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In this work, we describe the CRIMSON (CardiovasculaR Integrated Modelling and SimulatiON) software environment. CRIMSON provides a powerful, customizable and user-friendly system for performing three-dimensional and reduced-order computational haemodynamics studies via a pipeline which involves: 1) segmenting vascular structures from medical images; 2) constructing analytic arterial and venous geometric models; 3) performing finite element mesh generation; 4) designing, and 5) applying boundary conditions; 6) running incompressible Navier-Stokes simulations of blood flow with fluid-structure interaction capabilities; and 7) post-processing and visualizing the results, including velocity, pressure and wall shear stress fields. A key aim of CRIMSON is to create a software environment that makes powerful computational haemodynamics tools accessible to a wide audience, including clinicians and students, both within our research laboratories and throughout the community. The overall philosophy is to leverage best-in-class open source standards for medical image processing, parallel flow computation, geometric solid modelling, data assimilation, and mesh generation. It is actively used by researchers in Europe, North and South America, Asia, and Australia. It has been applied to numerous clinical problems; we illustrate applications of CRIMSON to real-world problems using examples ranging from pre-operative surgical planning to medical device design optimization., Author summary We provide the first full presentation in the literature of CRIMSON, the Cardiovascular Integrated Modelling and Simulation Package. CRIMSON consists of a graphical user interface desktop computer program for creating geometric models of blood vessels from medical imaging scans, specifying parameters such as the stiffness of the artery walls, the resistance of connected vessels which are not visible on the scans, and determining the appropriate parameters for all aspects of the model. CRIMSON additionally consists of the Flowsolver, a high-performance computing package which simulates the flow of blood through the models created in the graphical user interface. Whilst several packages which can simulate blood flow exist, most target general fluid simulations, and this lack of specialisation means that blood flow simulation is harder to perform, and can require ad hoc (and potentially scientifically-limiting) workflow decisions. CRIMSON’s specialisation deals with these problems, as well as presenting a number of unique features which are unavailable elsewhere.

Background Optimal management of acute type B aortic dissection with retrograde arch extension is controversial. The effect of retrograde arch extension on operative and long-term mortality has not been studied and is not incorporated into clinical treatment pathways. Methods The International Registry of Acute Aortic Dissection was queried for all patients presenting with acute type B dissection and an identifiable primary intimal tear. Outcomes were stratified according to management for patients with and without retrograde arch extension. Kaplan-Meier survival curves were constructed. Results Between 1996 and 2014, 404 patients (mean age, 63.3 ± 13.9 years) were identified. Retrograde arch extension existed in 67 patients (16.5%). No difference in complicated presentation was noted (36.8% vs 31.7%, p = 0.46), as defined by limb or organ malperfusion, coma, rupture, and shock. Patients with or without retrograde arch extension received similar treatment, with medical management in 53.7% vs 56.5% ( p = 0.68), endovascular treatment in 32.8% vs 31.1% ( p = 0.78), open operation in 11.9% vs 9.5% ( p = 0.54), or hybrid approach in 1.5% vs 3.0% ( p = 0.70), respectively. The in-hospital mortality rate was similar for patients with (10.7%) and without (10.4%) retrograde arch extension ( p = 0.96), and 5-year survival was also similar at 78.3% and 77.8%, respectively ( p = 0.27). Conclusions The incidence of retrograde arch dissection involves approximately 16% of patients with acute type B dissection. In the International Registry of Acute Aortic Dissection, this entity seems not to affect management strategy or early and late death.

Endovascular treatment modalities have decreased the mortality and morbidity of thoracic aortic diseases considerably in the past decades, due to the effectiveness of such interventions and the minimal invasive character. While endovascular treatment options have become more advanced, preoperative planning and follow-up outcomes are still mainly based on the measurement of the maximum diameter and growth rate of the thoracic aorta on static imaging. These measurements do not take into account the biomechanical aortic behavior over the cardiac cycle and do not visualize hemodynamic changes in blood flow.

OBJECTIVES Current endografts for thoracic endovascular aortic repair (TEVAR) are much stiffer than the aorta and have been shown to induce acute stiffening. In this study, we aimed to estimate the impact of TEVAR on left ventricular (LV) stroke work (SW) and mass using a non-invasive image-based workflow. METHODS The University of Michigan database was searched for patients treated with TEVAR for descending aortic pathologies (2013–2016). Patients with available pre-TEVAR and post-TEVAR computed tomography angiography and echocardiography data were selected. LV SW was estimated via patient-specific fluid–structure interaction analyses. LV remodelling was quantified through morphological measurements using echocardiography and electrocardiographic-gated computed tomography angiography data. RESULTS Eight subjects were included in this study, the mean age of the patients was 68 (73, 25) years, and 6 patients were women. All patients were prescribed antihypertensive drugs following TEVAR. The fluid–structure interaction simulations computed a 26% increase in LV SW post-TEVAR [0.94 (0.89, 0.34) J to 1.18 (1.11, 0.65) J, P = 0.012]. Morphological measurements revealed an increase in the LV mass index post-TEVAR of +26% in echocardiography [72 (73, 17) g/m2 to 91 (87, 26) g/m2, P = 0.017] and +15% in computed tomography angiography [52 (46, 29) g/m2 to 60 (57, 22) g/m2, P = 0.043]. The post- to pre-TEVAR LV mass index ratio was positively correlated with the post- to pre-TEVAR ratios of SW and the mean blood pressure (ρ = 0.690, P = 0.058 and ρ = 0.786, P = 0.021, respectively). CONCLUSIONS TEVAR was associated with increased LV SW and mass during follow-up. Medical device manufacturers should develop more compliant devices to reduce the stiffness mismatch with the aorta. Additionally, intensive antihypertensive management is needed to control blood pressure post-TEVAR.

Thoracic endovascular aortic repair (TEVAR) has been shown to lead to increased aortic stiffness. The aim of this study was to investigate the effect of stent graft type and stent graft length on aortic stiffness in a controlled, experimental setting.Twenty porcine thoracic aortas were connected to a pulsatile mock loop system. Intraluminal pressure was recorded at two sites in order to measure pulse wave velocity (PWV) for each aorta: before stent graft deployment (t1); after deployment of a 100-mm long stent graft (t2); and after distal extension through deployment of a second 100-mm long stent graft (t3). Four different types of stent grafts (Conformable Gore® TAG® Device, Bolton Relay® Device, Cook Zenith Alpha™, and Medtronic Valiant®) were evaluated.For the total cohort of 20 aortas, PWV increased by a mean 0.6 m/s or 8.9% of baseline PWV after deployment of a 100-mm proximal stent graft (P0.001), and by a mean 1.4 m/s or 23.0% of baseline PWV after distal extension of the stent graft (P0.001). Univariable regression analysis showed a significant correlation between aortic PWV and extent of stent graft coverage, (P0.001), but no significant effect of baseline aortic length, baseline aortic PWV, or stent graft type on the percentual increase in PWV at t2 or at t3.In this experimental set-up, aortic stiffness increased significantly after stent graft deployment with each of the four types of stent graft, with the increase in aortic stiffness depending on the extent of stent graft coverage.

Objectives Reference values of aortic deformation during the cardiac cycle can be valuable for the pre-operative planning of thoracic endovascular aortic repair (TEVAR) and for facilitating computational fluid dynamics. This study aimed to quantify normal aortic extensibility (longitudinal extension) and distensibility (radial expansion), as well as pulsatile strain, in a group of 10 (>60 years) individuals with abdominal or thoracic aortic aneurysms. Methods ECG gated CT images of the thoracic aorta were reconstructed into virtual 3D models of aortic geometry. The centre lumen line length of the thoracic aorta and three longitudinal segments, and the aortic diameter and luminal areas of four radial intersections were extracted with a dedicated software script to calculate extensibility, longitudinal strain, distensibility, and circumferential area strain. Results Mean extensibility and longitudinal strain of the entire thoracic aorta were 3.5 [1.3–6.8] × 10 −3 N −1 , and 2.7 [1.0–4.5]%, respectively. Extensibility and longitudinal strain were most pronounced in the ascending aorta (20.6 [5.7–36.2] × 10 −3 N −1 and 15.9 [6.6–31.9]%) and smallest in the descending aorta (4.4 [1.6–12.3] × 10 −3 N −1 and 2.2 [0.7–4.7]%). Mean distensibility and circumferential area strain were most pronounced at the sinotubular junction (1.7 [0.5–2.9] × 10 −3 mmHg −1 and 11.3 [3.3–18.5]%, respectively). Distensibility varied between 0.9 [0.3–2.5] × 10 −3 mmHg −1 and 1.2 [0.3–3.3] × 10 −3 mmHg −1 at the intersections in the aortic arch and descending aorta. Conclusions Pulsatile deformations in both longitudinal and circumferential directions are considerable throughout the thoracic aorta. These findings may have implications for pre-operative TEVAR planning and highlight the need for devices that can mimic the significant aortic longitudinal and circumferential strains.

Thoracic endovascular aortic repair (TEVAR) has been shown to lead to increased aortic stiffness. The aim of this study was to investigate the effect of stent graft type and stent graft length on aortic stiffness in a controlled, experimental setting. Methods: Twenty porcine thoracic aortas were connected to a pulsatile mock loop system. Intraluminal pressure was recorded at two sites in order to measure pulse wave velocity (PWV) for each aorta: before stent graft deployment (t1); after deployment of a 100-mm long stent graft (t2); and after distal extension through deployment of a second 100-mm long stent graft (t3). Four different types of stent grafts (Conformable Gore® TAG® Device, Bolton Relay® Device, Cook Zenith Alpha(TM), and Medtronic Valiant®) were evaluated. Results: For the total cohort of 20 aortas, PWV increased by a mean 0.6 m/s or 8.9% of baseline PWV after deployment of a 100-mm proximal stent graft (P

Background Aortic stiffness is an independent predictor of cardiovascular mortality. In this study, the effect of thoracic endovascular aortic repair (TEVAR) on aortic stiffness is investigated by measuring aortic pulse wave velocity (PWV) in an ex vivo porcine model. Methods Fifteen fresh porcine thoracic aortas were connected to a benchtop pulsatile system. Intraluminal pressures were recorded in the ascending aorta and at the celiac trunk using a needle connected to a pressure sensor. The distance between the needles was divided by the time difference between the base of the pressure peaks to calculate aortic PWV at baseline and after stent-graft deployment and distal stent-graft extension. Results Mean aortic PWV was 5.0 m/s at baseline. PWV increased by 4% after proximal stent-graft deployment (P = 0.09) and by 18% after stent-graft extension (P < 0.001). Pulse pressure in the nonstented ascending aorta increased by 11.0 ± 1.2 mm Hg after proximal stent-graft deployment (P < 0.001) and by 17.3 ± 1.5 mm Hg after stent-graft extension (P < 0.001). The increases in PWV and pulse pressure showed a positive linear correlation with the percentage of stent-graft coverage (P < 0.001 and P < 0.001). Conclusions In this experimental setup, aortic stiffness increased after stent-graft deployment, dependent on the percentage of the aorta that was covered by stent graft. These results show that TEVAR leads to significant changes in aortic hemodynamics, which merits evaluation in the clinical setting.

Introduction Thoracic aortic stent grafts are orders of magnitude stiffer than the native aorta. These devices have been associated with acute hypertension, elevated pulse pressure, cardiac remodelling and reduced coronary perfusion. However, a systematic assessment of such cardiovascular effects of thoracic endovascular aortic repair (TEVAR) is missing. The C ardi O vascular R emodelling following E ndovascular aortic repair (CORE) study aims to (1) quantify cardiovascular remodelling following TEVAR and compare echocardiography against MRI, the reference method; (2) validate computational modelling of cardiovascular haemodynamics following TEVAR using clinical measurements, and virtually assess the impact of more compliant stent grafts on cardiovascular haemodynamics; and (3) investigate diagnostic accuracy of ECG and serum biomarkers for cardiac remodelling compared to MRI. Methods and analysis This is a prospective, nonrandomised, observational cohort study. We will use MRI, CT, echocardiography, intraluminal pressures, ECG, computational modelling and serum biomarkers to assess cardiovascular remodelling in two groups of patients with degenerative thoracic aneurysms or penetrating aortic ulcers: (1) patients managed with TEVAR and (2) control patients managed with medical therapy alone. Power analysis revealed a minimum total sample size of 20 patients (α=0.05, power=0.97) to observe significant left ventricular mass increase following TEVAR after 1 year. Consequently, we will include 12 patients in both groups. Advanced MRI sequences will be used to assess myocardial and aortic strain and distensibility, myocardial perfusion and aortic flow. ECG, echocardiography and serum biomarkers will be collected and compared against the imaging data. Computational models will be constructed from each patient imaging data, analysed and validated. All measurements will be collected at baseline (prior to TEVAR) and 1-year follow-up. The expected study period is 3 years. Ethics and dissemination This study has been approved by the University of Michigan IRB. The results will be disseminated through scientific journals and conference presentations. Trial registration number NCT02735720.

Cardiovascular disease (CVD) is the number one cause of death in Europe, accounting for >4 million deaths per year, almost half of all mortality. More specifically, 51 % of deaths among females and 42 % among men are caused by CVD, compared to 19 and 23 % due to cancer, respectively (Fig. 10.1). Recent data showed in Europe a decrease of CVD mortality in many countries and a great variety of incidence among them [1].

To provide data on the management and outcomes of patients with acute retrograde aortic dissection (AD) originating from a tear in the descending aorta with extension into the aortic arch or ascending aorta. All patients enrolled in the International Registry of Acute Aortic Dissection from 1996-2015 were reviewed. Retrograde AD was defined by primary tear in the descending aorta with proximal extension into the arch or ascending aorta. Primary end points were in-hospital management strategy and mortality. We identified 101 patients with retrograde AD (67 men; 63.2 ± 14.0 years). During index hospitalization, medical (MED), open surgical (SURG), and endovascular (ENDO) therapies were undertaken in 44, 33, and 22 patients, respectively. The SURG group presented with larger ascending aorta (P = 0.04) and more frequent ascending aortic involvement (81.8% [27/33] vs 22.7% [15/66], P < 0.001) compared with the MED and ENDO groups. Early mortality rate was 9.1% (4/44), 18.2% (6/33), and 13.6% (3/22), for the MED, SURG, and ENDO groups (P = 0.51), respectively. A favorable early mortality rate was observed in patients with retrograde extension limited to the arch (8.6% [5/58]) vs into the ascending aorta (18.6% [8/43], P = 0.14). Early mortality rate of patients with retrograde AD with primary tear in the descending aorta (12.9% [13/101]) was significantly lower than those with classic type A AD presenting with primary tear in the ascending aorta (20.0% [195/977], P = 0.001). A subset of patients with acute retrograde AD originating from primary tear in the descending aorta might be managed less invasively with acceptable early results, particularly among those with proximal extension limited to the arch.

We present the possible utility of computational fluid dynamics in the assessment of thrombus formation and virtual surgical planning illustrated in a patient with aortic thrombus in a kinked ascending aortic graft following thoracic endovascular aortic repair.A patient-specific three-dimensional model was built from computed tomography. Additionally, we modeled 3 virtual aortic interventions to assess their effect on thrombosis potential: (1) open surgical repair, (2) conformable endografting, and (3) single-branched endografting. Flow waveforms were extracted from echocardiography and used for the simulations. We used the computational index termed platelet activation potential (PLAP) representing accumulated shear rates of fluid particles within a fluid domain to assess thrombosis potential.The baseline model revealed high PLAP in the entire arch (119.8 ± 42.5), with significantly larger PLAP at the thrombus location (125.4 ± 41.2, p0.001). Surgical repair showed a 37% PLAP reduction at the thrombus location (78.6 ± 25.3, p0.001) and a 24% reduction in the arch (91.6 ± 28.9, p0.001). Single-branched endografting reduced PLAP in the thrombus region by 20% (99.7 ± 24.6, p0.001) and by 14% in the arch (103.8 ± 26.1, p0.001), whereas a more conformable endograft did not have a profound effect, resulting in a modest 4% PLAP increase (130.6 ± 43.7, p0.001) in the thrombus region relative to the baseline case.Regions of high PLAP were associated with aortic thrombus. Aortic repair resolved pathologic flow patterns, reducing PLAP. Branched endografting also relieved complex flow patterns reducing PLAP. Computational fluid dynamics may assist in the prediction of aortic thrombus formation in hemodynamically complex cases and help guide repair strategies.

Purpose: To propose a standard measuring protocol for type B aortic dissections so as to improve comparability between studies reporting aortic dimensions. Methods: Fifteen computed tomography (CT) scans of type B aortic dissections were measured with a standard protocol by 2 independent observers using postprocessing software. The following parameters were assessed: true, false, and total lumen diameter; true and false lumen volume; and entry tear size, location, and number. Diameters were measured in a perpendicular plane at 2, 10, and 20 cm from the left subclavian artery and 5 cm from the most distal renal artery. True lumen volume was assessed from the left subclavian artery to the aortic bifurcation, while the false lumen volume was from the start to end up to the aortic bifurcation. Entry tear location was assessed in relation to the left subclavian artery. Intra- and interobserver repeatability and agreement were evaluated using the Bland-Altman method, an a priori set of acceptable differences, and Lin’s concordance correlation coefficient (LCCC). Results: Intra- and interobserver mean differences for aortic diameter and true and false lumen volumes were generally within the limits of agreement and the a priori differences; the LCCC showed excellent agreement. Entry tear location, size, and number were difficult to measure in a repeatable manner, with inconsistent correlation coefficients, especially between the 2 observers. Conclusion: This protocol showed acceptable repeatability for aortic diameter and aortic volume measurements. Assessment of entry tears proved challenging and associated with less favorable results. Additionally, investigators are urged to be more transparent regarding the measurement methodology used in studies describing aortic dimensions.

Stanford type B aortic dissection (TBAD) is a life-threatening aortic disease. The initial management goal is to prevent aortic rupture, propagation of the dissection, and symptoms by reducing the heart rate and blood pressure. Uncomplicated TBAD patients require prompt medical management to prevent aortic dilatation or rupture during subsequent follow-up. Complicated TBAD patients require immediate invasive management to prevent death or injury caused by rupture or malperfusion. Recent developments in diagnosis and management have reduced mortality related to TBAD considerably. In particular, the introduction of thoracic stent-grafts has shifted the management from surgical to endovascular repair, contributing to a fourfold increase in early survival in complicated TBAD. Furthermore, endovascular repair is now considered in some uncomplicated TBAD patients in addition to optimal medical therapy. For more challenging aortic dissection patients with involvement of the aortic arch, hybrid approaches, combining open and endovascular repair, have had promising results. Regardless of the chosen management strategy, strict antihypertensive control should be administered to all TBAD patients in addition to close imaging surveillance. Future developments in stent-graft design, medical therapy, surgical and hybrid techniques, imaging, and genetic screening may improve the outcomes of TBAD patients even further. We present a comprehensive review of the recommended management strategy based on current evidence in the literature.

Background Currently, the optimal management strategy for chronic type B aortic dissections (CBAD) is unknown. Therefore, we systematically reviewed the literature to compare results of open surgical repair (OSR), standard thoracic endovascular aortic repair (TEVAR) or branched and fenestrated TEVAR (BEVAR/FEVAR) for CBAD. Methods EMBASE and MEDLINE databases were searched for eligible studies between January 2000 and October 2015. Studies describing outcomes of OSR, TEVAR, B/FEVAR, or all, for CBAD patients initially treated with medical therapy, were included. Primary endpoints were early mortality, and one-year and five-year survival. Secondary endpoints included occurrence of complications. Furthermore, a Time until Treatment Equipoise (TUTE) graph was constructed. Results Thirty-five articles were selected for systematic review. A total of 1081 OSR patients, 1397 TEVAR patients and 61 B/FEVAR patients were identified. Early mortality ranged from 5.6% to 21.0% for OSR, 0.0% to 13.7% for TEVAR, and 0.0% to 9.7% for B/FEVAR. For OSR, one-year and five-year survival ranged 72.0%-92.0% and 53.0%-86.7%, respectively. For TEVAR, one-year survival was 82.9%-100.0% and five-year survival 70.0%-88.9%. For B/FEVAR only one-year survival was available, ranging between 76.4% and 100.0%. Most common postoperative complications included stroke (OSR 0.0%-13.3%, TEVAR 0.0%-11.8%), spinal cord ischemia (OSR 0.0%-16.4%, TEVAR 0.0%-12.5%, B/FEVAR 0.0%-12.9%) and acute renal failure (OSR 0.0%-33.3%, TEVAR 0.0%-34.4%, B/FEVAR 0.0%-3.2%). Most common long-term complications after OSR included aneurysm formation (5.8%-20.0%) and new type A dissection (1.7–2.2%). Early complications after TEVAR included retrograde dissection (0.0%-7.1%), malperfusion (1.3%–9.4%), cardiac complications (0.0%–5.9%) and rupture (0.5%–5.0%). Most common long-term complications after TEVAR were rupture (0.5%–7.1%), endoleaks (0.0%–15.8%) and cardiac complications (5.9%-7.1%). No short-term aortic rupture or malperfusion was observed after B/FEVAR. Long-term complications included malperfusion (6.5%) and endoleaks (0.0%-66.7%). Reintervention rates after OSR, TEVAR and B/FEVAR were 5.8%-29.0%, 4.3%-47.4% and 0.0%-53.3%, respectively. TUTE for OSR was 2.7 years, for TEVAR 9.9 months and for B/FEVAR 10.3 months. Conclusion We found a limited early survival benefit of standard TEVAR over OSR for CBAD. Complication rates after TEVAR are higher, but complications after OSR are usually more serious. Initial experiences with B/FEVAR show its feasibility, but long-term results are needed to compare it to OSR and standard TEVAR. We conclude that optimal treatment of CBAD remains debatable and merits a patient specific decision. TUTE seems a feasible and useful tool to better understand management outcomes of CBAD.

Background: Presentations and outcomes of acute aortic dissection (AD) with an entry tear in the ascending aorta may differ from retrograde dissection with an entry tear in the descending aorta. However, guidelines recommend urgent surgical repair for both entities. Methods and Results: All patients with AD enrolled in the International Registry of Acute Aortic Dissection (IRAD) between 1996 and 2014 were analyzed. We identified 99 patients (67 men; 63.2±14.0 years) with an entry tear in the descending aorta and retrograde extension into the arch or ascending aorta. Overall, independent predictors of retrograde type A AD were increasing age(OR 1.0; 95% CI, 1.0 to 1.0; P=0.004), history of cocaine abuse (OR 4.9; 95% CI, 1.7 to 13.6; P=0.003), back pain at presentation (OR 2.1; 95% CI, 1.3 to 3.3; P=0.002), and non-white race (OR 0.4; 95% CI, 0.2 to 0.6; P Conclusion: There is a subset of patients with acute retrograde type A AD who can be managed non-operatively with acceptable short and long-term results. This implies that a selective approach may be reasonable, particularly among those with proximal extension limited to the arch distal to the innominate artery.