Impact of combined plaque structural stress and wall shear stress on coronary plaque progression, regression, and changes in composition.

AIMS: The focal distribution of atherosclerotic plaques suggests that local biomechanical factors may influence plaque development. METHODS AND RESULTS: We studied 40 patients at baseline and over 12 months by virtual-histology intravascular ultrasound and bi-plane coronary angiography. We calculated plaque structural stress (PSS), defined as the mean of the maximum principal stress at the peri-luminal region, and wall shear stress (WSS), defined as the parallel frictional force exerted by blood flow on the endothelial surface, in areas undergoing progression or regression. Changes in plaque area, plaque burden (PB), necrotic core (NC), fibrous tissue (FT), fibrofatty tissue, and dense calcium were calculated for each co-registered frame. A total of 4029 co-registered frames were generated. In areas with progression, high PSS was associated with larger increases in NC and small increases in FT vs. low PSS (difference in ΔNC: 0.24 ± 0.06 mm2; P < 0.0001, difference in ΔFT: -0.15 ± 0.08 mm2; P = 0.049). In areas with regression, high PSS was associated with increased NC and decreased FT (difference in ΔNC: 0.15 ± 0.04; P = 0.0005, difference in ΔFT: -0.31 ± 0.06 mm2; P < 0.0001). Low WSS was associated with increased PB vs. high WSS in areas with progression (difference in ΔPB: 3.3 ± 0.4%; P < 0.001) with a similar pattern observed in areas with regression (difference in ΔPB: 1.2 ± 0.4%; P = 0.004). Plaque structural stress and WSS were largely independent of each other (R2 = 0.002; P = 0.001). CONCLUSION: Areas with high PSS are associated with compositional changes consistent with increased plaque vulnerability. Areas with low WSS are associated with more plaque growth in areas that progress and less plaque loss in areas that regress. The interplay of PSS and WSS may govern important changes in plaque size and composition.

A Multimodality Image-Based Fluid-Structure Interaction Modeling Approach for Prediction of Coronary Plaque Progression Using IVUS and Optical Coherence Tomography Data With Follow-Up.

Medical image resolution has been a serious limitation in plaque progression research. A modeling approach combining intravascular ultrasound (IVUS) and optical coherence tomography (OCT) was introduced and patient follow-up IVUS and OCT data were acquired to construct three-dimensional (3D) coronary models for plaque progression investigations. Baseline and follow-up in vivo IVUS and OCT coronary plaque data were acquired from one patient with 105 matched slices selected for model construction. 3D fluid-structure interaction (FSI) models based on IVUS and OCT data (denoted as IVUS + OCT model) were constructed to obtain stress/strain and wall shear stress (WSS) for plaque progression prediction. IVUS-based IVUS50 and IVUS200 models were constructed for comparison with cap thickness set as 50 and 200 µm, respectively. Lumen area increase (LAI), plaque area increase (PAI), and plaque burden increase (PBI) were chosen to measure plaque progression. The least squares support vector machine (LS-SVM) method was employed for plaque progression prediction using 19 risk factors. For IVUS + OCT model with LAI, PAI, and PBI, the best single predictor was plaque strain, local plaque stress, and minimal cap thickness, with prediction accuracy as 0.766, 0.838, and 0.890, respectively; the prediction accuracy using best combinations of 19 factors was 0.911, 0.881, and 0.905, respectively. Compared to IVUS + OCT model, IVUS50, and IVUS200 models had errors ranging from 1% to 66.5% in quantifying cap thickness, stress, strain and prediction accuracies. WSS showed relatively lower prediction accuracy compared to other predictors in all nine prediction studies.

Combining IVUS and Optical Coherence Tomography for More Accurate Coronary Cap Thickness Quantification and Stress/Strain Calculations: A Patient-Specific Three-Dimensional Fluid-Structure Interaction Modeling Approach.

Accurate cap thickness and stress/strain quantifications are of fundamental importance for vulnerable plaque research. Virtual histology intravascular ultrasound (VH-IVUS) sets cap thickness to zero when cap is under resolution limit and IVUS does not see it. An innovative modeling approach combining IVUS and optical coherence tomography (OCT) is introduced for cap thickness quantification and more accurate cap stress/strain calculations. In vivo IVUS and OCT coronary plaque data were acquired with informed consent obtained. IVUS and OCT images were merged to form the IVUS + OCT data set, with biplane angiography providing three-dimensional (3D) vessel curvature. For components where VH-IVUS set zero cap thickness (i.e., no cap), a cap was added with minimum cap thickness set as 50 and 180 µm to generate IVUS50 and IVUS180 data sets for model construction, respectively. 3D fluid-structure interaction (FSI) models based on IVUS + OCT, IVUS50, and IVUS180 data sets were constructed to investigate cap thickness impact on stress/strain calculations. Compared to IVUS + OCT, IVUS50 underestimated mean cap thickness (27 slices) by 34.5%, overestimated mean cap stress by 45.8%, (96.4 versus 66.1 kPa). IVUS50 maximum cap stress was 59.2% higher than that from IVUS + OCT model (564.2 versus 354.5 kPa). Differences between IVUS and IVUS + OCT models for cap strain and flow shear stress (FSS) were modest (cap strain <12%; FSS <6%). IVUS + OCT data and models could provide more accurate cap thickness and stress/strain calculations which will serve as basis for further plaque investigations.

An assessment of intra-patient variability on observed relationships between wall shear stress and plaque progression in coronary arteries.

BACKGROUND: Wall shear stress (WSS) has been associated with sites of plaque localization and with changes in plaque composition in human coronary arteries. Different values have been suggested for categorizing WSS as low, physiologic or high; however, uncertainties in flow rates, both across subjects and within a given individual, can affect the classification of WSS and thus influence the observed relationships between local hemodynamics and plaque changes over time. This study examines the effects of uncertainties in flow rate boundary conditions upon WSS values and investigates the influence of this variability on the observed associations of WSS with changes in VH-IVUS derived plaque components. METHODS: Three patients with coronary artery disease underwent baseline and 12 month follow-up angiography and virtual histology-intravascular ultrasound (VH-IVUS) measurements. Coronary artery models were reconstructed from the data and models with and without side-branches were created. Patient-specific Doppler ultrasound (DUS) data were employed as inflow boundary conditions and computational fluid dynamics was used to calculate the WSS in each model. Further, the influence of representative coronary artery flow waveforms upon WSS values was investigated and the concept of treating WSS using relative, rather than actual, values was explored. RESULTS: Models that included side-branch outflows and subject-specific DUS velocities were considered to be the reference cases. Hemodynamic differences were caused by the exclusion of side-branches and by imposing alternative velocity waveforms. One patient with fewer side-branches and a scaled generic waveform had little deviation from the reference case, while another patient with several side-branches excluded showed much larger departures from the reference situation. Differences between models and the respective reference cases were reduced when data were analyzed using relative, rather than actual, WSS. CONCLUSIONS: When considering individual subjects, large variations in patient-specific flow rates and exclusion of multiple side-branches in computational models can cause significant differences in observed associations between plaque evolution and ranges of computed WSS. These differences may contribute to the large variability typically found among subjects in pooled populations. Relative WSS may be more useful than actual WSS as a correlative variable when there is a large degree of uncertainty in flow rate data.

Endothelial shear stress computed from coronary computed tomography angiography: A direct comparison to intravascular ultrasound.

INTRODUCTION: Intravascular ultrasound (IVUS) studies have shown that biomechanical variables, particularly endothelial shear stress (ESS), add synergistic prognostic insight when combined with anatomic high-risk plaque features. Non-invasive risk assessment of coronary plaques with coronary computed tomography angiography (CCTA) would be helpful to enable broad population risk-screening. AIM: To compare the accuracy of ESS computation of local ESS metrics by CCTA vs IVUS imaging. METHODS: We analyzed 59 patients from a registry of patients who underwent both IVUS and CCTA for suspected CAD. CCTA images were acquired using either a 64- or 256-slice scanner. Lumen, vessel, and plaque areas were segmented from both IVUS and CCTA (59 arteries, 686 3-mm segments). Images were co-registered and used to generate a 3-D arterial reconstruction, and local ESS distribution was assessed by computational fluid dynamics (CFD) and reported in consecutive 3-mm segments. RESULTS: Anatomical plaque characteristics (vessel, lumen, plaque area and minimal luminal area [MLA] per artery) were correlated when measured with IVUS and CCTA: 12.7 â€‹± â€‹4.3 vs 10.7 â€‹± â€‹4.5 â€‹mm2, r â€‹= â€‹0.63; 6.8 â€‹± â€‹2.7 vs 5.6 â€‹± â€‹2.7 â€‹mm2, r â€‹= â€‹0.43; 5.9 â€‹± â€‹2.9 vs 5.1 â€‹± â€‹3.2 â€‹mm2, r â€‹= â€‹0.52; 4.5 â€‹± â€‹1.3 vs 4.1 â€‹± â€‹1.5 â€‹mm2, r â€‹= â€‹0.67 respectively. ESS metrics of local minimal, maximal, and average ESS were also moderately correlated when measured with IVUS and CCTA (2.0 â€‹± â€‹1.4 vs 2.5 â€‹± â€‹2.6 â€‹Pa, r â€‹= â€‹0.28; 3.3 â€‹± â€‹1.6 vs 4.2 â€‹± â€‹3.6 â€‹Pa, r â€‹= â€‹0.42; 2.6 â€‹± â€‹1.5 vs 3.3 â€‹± â€‹3.0 â€‹Pa, r â€‹= â€‹0.35, respectively). CCTA-based computation accurately identified the spatial localization of local ESS heterogeneity compared to IVUS, with Bland-Altman analyses indicating that the absolute ESS differences between the two CCTA methods were pathobiologically minor. CONCLUSION: Local ESS evaluation by CCTA is possible and similar to IVUS; and is useful for identifying local flow patterns that are relevant to plaque development, progression, and destabilization.

Differential predictability for high-risk plaque characteristics between fractional flow reserve and instantaneous wave-free ratio.

To evaluate the differential associations of high-risk plaque characteristics (HRPC) with resting or hyperemic physiologic indexes (instantaneous wave-free ratio [iFR] or fractional flow reserve [FFR]), a total of 214 vessels from 127 patients with stable angina or acute coronary syndrome who underwent coronary computed tomography angiography (CCTA) and invasive physiologic assessment were investigated. HPRC were classified into quantitative (minimal luminal area < 4 mm2 or plaque burden ≥ 70%) and qualitative features (low attenuation plaque, positive remodeling, napkin ring sign, or spotty calcification). Vessels with FFR ≤ 0.80 or iFR ≤ 0.89 had significantly higher proportions of HRPC than those with FFR > 0.80 or iFR > 0.89, respectively. FFR was independently associated with both quantitative and qualitative HRPC, but iFR was only associated with quantitative HRPC. Both FFR and iFR were significantly associated with the presence of ≥ 3 HRPC, and FFR demonstrated higher discrimination ability than iFR (AUC 0.703 vs. 0.648, P = 0.045), which was predominantly driven by greater discriminating ability of FFR for quantitative HRPC (AUC 0.832 vs. 0.744, P = 0.005). In conclusion, both FFR and iFR were significantly associated with CCTA-derived HRPC. Compared with iFR, however, FFR was independently associated with the presence of qualitative HRPC and showed a higher predictive ability for the presence of ≥ 3 HRPC.

Stent underexpansion is associated with high wall shear stress: a biomechanical analysis of the shear stent study.

Coronary stent underexpansion is associated with restenosis and stent thrombosis. In clinical studies of atherosclerosis, high wall shear stress (WSS) has been associated with activation of prothrombotic pathways, upregulation of matrix metalloproteinases, and future myocardial infarction. We hypothesized that stent underexpansion is predictive of high WSS. WSS distribution was investigated in patients enrolled in the prospective randomized controlled study of angulated coronary arteries randomized to undergo percutaneous coronary intervention with R-ZES or X-EES. WSS was calculated from 3D reconstructions of arteries from intravascular ultrasound (IVUS) and angiography using computational fluid dynamics. A logistic regression model investigated the relationship between WSS and underexpansion and the relationship between underexpansion and stent platform. Mean age was 63±11, 78% were male, 35% had diabetes, mean pre-stent angulation was 36.7°±14.7°. Underexpansion was assessed in 83 patients (6,181 IVUS frames). Frames with stent underexpansion were significantly more likely to exhibit high WSS (> 2.5 Pa) compared to those without underexpansion with an OR of 2.197 (95% CI = [1.233-3.913], p = 0.008). There was no significant association between underexpansion and low WSS (< 1.0 Pa) and no significant differences in underexpansion between R-ZES and X-EES. In the Shear Stent randomized controlled study, underexpanded IVUS frames were more than twice as likely to be associated with high WSS than frames without underexpansion.

Semi-Automatic Reconstruction of Patient-Specific Stented Coronaries based on Data Assimilation and Computer Aided Design.

PURPOSE: The interplay between geometry and hemodynamics is a significant factor in the development of cardiovascular diseases. This is particularly true for stented coronary arteries. To elucidate this factor, an accurate patient-specific analysis requires the reconstruction of the geometry following the stent deployment for a computational fluid dynamics (CFD) investigation. The image-based reconstruction is troublesome for the different possible positions of the stent struts in the lumen and the coronary wall. However, the accurate inclusion of the stent footprint in the hemodynamic analysis is critical for detecting abnormal stress conditions and flow disturbances, particularly for thick struts like in bioresorbable scaffolds. Here, we present a novel reconstruction methodology that relies on Data Assimilation and Computer Aided Design. METHODS: The combination of the geometrical model of the undeployed stent and image-based data assimilated by a variational approach allows the highly automated reconstruction of the skeleton of the stent. A novel approach based on computational mechanics defines the map between the intravascular frame of reference (called L-view) and the 3D geometry retrieved from angiographies. Finally, the volumetric expansion of the stent skeleton needs to be self-intersection free for the successive CFD studies; this is obtained by using implicit representations based on the definition of Nef-polyhedra. RESULTS: We assessed our approach on a vessel phantom, with less than 10% difference (properly measured) vs. a customized manual (and longer) procedure previously published, yet with a significant higher level of automation and a shorter turnaround time. Computational hemodynamics results were even closer. We tested the approach on two patient-specific cases as well. CONCLUSIONS: The method presented here has a high level of automation and excellent accuracy performances, so it can be used for larger studies involving patient-specific geometries.

Automated finite element approach to generate anatomical patient-specific biomechanical models of atherosclerotic arteries from virtual histology-intravascular ultrasound.

Despite advancements in early detection and treatment, atherosclerosis remains the leading cause of death across all cardiovascular diseases (CVD). Biomechanical analysis of atherosclerotic lesions has the potential to reveal biomechanically instable or rupture-prone regions. Treatment decisions rarely consider the biomechanics of the stenosed lesion due in-part to difficulties in obtaining this information in a clinical setting. Previous 3D FEA approaches have incompletely incorporated the complex curvature of arterial geometry, material heterogeneity, and use of patient-specific data. To address these limitations and clinical need, herein we present a user-friendly fully automated program to reconstruct and simulate the wall mechanics of patient-specific atherosclerotic coronary arteries. The program enables 3D reconstruction from patient-specific data with heterogenous tissue assignment and complex arterial curvature. Eleven arteries with coronary artery disease (CAD) underwent baseline and 6-month follow-up angiographic and virtual histology-intravascular ultrasound (VH-IVUS) imaging. VH-IVUS images were processed to remove background noise, extract VH plaque material data, and luminal and outer contours. Angiography data was used to orient the artery profiles along the 3D centerlines. The resulting surface mesh is then resampled for uniformity and tetrahedralized to generate the volumetric mesh using TetGen. A mesh convergence study revealed edge lengths between 0.04 mm and 0.2 mm produced constituent volumes that were largely unchanged, hence, to save computational resources, a value of 0.2 mm was used throughout. Materials are assigned and finite element analysis (FEA) is then performed to determine stresses and strains across the artery wall. In a representative artery, the highest average effective stress was in calcium elements with 235 kPa while necrotic elements had the lowest average stress, reaching as low as 0.79 kPa. After applying nodal smoothening, the maximum effective stress across 11 arteries remained below 288 kPa, implying biomechanically stable plaques. Indeed, all atherosclerotic plaques remained unruptured at the 6-month longitudinal follow up diagnosis. These results suggest our automated analysis may facilitate assessment of atherosclerotic plaque stability.

Assessment with clinical data of a coupled bio-hemodynamics numerical model to predict leukocyte adhesion in coronary arteries.

Numerical simulations of coupled hemodynamics and leukocyte transport and adhesion inside coronary arteries have been performed. Realistic artery geometries have been obtained for a set of four patients from intravascular ultrasound and angiography images. The numerical model computes unsteady three-dimensional blood hemodynamics and leukocyte concentration in the blood. Wall-shear stress dependent leukocyte adhesion is also computed through agent-based modeling rules, fully coupled to the hemodynamics and leukocyte transport. Numerical results have a good correlation with clinical data. Regions where high adhesion is predicted by the simulations coincide to a good approximation with artery segments presenting plaque increase, as documented by clinical data from baseline and six-month follow-up exam of the same artery. In addition, it is observed that the artery geometry and, in particular, the tortuosity of the centerline are a primary factor in determining the spatial distribution of wall-shear stress, and of the resulting leukocyte adhesion patterns. Although further work is required to overcome the limitations of the present model and ultimately quantify plaque growth in the simulations, these results are encouraging towards establishing a predictive methodology for atherosclerosis progress.

Multi-patient study for coronary vulnerable plaque model comparisons: 2D/3D and fluid-structure interaction simulations.

Several image-based computational models have been used to perform mechanical analysis for atherosclerotic plaque progression and vulnerability investigations. However, differences of computational predictions from those models have not been quantified at multi-patient level. In vivo intravascular ultrasound (IVUS) coronary plaque data were acquired from seven patients. Seven 2D/3D models with/without circumferential shrink, cyclic bending and fluid-structure interactions (FSI) were constructed for the seven patients to perform model comparisons and quantify impact of 2D simplification, circumferential shrink, FSI and cyclic bending plaque wall stress/strain (PWS/PWSn) and flow shear stress (FSS) calculations. PWS/PWSn and FSS averages from seven patients (388 slices for 2D and 3D thin-layer models) were used for comparison. Compared to 2D models with shrink process, 2D models without shrink process overestimated PWS by 17.26%. PWS change at location with greatest curvature change from 3D FSI models with/without cyclic bending varied from 15.07% to 49.52% for the seven patients (average = 30.13%). Mean Max-FSS, Min-FSS and Ave-FSS from the flow-only models under maximum pressure condition were 4.02%, 11.29% and 5.45% higher than those from full FSI models with cycle bending, respectively. Mean PWS and PWSn differences between FSI and structure-only models were only 4.38% and 1.78%. Model differences had noticeable patient variations. FSI and flow-only model differences were greater for minimum FSS predictions, notable since low FSS is known to be related to plaque progression. Structure-only models could provide PWS/PWSn calculations as good approximations to FSI models for simplicity and time savings in calculation.

Clinical and Prognostic Impact From Objective Analysis of Post-Angioplasty Fractional Flow Reserve Pullback.

OBJECTIVES: This study sought to evaluate clinical implications of the residual fractional flow reserve (FFR) gradient after angiographically successful percutaneous coronary intervention (PCI). BACKGROUND: Recent studies have demonstrated FFR measured after PCI is associated with clinical outcome after PCI. Although post-PCI FFR pull back tracings provide clinically relevant information on the residual FFR gradient, there are no objective criteria for assessing post-PCI FFR pull back tracings. METHODS: A total of 492 patients who underwent angiographically successful PCI and post-PCI FFR measurement with pull back tracings were analyzed. The presence of the major residual FFR gradient after PCI was assessed by both conventional visual interpretation of the pull back tracings and objective analysis using the instantaneous FFR gradient per unit time (dFFR(t)/dt) with a cutoff value of dFFR(t)/dt ≥0.035. Classification agreement between 2 independent operators for the presence of the major residual FFR gradient was compared before and after providing dFFR(t)/dt results. Target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization at 2 years, was compared according to the presence of the major residual FFR gradient. RESULTS: Among the study population, 33.9% had the major residual FFR gradient defined by dFFR(t)/dt. The classification agreement between operators' assessments for the major residual FFR gradient increased with dFFR(t)/dt results compared with conventional visual assessment (Cohen's kappa = 0.633 to 0.819; P < 0.001; intraclass correlation coefficient: 0.776 to 0.901; P < 0.001). Patients with major residual FFR gradient were associated with a higher risk of TVF at 2 years than those without major residual FFR gradient (9.0% vs 2.2%; P < 0.001). Inclusion of the major residual FFR gradient to a clinical prediction model significantly increased discrimination and reclassification ability (C-index = 0.539 vs 0.771; P = 0.006; net reclassification improvement = 0.668; P = 0.007; integrated discrimination improvement = 0.033; P = 0.017) for TVF at 2 years. The presence of the major residual FFR gradient was independently associated with TVF at 2 years, regardless of post-PCI FFR or percent FFR increase (adjusted hazard ratio: 3.930; 95% confidence interval: 1.353-11.420; P = 0.012). CONCLUSIONS: Objective analysis of post-PCI FFR pull back tracings using dFFR(t)/dt improved classification agreement on the presence of the major residual FFR gradient among operators. Presence of the major residual FFR gradient defined by dFFR(t)/dt after angiographically successful PCI was independently associated with an increased risk of TVF at 2 years. (Automated Algorithm Detecting Physiologic Major Stenosis and Its Relationship with Post-PCI Clinical Outcomes [Algorithm-PCI]; NCT04304677; Influence of FFR on the Clinical Outcome After Percutaneous Coronary Intervention [COE-PERSPECTIVE]; NCT01873560).

Physiological Distribution and Local Severity of Coronary Artery Disease and Outcomes After Percutaneous Coronary Intervention.

OBJECTIVES: The aim of this study was to evaluate prognostic implications of physiological 2-dimensional disease patterns on the basis of distribution and local severity of coronary atherosclerosis determined by quantitative flow ratio (QFR) virtual pull back. BACKGROUND: The beneficial effect of percutaneous coronary intervention (PCI) is determined by physiological distribution and local severity of coronary atherosclerosis. METHODS: The study population included 341 patients who underwent angiographically successful PCI and post-PCI fractional flow reserve (FFR) measurement. Using pre-PCI virtual pull backs of QFR, physiological distribution was determined by pull back pressure gradient index, with a cutoff value of 0.78 to define predominant focal versus diffuse disease. Physiological local severity was assessed by instantaneous QFR gradient per unit length, with a cutoff value of ≥0.025/mm to define a major gradient. Suboptimal post-PCI physiological results were defined as both post-PCI FFR ≤0.85 and percentage FFR increase ≤15%. Clinical outcome was assessed by target vessel failure (TVF) at 2 years. RESULTS: QFR pull back pressure gradient index was correlated with post-PCI FFR (R = 0.423; P < 0.001), and instantaneous QFR gradient per unit length was correlated with percentage FFR increase (R = 0.370; P < 0.001). Using the 2 QFR-derived indexes, disease patterns were classified into 4 categories: predominant focal disease with and without major gradient (group 1 [n = 150] and group 2 [n = 21], respectively) and predominant diffuse disease with and without major gradient (group 3 [n = 115] and group 4 [n = 55], respectively). Proportions of suboptimal post-PCI physiological results were significantly different according to the 4 disease patterns (18.7%, 23.8%, 22.6%, and 56.4% from group 1 to group 4, respectively; P < 0.001). Cumulative incidence of TVF after PCI was significantly higher in patients with predominant diffuse disease (8.1% in group 3 and 9.9% in group 4 vs 1.4% in group 1 and 0.0% in group 2; overall P = 0.024). CONCLUSIONS: Both physiological distribution and local severity of coronary atherosclerosis could be characterized without pressure-wire pull backs, which determined post-PCI physiological results. After successful PCI, TVF risk was determined mainly by the physiological distribution of coronary atherosclerosis. (Automated Algorithm Detecting Physiologic Major Stenosis and Its Relationship With Post-PCI Clinical Outcomes [Algorithm-PCI], NCT04304677; Influence of FFR on the Clinical Outcome After Percutaneous Coronary Intervention [PERSPECTIVE], NCT01873560).

Risk stratification of coronary plaques using physiologic characteristics by CCTA: Focus on shear stress.

The identification of factors determining whether a lesion progresses, destabilizes or becomes quiescent remains a challenge. Wall or endothelial shear stress (WSS or ESS, respectively), the frictional force acting on the lumen wall, is strongly associated with changes in the natural history of lesions. Several clinical intravascular imaging studies have shown a clear link between disturbed flow, typically characterized by low WSS, and plaque growth. In support of these studies, in-vitro experiments of shear stress have identified several mechanisms promoting atherosclerosis. More recently, the relationship between WSS and major adverse cardiac events has been explored. Improvements in coronary computed tomography angiography (CCTA) image resolution and quality has allowed for the calculation of WSS from CT. In this review, we provide an introduction to WSS, highlight important human and animal intravascular-based WSS studies, and discuss CT-based WSS studies to date. Finally, we discuss future directions of CCTA and WSS computation.

The role of primary care in management of rare diseases in Ireland.

BACKGROUND: 'Slaintecare' aims to address complex patient care needs in an integrated fashion with an emphasis on patient-centred, patient-empowered community care.Currently there is a lack of knowledge of the impact of rare disease management in primary care and of the information tools required by general practitioners to deliver integrated care for rare disease patients. AIMS: To complete a pilot survey to estimate the general practice clinical workload attributable to selected rare diseases and assess the use of relevant information sources. METHODS: A retrospective cross-sectional survey was carried out of general practice consultations (2013-2017) for patients with 22 commonly recognised rare diseases. RESULTS: Around 31 general practitioners from 10 Irish practices completed information on 171 patients with rare diseases over 3707 consultations. General practice-specific coding systems were inadequate for rare disease patient identification. Over 139 (81.3%) patients were adult, and 32 (18.7%) were children. Management of care was hospital and not primary care based in 63%. Those eligible for state-reimbursed care had a significantly higher median number of consultations (23 consultations, IQR = 13-37, or 5.8 consultations/year) than those who paid privately (10 consultations, IQR = 4-19, or 2.5 consultations/year) (p < 0.005).General practitioners had access to public information resources on rare diseases but few had knowledge of (35.5%), or had ever used (12.9%) Orphanet, the international rare disease information portal. CONCLUSIONS: Both specific rare disease-specific coding and use of the relevant rare disease information sources are lacking in general practice in Ireland.

Bioresorbable vascular scaffolds versus everolimus-eluting stents: a biomechanical analysis of the ABSORB III Imaging substudy.

AIMS: The Absorb bioresorbable vascular scaffold (BVS) has high rates of target lesion failure (TLF) at three years. Low wall shear stress (WSS) promotes several mechanisms related to device TLF. We investigated the impact of BVS compared to XIENCE V (XV) on coronary WSS after device deployment. METHODS AND RESULTS: In the prospective, randomised, controlled ABSORB III Imaging study (BVS [n=77] or XV [n=36]), computational fluid dynamics were performed on fused angiographic and intravascular ultrasound (IVUS) images of post-implanted vessels. Low WSS was defined as <1 Pa. There were no differences in demographics, clinical risks, angiographic reference vessel diameter or IVUS minimal lumen diameter between BVS and XV patients. A greater proportion of vessels treated with BVS compared to XV demonstrated low WSS across the whole device (BVS: 17/77 [22%] vs XV: 2/36 [6%], p<0.029). Compared to XV, BVS demonstrated lower median circumferential WSS (1.73 vs 2.21 Pa; p=0.036), outer curvature WSS (p=0.026), and inner curvature WSS (p=0.038). Similarly, BVS had lower proximal third WSS (p=0.024), middle third WSS (p=0.047) and distal third WSS (p=0.028) when compared to XV. In a univariable logistic regression analysis, patients who received BVS were 4.8 times more likely to demonstrate low WSS across the scaffold/stent when compared to XV patients. Importantly, in a multivariable linear regression model, hypertension (beta: 0.186, p=0.023), lower contrast frame count velocity (beta: -0.411, p<0.001), lower post-stent residual plaque burden (beta: -0.338, p<0.001), lower % underexpanded frames (beta: -0.170, p=0.033) and BVS deployment (beta: 0.251, p=0.002) remained independently associated with a greater percentage of stented coronary vessel areas exposed to low WSS. CONCLUSIONS: In this randomised controlled study, the Absorb BVS was 4.8 times more likely than the XV metallic stent to demonstrate low WSS. BVS implantation, lower blood velocity and lower residual post-stent plaque burden were independently associated with greater area of low WSS.

Automated Algorithm Using Pre-Intervention Fractional Flow Reserve Pullback Curve to Predict Post-Intervention Physiological Results.

OBJECTIVES: This study sought to develop an automated algorithm using pre-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) pullback recordings to predict post-PCI physiological results in the pre-PCI phase. BACKGROUND: Both FFR and percent FFR increase measured after PCI showed incremental prognostic implications. However, there is no current method to predict post-PCI physiological results using physiological assessment in the pre-PCI phase. METHODS: An automated algorithm that analyzes instantaneous FFR gradient per unit time (dFFR(t)/dt) was developed from the derivation cohort (n = 30). Using dFFR(t)/dt, the pattern of atherosclerotic disease in each patient was classified into 3 groups (major, mixed, and minor FFR gradient groups) in both the internal validation cohort with constant pullback method (n = 234) and the external validation cohort with nonstandardized pullback methods (n = 252). All patients in the validation cohorts underwent PCI on the basis of pre-PCI FFR ≤0.80. Suboptimal post-PCI physiological results were defined as both post-PCI FFR <0.84 and percent FFR increase ≤15%. From the derivation cohort, cutoffs of dFFR(t)/dt for major and minor FFR gradient were 0.035/s and 0.015/s, respectively. RESULTS: In validation cohorts, dFFR(t)/dt showed significant correlations with percent FFR increase (R = 0.801; p < 0.001) and post-PCI FFR (R = 0.099; p = 0.029). In both the internal and external validation cohorts, the major FFR gradient group showed significantly higher post-PCI FFR and percent FFR increase compared with those in the mixed or minor FFR gradient groups (all p values <0.001). The proportions of suboptimal post-PCI physiological results were significantly different among 3 groups (10.4% vs. 25.8% vs. 45.7% for the major, mixed, and minor FFR gradient groups, respectively; p < 0.001) in validation cohorts. Absence of major FFR gradient lesion (odds ratio: 2.435, 95% [CI]: 1.252 to 4.734; p = 0.009) and presence of minor FFR gradient lesion (odds ratio: 2.756, 95% confidence interval: 1.629 to 4.664; p < 0.001) were independent predictors for suboptimal post-PCI physiological results. CONCLUSIONS: The automated algorithm analyzing pre-PCI pullback curve was able to predict post-PCI physiological results. The incidence of suboptimal post-PCI physiological results was significantly different according to algorithm-based classifications in the pre-PCI physiological assessment. (Automated Algorithm Detecting Physiologic Major Stenosis and Its Relationship with Post-PCI Clinical Outcomes [Algorithm-PCI]; NCT04304677).

Fluid-structure interaction of a patient-specific abdominal aortic aneurysm treated with an endovascular stent-graft.

BACKGROUND: Abdominal aortic aneurysms (AAA) are local dilatations of the infrarenal aorta. If left untreated they may rupture and lead to death. One form of treatment is the minimally invasive insertion of a stent-graft into the aneurysm. Despite this effective treatment aneurysms may occasionally continue to expand and this may eventually result in post-operative rupture of the aneurysm. Fluid-structure interaction (FSI) is a particularly useful tool for investigating aneurysm biomechanics as both the wall stresses and fluid forces can be examined. METHODS: Pre-op, Post-op and Follow-up models were reconstructed from CT scans of a single patient and FSI simulations were performed on each model. The FSI approach involved coupling Abaqus and Fluent via a third-party software - MpCCI. Aneurysm wall stress and compliance were investigated as well as the drag force acting on the stent-graft. RESULTS: Aneurysm wall stress was reduced from 0.38 MPa before surgery to a value of 0.03 MPa after insertion of the stent-graft. Higher stresses were seen in the aneurysm neck and iliac legs post-operatively. The compliance of the aneurysm was also reduced post-operatively. The peak Post-op axial drag force was found to be 4.85 N. This increased to 6.37 N in the Follow-up model. CONCLUSION: In a patient-specific case peak aneurysm wall stress was reduced by 92%. Such a reduction in aneurysm wall stress may lead to shrinkage of the aneurysm over time. Hence, post-operative stress patterns may help in determining the likelihood of aneurysm shrinkage post EVAR. Post-operative remodelling of the aneurysm may lead to increased drag forces.

Improvement in health status with once-daily indacaterol/glycopyrronium 110/50 µg in COPD patients: real-world evidence from an observational study in Ireland.

AIMS: Indacaterol/glycopyrronium (IND/GLY) 110/50 µg is a once-daily (o.d.) fixed-dose combination of long-acting ß2-agonist/long-acting muscarinic antagonist approved in over 90 countries, including Ireland, for the management of COPD. The present study was conducted to evaluate health status of COPD patients, initiated on IND/GLY 110/50 µg o.d., using the Clinical COPD Questionnaire (CCQ) tool in a real-world primary care setting in Ireland. METHODS: This was a real-world, prospective, open-label study. COPD patients aged > 40 years and with a smoking history of > 10 pack-years were included and switched to once-daily IND/GLY 110/50 µg. Enrolment of patients into the study occurred only after the decision had been made by the physician to prescribe IND/GLY 110/50 µg. Data were collected at baseline and Week 26. Health status was assessed using the validated CCQ. RESULTS: A total of 200 patients were included in study. The mean CCQ total score decreased from 2.36 at baseline to 1.44 at Week 26 (Δ, 0.92; P < 0.0005). Of the 156 patients who completed study, 113 (72.4%) achieved minimum clinically important difference in CCQ total score with IND/GLY 110/50 µg. CCQ domain scores also decreased during the study. Improvement in health status was observed across all GOLD groups and irrespective of prior COPD treatment. Adverse events were reported by 20% of patients with COPD exacerbation/infected COPD being the most common AE, reported by 11 patients. CONCLUSIONS: In real-life clinical practice in Ireland, IND/GLY 110/50 µg o.d. demonstrated statistically significant and clinically important improvement in health status in patients with COPD.

Establishment of an Automated Algorithm Utilizing Optical Coherence Tomography and Micro-Computed Tomography Imaging to Reconstruct the 3-D Deformed Stent Geometry.

Percutaneous coronary intervention (PCI) is the prevalent treatment for coronary artery disease, with hundreds of thousands of stents implanted annually. Computational studies have demonstrated the role of biomechanics in the failure of vascular stents, but clinical studies is this area are limited by a lack of understanding of the deployed stent geometry, which is required to accurately model and predict the stent-induced in vivo biomechanical environment. Herein, we present an automated method to reconstruct the 3-D deployed stent configuration through the fusion of optical coherence tomography (OCT) and micro-computed tomography ( µ CT) imaging data. In an experimental setup, OCT and µ CT data were collected in stents deployed in arterial phantoms ( n=4 ). A constrained iterative deformation process directed by diffeomorphic metric mapping was developed to deform µ CT data of a stent wireframe to the OCT-derived sparse point cloud of the deployed stent. Reconstructions of the deployed stents showed excellent agreement with the ground-truth configurations, with the distance between corresponding points on the reconstructed and ground-truth configurations of [Formula: see text]. Finally, reconstructions required <30 min of computational time. In conclusion, the developed and validated reconstruction algorithm provides a complete spatially resolved reconstruction of a deployed vascular stent from commercially available imaging modalities and has the potential, with further development, to provide more accurate computational models to evaluate the in vivo post-stent mechanical environment, as well as clinical visualization of the 3-D stent geometry immediately following PCI.