Computational Fluid Dynamics Simulations to Predict False Lumen Enlargement After Surgical Repair of Type-A Aortic Dissection.

We aim to use computational fluid dynamics to investigate the hemodynamic conditions that may predispose to false lumen enlargement in this patient population. Nine patients who received surgical repairs of their type-A aortic dissections between 2017-2018 were retrospectively identified. Multiple contrast-enhanced post-operative CT scans were used to construct 3D models of aortic geometries. Computational fluid dynamics simulations of the models were run on a high-performance computing cluster using SimVascular - an open-source simulation package. Physiological pulsatile flow conditions (4.9 L/min) were used at the aortic true lumen inlet, and physiological vascular resistances were applied at the distal vascular ends. Exploratory analyses showed no correlation between rate of false lumen growth and blood pressure, immediate post-op aortic diameter, or the number of fenestrations (p = 0.2). 1-year post-operative CT scans showed a median false lumen growth rate of 4.31 (3.66, 14.67) mm/year Median (Interquartile range) peak systolic, mid-diastolic, and late diastolic velocity magnitudes were 0.90 (1.40); 0.10 (0.16); and 0.06 (0.06) cm/s respectively. Spearman's ranked correlations between fenestration velocity and 1-year false lumen growth rates were found to be statistically significant: Velocity magnitude at peak systolic (p = 0.025; rho = 0.75), mid diastolic (p = 0.025; rho = 0.75) and late diastolic phases of the cardiac cycle (p = 0.006; rho = 0.85). We have shown that false lumen growth is strongly correlated to fenestration flow velocity, which has potential implications for post-operative surveillance and risk stratification.

Predicting post-operative right ventricular failure using video-based deep learning.

Despite progressive improvements over the decades, the rich temporally resolved data in an echocardiogram remain underutilized. Human assessments reduce the complex patterns of cardiac wall motion, to a small list of measurements of heart function. All modern echocardiography artificial intelligence (AI) systems are similarly limited by design - automating measurements of the same reductionist metrics rather than utilizing the embedded wealth of data. This underutilization is most evident where clinical decision making is guided by subjective assessments of disease acuity. Predicting the likelihood of developing post-operative right ventricular failure (RV failure) in the setting of mechanical circulatory support is one such example. Here we describe a video AI system trained to predict post-operative RV failure using the full spatiotemporal density of information in pre-operative echocardiography. We achieve an AUC of 0.729, and show that this ML system significantly outperforms a team of human experts at the same task on independent evaluation.

Long-term survival in patients with post-LVAD right ventricular failure: multi-state modelling with competing outcomes of heart transplant.

BACKGROUND: Multicenter data on long term survival following LVAD implantation that make use of contemporary definitions of RV failure are limited. Furthermore, traditional survival analyses censor patients who receive a bridge to heart transplant. Here we compare the outcomes of LVAD patients who develop post-operative RV failure accounting for the transitional probability of receiving an interim heart transplantation. METHODS: We use a retrospective cohort of LVAD patients sourced from multiple high-volume centers based in the United States. Five- and ten-year survival accounting for transition probabilities of receiving a heart transplant were calculated using a multi-state Aalen Johansen survival model. RESULTS: Of the 897 patients included in the study, 238 (26.5%) developed post-operative RV failure at index hospitalization. At 10 years the probability of death with post-op RV failure was 79.28% vs 61.70% in patients without (HR 2.10; 95% CI 1.72 - 2.57; p = < .001). Though not significant, patients with RV failure were less likely to be bridged to a heart transplant (HR 0.87, p = .4). Once transplanted the risk of death between both patient groups remained equivalent; the probability of death after a heart transplant was 3.97% in those with post-operative RV failure shortly after index LVAD implant, as compared to 14.71% in those without. CONCLUSIONS AND RELEVANCE: Long-term durable mechanical circulatory support is associated with significantly higher mortality in patients who develop post-operative RV failure. Improving outcomes may necessitate expeditious bridge to heart transplant wherever appropriate, along with critical reassessment of organ allocation policies.

Patient-Specific Computational Fluid Dynamics Reveal Localized Flow Patterns Predictive of Post-Left Ventricular Assist Device Aortic Incompetence.

BACKGROUND: Progressive aortic valve disease has remained a persistent cause of concern in patients with left ventricular assist devices. Aortic incompetence (AI) is a known predictor of both mortality and readmissions in this patient population and remains a challenging clinical problem. METHODS: Ten left ventricular assist device patients with de novo aortic regurgitation and 19 control left ventricular assist device patients were identified. Three-dimensional models of patients' aortas were created from their computed tomography scans, following which large-scale patient-specific computational fluid dynamics simulations were performed with physiologically accurate boundary conditions using the SimVascular flow solver. RESULTS: The spatial distributions of time-averaged wall shear stress and oscillatory shear index show no significant differences in the aortic root in patients with and without AI (mean difference, 0.67 dyne/cm2 [95% CI, -0.51 to 1.85]; P=0.23). Oscillatory shear index was also not significantly different between both groups of patients (mean difference, 0.03 [95% CI, -0.07 to 0.019]; P=0.22). The localized wall shear stress on the leaflet tips was significantly higher in the AI group than the non-AI group (1.62 versus 1.35 dyne/cm2; mean difference [95% CI, 0.15-0.39]; P<0.001), whereas oscillatory shear index was not significantly different between both groups (95% CI, -0.009 to 0.001; P=0.17). CONCLUSIONS: Computational fluid dynamics serves a unique role in studying the hemodynamic features in left ventricular assist device patients where 4-dimensional magnetic resonance imaging remains unfeasible. Contrary to the widely accepted notions of highly disturbed flow, in this study, we demonstrate that the aortic root is a region of relatively stagnant flow. We further identified localized hemodynamic features in the aortic root that challenge our understanding of how AI develops in this patient population.

Vascular Complications in the Sapien 3 Era: Continued Role of Transapical Approach to Transcatheter Aortic Valve Replacement.

With the introduction of the latest generation Sapien 3 (S3) transcatheter aortic valve, there has been a reduction in the usage of transapical (TA) approach for transcatheter aortic valve replacements in many centers. However, despite the smaller sheath size and the more streamlined delivery system, vascular complications continue to occur, especially in patients with peripheral vascular disease. Thus, our institution has maintained a stringent TA protocol aiming to prevent these complications. We hypothesize that this protocol has helped to reduce vascular complications and improve outcomes at our institution even in the S3 era. All transcatheter aortic valve replacement procedures done at our institution were considered for analysis. Patients were grouped according to whether their procedure was done before (Pre-S3 era) or after (S3 era) the introduction of the S3 valve, as well as whether they underwent a TA or a transfemoral (TF) approach. A femoral artery intraluminal diameter of <7.5 mm in the Pre-S3 era and <5.5 mm in the S3 era with circumferential calcifications triggered TA approach consideration. Vascular complications included vascular perforation, dissection, flow-limiting stenosis, unplanned vascular surgery, significant postprocedural bleeding, hematoma at the access site, and retroperitoneal bleed. The Welch t test of unequal variance and chi-squared test were used as appropriate. An alpha of <0.05 was considered significant. A total of 275 patients were included in the analysis (121 Pre-S3 era and 154 S3 era). The TA approach was utilized in 45% in the Pre-S3 era vs 15% in the S3 era (P < 0.001). Within the S3 era, 131 underwent the TF approach compared with 23 who underwent the TA approach. TA and TF patients were similar in all preoperative characteristics except hypertension. Mortality was significantly lower in the S3 era (0% vs 4% in the pre-S3 era, P = 0.02). Overall rates of vascular complications were similar between the Pre-S3 and the S3 eras (16% vs 14%, P = 0.63). Overall adverse outcomes were similar between the TA and the TF groups. TA patients saw significantly longer intensive care unit stay and total hospital stay. Our results show that despite a smaller sheath size, vascular complications continue at a similar rate into the S3 era. This occurred in the setting of an ongoing aggressive TA utilization in select patients, specifically those with peripheral vascular disease. Maintaining this approach is likely a large contributor to both our current success and reduced mortality.

A regulated multiscale closed-loop cardiovascular model, with applications to hemorrhage and hypertension.

A computational tool is developed for simulating the dynamic response of the human cardiovascular system to various stressors and injuries. The tool couples 0-dimensional models of the heart, pulmonary vasculature, and peripheral vasculature to 1-dimensional models of the major systemic arteries. To simulate autonomic response, this multiscale circulatory model is integrated with a feedback model of the baroreflex, allowing control of heart rate, cardiac contractility, and peripheral impedance. The performance of the tool is demonstrated in 2 scenarios: neurogenic hypertension by sustained stimulation of the sympathetic nervous system and an acute 10% hemorrhage from the left femoral artery.

Are nonemergent cardiac operations performed during off-time associated with worse outcome?

BACKGROUND: With the implementation of value-based health care, it is of increasing interest to understand whether performing elective surgeries during off-time impacts surgical outcomes. The objective of this study was to evaluate the impact of start times on nonemergent cardiac operations. METHODS: The institutional Society of Thoracic Surgeons was used to identify all adult nonemergent cardiac operations performed between January 2008 and December 2015 at our institution. "Off-time" is defined as either operation "late starts," that is, an incision time after 3 PM and before 7 AM, or procedures occurring during the weekends. Univariate and multivariate logistic regression analyses were performed to examine its impact on in-hospital mortality and major adverse events. Available cost data were directly obtained from the departmental BIOME database. RESULTS: Of the 3406 cardiac operations included in the study, 2933 (86.1%) were normal-start and 473 (13.9%) were off-time-start operations. After adjusting for patient and operative characteristics, late operating room start times were not associated with increased in-hospital mortality (P = 0.28, confidence interval [CI] 95% = 0.99-1.03), readmissions (P = 0.21, CI 95% = 0.99-1.07), or major adverse events (P = 0.07, CI 95% = 1.00-1.12). In addition, there was no significant impact on total hospital cost (9.0% increase, P = 0.07). CONCLUSIONS: These findings suggest that late operating room start times are not associated with increased mortality or other complications in a tertiary-care academic medical center. Our findings should be considered during operative scheduling to optimize resource distribution and patient care strategies.

The impact of migration and antimicrobial resistance on the transmission dynamics of typhoid fever in Kathmandu, Nepal: A mathematical modelling study.

BACKGROUND: A substantial proportion of the global burden of typhoid fever occurs in South Asia. Kathmandu, Nepal experienced a substantial increase in the number of typhoid fever cases (caused by Salmonella Typhi) between 2000 and 2003, which subsequently declined but to a higher endemic level than in 2000. This epidemic of S. Typhi coincided with an increase in organisms with reduced susceptibility against fluoroquinolones, the emergence of S. Typhi H58, and an increase in the migratory population in Kathmandu. METHODS: We devised a mathematical model to investigate the potential epidemic drivers of typhoid in Kathmandu and fit this model to weekly data of S. Typhi cases between April 1997 and June 2011 and the age distribution of S. Typhi cases. We used this model to determine if the typhoid epidemic in Kathmandu was driven by heightened migration, the emergence of organisms with reduced susceptibility against fluoroquinolones or a combination of these factors. RESULTS: Models allowing for the migration of susceptible individuals into Kathmandu alone or in combination with the emergence of S. Typhi with reduced susceptibility against fluoroquinolones provided a good fit for the data. The emergence of organisms with reduced susceptibility against fluoroquinolones organisms alone, either through an increase in disease duration or increased transmission, did not fully explain the pattern of S. Typhi infections. CONCLUSIONS: Our analysis is consistent with the hypothesis that the increase in typhoid fever in Kathmandu was associated with the migration of susceptible individuals into the city and aided by the emergence of reduced susceptibility against fluoroquinolones. These data support identifying and targeting migrant populations with typhoid immunization programmes to prevent transmission and disease.

Current Methods and Advances in Simulation of Hemorrhage after Trauma.

As animal models fall out of favor, there is demand for simulators to train medical personnel in the management of trauma and hemorrhage. Realism is essential to the development of simulators for training in the management of trauma and hemorrhage, but is difficult to achieve because it is difficult to create models that accurately represent bleeding organs. We present a simulation platform that uses real-time mathematical modeling of hemodynamics after hemorrhage and trauma and visually represents the injury described by the model. Using patient-specific imaging, 3D-mesh representations of the liver were created and merged with an anatomically accurate vascular tree. By using anatomically accurate representations of the vasculature, we were able to model the cardiovascular response to hemorrhage in a specific artery. The incorporation of autonomic tone allowed for the calculation of bleeding rate and aortic pressures. The 3D-mesh representation of the liver allowed us to simulate blood flow from the liver after trauma. For the first time, we have successfully incorporated tissue modeling and fluid dynamics with a model of the cardiovascular system to create a simulator. These simulations may aid in the creation of realistic virtual environments for training.

Use of preoperative aspirin in combined coronary and valve operations.

BACKGROUND: The aim of this study was to determine the relationship between preoperative aspirin use and postoperative outcomes in patients undergoing combined coronary artery bypass grafting and valve operations. METHODS: All combined coronary artery bypass grafting and valve procedures from 2008 to 2015 at our institution were identified. After exclusions, patients were stratified according to those that received preoperative aspirin and those who did not. Propensity score methodology was used to match the 2 groups using baseline and operative characteristics. Logistic regression models were then developed to assess differences in postoperative outcomes between groups. RESULTS: Of the 563 patients identified, 534 met inclusion criteria: preoperative aspirin = 327 (61.2%), no preoperative aspirin = 207 (38.8%). After propensity matching, 194 patient pairs were analyzed, with no significant differences in preoperative characteristics. No significant differences were observed between the preoperative aspirin and no preoperative aspirin groups in rates of 30-day mortality (3.6% vs 4.1%, P = 1.00), major adverse cardiovascular events (23.2% vs 24.2%, P = .91), or 30-day readmission (12.4% vs 11.9%, P = 1.00), among others. CONCLUSION: Preoperative aspirin use in patients undergoing combined coronary artery bypass grafting and valve operations was not associated with significant differences in major postoperative outcomes. Large-scale, randomized trials are needed to better establish the role of preoperative aspirin in this population.

Accounting for Behavior in Treatment Effects: New Applications for Blind Trials.

The double-blind randomized controlled trial (DBRCT) is the gold standard of medical research. We show that DBRCTs fail to fully account for the efficacy of treatment if there are interactions between treatment and behavior, for example, if a treatment is more effective when patients change their exercise or diet. Since behavioral or placebo effects depend on patients' beliefs that they are receiving treatment, clinical trials with a single probability of treatment are poorly suited to estimate the additional treatment benefit that arises from such interactions. Here, we propose methods to identify interaction effects, and use those methods in a meta-analysis of data from blinded anti-depressant trials in which participant-level data was available. Out of six eligible studies, which included three for the selective serotonin re-uptake inhibitor paroxetine, and three for the tricyclic imipramine, three studies had a high (>65%) probability of treatment. We found strong evidence that treatment probability affected the behavior of trial participants, specifically the decision to drop out of a trial. In the case of paroxetine, but not imipramine, there was an interaction between treatment and behavioral changes that enhanced the effectiveness of the drug. These data show that standard blind trials can fail to account for the full value added when there are interactions between a treatment and behavior. We therefore suggest that a new trial design, two-by-two blind trials, will better account for treatment efficacy when interaction effects may be important.

Predicting the impact of vaccination on the transmission dynamics of typhoid in South Asia: a mathematical modeling study.

BACKGROUND: Modeling of the transmission dynamics of typhoid allows for an evaluation of the potential direct and indirect effects of vaccination; however, relevant typhoid models rooted in data have rarely been deployed. METHODOLOGY/PRINCIPAL FINDINGS: We developed a parsimonious age-structured model describing the natural history and immunity to typhoid infection. The model was fit to data on culture-confirmed cases of typhoid fever presenting to Christian Medical College hospital in Vellore, India from 2000-2012. The model was then used to evaluate the potential impact of school-based vaccination strategies using live oral, Vi-polysaccharide, and Vi-conjugate vaccines. The model was able to reproduce the incidence and age distribution of typhoid cases in Vellore. The basic reproductive number (R 0) of typhoid was estimated to be 2.8 in this setting. Vaccination was predicted to confer substantial indirect protection leading to a decrease in the incidence of typhoid in the short term, but (intuitively) typhoid incidence was predicted to rebound 5-15 years following a one-time campaign. CONCLUSIONS/SIGNIFICANCE: We found that model predictions for the overall and indirect effects of vaccination depend strongly on the role of chronic carriers in transmission. Carrier transmissibility was tentatively estimated to be low, consistent with recent studies, but was identified as a pivotal area for future research. It is unlikely that typhoid can be eliminated from endemic settings through vaccination alone.