Hemodynamics inside the neo- and native sinus after TAVR: Effects of implant depth and cardiac output on flow field and coronary flow.

Transcatheter aortic valve replacement (TAVR) has emerged as a widely used therapy for aortic valve diseases. With TAVR, flow hemodynamics may change leading to areas of flow stagnation prone to thrombosis risk. The neo-sinus, created by introducing a prosthesis inside the diseased native valve, may prompt leaflet thrombosis due to areas of flow stasis. This study attempted to understand the effect of different prosthesis implant depths on the flow field within the neo- and native sinus and on the coronary perfusion. Experiments were performed inside an in vitro pulse duplicator producing physiological conditions according to ISO 5840-1:2015 standard. Flow fields were obtained for two cardiac outputs (CO) using particle image velocimetry (PIV). Washout was calculated as a measure of flow stasis. The two main results are: a lower implant position and a lower CO/frequency led to better native sinus washout, but worsened neo-sinus washout. In contrast, a higher implant position led to higher coronary flow (for higher CO/frequency). No significant effect of implant depth on coronary flow was observed for lower CO/frequency. In summary, a higher implant position using this self-expanding prosthesis is associated with reduced neo-sinus flow stasis. Hereby, washout of the native sinus, as well as coronary flow, are dependent on cardiac output.

Parametric Hemodynamic 4D Flow MRI Maps for the Characterization of Chronic Thoracic Descending Aortic Dissection.

BACKGROUND: Systematic evaluation of complex flow in the true lumen and false lumen (TL, FL) is needed to better understand which patients with chronic descending aortic dissection (DAD) are predisposed to complications. PURPOSE: To develop quantitative hemodynamic maps from 4D flow MRI for evaluating TL and FL flow characteristics. STUDY TYPE: Retrospective. POPULATION: In all, 20 DAD patients (age = 60 ± 11 years; 12 male) (six medically managed type B AD [TBAD], 14 repaired type A AD [rTAAD] now with ascending aortic graft [AAo] or elephant trunk [ET1] repair) and 21 age-matched controls (age = 59 ± 10 years; 13 male) were included. FIELD STRENGTH/SEQUENCE: 1.5T, 3T, 4D flow MRI. ASSESSMENT: 4D flow MRI was acquired in all subjects. Data analysis included 3D segmentation of TL and FL and voxelwise calculation of forward flow, reverse flow, flow stasis, and kinetic energy as quantitative hemodynamics maps. STATISTICAL TESTS: Analysis of variance (ANOVA) or Kruskal-Wallis tests were performed for comparing subject groups. Correlation and Bland-Altman analysis was performed for the interobserver study. RESULTS: Patients with rTAAD presented with elevated TL reverse flow (AAo repair: P = 0.004, ET1: P = 0.018) and increased TL kinetic energy (AAo repair: P = 0.0002, ET1: P = 0.011) compared to controls. In addition, TL kinetic energy was increased vs. patients with TBAD (AAo repair: P = 0.021, ET1: P = 0.048). rTAAD was associated with higher FL kinetic energy and lower FL stasis compared to patients with TBAD (AAo repair: P = 0.002, ET1: P = 0.024 and AAo repair: P = 0.003, ET1: P = 0.048, respectively). DATA CONCLUSION: Quantitative maps from 4D flow MRI demonstrated global and regional hemodynamic differences between DAD patients and controls. Patients with rTAAD vs. TBAD had significantly altered regional TL and FL hemodynamics. These findings indicate the potential of 4D flow MRI-derived hemodynamic maps to help better evaluate patients with DAD. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2020;51:1357-1368.

Early endovascular stenting for extracranial carotid artery dissection with angiographic flow stasis: A series of four cases.

Extracranial carotid artery dissection is a major cause of ischemic stroke in young patients. Progressive stroke or recurrent ischemic symptoms may occur despite adequate medical treatment. Our treatment policy for these conditions is based on the fact that immediate vascular reconstruction is necessary in the cases with angiographic flow stasis in the true lumen beyond the dissection site. We report our experiences with four consecutive extracranial carotid artery dissections successfully treated with early endovascular stenting and discuss the indication of this treatment with a special emphasis on the angiographic findings.

Thrombotic triad in microgravity.

Thrombotic disease may be an underdiagnosed condition of prolonged exposure to microgravity and yet the underlying factors remain poorly defined. Recently, an internal jugular vein thrombosis was diagnosed in a low-risk female astronaut after an approximately 7-week space mission. Six of the additional 10 crew members demonstrated jugular venous flow risk factors, such as suspicious stagnation or retroversion. Fortunately, all were asymptomatic. Observations in space as well as clinical and in vitro microgravity studies on Earth, where experiments are designed to recapitulate the conditions of space, suggest effects on blood flow stasis, coagulation, and vascular function. In this article, the related literature on thrombotic disease in space is reviewed, with consideration of these elements of Virchow's triad.

Effect of Ascending Aortic Curvature on Flow in the Sinus and Neo-sinus Following TAVR: A Patient-Specific Study.

Patient-specific aortic geometry and its influence on the flow in the vicinity of Transcatheter Aortic Valve (TAV) has been highlighted in numerous studies using both in silico and in vitro experiments. However, there has not yet been a detailed Particle Image Velocimetry (PIV) experiment conducted to quantify the relationship between the geometry, flow downstream of TAV, and the flow in the sinus and the neo-sinus. We tested six different patient-specific aorta models with a 26-mm SAPIEN 3 valve (Edwards Lifesciences, Irvine, CA, USA) in a left heart simulator with coronary flow. Velocities in all three cusps and circulation downstream of TAV were computed to evaluate the influence of the ascending aorta curvature on the flow field. The in vitro analysis showed that the patient-specific aortic curvature had positive correlation to the circulation in the ascending aorta (p = 0.036) and circulation had negative correlation to the particle washout time in the cusps (p = 0.011). These results showed that distinct vortical flow patterns in the ascending aorta as the main jet impinges on the aortic wall causes a recirculation region that facilitates the flow back into the sinus and the neo-sinus, thus reducing the risk of flow stagnation and washout time.

Angiographic predictors of spontaneous obliteration of transarterial partially embolized brain arteriovenous malformations.

BACKGROUND: Spontaneous obliteration of cerebral arteriovenous malformations is uncommon but could occur after partial embolization. METHODS: A retrospective study of 140 patients that underwent embolization for cerebral AVMs from 2005 to August 2019 using liquid embolic agents. The angiographic outcome of patients was classified as regard complete embolization, partial embolization, and complete obliteration after partial embolization. The parameters studied included size, location, number of arterial feeders, number of draining veins, rupture status, embolic agent, and patient factors as well. RESULTS: The study patients included 74 (53%) females and 66 (47%) males. Their age ranged from 7 to 43 years old. One hundred and eight patients (77%) presented with hemorrhage. The AVM grades were grade II in 57 (40.7%) patients and grade III in 56 (39.3%) patients. Sixty-one (43.57%) patients were treated by n-Butyl Cyanoacrylate and 71 (50.71%) patients were treated with Onyx, and both materials were used together in 8 cases. Follow-up angiography was done from 6 to 36 months after embolization. The rate of complete occlusion in all patients was 61.43% (86 patients). There were three groups of patients, the first group had complete occlusion of the nidus at the time of embolization and included 68 (48.57%) patients. The second group had partial embolization with partial occlusion of the nidus 54 patients (38.57%). The 3rd group included 18 patients (12.85%) with complete nidal occlusion on follow up after partial embolization. The delay in the venous drainage of the AVM to the late arterial phase or early venous phase with flow stasis was a significant predictor of future obliteration on follow up after partial embolization. Other significant parameters that were associated with the progressive disappearance of the AVM nidus on follow up after partial embolization are presentation with hemorrhage, AVMs size less than 3 cm, the presence of single draining or double draining veins, superficial venous drainage, and one or 2 arterial feeders. CONCLUSION: Spontaneous closure of intracranial arteriovenous malformations after partial embolization may be encountered in cases of stasis of flow during embolization procedure with a delay of the venous drainage. A long-term follow-up of more cases over many years is required to confirm the validity of this conclusion.

Subclinical Leaflet Thrombosis in Supra-annular Transcatheter Aortic Valves: the Role of Leaflet Design.

Subclinical leaflet thrombosis has been increasingly observed in patients undergoing transcatheter aortic valve replacement. Intra-annular transcatheter aortic valves (TAVs) have a larger neo-sinus volume than supra-annular devices and are potentially at a higher risk of hypoattenuated leaflet thickening (HALT). However, clinical data from randomized clinical trials have shown that approximately one-third of patients undergoing TAVR with intra- or supra-annular devices develop HALT in 1 year. The findings point to the potential role of leaflet design in developing HALT. The study aimed to systematically investigate leaflet kinematics of a supra-annular TAV, Medtronic CoreValve, and determine regions of blood stasis. Fluid-solid interaction simulations demonstrated the limited movement of CoreValve leaflets in the lower belly region that created regions of blood stasis on the surface of the leaflets. The findings provide insights into potential improvements in leaflet design in the next generation of TAVs to reduce the risk of HALT and leaflet immobility.

Determining flow stasis zones in the intracranial aneurysms and the relation between these zones and aneurysms' aspect ratios after flow diversions.

BACKGROUND: Flow diverter stents (FDSs) are widely used to treat aneurysms in the clinic. However, even the same flow diverter (FD) use on different patients' aneurysm sites can cause unexpected hemodynamics at the aneurysm region yielding low success rates for the overall treatment. Therefore, the present study aims to unfold why FDs do not work as they are supposed to for some patients and propose empirical correlation along with a contingency table analysis to estimate the flow stasis zones in the aneurysm sacs. METHODS: The present work numerically evaluated the use of FRED4518 FDS on six patients' intracranial aneurysms based on patient-specific aneurysm geometries. Computational fluid dynamics (CFD) simulation results were further processed to identify the time evolution of weightless blood particles for six patients' aneurysms. RESULTS: Stagnation zone formation, incoming and outgoing blood flow at the aneurysm neck, and statistical analysis of six patients indicated that FRED4518 showed a large flow stasis zone for an aspect ratio larger than 0.75. However, FRED4518, used for aneurysms with an aspect ratio of less than 0.65, caused small stagnant flow zones based on the number of blood particles that stayed in the aneurysm sac. CONCLUSION: A patient-specific empirical equation is derived considering aneurysms' morphological characteristics to determine the amount of stagnated fluid flow zones and magnitude of the mean aneurysm velocity in the aneurysm sac for FRED4518 based on weightless fluid particle results for the first time in the literature. As a result, numerical simulation results and patient data-driven equation can help perceive stagnated fluid zone amount before FRED4518 placement by shedding light on neuro-interventional surgeons and radiologists.

The role of flow stasis in transcatheter aortic valve leaflet thrombosis.

OBJECTIVE: With the recent expanded indication for transcatheter aortic valve replacement to low-risk surgical patients, thrombus formation in the neosinus is of particular interest due to concerns of reduced leaflet motion and long-term transcatheter heart valve durability. Although flow stasis likely plays a role, a direct connection between neosinus flow stasis and thrombus severity is yet to be established. METHODS: Patients (n = 23) were selected to minimize potential confounding factors related to thrombus formation. Patient-specific 3-dimensional reconstructed in vitro models were created to replicate in vivo anatomy and valve deployment using the patient-specific cardiac output and idealized coronary flows. Dye was injected into each neosinus to quantify washout time as a measure of flow stasis. RESULTS: Flow stasis (washout time) showed a significant, positive correlation with thrombus volume in the neosinus (rho = 0.621, P < .0001). Neither thrombus volume nor washout time was significantly different in the left, right, and noncoronary neosinuses (P ≥ .54). CONCLUSIONS: This is the first patient-specific study correlating flow stasis with thrombus volume in the neosinus post-transcatheter aortic valve replacement across multiple valve types and sizes. Neosinus-specific factors create hemodynamic and thrombotic variability within individual patients. Measurement of neosinus flow stasis may guide strategies to improve outcomes in transcatheter aortic valve replacement.

Predictive Model for Thrombus Formation After Transcatheter Valve Replacement.

PURPOSE: Leaflet thrombosis is a significant adverse event after transcatheter aortic valve (TAV) replacement (TAVR). The purpose of our study was to present a semi-empirical, mathematical model that links patient-specific anatomic, valve, and flow parameters to predict likelihood of leaflet thrombosis. METHODS: The two main energy sources of neo-sinus (NS) washout after TAVR include the jet flow downstream of the TAV and NS geometric change in volume due to the leaflets opening and closing. Both are highly dependent on patient anatomic and hemodynamic factors. As rotation of blood flow is prevalent in both the sinus of Valsalva and then the NS, we adopted the vorticity flux or circulation (Г) as a metric quantifying overall washout. Leaflet thrombus volumes were segmented based on hypo-attenuating leaflet thickening (HALT) in post-TAVR patient's gated computed tomography. Г was assessed using dimensional scaling as well as computational fluid dynamics (CFD) respectively and correlated to the thrombosis volumes using sensitivity and specificity analysis. RESULTS: Г in the NS, that accounted for patient flow and anatomic conditions derived from scaling arguments significantly better predicted the occurrence of leaflet thrombus than CFD derived measures such as stasis volumes or wall shear stress. Given results from the six patient datasets considered herein, a threshold Г value of 28.0 yielded a sensitivity and specificity of 100% where patients with Gamma < 28 developed valve thrombosis. A 10% error in measurements of all variables can bring the sensitivity specificity down to 87%. CONCLUSION: A predictive model relating likelihood of valve thrombosis using Г in the NS was developed with promising sensitivity and specificity. With further studies and improvements, this predictive technology may lead to alerting physicians on the risk for thrombus formation following TAVR.

Hemodynamic Assessment in Bicuspid Aortic Valve Disease and Aortic Dilation: New Insights From Voxel-By-Voxel Analysis of Reverse Flow, Stasis, and Energetics.

Objectives: Clinical management decisions surrounding ascending aorta (AAo) dilation in bicuspid aortic valve (BAV) disease benefit from personalized predictive tools. 4D-flow MRI may provide patient-specific markers reflective of BAV-associated aortopathy. This study aims to explore novel 4D-flow MRI parametric voxel-by-voxel forward flow, reverse flow, kinetic energy and stasis in BAV disease. We hypothesize that novel parametric voxel-by-voxel markers will be associated with aortic dilation and referral for surgery and can enhance our understanding of BAV hemodynamics beyond standard metrics. Methods: A total of 96 subjects (73 BAV patients, 23 healthy controls) underwent MRI scan. Healthy controls had no known cardiovascular disease. Patients were clinically referred for AAo dilation assessment. Indexed diameters were obtained by dividing the aortic diameter by the patient's body surface area. Patients were followed for the occurrence of aortic surgery. 4D-flow analysis was performed by a single observer in five regions: left ventricular outflow tract (LVOT), AAo, arch, proximal descending aorta (PDAo), and distal descending aorta (DDAo). In each region peak velocity, kinetic energy (KE), forward flow (FF), reverse flow (RF), and stasis were measured on a voxel-by-voxel basis. T-tests (or non-parametric equivalent) compared flow parameters between cohorts. Univariate and multivariate analyses explored associations between diameter and parametric voxel-by-voxel parameters. Results: Compared to controls, BAV patients showed reduced stasis (p < 0.01) and increased RF and FF (p < 0.01) throughout the aorta, and KE remained similar. In the AAo, indexed diameter correlated with age (R = 0.326, p = 0.01), FF (R = -0.648, p < 0.001), RF (R = -0.441, p < 0.001), and stasis (R = -0.288, p < 0.05). In multivariate analysis, FF showed a significant inverse association with AAo indexed diameter, independent of age. During a median 179 ± 180 days of follow-up, 23 patients (32%) required aortic surgery. Compared to patients not requiring surgery, they showed increased KE and peak velocity in the proximal aorta (p < 0.01), accompanied by increased RF and reduced stasis throughout the entire aorta (p < 0.01). Conclusion: Novel voxel-by-voxel reverse flow and stasis were altered in BAV patients and are associated with aortic dilation and surgical treatment.

In-Vitro Assessment of the Effects of Transcatheter Aortic Valve Leaflet Design on Neo-Sinus Geometry and Flow.

Transcatheter aortic valve (TAV) leaflet thrombosis is a clinical risk with potentially fatal consequences. Studies have identified neo-sinus flow stasis as a cause of leaflet thrombosis. Flow stasis is influenced by the TAV leaflets, which affect the local fluid dynamics in the aortic sinus and neo-sinus. This study evaluated the effects of TAV leaflet features on the neo-sinus flow as a measure of leaflet thrombosis risk. Five TAVs of varied leaflet length and insertion height were tested in a simulator. Hydrodynamics and leaflet kinematics through en-phase imaging were quantified. Velocity fields were assessed using high-speed particle image velocimetry. Regions of flow stasis and particle residence times (PRTs) were quantified. TAVs with shorter leaflet length exhibited larger orifice areas and lower transvalvular pressure gradients. Shorter leaflet length and increased leaflet insertion TAVs additionally exhibited lower neo-sinus PRTs (0.44 ± 0.21 vs 2.83 ± 0.48 cycles, p < 0.05) and higher neo-sinus peak velocities (0.15 ± 0.009 vs 0.07 ± 0.005 m/s, p < 0.05) than TAVs with longer leaflet length and lower leaflet insertion. The average neo-sinus volume positively correlated with PRT(r = 0.810, p < 0.001), and extent of flow stasis (r = 0.682, p < 0.05). These results suggest that a small neo-sinus volume may reduce flow stagnation and particle residence, potentially reducing the risk of leaflet thrombosis. We propose that leaflet design features might be proactively controlled in the design of future transcatheter aortic valves.

An Evaluation of the Influence of Coronary Flow on Transcatheter Heart Valve Neo-Sinus Flow Stasis.

Transcatheter heart valve (THV) leaflet thrombosis in the neo-sinus and associated reduced leaflet motion is of clinical concern due to risks of embolism and worsened valve hemodynamics. Flow stasis in the neo-sinus (the space between the native and THV leaflets) is a known risk factor, but the role of proximal coronary flow is yet to be investigated. We tested two replicas of FDA approved commercial THVs-intra-annular and supra-annular (similar to the SAPIEN 3 and CoreValve families)-in a left heart simulator with coronary flow. Velocity fields in the left coronary cusp (LCC) and non (NCC) neo-sinus were quantified using high speed particle image velocimetry and particle residence times (PRT) were computed to evaluate flow stasis in the region. The supra-annular THV LCC neo-sinus had shorter PRT than its NCC neo-sinus (0.66 ± 0.00 vs. 0.76 ± 0.04, p = 0.038), while the intra-annular THV LCC neo-sinus had similar PRT to its NCC neo-sinus (1.93 ± 0.05 vs. 1.92 ± 0.03 cycles, p = 0.889). The supra-annular valve LCC and NCC neo-sinuses had shorter PRT than their intra-annular valve counterparts (p < 0.001). These results showed that coronary flow reduces flow stasis in the supra-annular THV neo-sinus and, ostensibly, thrombosis risk in the region. This effect was not significant in the intra-annular valve.

Visualizing and quantifying flow stasis in abdominal aortic aneurysms in men using 4D flow MRI.

PURPOSE: To examine methods for visualizing and quantifying flow stasis in abdominal aortic aneurysms (AAA) using 4D Flow MRI. METHODS: Three methods were investigated: conventional volumetric residence time (VRT), mean velocity analysis (MVA), and particle travel distance analysis (TDA). First, ideal 4D Flow MRI data was generated using numerical simulations and used as a platform to explore the effects of noise and background phase-offset errors, both of which are common 4D Flow MRI artifacts. Error-free results were compared to noise or offset affected results using linear regression. Subsequently, 4D Flow MRI data for thirteen (13) subjects with AAA was acquired and used to compare the stasis quantification methods against conventional flow visualization. RESULTS: VRT (R2 = 0.69) was more sensitive to noise than MVA (R2 = 0.98) and TDA (R2 = 0.99) at typical non-contrast signal-to-noise ratio levels (SNR = 20). VRT (R2 = 0.14) was more sensitive to background phase-offsets than MVA (R2 = 0.99) and TDA (R2 = 0.96) when considering a 95% effective background phase-offset correction. Qualitatively, TDA outperformed MVA (Wilcoxon p < 0.005, mean score improvement 1.6/5), and had good agreement (median score 4/5) with flow visualizations. CONCLUSION: Flow stasis can be quantitatively assessed using 4D Flow MRI. While conventional residence time calculations fail due to error accumulation as a result of imperfect measured velocity fields, methods that do not require lengthy particle tracking perform better. MVA and TDA are less sensitive to measurement errors, and TDA generates results most similar to those obtained using conventional flow visualization.