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      The Use of Biophysical Flow Models in the Surgical Management of Patients Affected by Chronic Thromboembolic Pulmonary Hypertension

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          Abstract

          Introduction: Chronic Thromboembolic Pulmonary Hypertension (CTEPH) results from progressive thrombotic occlusion of the pulmonary arteries. It is treated by surgical removal of the occlusion, with success rates depending on the degree of microvascular remodeling. Surgical eligibility is influenced by the contributions of both the thrombus occlusion and microvasculature remodeling to the overall vascular resistance. Assessing this is challenging due to the high inter-individual variability in arterial morphology and physiology. We investigated the potential of patient-specific computational flow modeling to quantify pressure gradients in the pulmonary arteries of CTEPH patients to assist the decision-making process for surgical eligibility.

          Methods: Detailed segmentations of the pulmonary arteries were created from postoperative chest Computed Tomography scans of three CTEPH patients. A focal stenosis was included in the original geometry to compare the pre- and post-surgical hemodynamics. Three-dimensional flow simulations were performed on each morphology to quantify velocity-dependent pressure changes using a finite element solver coupled to terminal 2-element Windkessel models. In addition to transient flow simulations, a parametric modeling approach based on constant flow simulations is also proposed as faster technique to estimate relative pressure drops through the proximal pulmonary vasculature.

          Results: An asymmetrical flow split between left and right pulmonary arteries was observed in the stenosed models. Removing the proximal obstruction resulted in a reduction of the right-left pressure imbalance of up to 18%. Changes were also observed in the wall shear stresses and flow topology, where vortices developed in the stenosed model while the non-stenosed retained a helical flow. The predicted pressure gradients from constant flow simulations were consistent with the ones measured in the transient flow simulations.

          Conclusion: This study provides a proof of concept that patient-specific computational modeling can be used as a noninvasive tool for assisting surgical decisions in CTEPH based on hemodynamics metrics. Our technique enables determination of the proximal relative pressure, which could subsequently be compared to the total pressure drop to determine the degree of distal and proximal vascular resistance. In the longer term this approach has the potential to form the basis for a more quantitative classification system of CTEPH types.

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          Most cited references42

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          Progressive right ventricular dysfunction in patients with pulmonary arterial hypertension responding to therapy.

          The purpose of this study was to examine the relationship between changes in pulmonary vascular resistance (PVR) and right ventricular ejection fraction (RVEF) and survival in patients with pulmonary arterial hypertension (PAH) under PAH-targeted therapies. Despite the fact that medical therapies reduce PVR, the prognosis of patients with PAH is still poor. The primary cause of death is right ventricular (RV) failure. One possible explanation for this apparent paradox is the fact that a reduction in PVR is not automatically followed by an improvement in RV function. A cohort of 110 patients with incident PAH underwent baseline right heart catheterization, cardiac magnetic resonance imaging, and 6-min walk testing. These measurements were repeated in 76 patients after 12 months of therapy. Two patients underwent lung transplantation, 13 patients died during the first year, and 17 patients died in the subsequent follow-up of 47 months. Baseline RVEF (hazard ratio [HR]: 0.938; p = 0.001) and PVR (HR: 1.001; p = 0.031) were predictors of mortality. During the first 12 months, changes in PVR were moderately correlated with changes in RVEF (R = 0.330; p = 0.005). Changes in RVEF (HR: 0.929; p = 0.014) were associated with survival, but changes in PVR (HR: 1.000; p = 0.820) were not. In 68% of patients, PVR decreased after medical therapy. Twenty-five percent of those patients with decreased PVR showed a deterioration of RV function and had a poor prognosis. After PAH-targeted therapy, RV function can deteriorate despite a reduction in PVR. Loss of RV function is associated with a poor outcome, irrespective of any changes in PVR. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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            Pulmonary endarterectomy: experience and lessons learned in 1,500 cases.

            The incidence of pulmonary hypertension resulting from chronic thrombotic occlusion of the pulmonary arteries is significantly underestimated. Although medical therapy for the condition is supportive only, surgical therapy is curative. Our pulmonary endarterectomy program was begun in 1970, and 188 patients were operated on in the subsequent 20 years. With the increased recognition of the disease and the success of operative therapy, however, more than 1,400 operations have been done since 1990 at our center. The safety and efficacy of the operation was assessed with changes made through increased experience. We examined in detail the results of our last 500 consecutive patients. Median sternotomy, cardiopulmonary bypass, profound hypothermia, and circulatory arrest were found to be essential to the success of the operation. All occluding material could be removed at operation. We currently believe that there is no degree of embolic occlusion within the pulmonary vascular tree that is inaccessible and no degree of right ventricular impairment or any level of pulmonary vascular resistance that is inoperable. With shorter cardiac arrest periods and the use of a cooling jacket to the head, cerebral impairment has been eliminated. The pulmonary artery pressures and pulmonary vascular resistance in a recent cohort of 500 patients is examined. The mortality rate for the operation has been reduced steadily, and was 22 of the last 500 patients operated on (4.4%). The operation is considered curative and therefore greatly superior to transplantation for this condition. Current techniques of operation make the procedure relatively safe.
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              Aneurysm growth occurs at region of low wall shear stress: patient-specific correlation of hemodynamics and growth in a longitudinal study.

              Evolution of intracranial aneurysmal disease is known to be related to hemodynamic forces acting on the vessel wall. Low wall shear stress (WSS) has been reported to have a negative effect on endothelial cells normal physiology and may be an important contributor to local remodeling of the arterial wall and to aneurysm growth and rupture. Seven patient-specific models of intracranial aneurysms were constructed using MR angiography data acquired at two different time points (mean 16.4+/-7.4 months between the two time points). Numeric simulations of the flow in the baseline geometries were performed to compute WSS distributions. The lumenal geometries constructed from the two time points were manually coregistered, and the radial displacement of the wall was calculated on a pixel-by-pixel basis. This displacement, corresponding to the local growth of the aneurysm, was compared to the time-averaged wall shear stress (WSS TA) through the cardiac cycle at that location. For statistical analysis, radial displacement was considered to be significant if it was larger than half of the MR pixel resolution (0.3 mm). Mean WSS TA values obtained for the areas with a displacement smaller and greater than 0.3 mm were 2.55+/-3.6 and 0.76+/-1.5 Pa, respectively (P<0.001). A linear correlation analysis demonstrated a significant relationship between WSS TA and surface displacement (P<0.001). These results indicate that aneurysm growth is likely to occur in regions where the endothelial layer lining the vessel wall is exposed to abnormally low wall shear stress.
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                Author and article information

                Contributors
                Journal
                Front Physiol
                Front Physiol
                Front. Physiol.
                Frontiers in Physiology
                Frontiers Media S.A.
                1664-042X
                13 March 2018
                2018
                : 9
                : 223
                Affiliations
                [1] 1King's College London, GKT School of Medical Education , London, United Kingdom
                [2] 2Cardiothoracic Surgery Unit, Papworth Hospital NHS Foundation Trust , Cambridge, United Kingdom
                [3] 3King's College London, School of Biomedical Engineering and Imaging Sciences, St. Thomas' Hospital , London, United Kingdom
                Author notes

                Edited by: Mariano Vázquez, Barcelona Supercomputing Center, Spain

                Reviewed by: Jeannette Spühler, Royal Institute of Technology, Sweden; Jacopo Biasetti, Johns Hopkins University, United States

                *Correspondence: Adelaide de Vecchi adelaide.de_vecchi@ 123456kcl.ac.uk

                This article was submitted to Computational Physiology and Medicine, a section of the journal Frontiers in Physiology

                Article
                10.3389/fphys.2018.00223
                5859070
                29593574
                41839a10-75a7-44c9-ad4b-b60759925e34
                Copyright © 2018 Spazzapan, Sastry, Dunning, Nordsletten and de Vecchi.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 15 December 2017
                : 28 February 2018
                Page count
                Figures: 4, Tables: 4, Equations: 3, References: 50, Pages: 13, Words: 8902
                Funding
                Funded by: Engineering and Physical Sciences Research Council 10.13039/501100000266
                Award ID: EN/N011554/1
                Award ID: EP/R003866/1
                Funded by: Wellcome Trust 10.13039/100004440
                Award ID: WT 203148/Z/16/Z
                Categories
                Physiology
                Original Research

                Anatomy & Physiology
                cteph,hpc-based computational modeling,biophysical flow modeling,patient specific computational modeling,computational physiology

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