate pro-calcific changes in the prosthetic leaflets leading to bioprosthetic valve degeneration.

Effect of aortic curvature on bioprosthetic aortic valve performance.

Transvalvular pressure gradient (ΔP) after aortic valve replacement is an important surrogate of aortic bioprostheses performance. Invasive ΔP is often measured after transcatheter aortic valve replacement to exclude patient-prosthetic mismatch. However, invasive aortic pressures are usually recorded in the pressure recovery (PR) zone downstream of the valve, potentially resulting in ΔP underestimation compared to noninvasive measurements. PR was extensively studied in straight ascending aortas. However, the impact of various aortic arch configurations on ΔP has not been explored. PR was assessed in a pulse duplicating simulator at various cardiac conditions of cardiac output, heart rates and pressures. Three different aortic geometries with identical root dimensions but with different aortic arches were used: (1) curvature 1, (2) curvature 2, and (3) straight aortic models. Instantaneous pressure and peak ΔP measurements were recorded incrementally along the models for each cardiac condition. The models with aortic arches produced two distinct PR zones (after the valve and after the aortic arch), whereas the model without an aortic arch produced only one PR zone (after the valve). The trend of the pressure and ΔP curves for each model was independent of the cardiac condition used, but the individually measured pressure magnitudes did change with different conditions. In this study, we illustrated the differences in PR between distinct aortic curvatures and straight aorta. PR affects pressure and ΔP measurements. These effects are clear when recording aortic pressures by catheterization and echocardiography.

A Preliminary Study on the Usage of a Data-Driven Probabilistic Approach to Predict Valve Performance Under Different Physiological Conditions.

Predicting potential complications after aortic valve replacement (AVR) is a crucial task that would help pre-planning procedures. The goal of this work is to generate data-driven models based on logistic regression, where the probability of developing transvalvular pressure gradient (DP) that exceeds 20 mmHg under different physiological conditions can be estimated without running extensive experimental or computational methods. The hemodynamic assessment of a 26 mm SAPIEN 3 transcatheter aortic valve and a 25 mm Magna Ease surgical aortic valve was performed under pulsatile conditions of a large range of systolic blood pressures (SBP; 100-180 mmHg), diastolic blood pressures (DBP; 40-100 mmHg), and heart rates of 60, 90 and 120 bpm. Logistic regression modeling was used to generate a predictive model for the probability of having a DP > 20 mmHg for both valves under different conditions. Experiments on different pressure conditions were conducted to compare the probabilities of the generated model and those obtained experimentally. To test the accuracy of the predictive model, the receiver operation characteristics curves were generated, and the areas under the curve (AUC) were calculated. The probabilistic predictive model of DP > 20 mmHg was generated with parameters specific to each valve. The AUC obtained for the SAPIEN 3 DP model was 0.9465 and that for Magna Ease was 0.9054 indicating a high model accuracy. Agreement between the DP probabilities obtained between experiments and predictive model was found. This model is a first step towards developing a larger statistical and data-driven model that can inform on certain valves reliability during AVR pre-procedural planning.

Effect of catheter ablation on the hemodynamics of the left atrium : Hemodynamics of ablation.

BACKGROUND: This study aims to evaluate the impact of catheter ablation for atrial fibrillation (AF) on left atrial (LA) flow dynamics and geometrical changes. METHODS: This exploratory study included computational flow simulations from 10 patients who underwent catheter ablation for AF. Complete cardiac cycle dataset was simulated before and after ablation using computational fluid dynamics. The study main endpoints were the changes in LA volume, LA velocity, LA wall shear stress (WSS), circulation (Γ), vorticity, pulmonary vein (PV) ostia area, and LA vortices before and after ablation. RESULTS: There was an average decrease in LA volume (11.58 ± 15.17%) and PV ostia area (16.6 ± 21.41%) after ablation. A non-uniform trend of velocity and WSS changes were observed after ablation. Compared with pre-ablation, 4 patients exhibited lower velocities, WSS distributions, and a decreased Γ (> 8.5%), while 6 developed higher velocities and WSS distributions. These geometrical changes dictated different flow mixing in the LA and distinct vortex patterns, characterized by different spinning velocities, vorticities, and rotational directions. Regions with q-criterion > 0 were found to be dominant in the LA, indicating prevalent rotational vortex structures. CONCLUSION: Catheter ablation for AF induced different geometrical changes on the LA and the PVs, therefore influencing flow mixing and vortex patterns in the LA, in addition to overall velocity and WSS distribution. Further exploration of the impact of catheter ablation on intracardiac flow dynamics is warranted to discern patterns that may correlate with clinical outcomes.

Flow dynamics in the sinus and downstream of third and fourth generation balloon expandable transcatheter aortic valves.

OBJECTIVE: The early success of transcatheter aortic valve (TAV) replacement (TAVR) has fueled further innovations in the field leading to the emergence multiple iterations of TAV designs. Whether these newer designs are associated with similar hemodynamic outcomes remains unknown. Recently, the SAPIEN 3 Ultra valve received FDA approval for use in patients with published clinical outcomes. The aim of this study is (1) to evaluate and compare the flow dynamics downstream of the SAPIEN 3 Ultra and a SAPIEN 3 (2) and to evaluate and compare the resulting sinus hemodynamics and washout characteristics for a complete hemodynamic characterization. METHODS: The hemodynamic assessment was performed in a pulse duplicating system and particle image velocimetry was used to assess the flow dynamics. Pressure gradient (ΔP), effective orifice area (EOA), leakage fraction (LF), velocity in the flow downstream and the sinus, viscous shear stress (VSS) downstream and adjacent to the leaflet in the sinus, and sinus washout were calculated. RESULTS: EOA for the SAPIEN 3 Ultra was 1.81 ± 0.05 cm2 and 1.86 ± 0.05 cm2 with the SAPIEN 3, ΔP with the SAPIEN 3 Ultra was 10.56 ± 0.62 mmHg and 14.73 ± 0.79 mmHg with the SAPIEN 3, and LF with the SAPIEN 3 Ultra was 10.4 ± 0.5% and 9.7 ± 0.4% with the SAPIEN 3 (p<0.05). The instantaneous VSS for both valves ≤15 Pa, which is not sufficient to induce hemolysis, but may lead to platelet activation. RSS - an indicator of blood damage - exceeded 100 Pa at peak systole with both TAVs. The sinus velocity at peak systole was 0.24 ± 0.08 m/s with the SAPIEN 3 Ultra and 0.22 ± 0.10 m/s with the SAPIEN 3. VSS range reached 3.9 Pa with the SAPIEN 3 Ultra and 4.0 Pa with the SAPIEN 3. Complete sinus washout was achieved in ∼1.5 and ∼2.4 cardiac cycles for the SAPIEN 3 Ultra and SAPIEN 3, respectively. CONCLUSION: Compared to its predecessor, the hemodynamic performance and sinus hemodynamics of SAPIEN 3 Ultra are comparable.

Impact of calcific aortic valve disease on valve mechanics.

The aortic valve is a highly dynamic structure characterized by a transvalvular flow that is unsteady, pulsatile, and characterized by episodes of forward and reverse flow patterns. Calcific aortic valve disease (CAVD) resulting in compromised valve function and increased pressure overload on the ventricle potentially leading to heart failure if untreated, is the most predominant valve disease. CAVD is a multi-factorial disease involving molecular, tissue and mechanical interactions. In this review, we aim at recapitulating the biomechanical loads on the aortic valve, summarizing the current and most recent research in the field in vitro, in-silico, and in vivo, and offering a clinical perspective on current strategies adopted to mitigate or approach CAVD.

Impact of blood pressure on coronary perfusion and valvular hemodynamics after aortic valve replacement.

OBJECTIVE: Our objective was to evaluate the impact of various blood pressures (BPs) on coronary perfusion and valvular hemodynamics following aortic valve replacement (AVR). BACKGROUND: Lower systolic and diastolic (SBP/DBP) pressures from the recommended optimal target range of SBP < 120-130 mmHg and DBP < 80 mmHg after AVR have been independently associated with increased cardiovascular and all-cause mortality. METHODS: The hemodynamic assessment of a 26 mm SAPIEN 3 transcatheter aortic valve (TAV), 29 mm Evolut R TAV, and 25 mm Magna Ease surgical aortic valve (SAV) was performed in a pulsed left heart simulator with varying SBP, DBP, and heart rate (HR) conditions (60 and 120 bpm) at 5 L/min cardiac output (CO). Average coronary flow (CF), effective orifice areas (EOAs), and valvulo-arterial impedance (Zva) were calculated. RESULTS: At HR of 60 bpm, at SBP < 120 mmHg and DBP < 60 mmHg, CF decreased below the physiological lower limit with several different valves. Zva and EOA were found to increase and decrease respectively with increasing SBP and DBP. The same results were found with an HR of 120 bpm. The trends of CF variation with BP were similar in all valves however the drop below the lower physiological CF limit was valve dependent. CONCLUSION: In a controlled in vitro system, with different aortic valve prostheses in place, CF decreased below the physiologic minimum when SBP and DBP were in the range targeted by blood pressure guidelines. Combined with recent observations from patients treated with AVR, these findings underscore the need for additional studies to identify the optimal BP in patients treated with AVR for AS.

Engineered Three-Dimensional Scaffolds Modulating Fate of Breast Cancer Cells Using Stiffness and Morphology Related Cell Adhesion.

Goal: Artificially engineering the tumor microenvironment in vitro as a vital tool for understanding the mechanism of tumor progression. In this study, we developed three-dimensional cell scaffold systems with different topographical features and mechanical properties but similar surface chemistry. The cell behavior was modulated by the topography and mechanical properties of the scaffold. Methods: Adenocarcinoma (MCF7), triple-negative (MDA-MB-231) and premalignant (MCF10AneoT) breast cancer cells were seeded on the scaffold systems. The cell viability, cell-cell interaction and cell-matrix interactions were analyzed. The preferential growth and alignment of specific population of cells were demonstrated. Results: Among the different scaffolds, triple-negative breast cancer cells preferred honeycomb scaffolds while adenocarcinoma cells favored mesh scaffolds and premalignant cells preferred the aligned scaffolds. Conclusions: The 3D model system developed here can be used to support growth of only specific cell populations or for the growth of tumors. This model can be used for understanding the topographical and mechanical features affecting tumorigenesis, cancer cell growth and migration behavior of malignant and metastatic cancer cells.