Personalized coronary and myocardial blood flow models incorporating CT perfusion imaging and synthetic vascular trees.

Computational simulations of coronary artery blood flow, using anatomical models based on clinical imaging, are an emerging non-invasive tool for personalized treatment planning. However, current simulations contend with two related challenges - incomplete anatomies in image-based models due to the exclusion of arteries smaller than the imaging resolution, and the lack of personalized flow distributions informed by patient-specific imaging. We introduce a data-enabled, personalized and multi-scale flow simulation framework spanning large coronary arteries to myocardial microvasculature. It includes image-based coronary anatomies combined with synthetic vasculature for arteries below the imaging resolution, myocardial blood flow simulated using Darcy models, and systemic circulation represented as lumped-parameter networks. We propose an optimization-based method to personalize multiscale coronary flow simulations by assimilating clinical CT myocardial perfusion imaging and cardiac function measurements to yield patient-specific flow distributions and model parameters. Using this proof-of-concept study on a cohort of six patients, we reveal substantial differences in flow distributions and clinical diagnosis metrics between the proposed personalized framework and empirical methods based purely on anatomy; these errors cannot be predicted a priori. This suggests virtual treatment planning tools would benefit from increased personalization informed by emerging imaging methods.

Hemodynamics and Wall Mechanics of Vascular Graft Failure.

Blood vessels are subjected to complex biomechanical loads, primarily from pressure-driven blood flow. Abnormal loading associated with vascular grafts, arising from altered hemodynamics or wall mechanics, can cause acute and progressive vascular failure and end-organ dysfunction. Perturbations to mechanobiological stimuli experienced by vascular cells contribute to remodeling of the vascular wall via activation of mechanosensitive signaling pathways and subsequent changes in gene expression and associated turnover of cells and extracellular matrix. In this review, we outline experimental and computational tools used to quantify metrics of biomechanical loading in vascular grafts and highlight those that show potential in predicting graft failure for diverse disease contexts. We include metrics derived from both fluid and solid mechanics that drive feedback loops between mechanobiological processes and changes in the biomechanical state that govern the natural history of vascular grafts. As illustrative examples, we consider application-specific coronary artery bypass grafts, peripheral vascular grafts, and tissue-engineered vascular grafts for congenital heart surgery as each of these involves unique circulatory environments, loading magnitudes, and graft materials.

Almanac - Retrieval-Augmented Language Models for Clinical Medicine.

BACKGROUND: Large language models (LLMs) have recently shown impressive zero-shot capabilities, whereby they can use auxiliary data, without the availability of task-specific training examples, to complete a variety of natural language tasks, such as summarization, dialogue generation, and question answering. However, despite many promising applications of LLMs in clinical medicine, adoption of these models has been limited by their tendency to generate incorrect and sometimes even harmful statements. METHODS: We tasked a panel of eight board-certified clinicians and two health care practitioners with evaluating Almanac, an LLM framework augmented with retrieval capabilities from curated medical resources for medical guideline and treatment recommendations. The panel compared responses from Almanac and standard LLMs (ChatGPT-4, Bing, and Bard) versus a novel data set of 314 clinical questions spanning nine medical specialties. RESULTS: Almanac showed a significant improvement in performance compared with the standard LLMs across axes of factuality, completeness, user preference, and adversarial safety. CONCLUSIONS: Our results show the potential for LLMs with access to domain-specific corpora to be effective in clinical decision-making. The findings also underscore the importance of carefully testing LLMs before deployment to mitigate their shortcomings. (Funded by the National Institutes of Health, National Heart, Lung, and Blood Institute.).

Results following implementation of a cardiac surgery ERAS protocol.

INTRODUCTION: Adequate peri-operative care is essential to ensuring a satisfactory outcome in cardiac surgery. In this study, we look at the impact of evidence-based protocols implemented at Stanford Hospital. METHODS: This study is a single-center, retrospective analysis. Enhanced recovery after surgery (ERAS) protocols were implemented for CABG/Valve and open Aortic operations on 11/1/2017 and 6/1/2018, respectively. Propensity-score matched analysis was used to compare 30-day mortality and morbidity of patients from the pre- and post-implementation cohorts. Secondary endpoints included the following: total hospital length of stay (LOS), ICU LOS, time until extubation, and time until urinary catheter removal. RESULTS: After the implementation of the ERAS protocols for CABG/Valve operations, the median post-op LOS decreased from 7.0 days to 6.1 days (p<0.001), and median ICU LOS decreased from 69.9 hours to 54.0 (p = 0.098). There was no significant decrease in 30-day mortality (4% to 3.3%, p = 0.47). However, the incidence of post-op ventilator associated pneumonia (VAP) decreased from 5.0% to 2.1% (p = 0.003) and post-op urinary tract infections (UTIs) from 8.3% to 3.6% (p<0.001). Patients who underwent open aortic procedures experienced an improvement in 30-day mortality (7% to 3.5%, p = 0.012), decrease in median ICU LOS (91.7 hours to 69.6 hours, p<0.001), and a decrease in duration of mechanical ventilation (79.3 hours to 46.3 hours, p = 0.003). There was a decrease in post-op LOS, post-op VAP, and post-op UTI, although statistical significance was not attained. CONCLUSION: At Stanford Hospital, ERAS pathways have led to decreased morbidity and LOS while simultaneously improving mortality amongst our critically ill patient population.

Almanac: Retrieval-Augmented Language Models for Clinical Medicine.

Large-language models have recently demonstrated impressive zero-shot capabilities in a variety of natural language tasks such as summarization, dialogue generation, and question-answering. Despite many promising applications in clinical medicine, adoption of these models in real-world settings has been largely limited by their tendency to generate incorrect and sometimes even toxic statements. In this study, we develop Almanac, a large language model framework augmented with retrieval capabilities for medical guideline and treatment recommendations. Performance on a novel dataset of clinical scenarios (n= 130) evaluated by a panel of 5 board-certified and resident physicians demonstrates significant increases in factuality (mean of 18% at p-value < 0.05) across all specialties, with improvements in completeness and safety. Our results demonstrate the potential for large language models to be effective tools in the clinical decision-making process, while also emphasizing the importance of careful testing and deployment to mitigate their shortcomings.

Integration of Reinforcement Learning in a Virtual Robotic Surgical Simulation.

Background. The revolutions in AI hold tremendous capacity to augment human achievements in surgery, but robust integration of deep learning algorithms with high-fidelity surgical simulation remains a challenge. We present a novel application of reinforcement learning (RL) for automating surgical maneuvers in a graphical simulation.Methods. In the Unity3D game engine, the Machine Learning-Agents package was integrated with the NVIDIA FleX particle simulator for developing autonomously behaving RL-trained scissors. Proximal Policy Optimization (PPO) was used to reward movements and desired behavior such as movement along desired trajectory and optimized cutting maneuvers along the deformable tissue-like object. Constant and proportional reward functions were tested, and TensorFlow analytics was used to informed hyperparameter tuning and evaluate performance.Results. RL-trained scissors reliably manipulated the rendered tissue that was simulated with soft-tissue properties. A desirable trajectory of the autonomously behaving scissors was achieved along 1 axis. Proportional rewards performed better compared to constant rewards. Cumulative reward and PPO metrics did not consistently improve across RL-trained scissors in the setting for movement across 2 axes (horizontal and depth).Conclusion. Game engines hold promising potential for the design and implementation of RL-based solutions to simulated surgical subtasks. Task completion was sufficiently achieved in one-dimensional movement in simulations with and without tissue-rendering. Further work is needed to optimize network architecture and parameter tuning for increasing complexity.

Career Progression and Research Productivity of Women in Academic Cardiothoracic Surgery.

BACKGROUND: The objective of this work was to delineate career progression and research productivity of women practicing cardiothoracic surgery in the academic setting. METHODS: Cardiothoracic surgeons at the 79 accredited US cardiothoracic surgery training programs in 2020 were included in this cross-sectional analysis. Data regarding subspecialization, training, practice history, and publications were gathered from public sources including department websites, CTSNet, and Scopus. RESULTS: A total of 1065 surgeons (51.3% cardiac, 32.1% thoracic, 16.6% congenital) were identified. Women accounted for 10.6% (113) of the population (7.9% of cardiac, 15.5% of thoracic, 9.6% of congenital surgeons). The median number of cardiothoracic surgeons per institution was 12 (interquartile range [IQR], 10-17), with a median of 1 woman (IQR, 0-2). Fifteen of 79 programs (19%) had no women. Among women faculty 5.3% were clinical instructors, 51.3% were assistant professors, 23.0% were associate professors, 16.8% were full professors, and 3.5% had unspecified titles (vs 2.0%, 32.9%, 23.0%, 37.5%, and 4.6% among men, respectively; P < .001). Women and men authored a comparable number of first-author (0.4 [IQR, 0.0-1.3] vs 0.5 [IQR, 0.0-1.1], P = .56) publications per year but fewer last-author (0.1 [IQR, 0.0-0.7] vs 0.4 [IQR, 0.0-1.3], P < .0001) and total publications per year (2.7 [IQR, 1.0-6.2] vs 3.7 [IQR, 1.3-7.8], P = .05) than men. The H-index was lower for women than for men overall (8.0 [IQR, 3.0-15.0] vs 15.0 [IQR, 7.0-28.0], P < .001) but was similar between men and women who had been practicing for 10 to 20 years. CONCLUSIONS: Gender disparities persist in academic cardiothoracic surgery. Efforts should be made to support women in achieving senior roles and academic productivity.

A value-based approach to optimize red blood cell transfusion in patients receiving extracorporeal membrane oxygenation.

INTRODUCTION: The risk, cost, and adverse outcomes associated with packed red blood cell (RBC) transfusions in patients with cardiopulmonary failure requiring extracorporeal membrane oxygenation (ECMO) have raised concerns regarding the overutilization of RBC products. It is, therefore, necessary to establish optimal transfusion criteria and protocols for patients supported with ECMO. The goal of this study was to establish specific criteria for RBC transfusions in patients undergoing ECMO. METHODS: This was a retrospective cohort study conducted at Stanford University Hospital. Data on RBC utilization during the entire hospital stay were obtained, which included patients aged ≥18 years who received ECMO support between 1 January 2017, and 30 June 2020 (n = 281). The primary outcome was in-hospital mortality. RESULTS: Hemoglobin (HGB) levels >10 g/dL before transfusion did not improve in-hospital survival. Therefore, we revised the HGB threshold to ≤10 g/dL to guide transfusion in patients undergoing ECMO. To validate this intervention, we prospectively compared the pre- and post-intervention cohorts for in-hospital mortality. Post-intervention analyses found 100% compliance for all eligible records and a decrease in the requirement for RBC transfusion by 1.2 units per patient without affecting the mortality. CONCLUSIONS: As an institution-driven value-based approach to guide transfusion in patients undergoing ECMO, we lowered the threshold HGB level. Validation of this revised intervention demonstrated excellent compliance and reduced the need for RBC transfusion while maintaining the clinical outcome. Our findings can help reform value-based healthcare in this cohort while maintaining the outcome.

SARS-CoV-2 infection drives an inflammatory response in human adipose tissue through infection of adipocytes and macrophages.

Obesity, characterized by chronic low-grade inflammation of the adipose tissue, is associated with adverse coronavirus disease 2019 (COVID-19) outcomes, yet the underlying mechanism is unknown. To explore whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of adipose tissue contributes to pathogenesis, we evaluated COVID-19 autopsy cases and deeply profiled the response of adipose tissue to SARS-CoV-2 infection in vitro. In COVID-19 autopsy cases, we identified SARS-CoV-2 RNA in adipocytes with an associated inflammatory infiltrate. We identified two distinct cellular targets of infection: adipocytes and a subset of inflammatory adipose tissue-resident macrophages. Mature adipocytes were permissive to SARS-CoV-2 infection; although macrophages were abortively infected, SARS-CoV-2 initiated inflammatory responses within both the infected macrophages and bystander preadipocytes. These data suggest that SARS-CoV-2 infection of adipose tissue could contribute to COVID-19 severity through replication of virus within adipocytes and through induction of local and systemic inflammation driven by infection of adipose tissue-resident macrophages.

Quantitative goals for research output and scholarly impact to enhance basic science R01 grant renewal for cardiothoracic surgeons.

Objectives: Cardiothoracic (CT) surgeons with National Institutes of Health (NIH) R01 funding face a highly competitive renewal process. The factors that contribute to successful grant renewal for CT surgeons remain poorly defined. We hypothesized that renewed basic science grants are associated with high research output and scholarly impact during the preceding award cycle. Methods: Using a database of academic CT surgeons (n = 992) at accredited training institutions in 2018, we identified basic science R01 grants awarded to CT surgeon principal investigators since 1985. Data for each award were obtained from publicly available online sources. Scholarly impact was evaluated using the NIH-validated relative citation ratio (RCR), defined as an article's citation rate divided by that of R01-funded publications in the same field. Continuous data are presented as medians and analyzed using the Mann-Whitney test. Results: We identified 102 basic science R01 award cycles, including 33 that were renewed (32.4%). Renewed and nonrenewed awards had a similar start year and funding period. Principal investigators of renewed versus nonrenewed awards were similar in surgical subspecialty, research training, attending experience, academic rank, and previous NIH funding. Renewed awards produced more publications per year over the funding cycle (3.4 vs 1.5; P = .0010) and exhibited a greater median RCR during the funding cycle (0.84 vs 0.66; P = .0183). Conclusions: CT surgery basic science R01 grants are associated with high research output and scholarly impact. At the 50th percentile among renewed grants, CT surgeons published 3.4 funded manuscripts per year with a median RCR of 0.84 during the previous award cycle.

An automated line-clearing chest tube system after cardiac surgery.

Objective: To complete the first in-human study of the automated line clearance Thoraguard chest tube system. The study focuses on the viability and efficacy of the device in comparison with conventional models as well as secondary matters such as patient experience and ease of use. Methods: This was a single-center, prospective, open-label study involving adult patients (n = 27) who underwent nonemergent, first-time, cardiac surgery. Patients received automated clearance chest tubes for surgical drainage in both the mediastinal and pleural spaces. The control group was retrospective (n = 80); individuals received conventional chest tubes placed and secured in locations determined at the surgeon's discretion. Results: The automated-clearance tubes exhibited a similar drainage profile at 1, 3, 6, 12, and 24 hours compared with the conventional chest tubes. The final output at the time of tube removal was also similar (1150 [750-1590] vs 1289 [766.3-1890] mL, respectively, P = .76). The number of patients readmitted for drainage of an effusion was similar in both groups (1/27 [3.7%] vs 3/80 [3.75%], P > .99). Conclusions: This study has shown that the Centese Thoraguard chest tube system is a viable option for surgical chest drainage and effective when used in routine cardiac surgery operations.

Biodegradable external wrapping promotes favorable adaptation in an ovine vein graft model.

Vein grafts, the most commonly used conduits in multi-vessel coronary artery bypass grafting surgery, have high intermediate- and long-term failure rates. The abrupt and marked increase in hemodynamic loads on the vein graft is a known contributor to failure. Recent computational modeling suggests that veins can more successfully adapt to an increase in mechanical load if the rate of loading is gradual. Applying an external wrap or support at the time of surgery is one way to reduce the transmural load, and this approach has improved performance relative to an unsupported vein graft in several animal studies. Yet, a clinical trial in humans has shown benefits and drawbacks, and mechanisms by which an external wrap affects vein graft adaptation remain unknown. This study aims to elucidate such mechanisms using a multimodal experimental and computational data collection pipeline. We quantify morphometry using magnetic resonance imaging, mechanics using biaxial testing, hemodynamics using computational fluid dynamics, structure using histology, and transcriptional changes using bulk RNA-sequencing in an ovine carotid-jugular interposition vein graft model, without and with an external biodegradable wrap that allows loads to increase gradually. We show that a biodegradable external wrap promotes luminal uniformity, physiological wall shear stress, and a consistent vein graft phenotype, namely, it prevents over-distension, over-thickening, intimal hyperplasia, and inflammation, and it preserves mechanotransduction. These mechanobiological insights into vein graft adaptation in the presence of an external support can inform computational growth and remodeling models of external support and facilitate design and manufacturing of next-generation external wrapping devices. STATEMENT OF SIGNIFICANCE: External mechanical support is emerging as a promising technology to prevent vein graft failure following coronary bypass graft surgery. While variants of this technology are currently under investigation in clinical trials, the fundamental mechanisms of adaptation remain poorly understood. We employ an ovine carotid-jugular interposition vein graft model, with and without an external biodegradable wrap to provide mechanical support, and probe vein graft adaptation using a multimodal experimental and computational data collection pipeline. We quantify morphometry using magnetic resonance imaging, mechanics using biaxial testing, fluid flow using computational fluid dynamics, vascular composition and structure using histology, and transcriptional changes using bulk RNA sequencing. We show that the wrap mitigates vein graft failure by promoting multiple adaptive mechanisms (across biological scales).

Diminishing Basic Science Research Experience Among United States Cardiothoracic Surgery Trainees.

INTRODUCTION: There is growing concern regarding the attrition of surgeon-scientists. To understand the decline of basic science research (BSR), it is essential to examine trends in research conducted by trainees. We hypothesized that, over recent decades, cardiothoracic (CT) surgery trainees have published fewer BSR articles. MATERIALS AND METHODS: CT surgeons at United States training institutions in 2020 who completed training in the past three decades, excluding international trainees, were analyzed (1991-2000: n = 148; 2001-2010: n = 228; 2011-2020: n = 247). Publication records were obtained from Scopus. Articles with medical subject heading terms involving molecular/cellular or animal research were classified as BSR using the National Institutes of Health iCite Translation module. Data were analyzed using Fisher's exact test or the Wilcoxon rank-sum test. RESULTS: While the proportion of surgeons who published a first-author paper during training remained stable over the past two decades (178/228 [78.1%] versus 189/247 [76.5%], P = 0.7427), the proportion who published a first-author BSR paper decreased significantly (135/228 [59.2%] versus 96/247 [38.9%], P < 0.0001). Among surgeons who published a first-author paper in training, the total papers published by each trainee did not change over the past two decades (3.5 versus 3.3 first-author papers per 10 y of training, P = 0.8819). However, the number of BSR papers published during training decreased significantly (1.7 versus 0.8 first-author papers per 10 y of training, P < 0.0001). CONCLUSIONS: CT surgery trainees are publishing fewer BSR papers. Additional efforts are needed to increase exposure of trainees to BSR and reaffirm that BSR is a valuable and worthwhile pursuit for academic surgeons.

Impact of PhD Degree Versus Non-PhD Research Fellowship on Future Research Productivity Among Academic Cardiothoracic Surgeons.

BACKGROUND: A PhD degree can offer significant research experience, but previous studies yielded conflicting conclusions on the relationship between a PhD degree and future research output. We compared the impact of a PhD degree versus research fellowship (RF) training on research productivity in cardiothoracic surgeons, hypothesizing that training pathways may influence potential associations. METHODS: CT surgeons practicing at all accredited United States CT surgery training programs in 2018 who pursued dedicated time for research (n = 597), including earning a PhD degree (n = 92) or completing a non-PhD RF (n = 505), were included. To control for training pathways, we performed subanalyses of U.S. medical school graduates (n = 466) and international medical school graduates (IMGs) (n = 131). Surgeon-specific data were obtained from publicly available sources (e.g., institutional webpages, Scopus). RESULTS: PhD surgeons published greater total papers (68.5 vs. 52.0, p = 0.0179) and total papers per year as an attending (4.6 vs. 3.0, p = 0.0150). For U.S. medical school graduates, there were 40 PhD surgeons and 426 non-PhD RF surgeons; both groups published a similar number of total papers (64.5 vs. 54.0, p = 0.3738) and total papers per year (3.2 vs. 3.0, p = 0.7909). For IMGs, there were 52 PhD surgeons and 79 non-PhD RF surgeons; the PhD surgeons published greater total papers (80.5 vs. 45.0, p = 0.0101) and total papers per year (5.7 vs. 2.7, p = 0.0037). CONCLUSION: CT surgeons with dedicated research training are highly academically productive. Although a PhD degree may be associated with enhanced career-long research productivity for IMGs, this association was not observed for U.S. medical school graduates.

Human Coronary Plaque T Cells Are Clonal and Cross-React to Virus and Self.

BACKGROUND: Coronary artery disease is an incurable, life-threatening disease that was once considered primarily a disorder of lipid deposition. Coronary artery disease is now also characterized by chronic inflammation' notable for the buildup of atherosclerotic plaques containing immune cells in various states of activation and differentiation. Understanding how these immune cells contribute to disease progression may lead to the development of novel therapeutic strategies. METHODS: We used single-cell technology and in vitro assays to interrogate the immune microenvironment of human coronary atherosclerotic plaque at different stages of maturity. RESULTS: In addition to macrophages, we found a high proportion of αß T cells in the coronary plaques. Most of these T cells lack high expression of CCR7 and L-selectin, indicating that they are primarily antigen-experienced memory cells. Notably, nearly one-third of these cells express the HLA-DRA surface marker, signifying activation through their TCRs (T-cell receptors). Consistent with this, TCR repertoire analysis confirmed the presence of activated αß T cells (CD4

Analyzing the Scholarly Impact of Cardiothoracic Surgery Research Using the Relative Citation Ratio.

INTRODUCTION: The National Institutes of Health (NIH) recently developed the relative citation ratio (RCR), calculated as article citations benchmarked to NIH-funded publications in the same field. Here, we characterized the scholarly impact of academic cardiothoracic (CT) surgeons and their research using the RCR. MATERIALS AND METHODS: Using a database of 992 CT surgeons, we calculated the RCR for all articles published by each surgeon since 1980 using the NIH iCite database. All data were collected from publicly available online sources. Data are presented as median (interquartile range) or as odds ratios (ORs) for multivariable logistic regression analysis. RESULTS: Where RCR 1.00 indicates equal impact as an NIH-funded publication, the RCR among all 37,402 CT surgery articles was 0.84 (0.33-1.83) and the RCR among NIH-funded CT surgery articles was 1.07 (0.53-2.17). CT surgeons exhibited a career median RCR of 0.82 (0.54-1.13) and maximum RCR of 6.20 (3.04-13.57). Predictors of career median RCR >1.00 included female gender (OR 2.23, P = 0.001), thoracic subspecialization (OR 2.50, P < 0.001), full professor rank (OR 1.89, P = 0.001), and NIH funding (OR 1.75, P = 0.001). Predictors of career maximum RCR >50th percentile among CT surgeons included male gender (OR 1.87, P = 0.030), thoracic subspecialization (OR 2.05, P < 0.001), full professor rank (OR 4.89, P < 0.001), NIH funding (OR 3.17, P < 0.001), and career duration (OR 1.03, P = 0.002). CONCLUSIONS: We present the first assessment of the NIH-validated RCR for academic CT surgery. CT surgery research is highly impactful, although gender disparities persist with respect to the highest-impact research of our specialty.

Post-Transplant Extracorporeal Membrane Oxygenation for Severe Primary Graft Dysfunction to Support the Use of Marginal Donor Hearts.

Severe primary graft dysfunction (PGD) is the leading cause of early postoperative mortality following orthotopic heart transplantation (OHT). Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been used as salvage therapy. This study aimed to evaluate the outcomes in adult OHT recipients who underwent VA-ECMO for severe PGD. We retrospectively reviewed 899 adult (≥18 years) patients who underwent primary OHT at our institution between 1997 and 2017. Recipients treated with VA-ECMO (19, 2.1%) exhibited a higher incidence of previous cardiac surgery (p = .0220), chronic obstructive pulmonary disease (p = .0352), and treatment with a calcium channel blocker (p = .0018) and amiodarone (p = .0148). Cardiopulmonary bypass (p = .0410) and aortic cross-clamp times (p = .0477) were longer in the VA-ECMO cohort and they were more likely to have received postoperative transfusion (p = .0013); intra-aortic balloon pump (IABP, p < .0001), and reoperation for bleeding or tamponade (p < .0001). The 30-day, 1-year, and overall survival after transplantation of non-ECMO patients were 95.9, 88.8, and 67.4%, respectively, compared to 73.7, 57.9, and 47.4%, respectively in the ECMO cohort. Fourteen (73.7%) of the ECMO patients were weaned after a median of 7 days following OHT (range: 1-12 days). Following OHT, VA-ECMO may be a useful salvage therapy for severe PGD and can potentially support the usage of marginal donor hearts.

Colocalization of Coronary Plaque with Wall Shear Stress in Myocardial Bridge Patients.

PURPOSE: Patients with myocardial bridges (MBs) have a higher prevalence of atherosclerosis. Wall shear stress (WSS) has previously been correlated with plaque in coronary artery disease patients, but such correlations have not been investigated in symptomatic MB patients. The aim of this paper was to use a multi-scale computational fluid dynamics (CFD) framework to simulate hemodynamics in MB patient, and investigate the co-localization of WSS and plaque. METHODS: We identified N = 10 patients from a previously reported cohort of 50 symptomatic MB patients, all of whom had plaque in the proximal vessel. Dynamic 3D models were reconstructed from coronary computed tomography angiography (CCTA), intravascular ultrasound (IVUS) and catheter angiograms. CFD simulations were performed to compute WSS proximal to, within and distal to the MB. Plaque was quantified from IVUS images in 2 mm segments and registered to CFD model. Plaque area was compared to absolute and patient-normalized WSS. RESULTS: WSS was lower in the proximal segment compared to the bridge segment (6.1 ± 2.9 vs. 16.0 ± 7.1 dynes/cm2, p value < 0.01). Plaque area and plaque burden measured from IVUS peaked at 1-3 cm proximal to the MB entrance, coinciding with the first diagonal branch. Normalized WSS showed a statistically significant moderate correlation with plaque area (r = 0.41, p < 0.01). CONCLUSION: WSS may be obtained non-invasively in MB patients and provides a surrogate marker of plaque area. Using CFD, it may be possible to non-invasively assess the extent of plaque area, and identify patients who could benefit from frequent monitoring or medical management.