CRIMSON: An open-source software framework for cardiovascular integrated modelling and simulation.

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.

Impact of Patient-Specific Inflow Velocity Profile on Hemodynamics of the Thoracic Aorta.

Computational fluid dynamics (CFD) provides a noninvasive method to functionally assess aortic hemodynamics. The thoracic aorta has an anatomically complex inlet comprising of the aortic valve and root, which is highly prone to different morphologies and pathologies. We investigated the effect of using patient-specific (PS) inflow velocity profiles compared to idealized profiles based on the patient's flow waveform. A healthy 31 yo with a normally functioning tricuspid aortic valve (subject A), and a 52 yo with a bicuspid aortic valve (BAV), aortic valvular stenosis, and dilated ascending aorta (subject B) were studied. Subjects underwent MR angiography to image and reconstruct three-dimensional (3D) geometric models of the thoracic aorta. Flow-magnetic resonance imaging (MRI) was acquired above the aortic valve and used to extract the patient-specific velocity profiles. Subject B's eccentric asymmetrical inflow profile led to highly complex velocity patterns, which were not replicated by the idealized velocity profiles. Despite having identical flow rates, the idealized inflow profiles displayed significantly different peak and radial velocities. Subject A's results showed some similarity between PS and parabolic inflow profiles; however, other parameters such as Flowasymmetry were significantly different. Idealized inflow velocity profiles significantly alter velocity patterns and produce inaccurate hemodynamic assessments in the thoracic aorta. The complex structure of the aortic valve and its predisposition to pathological change means the inflow into the thoracic aorta can be highly variable. CFD analysis of the thoracic aorta needs to utilize fully PS inflow boundary conditions in order to produce truly meaningful results.

Functional assessment of thoracic aortic aneurysms - the future of risk prediction?

Introduction: Treatment guidelines for the thoracic aorta concentrate on size, yet acute aortic dissection or rupture can occur when aortic size is below intervention criteria. Functional imaging and computational techniques are a means of assessing haemodynamic parameters involved in aortic pathology. Sources of data: Original articles, reviews, international guidelines. Areas of agreement: Computational fluid dynamics and 4D flow MRI allow non-invasive assessment of blood flow parameters and aortic wall biomechanics. Areas of controversy: Aortic valve morphology (particularly bicuspid aortic valve) is associated with aneurysm of the ascending aorta, although the exact mechanism of aneurysm formation is not yet established. Growing points: Haemodynamic assessment of the thoracic aorta has highlighted parameters which are linked with both clinical outcome and protein changes in the aortic wall. Wall shear stress, flow displacement and helicity are elevated in patients with bicuspid aortic valve, particularly at locations of aneurysm formation. Areas timely for developing research: With further validation, functional assessment of the aorta may help identify patients at risk of aortic complications, and introduce new haemodynamic indices into management guidelines.

Predictors of Failure in Fast-Track Cardiac Surgery.

OBJECTIVES: Fast-track (FT) management of cardiac surgery patients is associated with early extubation and reduced length of intensive care unit (ICU) stay, with potential benefit of reduced hospital costs. The authors examined perioperative factors and their influence on failure of FT and what implications this failure had. DESIGN: Prospective data collection from all adult cardiac surgeries between 2011 and 2013. SETTING: Single-institution study. PARTICIPANTS: The study included 2,770 consecutive adult cardiac surgery patients. INTERVENTIONS: All participants underwent adult cardiac surgeries. Of those, 451 (16.3%) patients were selected to undergo FT management. MEASUREMENTS AND MAIN RESULTS: Failure of FT was defined as early (admission to ICU on day of surgery) or late (patients later admitted to the ICU from the ward). Univariate and multivariate regression analyses were used to identify which variables predicted FT failure. Of the 451 patients included in this study, 138 (30.6%) failed the FT, with 115 (83.3%) early failures and 23 (16.7%) late failures. Predictors of failure were reduced renal function, hypertension, age, EuroSCORE, cardiopulmonary bypass time, first lactate or base deficit after surgery (all p<0.01), and cross-clamp time (p<0.05). Multivariate analysis showed that the strongest predictor of failure was glomerular filtration rate (GFR)<65 mL/min/BSA (sensitivity, 54%; specificity, 61%; likelihood ratio, 1.39; area under receiver operating characteristics curve, 0.59; 95% confidence interval, 0.53-0.64). Median length of hospital stay was longer for the failed group (5 v 7 days, p<0.001). There were no mortalities in any of the patients selected for FT. CONCLUSIONS: A number of perioperative factors are associated with failure to FT, the strongest predictor being GFR. Failure to FT can lead to significantly longer hospital stay.

External aortic annuloplasty with a dedicated expansible ring improves outcomes in remodeling root repair compared with homemade Dacron ring.

OBJECTIVES: In remodeling valve-sparing root replacement with external annuloplasty, we compare long-term outcomes of a calibrated expansible extra-aortic ring with a homemade Dacron ring. METHODS: All patients (2003-2020) operated for root aneurysm with/without aortic insufficiency (AI) were included. The standardized CAVIAAR (conservation aortique valvulaire dans les insuffisances aortiques et anévrysmes de la racine-Valve sparing in aortic insufficiencies and root aneurysms) technique was root remodeling and external annuloplasty ring with the EXTRA-AORTIC Ring or homemade Dacron ring. RESULTS: Among 486 patients (age 52.3 ± 14.0 years) operated for root aneurysm, 375 (repair rate: 77.1%) underwent root remodeling with annuloplasty (extra-aortic ring, n = 289, vs Dacron ring, n = 86). At 10 years (median follow-up, 4.08 years' interquartile range, 1.95-7.61), unmatched and matched analysis showed that patients with extra-aortic ring had greater survival, similar to the general population (93.3% vs 79.9%, P = .097), lower reoperation incidence (2.0% vs 9.7%, P = .0098), and lower AI grade >2 recurrence (1.9% vs 11.2%, P = .0042), compared with patients with a Dacron ring. Mixed-effect model showed that with extra-aortic ring annuloplasty, annular dilation over time (P = .0033) was prevented and, compared with the homemade Dacron ring, root expansibility was better preserved (3.22% vs 2.12%, P = .002) and mean transvalvular gradient was lower (6.58 mm Hg vs 7.94 mm Hg, P = .001). Tricuspid and bicuspid valves with extra-aortic ring had similar reoperation (4.3% vs 0.85%, P = .65) and AI grade >2 incidence (2.7% vs 1.2%, P = .61), expansibility (P = .29), and diameter (P = .47), whereas mean transvalvular gradient was lower for tricuspid valves (5.58 mm Hg vs 7.60 mm Hg, P = .004). CONCLUSIONS: Valve-sparing root remodeling with calibrated expansible extra-aortic ring annuloplasty improves the outcomes of reoperation and recurrent AI compared with a homemade Dacron ring. It prevents dilation and maintains physiological root dynamics for durable valve repair.

Evaluation of factors affecting post-treatment quality of life in oral and oropharyngeal cancer patients primarily treated with curative surgery: an exploratory study.

The aim was to explore the impact of important clinico-demographic factors on the post-treatment quality of life (QOL) in surgically treated oral and oropharyngeal cancer patients. 63 consecutive follow-up oral and oropharyngeal cancer patients treated primarily with surgery were recruited. 55 patients sent the completed questionnaires and finally included in this study. QOL and important sub-domains of the QOL were assessed. Mean QOL scores (SD) were computed, level of significance was set at P < 0.05. The mean composite QOL score and standard deviation (SD) for oral and oropharyngeal cancer patients were 76.6 (15.2) and 73.4 (13.9), respectively. Patients with higher T-stage (T3 and T4) and higher overall-stage (III and IV) had lower mean QOL scores as against early T (T1 and T2) and overall early-stage (I and II); mean scores (SD) 64.3 (13.6) and 72.3 (13.8), and 76.6 (13.6) and 81.7 (14.1), respectively. Younger patients had lower mean scores (SD) than older patients; mean QOL scores (SD) 69.7 (14.0) and 79.6 (SD), respectively. Patients with reconstruction had lower mean QOL scores as compared to those without reconstruction; mean scores (SD) 67.6 (16.0) and 77.4 (12.5), respectively. In conclusion, tumor-stage, overall-stage, age of patients, and reconstruction had a significant direct effect on the post-treatment QOL of oral and oropharyngeal cancer patients.

Bicuspid valve repair outcomes are improved with reduction and stabilization of sinotubular junction and annulus with external annuloplasty.

OBJECTIVE: We investigated long-term outcomes of bicuspid aortic valve (BAV) repair, with external annuloplasty, according to aorta phenotype. METHODS: Between 2003 and 2020, all patients with BAV operated on for aortic insufficiency (AI) and/or aneurysm were included. Repairs included isolated AI repair with subvalvular with or without sinotubular junction (STJ) (single or double) annuloplasty, supracoronary aorta replacement (with or without hemiroot remodeling), and root remodeling with external subvalvular ring annuloplasty. RESULTS: Among 343 patients operated, reparability rate was 81.3% (n = 279; age 46 ± 13.3 years). At 10 years (median follow-up: 3.42 years; interquartile range, 1.1, 5.8), survival was 93.9% (n = 8 deaths, similar to general population), cumulative incidence of reoperation was 6.2% (n = 10), AI grade >2 was 5.8% (n = 9), and grade >1 was 23.0% (n = 30). BAV repair stabilizing both the annulus and STJ with annuloplasty, compared with nonstabilized STJ repair (single annuloplasty), had lower incidence of reoperation (2.6% vs 22.5%, P = .0018) and AI grade >2 (1.2% vs 23.6%, P < .001) at 9 years. Initial commissural angle <160° was not a risk factor for reoperation, compared with angle ≥160° if symmetrical repair was achieved (2.7% and 4.1%, respectively, at 6 years, P = .85). Multivariable model showed that absence of STJ stabilization (odds ratio, 6.7; 95% confidence interval, 2.1-20, P = .001) increased recurrent AI, but not initial commissural angle <160° (odds ratio, 1.01; 95% confidence interval, 0.39-2.63, P = .98). Commissures adjusted symmetrically led to lower transvalvular gradient, compared with nonsymmetrical repair (8.7 mm Hg vs 10.2 mm Hg, P = .029). CONCLUSIONS: BAV repair, tailored to aorta phenotype, is associated with excellent durable outcomes if both annulus and STJ are reduced and stabilized with external ring annuloplasty. Commissural angle <160° is not associated with reoperation if symmetrical repair is achieved.

Aortic valve fenestration: respect it or fix it?

OBJECTIVES: We investigated whether aortic valve fenestrations (respected or fixed) represent a factor associated with recurrent aortic insufficiency or reoperation after repair. METHODS: Between 2003 and 2019, patients who underwent aortic valve repair were included. Aortic insufficiency phenotypes were root aneurysm (repair: root remodelling + annuloplasty), ascending aorta aneurysm (repair: tubular aortic replacement + annuloplasty) and isolated regurgitation (repair: single/double annuloplasty). Fenestrations were either respected or fixed according to their features. RESULTS: A total of 618 patients (out of 798 operated on; 77.4%) had their valve repaired, with 167 cases of fenestrations (128 were respected, 39 fixed-32 with a patch, 6 with running suture and 1 with both). After conducting propensity score matching between no-fenestration (n = 167) and fenestration groups (n = 167), respectively, we noted the following: survival [90.3% (n = 7 deaths) vs 95.8% (n = 4)], cumulative incidence of reoperation [6.7% (n = 7) vs 5.2% (n = 4)], aortic insufficiency grade ≥ 3 [6.4% (n = 6) vs 4.4% (n = 4)] and grade ≥ 2 [28.9% (n = 28) vs 37.1% (n = 35)] were similar at 9 years [P = 0.94; median follow-up: 2.2, interquartile range: (0.8, 5.8)], whether fenestration was respected (P = 0.55) or fixed (P = 0.6, at 6 years). Standardization of the surgical approach (consisting of double annuloplasty in isolated regurgitation phenotype and expansible subvalvular annuloplasty with effective height assessment with remodelling repair for root aneurysm phenotype) reduced the risk of reoperation (era before standardization: hazard ratio: 5.4, 95% confidence interval: 1.9-15.7, P = 0.002). CONCLUSIONS: Fenestration, respected or fixed, is not a factor associated with reoperation or recurrence of significant aortic insufficiency after valve repair if the surgical approach is standardized.

Root repair with aortic ring annuloplasty using the standard approach.

Standardization of aortic valve repair techniques with use of a calibrated annuloplasty have led to improved long-term outcomes in dystrophic aortic insufficiency. It can also improve dissemination of techniques and rates of aortic valve repair. Dystrophic aortic insufficiency can be found in three aortic phenotypes: dilated aortic root, dilated ascending aorta and isolated aortic insufficiency. The aortic annulus is invariably dilated above 25 mm in the vast majority of cases of aortic insufficiency, regardless of whether the aorta is dilated or not. A dilated annulus is a risk factor for late failure of aortic valve repair if not addressed at the time of surgery. We perform a calibrated annuloplasty at both sub- and supra-valvular levels in order to restore the ratio of sinotubular junction and annulus. Current evidence shows aortic valve repair reduces valve-related mortality compared to prosthetic valve replacement, with an improved quality of life.

Aortic annulus and the importance of annuloplasty.

Dystrophic aortic insufficiency accounts for the majority of Western cases of aortic insufficiency and can be divided into the three phenotypes of isolated aortic insufficiency, dilated aortic root, and dilated ascending aorta. Each of these phenotypes is associated with a dilated annulus and/or sinotubular junction. Recent international guidelines recommend reimplantation or remodeling with aortic annuloplasty for valve-sparing root replacement, as well as consideration of aortic valve repair in cases of aortic insufficiency. A dilated aortic annulus is a major risk factor for failure of aortic valve repair procedures, indicating the need to address the annulus at the time of aortic valve or root repair. Calibrated annuloplasty should be performed at sub- and supravalular levels in order to restore the ratio of the sinotubular junction and annulus and be adapted according to the phenotype of the root and ascending aorta. Standardization of aortic valve repair techniques with use of a calibrated annuloplasty will improve dissemination of techniques and rate of aortic valve repair. Current medical evidence shows that aortic valve repair is safe, produces better quality of life, and reduces valve-related mortality compared to prosthetic valve replacement.

Rationale for aortic annuloplasty to standardise aortic valve repair.

Available evidence shows that aortic valve repair reduces valve-related mortality and improves quality of life compared to prosthetic aortic valve replacement. One of the most important predictors of bicuspid and tricuspid aortic valve repair failure is the absence of treating a dilated aortic annulus greater than 25-28 mm. Competency of the aortic valve depends on multiple factors including the diameter of the annulus, sinotubular junction, valve cusps and commissures. Dystrophic aortic insufficiency (AI) is the commonest cause of AI in the Western world and is characterised by dilatation of the aortic annulus (≥25 mm), sinuses and/or sinotubular junction (≥30 mm). Depending on whether the sinuses of Valsalva and/or tubular ascending aorta are dilated, three phenotypes can be identified: dilated aortic root, dilated ascending aorta and isolated AI. All three phenotypes are associated with a dilated aortic annulus. Aortic annuloplasty reduces the dilated aortic annulus and improves the surface of coaptation, as in the case of mitral valve repair. In treating AI, it is also important to restore the physiological sinotubular junction/annulus ratio, which can be carried out with remodeling root repair + subvalvular annuloplasty (for dilated aortic root), tubular ascending aorta replacement + subvalvular annuloplasty (for dilated ascending aorta) and double sub- and supra-valvular annuloplasty (for isolated AI). Aortic annuloplasty is now considered an essential component of aortic valve repair and valve-sparing root surgery.

Novel Approach to Repairing a Traumatic Aortic Arch Pseudoaneurysm Following a Fall.

Traumatic pseudoaneurysms of the aortic arch are often treated with surgical repair regardless of the lesion size or age. The authors report a simple, less invasive surgical repair in a patient who sustained blunt aortic injury following a fall.

Bicuspid aortic valve repair adapted to aortic phenotype.

The bicuspid aortic valve (BAV) is the most common congenital cardiovascular anomaly and may present with differing phenotypes including almost constant annular dilation. We have developed a standardized approach to BAV repair with a systematic adjunct of aortic annuloplasty according to the three phenotypes of the proximal aorta, which include a dilated aortic root, dilated ascending aorta and normal root and ascending aorta. In our cohort of 191 patients, freedom from AV-related re-intervention was 98% for remodeling with annuloplasty (n=100) and 100% for tubular aortic replacement with annuloplasty (n=31) at 8 years. In an isolated aortic insufficiency (AI) group, freedom from AV-related re-intervention varied from 72.4% with a single subvalvular annuloplasty ring (n=31) compared to 100% at 6 years when a double sub- and supra-valvular (STJ) annuloplasty ring was performed (n=29). Restoration of the annulus: sinotubular junction (STJ) ratio is a key factor to ensure longevity of the bicuspid valve repair and freedom from re-intervention.

Haemodynamic assessment of bicuspid aortic valve aortopathy: a systematic review of the current literature.

Both genetic and haemodynamic theories explain the aetiology, progression and optimal management of bicuspid aortic valve aortopathy. In recent years, the haemodynamic theory has been explored with the help of magnetic resonance imaging and computational fluid dynamics. The objective of this review was to summarize the findings of these investigations with focus on the blood flow pattern and associated variables, including flow eccentricity, helicity, flow displacement, cusp opening angle, systolic flow angle, wall shear stress (WSS) and oscillatory shear index. A structured literature review was performed from January 1990 to January 2018 and revealed the following 3 main findings: (i) the bicuspid aortic valve is associated with flow eccentricity and helicity in the ascending aorta compared to healthy and diseased tricuspid aortic valve, (ii) flow displacement is easier to obtain than WSS and has been shown to correlate with valve morphology and type of aortopathy and (iii) the stenotic bicuspid aortic valve is associated with elevated WSS along the greater curvature of the ascending aorta, where aortic dilatation and aortic wall thinning are commonly found. We conclude that new haemodynamic variables should complement ascending aorta diameter as an indicator for disease progression and the type and timing of intervention. WSS describes the force that blood flow exerts on the vessel wall as a function of viscosity and geometry of the vessel, making it a potentially more reliable marker of disease progression.

Aortic valve opening and closure: the clover dynamics.

BACKGROUND: Systolic aortic root expansion is reported to facilitate valve opening, but the precise dynamics remain unknown. A sonometric study with a high data sampling rate (200 to 800 Hz) was conducted in an acute ovine model to better understand the timing, mechanisms, and shape of aortic valve opening and closure. METHODS: Eighteen piezoelectric crystals were implanted in 8 sheep at each annular base, commissures, sinus of Valsalva, sinotubular junction, nodulus of Arantius, and ascending aorta (AA). Geometric changes were time related to pressures and flows. RESULTS: The aortic root was hemodynamically divided into left ventricular (LV) and aortic compartments situated, respectively, below and above the leaflets. During isovolumetric contraction (IVC), aortic root expansion started in the LV compartment, most likely due to volume redistribution in the LV outflow tract below the leaflets. This expansion initiated leaflet separation prior to ejection (2.1%±0.5% of total opening area). Aortic compartment expansion was delayed toward the end of IVC, likely related to volume redistribution above the leaflets due to accelerating aortic backflow toward the aortic valve and coronary flow reduction due to myocardial contraction. Maximum valve opening during the first third of ejection acquired a truncated cone shape [leaflet free edge area smaller than annular base area (-41.5%±5.5%)]. The distal orifice became clover shaped because the leaflet free edge area is larger than the commissural area by 16.3%±2.0%. CONCLUSIONS: Aortic valve opening is initiated prior to ejection related to delicate balance between LV, aortic root, and coronary dynamics. It is clover shaped at maximum opening in systole. A better understanding of these mechanisms should stimulate more physiological surgical approaches of valve repair and replacement.

Aortic Valve Surgery in Nonelderly Patients: Insights Gained From AVIATOR.

Aortic valve surgery in non-elderly patients represents a very challenging patient population. The younger the patient is at the point of aortic valve intervention, the longer their anticipated life expectancy will be, with longer exposure to valve-related complications and risk for re-operation. Although the latest international guidelines recommend aortic valve repair in patients with aortic valve insufficiency, what we see in the real world is that the vast majority of these aortic valves are replaced. However, current prosthetic valves has now been shown to lead to significant loss of life expectancy for non-elderly patients up to 50% for patients in their 40s undergoing mechanical aortic valve replacement. Bioprostheses carry an even worse long-term survival, with higher rates of re-intervention. The promise of trans-catheter valve-in-valve technology is accentuating the trend of bioprosthetic implantation in younger patients, without yet the appropriate evidence. In contrast, aortic valve repair has shown excellent outcomes in terms of quality of life, freedom from re-operation and freedom from major adverse valve-related events with similar life expectancy to general population as it is also found for the Ross procedure, the only available living valve substitute. We are at a time when the paradigm of aortic valve surgery needs to change for the better. To better serve our patients, we must acquire high quality real-world evidence from multiple centers globally - this is the vision of the AVIATOR registry and our common responsibility.

Optimal B-spline Mapping of Flow Imaging Data for Imposing Patient-specific Velocity Profiles in Computational Hemodynamics.

OBJECTIVE: We propose a novel method to map patient-specific blood velocity profiles obtained from imaging data such as 2D flow MRI or 3D colour Doppler ultrasound) to geometric vascular models suitable to perform CFD simulations of haemodynamics. We describe the implementation and utilisation of the method within an open-source computational hemodynamics simulation software (CRIMSON). METHODS: The proposed method establishes point-wise correspondences between the contour of a fixed geometric model and time-varying contours containing the velocity image data, from which a continuous, smooth and cyclic deformation field is calculated. Our methodology is validated using synthetic data, and demonstrated using two different in-vivo aortic velocity datasets: a healthy subject with normal tricuspid valve and a patient with bicuspid aortic valve. RESULTS: We compare our method with the state-of-the-art Schwarz-Christoffel method, in terms of preservation of velocities and execution time. Our method is as accurate as the Schwarz-Christoffel method, while being over 8 times faster. CONCLUSIONS: Our mapping method can accurately preserve either the flow rate or the velocity field through the surface, and can cope with inconsistencies in motion and contour shape. SIGNIFICANCE: The proposed method and its integration into the CRIMSON software enable a streamlined approach towards incorporating more patient-specific data in blood flow simulations.

Fate of the Aortic Arch Following Surgery on the Aortic Root and Ascending Aorta in Bicuspid Aortic Valve.

BACKGROUND: Recent guidelines support more aggressive surgery for aneurysms of the ascending aorta and root in patients with bicuspid aortic valve. However, the fate of the arch after surgery of the root and ascending aorta is unknown. We set out to assess outcomes following root and ascending aortic surgery and subsequent growth of the arch. METHODS: Between 2005 and 2016, 536 consecutive patients underwent surgery for aneurysm of the root and ascending aorta; 168 had bicuspid aortic valve. Patients with dissection were excluded. Arch diameter was measured before and after surgery, at 6 months and then annually. RESULTS: Of 168 patients, 127 (75.6%) had aortic root replacement and 41 (24.4%) had ascending replacement. Mean age was 57 ± 12.8 years, 82.7% were men, and 5 operations were performed during pregnancy. There was 1 (0.6%) hospital death. One (0.6%) patient had a stroke and 1 (0.6%) had resternotomy for bleeding. Median intensive care unit and hospital stays were 1 and 6 days, respectively. Follow-up was complete for 94% at a median of 5.9 years (range, 1 to 139 months). Aortic arch diameter was 2.9 cm preoperatively and 3.0 cm at follow-up. There was 97% freedom from reoperation and none of the patients required surgery on the arch. CONCLUSIONS: Prophylactic arch replacement during aortic root and ascending aortic surgery in patients with bicuspid aortic valve is not supported. Our data do not support long-term surveillance of the rest of the aorta in this population.