Towards patient-specific risk assessment of abdominal aortic aneurysm

Diagnosis of vascular disease and selection and planning of therapy are to a large extent based on the geometry of the diseased vessel. Treatment of a particular vascular disease is usually considered if the geometrical parameter that characterizes the severity of the disease, e.g. % vessel narrowing, exceeds a threshold. The thresholds that are used in clinical practice are based on epidemiological knowledge, which has been obtained by clinical studies including large numbers of patients. They may apply “on average”, but they can be sub-optimal for individual patients. To realize more patient-specific treatment decision criteria, more detailed knowledge may be required about the vascular hemodynamics, i.e. the blood flow and pressure in the diseased vessel and the biomechanical reaction of the vessel wall to this flow and pressure. Over the last decade, a substantial number of publications have appeared on hemodynamic modeling. Some studies have provided first evidence that this modeling may indeed be used to support therapeutic decisions. The goal of the research reported in this paper is to go one step further, namely to investigate the feasibility of a patient-specific hemodynamic modeling methodology that is not only effective (improves therapeutic decisions), but that is also efficient (easy to use, fast, as much as possible automatic) and robust (insensitive to variation in the quality of the input data, same outcome for different users). A review is presented of our research performed during the last 5 years and the results that were achieved. This research focused on the risk assessment for one particular disease, namely abdominal aortic aneurysm, a life-threatening dilatation of the abdominal aorta.     

Retrocaval ureter and preaortic iliac venous confluence in a patient with an abdominal aortic aneurysm

Anomalous anatomic location of a large venous system poses a potential hazard in aortic operations. We encountered a patient with an infrarenal abdominal aortic aneurysm who was also found at preoperative contrast-enhanced computed tomography to have a retrocaval right ureter and a preaortic iliac vein confluence. This combined anomaly has not previously been reported except for one postmortem case. As abdominal aortic surgery is currently performed routinely, care must be taken to avoid injury to surrounding organs due to rare anatomic anomalies.     

Assessment of endoleak significance after endovascular repair of abdominal aortic aneurysms: a lumped parameter model

The outcome of endovascular repair of abdominal aortic aneurysms (AAAs) is greatly compromised by the possible occurrence of endoleak. Previously, the causes and effects of endoleak on a patient-specific basis have mainly been investigated in experimental studies. In order to both reconcile and physically substantiate the various experimental findings, a lumped parameter model of an incompletely excluded AAA was developed. After experimental validation, the model was applied to study the effects on the intrasac pressure of the degree of endoleak, the degree of stent-graft compliance, and the resistance of a possible outflow tract formed by a branching vessel. It is concluded that the presence of endoleak leads to elevated intrasac pressure, the mean of which is mainly governed by the outflow tract resistance, while the pulse pressure is governed by both the endoleak resistance and the stent-graft compliance. Based on the agreement of the current results with previous findings, it is further concluded that the lumped parameter modelling method provides a useful numerical tool for validating experimental endoleak studies.     

Computational simulation of aortic aneurysm using FSI method: influence of blood viscosity on aneurismal dynamic behaviors

It is well-established that blood viscosity plays a significant role in the determination of the health of the individual. It has been reported that many cardiovascular diseases are associated with blood viscosity. In this paper, the dynamic behaviors of aortic aneurysm subject to physiological blood flow with normal and high viscosities are presented. Fluid–structure interaction (FSI) method was used in the computational simulation. The influence of blood viscosity on flow dynamics within the aneurysm sac, aneurismal diameter, cross sectional shape, wall axial displacement and wall shear stress (WSS) was studied in detail. This investigation uncovered the correlations between blood viscosity and the dynamic behaviors of aortic aneurysm, which have rarely been found in existing literatures. We believe that these findings may provide important implications for individualized endovascular treatment for patient with aortic aneurysm.     

腹主动脉瘤的数值计算模型比较研究

目的分别采用纯流体模型和流固耦合模型来计算腹主动脉瘤的血流动力学特征,比较两种数值模型的不同,并讨论在研究腹主动脉瘤中的应用。方法使用Gambit 2.2.30和COMSOL Multiphysics 4.2建立腹主动脉瘤的理想模型,分别基于有限体的方法分析纯流体模型,基于任意拉格朗日-欧拉算法(Arbitrary Lagrangian-Eulerian)计算流固耦合模型。结果同样的入口速度下,纯流体模型出现4个涡流和6个局部压力集中;流固耦合模型只有2个涡流和局部压力集中,且涡流中心更接近腹主动脉瘤的远端。在边界层分离点、血流回帖位置以及腹主动脉瘤的近端和远端,两种模型均出现壁剪切力极值。血管壁的最大形变和最大壁应力出现在腹主动脉瘤的近端和远端。结论两种模型的涡流个数和涡流中心的位置均不一样,与瘤体的生长有着密切的关联;流固耦合模型中的最大壁剪切力比纯流体模型要小36%;最大壁应力和最大血管壁的形变量与出口血压呈正相关。在研究血管瘤生长与血流动力学的关系时需要考虑使用流固耦合模型。     

Assessment of the influence of the compliant aortic root on aortic valve mechanics by means of a geometrical model

In recent years several researchers have suggested that the changes in the geometry and angular dimensions of the aortic root which occur during the cardiac cycle are functional to the optimisation of aortic valve function, both in terms of diminishing leaflet stresses and of fluid-dynamic behaviour. The paper presents an analytical parametric model of the aortic valve which includes the aortic root movement. The indexes used to evaluate the valve behaviour are: the circumferential membrane stress and the stress at the free edge of the leaflet, the index of bending strain, the bending of the leaflet at the line attachment in the radial and circumferential directions and the shape of the conduit formed by the leaflets during systole. In order to evaluate the role of geometric changes in valve performance, two control cases were considered, with different reference geometric configuration, where the movement of the aortic root was ignored. The results obtained appear consistent with physiological data, especially with regard to the late diastolic phase and the early ejection phase, and put in evidence the role of the aortic root movement in the improvement of valve behaviour.     

Combining two potential causes of metalloproteinase secretion causes abdominal aortic aneurysms in rats: a new experimental model

Progress in understanding the pathophysiology of abdominal aortic aneurysms (AAA) is dependent in part on the development and application of effective animal models that recapitulate key aspects of the disease. The objective was to produce an experimental model of AAA in rats by combining two potential causes of metalloproteinase (MMP) secretion: inflammation and turbulent blood flow. Male Wistar rats were randomly divided in four groups: Injury, Stenosis, Aneurysm and Control (40/group). The Injury group received a traumatic injury to the external aortic wall. The Stenosis group received an extrinsic stenosis at a corresponding location. The Aneurysm group received both the injury and stenosis simultaneously, and the Control group received a sham operation. Animals were euthanized at days 1, 3, 7 and 15. Aorta and/or aneurysms were collected and the fragments were fixed for morphologic, immunohistochemistry and morphometric analyses or frozen for MMP assays. AAAs had developed by day 3 in 60-70% of the animals, reaching an aortic dilatation ratio of more than 300%, exhibiting intense wall remodelling initiated at the adventitia and characterized by an obvious inflammatory infiltrate, mesenchymal proliferation, neoangiogenesis, elastin degradation and collagen deposition. Immunohistochemistry and zymography studies displayed significantly increased expressions of MMP-2 and MMP-9 in aneurysm walls compared to other groups. The haemo-dynamic alterations caused by the stenosis may have provided additional contribution to the MMPs liberation. This new model illustrated that AAA can be multifactorial and confirmed the key roles of MMP-2 and MMP-9 in this dynamic remodelling process.     

Predictors of postoperative mortality of ruptured abdominal aortic aneurysm: a retrospective clinical study

Purpose

Despite significant improvements in surgery, anesthesia, and postoperative critical care, the postoperative mortality rate of ruptured abdominal aortic aneurysm (RAAA) has remained at 40% to 50% for several decades. Therefore, we evaluated factors associated with the postoperative mortality of RAAA.

Materials and Methods

From January 1999 to December 2008, a retrospective study was performed with 34 patients who underwent open repair of RAAA. The preoperative factors included age, sex, smoking, comorbidities, serum creatinine, hemoglobin, shock, pulse rate, and time from emergency room to operation room. The intraoperative factors included blood loss, transfusion, aortic clamping site and time, aneurysmal characteristics, rupture type, graft type, hourly urine output (HUO), and operative time. The postoperative factors included inotropic support, renal replacement therapy (RRT), reoperation, bowel ischemia, multiple organ failure (MOF), and intensive care unit stay. The 2-day and the 30-day mortality rates were analyzed separately.

Results

The 2-day and the 30-day mortality rates were 14.7% and 41.2%, respectively. On univariate analysis, shock, transfusion, HUO, inotropic support and MOF for the 2-day mortality and serum creatinine, transfusion, aortic clamping site, HUO, inotropic support, RRT and MOF for the 30-day mortality were statistically significant. On multivariate analysis, shock, inotropic support and MOF for the 2-day mortality and aortic clamping site, RRT and MOF for the 30-day mortality were statistically significant.

Conclusion

To decrease the postoperative mortality rate of RAAA, prevention of massive hemorrhage and acute renal failure with infrarenal aortic clamping, as well as prompt operative control of bleeding and maintenance of systemic perfusion are important.     

基于三维有限元模型的脊柱生物力学特性研究进展

脊柱相关疾病研究是一门新兴的边缘学科,其研究重点即为脊柱的生物力学特性.综合分析了基于三维有限元模型的腰椎和颈椎生物力学特性研究方法;总结出有限元建模的三种方法,即几何建模法、三维坐标仪建模法以及图像建模法;提炼出图像建模法的关键步骤,即几何模型的建立、椎骨和软组织的材料特性定义、边界条件定义以及模型验证分析;最后提出有限元建模的两个主要改进方面及其研究趋势.     

Experience of an abdominal aortic aneurysm in a patient having crossed ectopia with fusion anomaly of the kidney

We report a case of surgically treated abdominal aortic aneurysm (AAA) in a patient having crossed ectopia with fusion anomaly of the kidney. One artery from the abdominal aorta above the aneurysm supplies the right kidney while three renal arteries (two from the aneurysm itself and one from the left common iliac artery) supply the crossed ectopic kidney. Preoperative imaging to define the arterial and collecting systems along with a detailed planning of the operation is essential to prevent ischemic renal injury as well as ureteral injury during AAA repair.     

Profiles of immune infiltration in abdominal aortic aneurysm and their associated marker genes: a gene expression-based study

Immune-mediated inflammation plays a key role in the pathology of abdominal aortic aneurysm (AAA). We aimed to use a computational approach to profile the immune infiltration patterns and related core genes in AAA samples based on the overexpression of gene signatures. The microarray datasets of AAA and normal abdominal tissues were acquired from gene expression omnibus (GEO) database. We evaluated the composition of immune infiltrates through microenvironment cell populations (MCP)-counter. Weighted gene correlation network analysis (WGCNA) was employed to construct the co-expression network and extract gene information in the most relevant module. Functional and pathway enrichment analysis was performed and immune infiltration related core genes were screened. AAA tissues had a higher level of infiltration by cytotoxic lymphocytes, NK cells, T cells, fibroblasts, myeloid dendritic cells, and neutrophils than normal aorta. The red module was strongly correlated with the infiltrating levels of T cells and cytotoxic lymphocytes. Gene ontology (GO) and pathway analyses revealed that genes in the most relevant module were mainly enriched in T cell activation, regulation of lymphocyte activation, cytokine-cytokine receptor interaction, and chemokine signaling pathway, etc. The expression of GZMK, CCL5, GZMA, CD2, and EOMES showed significant correlations with cytotoxic lymphocytes, while CD247, CD2, CD6, RASGRP1, and CD48 expression were positively associated with T cell infiltration. In conclusion, we comprehensively analyzed profiles of infiltrated immune cells in AAA tissues and their associated marker genes. Our data may provide a novel clue to indicate the underlying molecular mechanisms of AAA formation in terms of immune infiltration.     

Alveolar-capillary diffusion and ventilation-perfusion inhomogeneity: a mathematical model

In analysis of ventilation-perfusion inhomogeneity with inert gases, it is commonly assumed that the effects of alveolar-capillary diffusion can be ignored. This approximation may not be valid during exercise or in the presence of oedema or emphysema. A mathematical model is presented of inert gas exchange that allows for a diffusion limitation as well as ventilation-perfusion inhomogeneity. These effects can be distinguished by examining how partial pressure ratios of various inert gases change with solubility and alveolar-capillary diffusivity. Furthermore, the model suggests that the input of inert gases by inhalation rather than venous infusion is feasible and that sampling of mixed-venous blood is unnecessary. Hence, the inert gas study of abnormal pulmonary gas exchange may yield more information and may be more readily applied to clinical studies than currently recognised.     

A patient-specific computational model of fluid-structure interaction in abdominal aortic aneurysms

It is generally believed that knowledge of the wall stress distribution could help to find better rupture risk predictors of abdominal aortic aneurysms (AAAs). Although AAA wall stress results from combined action between blood, wall and intraluminal thrombus, previously published models for patient-specific assessment of the wall stress predominantly did not include fluid-dynamic effects. In order to facilitate the incorporation of fluid–structure interaction in the assessment of AAA wall stress, in this paper, a method for generating patient-specific hexahedral finite element meshes of the AAA lumen and wall is presented. The applicability of the meshes is illustrated by simulations of the wall stress, blood velocity distribution and wall shear stress in a characteristic AAA. The presented method yields a flexible, semi-automated approach for generating patient-specific hexahedral meshes of the AAA lumen and wall with predefined element distributions. The combined fluid/solid mesh allows for simulations of AAA blood dynamics and AAA wall mechanics and the interaction between the two. The mechanical quantities computed in these simulations need to be validated in a clinical setting, after which they could be included in clinical trials in search of risk factors for AAA rupture.     

Repair of ruptured abdominal aortic aneurysms with bifurcated endografts: a single-center study

OBJECTIVE:

The aim of this study was to describe our early experience in the treatment of ruptured abdominal aortic aneurysms with bifurcated endografts. We report on our initial twelve-month experience using this approach.

METHODS:

Clinical data on patients with ruptured abdominal aortic aneurysms treated at a single tertiary center in Brazil were prospectively recorded. The eligibility for endovascular treatment was evaluated by computed tomography scanning and anatomical features were determined based on the method of treatment.

RESULTS:

From February 2012 to January 2013 (12 months), 28 consecutive patients (mean age 67.2 years, range 45-85 years) underwent treatment for ruptured abdominal aortic aneurysms at our hospital. Eighteen patients (64.3%) were suitable for and underwent endovascular treatment with bifurcated endografts (16 patients) or aortouniiliac endografts (two patients). Ten patients who were considered unsuitable for endograft repair underwent open repair. Seven patients were classified as hemodynamically unstable (Endovascular, 5; Open, 2), and 21 were classified as stable (Endovascular, 13; Open, 8). The overall 30-day mortality rate associated with endovascular treatment was 27.8% (stable, 18.7%; unstable, 40%) and the rate associated with open repair was 50% (stable, 37.5%; unstable, 100%).

CONCLUSIONS:

In this study, the suitability of patients for endovascular repair of ruptured abdominal aortic aneurysms was high and the overall results of endovascular treatment remain encouraging. Indeed, bifurcated endografts are a feasible option for treating anatomically eligible ruptured abdominal aortic aneurysms.     

Use of a model for simulating individual aortic dynamics in man

A simulation model is suggested for the analysis of aortic dynamics in man. The aortic model consists of six segments and is part of a larger model of the closed-loop human circulation. The model is simulated on a special-purpose analogue computer. Three parameters are employed to characterise the arterial system; peripheral resistance, aortic compliance and peripheral damping. Using a method for adapting the model to the individual patient, measurements of aortic pressure, cardiac output and pulse transmission time from 29 patients were used to test the validity of this approach. The model is able to simulate the pressure course along the aorta satisfactorily. The compliance calculated from the transmission properties of the aorta was compared with the complicance calculated from the stroke volume and pressure pulse. An adequate correlation (r=0.98) was found between these two independent methods. The mean compliance of the total aorta was 0.6 ml/mm Hg at a mean pressure of 104 mm Hg. The compliance showed large individual variations and decreasing values with increasing age of the patient. It is concluded that the model enables simulation of the individual aorta.     

Intrathoracic pressure fluctuations move blood during CPR: Comparison of hemodynamic data with predictions from a mathematical model

Whether blood flow during cardiopulmonary resuscitation (CPR) results from intrathoracic pressure fluctuations or direct cardiac compression remains controversial. We developed a mathematical model that predicts that blood flow due to intrathoracic pressure fluctuations should be insensitive to compression rate over a wide range but dependent on the applied force and compression duration. If direct compression of the heart plays a major role, however, the model predicts that flow should be dependent on compression rate and force, but above a threshold, insensitive to compression duration. These differences in hemodynamics produced by changes in rate and duration form a basis for determining whether blood flow during CPR results from intrathoracic pressure fluctuations or from direct cardiac compression. The model was validated for direct cardiac compression by studying the hemodynamics of cyclic cardiac deformation following thoracotomy in four anesthetized, 21–32-kg dogs. As predicted by the model, there was no change in myocardial or cerebral perfusion pressures when the duration of compression was increased from 15% to 45% of the cycle at a constant rate of 60/min. There was, however, a significant increase in perfusion pressures when rate was increased from 60 to 150/min at a constant duration of 45%. The model was validated for intrathoracic pressure changes by studying the hemodynamics produced by a thoracic vest (vest CPR) in eight dogs. The vest contained a bladder that was inflated and deflated. Vest CPR changed intrathoracic pressure without direct cardiac compression, since sternal displacement was <0.8 cm. As predicted by the model and opposite to direct cardiac compression, there was no change in perfusion pressures when the rate was increased from 60 to 150/min at a constant duration of 45% of the cycle. Manual CPR was then studied in eight dogs. There was no surgical manipulation of the chest. Myocardial and cerebral blood flows were determined with radioactive microspheres and behaved as predicted from the model of intrathoracic pressure, not direct cardiac compression. At nearly constant peak sternal force (378–426 N), flow was significantly increased when the duration of compression was increased from short (13%–19% of the cycle) to long (40%–47%), at a rate of 60/min. Flow was unchanged, however, for an increase in rate from 60 to 150/min at constant compression duration. In addition, myocardial and cerebral flow correlated with their respective perfusion pressures. Thus vital organ perfusion pressures and flow for manual external chest compression are dependent on the duration of compression, but not on rates of compression of 60 and 150/min. These data are of course similar to those produced by vest CPR, where intrathoracic pressure is manipulated without sternal displacement, and to those predicted for movement of blood by intrathoracic pressure changes. These data are, however, opposite to those produced by cardiac deformation and to those predicted for movement blood by direct cardiac compression. We conclude that intrathoracic pressure fluctuations generate blood flow during manual CPR.     

Preservation of aortic root architecture and properties using a detergent-enzymatic perfusion protocol

Aortic valve degeneration and dysfunction is one of the leading causes for morbidity and mortality. The conventional heart-valve prostheses have significant limitations with either life-long anticoagulation therapeutic associated bleeding complications (mechanical valves) or limited durability (biological valves). Tissue engineered valve replacement recently showed encouraging results, but the unpredictable outcome of tissue degeneration is likely associated to the extensive tissue processing methods. We believe that optimized decellularization procedures may provide aortic valve/root grafts improved durability. We present an improved/innovative decellularization approach using a detergent-enzymatic perfusion method, which is both quicker and has less exposure of matrix degenerating detergents, compared to previous protocols. The obtained graft was characterized for its architecture, extracellular matrix proteins, mechanical and immunological properties. We further analyzed the engineered aortic root for biocompatibility by cell adhesion and viability in vitro and heterotopic implantation in vivo. The developed decellularization protocol was substantially reduced in processing time whilst maintaining tissue integrity. Furthermore, the decellularized aortic root remained bioactive without eliciting any adverse immunological reaction. Cell adhesion and viability demonstrated the scaffold's biocompatibility. Our optimized decellularization protocol may be useful to develop the next generation of clinical valve prosthesis with a focus on improved mechanical properties and durability.     

A comparison of haemophagocytic syndrome signs in aortic aneurysm and angina pectoris cases at postoperative death: HPS diagnosis and prediction

Although hemophagocytic syndrome (HPS) signs are more severe in aortic aneurysm cases than in angina pectoris cases, HPS-associated postoperative death should be considered more in both cases. This study analyzed a total of 183 Japanese patients, with 101 aneurysms, 79 anginas, and 3 with both, who underwent aortic replacement (AR) or/and aortocoronary bypass grafting (ACBG) during a period of 1.92 years. In seven aneurysm and eight angina cases with 7.6–12.1 g/dl of hemoglobin (Hb), iron metabolism was studied. As clinical outcomes, diabetes, chronic renal failure (CRF), and thrombosis were more prevalent in the angina cases than in the aneurysm cases. In six cases of aneurysm (6:101) who died after AR, five who died of acute myocardial infarction (AMI) or pulmonary embolism (PE) during postoperative 3–101 days developed HPS, and no detail data was available for one case. Among the five diabetic cases of angina (5:79) who died 7–74 days after ACBG, four cases with cerebral infarction (CI) had infection-associated HPS, and one case had severe kidney atrophy without CI and HPS. Postoperative HPS signs in the aneurysm cases were also generally more severe than those of the angina cases. The aneurysm case with no CRF showed mostly typical HPS and died of AMI. She had pancytopenia, anemia with anisocytosis and nucleated red cells, leukopenia with immature myeloid cells, thrombocytopenia with coagulopathy, elevated lactate dehydrogenase, hyperbilirubinemia, liver dysfunction, and numerous phagocytes containing hemosiderin in the specimen of the aorta examined before the operation. Preoperatively, she also showed high levels of serum ferritin (SF) and low levels of both serum iron (S–Fe) and total iron-binding capacity (TIBC). All the 15 patients in whom iron metabolism was evaluated had low levels of S–Fe. Low levels of TIBC and high levels of SF were observed in 11:15 patients. Cardiac hemophagocytosis with no CRF was a suggestive of HPS. AR and ACBG operations became a direct trigger of HPS. Postoperative AMI, sepsis, and PE became a HPS trigger, but CI alone and CRF did not. For postoperative survival, it was important to protect the patients from infections.     

Open and endovascular repair of juxtarenal abdominal aortic aneurysms: a systematic review

This systematic review focuses on the 30-day mortality associated with open surgery and fenestrated endografts for short-necked (<15 mm) juxtarenal abdominal aortic aneurysms. A search for studies published in English and indexed in the PubMed and Medline electronic databases from 2002 to 2012 was performed, using “juxtarenal abdominal aortic aneurysm” and “treatment” as the main keywords. Among the 110 potentially relevant studies that were initially identified, eight were in accordance with the inclusion criteria in the analysis. Similar outcomes for open and endovascular repair were observed for 30-day mortality. No differences were observed regarding the secondary outcomes (duration of surgery, hospital stay, postoperative renal dysfunction and late mortality), except that the late mortality rate was significantly higher for the patients treated with open repair after a median follow-up of 24 months. Fenestrated endografting is a viable alternative to conventional surgery in juxtarenal abdominal aortic aneurysms with a proximal neck <15 mm.