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1. Aortic tissue stiffness and tensile strength are correlated with density changes following proteolytic treatment

   https://doi.org/10.1016/j.jbiomech.2024.112226  

   Gueldner, Pete H; Darvish, Cyrus J; Chickanosky, Isabelle KM; Ahlgren, Emma E; Fortunato, Ronald; Chung, Timothy K; Rajagopal, Keshava; Benjamin, Chandler C; Maiti, Spandan; Rajagopal, Kumbakonam R; et al (July 2024, Journal of Biomechanics)

   Introduction: Dissection or rupture of the aorta is accompanied by high mortality rates, and there is a pressing need for better prediction of these events for improved patient management and clinical outcomes. Biomechanically, these events represent a situation wherein the locally acting wall stress exceed the local tissue strength. Based on recent reports for polymers, we hypothesized that aortic tissue failure strength and stiffness are directly associated with tissue mass density. The objective of this work was to test this novel hypothesis for porcine thoracic aorta. Methods: Three tissue specimens from freshly harvested porcine thoracic aorta were treated with either collagenase or elastase to selectively degrade structural proteins in the tissue, or with phosphate buffer saline (control). The tissue mass and volume of each specimen were measured before and after treatment to allow for density calculation, then mechanically tested to failure under uniaxial extension. Results: Protease treatments resulted in statistically significant tissue density reduction (sham vs. collagenase p = 0.02 and sham vs elastase p = 0.003), which in turn was significantly and directly correlated with both ultimate tensile strength (sham vs. collagenase p = 0.02 and sham vs elastase p = 0.03) and tangent modulus (sham vs. collagenase p = 0.007 and sham vs elastase p = 0.03). Conclusions: This work demonstrates for the first time that tissue stiffness and tensile strength are directly correlated with tissue density in proteolytically-treated aorta. These findings constitute an important step towards understanding aortic tissue failure mechanisms and could potentially be leveraged for non-invasive aortic strength assessment through density measurements, which could have implications to clinical care. 

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2. Deep Learning Analysis of Surgical Video Recordings to Assess Nontechnical Skills

   https://doi.org/10.1001/jamanetworkopen.2024.22520  

   Harari, Rayan Ebnali; Dias, Roger D; Kennedy-Metz, Lauren R; Varni, Giovanna; Gombolay, Matthew; Yule, Steven; Salas, Eduardo; Zenati, Marco A (July 2024, JAMA Network Open)

   ImportanceAssessing nontechnical skills in operating rooms (ORs) is crucial for enhancing surgical performance and patient safety. However, automated and real-time evaluation of these skills remains challenging. ObjectiveTo explore the feasibility of using motion features extracted from surgical video recordings to automatically assess nontechnical skills during cardiac surgical procedures. Design, Setting, and ParticipantsThis cross-sectional study used video recordings of cardiac surgical procedures at a tertiary academic US hospital collected from January 2021 through May 2022. The OpenPose library was used to analyze videos to extract body pose estimations of team members and compute various team motion features. The Non-Technical Skills for Surgeons (NOTSS) assessment tool was employed for rating the OR team’s nontechnical skills by 3 expert raters. Main Outcomes and MeasuresNOTSS overall score, with motion features extracted from surgical videos as measures. ResultsA total of 30 complete cardiac surgery procedures were included: 26 (86.6%) were on-pump coronary artery bypass graft procedures and 4 (13.4%) were aortic valve replacement or repair procedures. All patients were male, and the mean (SD) age was 72 (6.3) years. All surgical teams were composed of 4 key roles (attending surgeon, attending anesthesiologist, primary perfusionist, and scrub nurse) with additional supporting roles. NOTSS scores correlated significantly with trajectory (r = 0.51,P = .005), acceleration (r = 0.48,P = .008), and entropy (r = −0.52,P = .004) of team displacement. Multiple linear regression, adjusted for patient factors, showed average team trajectory (adjustedR² = 0.335; coefficient, 10.51 [95% CI, 8.81-12.21];P = .004) and team displacement entropy (adjustedR² = 0.304; coefficient, −12.64 [95% CI, −20.54 to −4.74];P = .003) were associated with NOTSS scores. Conclusions and RelevanceThis study suggests a significant link between OR team movements and nontechnical skills ratings by NOTSS during cardiac surgical procedures, suggesting automated surgical video analysis could enhance nontechnical skills assessment. Further investigation across different hospitals and specialties is necessary to validate these findings. 

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3. Shear and endothelial induced late-stage calcific aortic valve disease-on-a-chip develops calcium phosphate mineralizations

   https://doi.org/10.1039/d1lc00931a  

   Mendoza, Melissa; Chen, Mei-Hsiu; Huang, Peter; Mahler, Gretchen J. (March 2022, Lab on a Chip)

   Calcific aortic valve disease (CAVD) is an active pathobiological process leading to severe aortic stenosis, where the only treatment is valve replacement. Late-stage CAVD is characterized by calcification, disorganization of collagen, and deposition of glycosaminoglycans, such as chondroitin sulfate (CS), in the fibrosa. We developed a three-dimensional microfluidic device of the aortic valve fibrosa to study the effects of shear stress (1 or 20 dyne per cm 2 ), CS (1 or 20 mg mL −1 ), and endothelial cell presence on calcification. CAVD chips consisted of a collagen I hydrogel, where porcine aortic valve interstitial cells were embedded within and porcine aortic valve endothelial cells were seeded on top of the matrix for up to 21 days. Here, we show that this CAVD-on-a-chip is the first to develop human-like calcified nodules varying in calcium phosphate mineralization maturity resulting from high shear and endothelial cells, specifically di- and octa-calcium phosphates. Long-term co-culture microfluidic studies confirmed cell viability and calcium phosphate formations throughout 21 days. Given that CAVD has no targeted therapies, the creation of a physiologically relevant test-bed of the aortic valve could lead to advances in preclinical studies. 

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4. Patient–Specific Immersed Finite Element–Difference Model of Transcatheter Aortic Valve Replacement

   https://doi.org/10.1007/s10439-022-03047-3  

   Brown, Jordan A.; Lee, Jae H.; Smith, Margaret Anne; Wells, David R.; Barrett, Aaron; Puelz, Charles; Vavalle, John P.; Griffith, Boyce E. (January 2023, Annals of Biomedical Engineering)

   Abstract Transcatheter aortic valve replacement (TAVR) first received FDA approval for high-risk surgical patients in 2011 and has been approved for low-risk surgical patients since 2019. It is now the most common type of aortic valve replacement, and its use continues to accelerate. Computer modeling and simulation (CM&S) is a tool to aid in TAVR device design, regulatory approval, and indication in patient-specific care. This study introduces a computational fluid-structure interaction (FSI) model of TAVR with Medtronic’s CoreValve Evolut R device using the immersed finite element-difference (IFED) method. We perform dynamic simulations of crimping and deployment of the Evolut R, as well as device behavior across the cardiac cycle in a patient-specific aortic root anatomy reconstructed from computed tomography (CT) image data. These IFED simulations, which incorporate biomechanics models fit to experimental tensile test data, automatically capture the contact within the device and between the self-expanding stent and native anatomy. Further, we apply realistic driving and loading conditions based on clinical measurements of human ventricular and aortic pressures and flow rates to demonstrate that our Evolut R model supports a physiological diastolic pressure load and provides informative clinical performance predictions. 

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5. Abstract P332: Microfluidic Model Of Late-stage Calcific Aortic Valve Disease Develops Calcium Phosphate Mineralizations

   https://doi.org/10.1161/res.129.suppl_1.P332  

   Mendoza, Melissa; Chen, Mei-Hsiu; Murray, Bruce; Huang, Peter; Mahler, Gretchen (September 2021, Circulation Research)

   Introduction: Calcific aortic valve disease (CAVD) is an active pathological process leading to severe valve calcification. Late-stage CAVD is characterized by increased leaflet stiffness, disorganized collagen bundles and the deposition of glycosaminoglycans, such as chondroitin sulfate (CS), in the fibrosa layer. However, many details of the cellular pathological cascade remain unknown. Animal models such as mice, rabbits, and pigs are used in understanding human CAVD, but mice do not have similar anatomy, rabbits cannot spontaneously develop atherosclerotic lesions, and pigs require long, expensive and complex studies. Here we utilize microfluidic devices of the aortic valve fibrosa to model late-stage CAVD. Hypothesis: We assessed the hypothesis that microfluidic calcification will increase with increased shear rates and CS content. Methods: Valve-on-a-chip devices contained a hydrogel of 1.5 mg/mL collagen I-only healthy controls or 1.5 mg/mL collagen I with 1 mg/mL or 20 mg/mL CS. Porcine aortic valve interstitial cells (PAVIC) were embedded within and endothelial cells (PAVEC) were seeded onto the matrix. Steady shear stress at 1 dyne/cm 2 and 20 dyne/cm 2 were applied using a peristaltic pump for 14 days. Alizarin Red S (ARS), an assay to assess calcium deposition, was used to quantify calcific nodule formation. Scanning electron microscopy with energy dispersive x-ray (SEM/EDX) was used to further analyze sample mineralization. Results: Co-cultures in the presence of increasing shear stress and CS exhibit increased calcific nodule formation compared to static controls, both qualitatively and quantitatively (n≥3). SEM revealed the microstructure of calcified nodules and EDX confirmed calcium phosphate mineralization with physiologically-relevant calcium to phosphorous ratios (Ca/P= 0.88 - 1.4). Conclusions: These results show that in vitro calcification is driven by shear stress in the presence of PAVEC and CS. As seen in ex vivo studies of human calcification, these microfluidic-derived nodules are similarly composed of a range of naturally-occurring calcium phosphates. Given that CAVD has no targeted therapy, the creation of a physiologically relevant model of the aortic valve can provide a test bed for novel therapeutic interventions. 

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