Patient-Specific Modeling of Hemodynamics: Supporting Surgical Planning in a Fontan Circulation Correction

Computational fluid dynamics (CFD) is a modeling technique that enables calculation of the behavior of fluid flows in complex geometries. In cardiovascular medicine, CFD methods are being used to calculate patient-specific hemodynamics for a variety of applications, such as disease research, noninvasive diagnostics, medical device evaluation, and surgical planning. This paper provides a concise overview of the methods to perform patient-specific computational analyses using clinical data, followed by a case study where CFD-supported surgical planning is presented in a patient with Fontan circulation complicated by unilateral pulmonary arteriovenous malformations. In closing, the challenges for implementation and adoption of CFD modeling in clinical practice are discussed.     

光学相干断层成像与血管内超声对比检测冠状动脉斑块破裂和血栓形成

目的评价光学相干断层成像(OCT)和血管内超声(IVUS)检测冠状动脉斑块破裂和继发血栓形成的准确性。方法选择2008年2—9月间的27例患者,进行冠状动脉造影、OCT及IVUS检查,共检查了30处病变,其中8处为药物支架植入后病变,其余22处为未经介入治疗干预的病变,对其中19处病变进行了支架植入术。结果对22例未经介入治疗干预的病变行OCT及IVUS检查,结果显示OCT检出富含脂质斑块伴薄纤维帽12例,IVUS检出2例;其中斑块破裂形成内膜轻微撕裂4例,IVUS未检出;斑块破裂伴夹层形成5例,IVUS检出1例;OCT检出血栓形成5例,其中红色血栓3例,白色血栓2例,IVUS检出1例,不能判断是红色血栓还是白色血栓。结论OCT在检测不稳定斑块方面优于IVUS,在检测斑块破裂致轻微内膜撕裂或夹层形成,以及继发血栓形成方面呈现优于IVUS趋势。     

Boundary Conditions in Simulation of Stenosed Coronary Arteries

A powerful alternative means to studying hemodynamics in diseased or healthy coronary arteries can be achieved by providing a numerical model in which blood flow can be virtually simulated, for instance, using the computational fluid dynamics (CFD) method. In fact, it is well documented that CFD allows reliable physiological blood flow simulation and measurements of flow parameters. A requisite for obtaining reliable results from coronary CFD is to use exact anatomical models and realistic boundary conditions. To date, in almost all of the modeling studies on hemodynamics of stenosed coronary arteries, a velocity based boundary conditions has been assigned. The objective of this study is to show that inlet velocity actually depends on the degree of stenosis and thus for severe constriction in coronary artery, a velocity based boundary conditions cannot be realistic. We then prove that regardless of severity of stenosis in coronary arteries, the upstream pressure, systemic pressure, is always constant, thus, should be used as boundary conditions instead. The two sets of boundary conditions are implemented to demonstrate the robustness of each in modeling of stenosed coronary artery in a CFD study. These boundary conditions are applied in a stenosed cylindrical pipe including three categories of symmetrical stenosis (mild, moderate and severe stenosis starting from 15 to 95% diameter reduction) for steady state and pulsatile flow. Results strongly indicate that inlet velocity boundary conditions are no longer valid when effective diameter in stenosis goes below ~2.8 mm (a healthy diameter is considered 3.2 mm) which corresponds to 10–15% diameter reduction. Further work will determine the effect of flow reduction on the oxygen tension in blood to better define conditions for clinical symptoms such as angina.     

Method analysis for optimal continuous imaging using intravascular optical coherence tomography

OBJECTIVES: Optical coherence tomography(OCT)is a high-resolution imaging method that can clearly visualize vessels through the displacement of blood with flushing agents. Continuous imaging methods have not been established. This study investigated optimal methods for continuous OCT imaging. METHODS: Thirty-four arteries with stent implantation (24 peripheral and 10 coronary arteries)in 14 pigs were examined using OCT with a motorized pullback device. Two imaging methods (flush alone by liquid substance and flush with occlusion) were compared. Adequate image acquisition was defined as the entire circumferential intimal layer being detectable within continuous segments. To investigate factors that could influence image quality, stented regions were divided into 4-5 mm segments. RESULTS: The flush with occlusion method provided better OCT images compared to flush alone (flush with occlusion: 60.9%, flush alone: 8.7%, p = 0.0002). Using the flush with occlusion method, the rate of adequate image acquisition was 64.4% and visualization of > 75% intimal circumference was 83.5%. Intravascular ultrasound could detect all stented regions. Segmental analyses found more adequate images were detected in smaller vessels (adequate segment: 3.8 +/- 0.4 mm, inadequate segment: 4.2 +/- 0.8 mm, p < 0.0001) or with centered image wire position (adequate segment: center 35%, inadequate segment: center 14%, p = 0.003). In addition, side branches did not affect image quality. CONCLUSIONS: To acquire continuous OCT images, the flush with occlusion method was more effective compared to flush alone. Moreover, image quality is affected by vessel size and imaging wire position. These results suggest that optimized OCT imaging can provide continuous vessel detection.     

Intracoronary imaging using attenuation-compensated optical coherence tomography allows better visualisation of coronary artery diseases

PurposeTo allow an accurate diagnosis of coronary artery diseases by enhancing optical coherence tomography (OCT) images of atheromatous plaques using a novel automated attenuation compensation technique.BackgroundOne of the major drawbacks of coronary OCT imaging is the rapid attenuation of the OCT signal, limiting penetration in tissue to only few millimetres. Visualisation of deeper anatomy is however critical for accurate assessment of plaque burden in-vivo.MethodsA compensation algorithm, previously developed to correct for light attenuation in soft tissues and to enhance contrast in ophthalmic OCT images, was applied to intracoronary plaque imaging using spectral-domain OCT.ResultsApplication of the compensation algorithm significantly increased tissue contrast in the vessel wall and atherosclerotic plaque boundaries. Contrast enhancement allows a better differentiation of plaque morphology, which is particularly important for the identification of lipid rich fibro atheromatous plaques and to guide decision on treatment strategy.ConclusionThe analysis of arterial vessel structure clinically captured with OCT is improved when used in conjunction with automated attenuation compensation. This approach may improve the OCT-based interpretation of coronary plaque morphology in clinical practice.     

Biomechanical Modeling to Improve Coronary Artery Bifurcation Stenting: Expert Review Document on Techniques and Clinical Implementation

Treatment of coronary bifurcation lesions remains an ongoing challenge for interventional cardiologists. Stenting of coronary bifurcations carries higher risk for in-stent restenosis, stent thrombosis, and recurrent clinical events. This review summarizes the current evidence regarding application and use of biomechanical modeling in the study of stent properties, local flow dynamics, and outcomes after percutaneous coronary interventions in bifurcation lesions. Biomechanical modeling of bifurcation stenting involves computational simulations and in vitro bench testing using subject-specific arterial geometries obtained from in vivo imaging. Biomechanical modeling has the potential to optimize stenting strategies and stent design, thereby reducing adverse outcomes. Large-scale clinical studies are needed to establish the translation of pre-clinical findings to the clinical arena.     

Techniques to Optimize the Use of Optical Coherence Tomography: Insights from the Manufacturer and User Facility Device Experience (MAUDE) Database

Background/purposeOptical coherence tomography (OCT) is a high-resolution intravascular imaging modality used to assess coronary arteries and as an adjunctive tool for optimization of percutaneous coronary interventions. Overall, the rate of complications and adverse events related to intravascular imaging is low. Limited data exist on the most commonly reported complications and modes of failure related to the use of OCT. Therefore, we analyzed the post-marketing surveillance data from the Food and Drug Administration Manufacturer and User Facility Device Experience (MAUDE) database to assess the reported complications and failure modes for OCT and reviewed techniques to optimize device use.Methods/materialsThe MAUDE database was queried for all event reports involving coronary OCT devices. Two independent reviewers identified 49 device reports included in the final analysis. Modes of failure and device-related patient complications were assessed.ResultsOf the 49 cases with reported device-related issues, 6.1% involved malfunction prior to insertion of the OCT catheter, and 30.6% of reported events did not result in an associated patient-related adverse event. The most commonly reported adverse events included coronary dissection and difficulty removing the catheter within a previously stented segment. No events of contrast-induced nephropathy were reported.ConclusionsFindings from the MAUDE database highlight the modes of device-related events associated with OCT. Device issues are uncommon, and as a result, users should be aware of optimal techniques to prevent and minimize adverse events related to device use.     

An expert system for the labeling and 3D reconstruction of the coronary arteries from two projections

Summary In this paper we present a rule-based expert system for the automatic delineation and 3D reconstruction of the left coronary artery on standard RAO and LAO angiographic projections. The approach is based on the application of a general blood vessel model and on anatomical models which take into account the normal variations of the coronary artery structure. In a first step, the arteries are delineated by detecting the maximum intensity on the centerline of the vessels. Then, we label the blood vessel segments according to an anatomical model of the left coronary artery. In general, only 1–2 labels remain for each blood vessel segment. Finally, these results are used for an automatic 3D reconstruction of the left coronary artery from two projections. Results from clinical RAO and LAO angiograms will be presented.     

The role of optical coherence tomography in coronary intervention

Optical coherence tomography (OCT) is an optical analog of intravascular ultrasound (IVUS) that can be used to examine the coronary arteries and has 10-fold higher resolution than IVUS. Based on polarization properties, OCT can differentiate tissue characteristics (fibrous, calcified, or lipid-rich plaque) and identify thin-cap fibroatheroma. Because of the strong attenuation of light by blood, OCT systems required the removal of blood during OCT examinations. A recently developed frequency-domain OCT system has a faster frame rate and pullback speed, making the OCT procedure more user-friendly and not requiring proximal balloon occlusion. During percutaneous coronary intervention (PCI), OCT can provide detailed information (dissection, tissue prolapse, thrombi, and incomplete stent apposition [ISA]). At follow-up examinations after stent implantation, stent strut coverage and ISA can be assessed. Several OCT studies have demonstrated delayed neointimal coverage following drug-eluting stent (DES) implantation vs. bare metal stent (BMS) placement. While newer DESs promote more favorable vascular healing, the clinical implications remain unknown. Recent OCT studies have provided insights into restenotic tissue characteristics; DES restenotic morphologies differ from those with BMSs. OCT is a novel, promising imaging modality; with more in-depth assessments of its use, it may impact clinical outcomes in patients with symptomatic coronary artery disease.     

New possibilities of the thermodilution method in studying coronary circulation and intracardiac hemodynamics]

The new possibilities of determining the coronary blood flow and intracardiac hemodynamics by the thermodilution method were studied in experiments on 40 mongrel dogs. A method for measuring the true coronary blood flow without catheterization of the coronary arteries and coronary sinus as well as a modified Holt's method for determining the end diastolic volume of the heart ventricles are suggested. The method is simple and therefore creates favourable prospects for its wide use both in experiments and in clinical studies.     

Preventive effects of the heparin-coated stent on restenosis in the porcine model.

The coronary stent reduces acute coronary arterial occlusion and late restenosis during and after coronary intervention. However, stent thrombosis and restenosis are still major limitations in the widespread use of the coronary stent. Local drug delivery using the heparin-coated stent may be a new approach, which reduces the incidence of stent thrombosis and restenosis. In order to evaluate the effects of the heparin-coated stent on stent restenosis, heparin-coated stents were compared with control stents in a porcine coronary stent restenosis model. Stent overdilation injury (stent:artery = 1.3:1.0) was performed with bare Wiktor stents (group I, n = 10) and heparin-coated Wiktor stents (group II, n = 20; HEPAMED, Medtronics) in porcine coronary arteries. Follow-up quantitative coronary angiography (QCA) was performed at 4 weeks after stenting, and histo-pathologic assessments of stented porcine coronary arteries were compared in both groups. On QCA, percent diameter stenosis was significantly higher in group I than in group II (16.3% +/- 6.62% vs. 9.6% +/- 5.06%, P < 0.05). The injury score of stented porcine coronary arteries was the same in both groups (1. 26 +/- 0.23 vs. 1.20 +/- 0.22). The area of pathologic stenosis of the stented arteries was higher in group I than in group II (41.6% +/- 12.5% vs. 27.1% +/- 9.9%, P < 0.005). The neointimal area was higher in group I than in group II (4.58 +/- 1.41 mm(2) vs. 2.57 +/- 1.07 mm(2), P < 0.05). By immunohistochemistry, the proliferating cell nuclear antigen (PCNA) index was higher in group I compared with group II (11.2% +/- 6.75% vs. 6.3% +/- 4.14%, P < 0.05). The heparin-coated stent is effective in the prevention of late coronary stent restenosis in a porcine coronary stent restenosis model. This may be related to the inhibition of neointimal cell proliferation.     

Increased intimal hyperplasia in experimental vein graft stenting compared to arterial stenting: comparisons in a new rabbit model of stent injury

BACKGROUND: In-stent restenosis due to intimal hyperplasia is an important clinical problem. Animal models of stent injury are limited by inconsistent arterial responses to stenting, and less intimal hyperplasia than diseased human vessels. To address these issues, we aimed to compare the degree of intimal hyperplasia in stented rabbit jugular-carotid interposition grafts (vein grafts) versus stented carotid arteries. METHODS: Jugular-carotid vein grafts were constructed in rabbits, then stented or left unstented. Carotid arteries were treated with similar stents or left instrumented only. After 3 or 28 days, vessels were perfusion fixed, embedded in resin, and sections were cut with a diamond saw. Intimal and medial thicknesses were measured in stained sections. RESULTS: After 3 days, inflammatory changes were observed in the intima of all stented vessels. After 28 days, intimal thickness in stented vein grafts was 2-fold greater than in control vein grafts and approximately 4-fold greater than in stented carotid arteries. In addition, the intimal hyperplasia response was markedly more consistent in stented vein grafts compared with stented carotid arteries. CONCLUSIONS: Stent deployment in experimental vein grafts results in increased and more reproducible smooth muscle cell intimal hyperplasia than carotid arterial stenting. This is a promising small-animal model for investigating the intimal response to stenting.     

Comparison of outcomes in patients undergoing coronary bypass of patent versus restenosed bare metal stented coronary arteries

It is unclear whether bypass of a patent stented artery affects clinical outcomes. We sought to compare the survival of patients who, as part of multisystem coronary artery bypass grafting, underwent revascularization of arteries with patent stents (<50% stenosis) or in-stent restenosis (>50% diameter stenosis). Of 550 consecutive patients with previously placed stents who underwent coronary artery bypass grafting from May 1995 to October 2003, we studied 399 who had only 1 stented vessel bypassed at surgery. Of these, 128 had coronary bypass to an artery with a patent stent and 271 had bypass to an artery with in-stent restenosis. Nonparametric survival estimates were obtained using the Kaplan-Meier method. A propensity-adjusted multivariate hazard model of group differences was generated using variables identified by bootstrap bagging. The unadjusted survival rate at 1 month, 1 year, and 5 years was 99.7%, 97.3%, and 89.1%, respectively, for the patent stent group and 96.6%, 93.9%, and 86.2%, respectively, for the in-stent restenosis group, a result of high early risk in the latter group. After adjusting for clinical variables, neither stent patency (p = 0.9) nor interval (p = 0.3) from stent placement was a risk factor, although advanced age, increased blood urea nitrogen, and preoperative atrial fibrillation were associated with poorer survival. In conclusion, survival after bypassing a patent stented coronary artery is comparable to that after bypassing a stented restenotic coronary artery.     

Leukemia inhibitory factor is upregulated in coronary arteries of Ossabaw miniature swine after stent placement

Leukemia inhibitory factor (LIF), an IL-6 class cytokine, is reported to be antiatherosclerotic. Thus, we hypothesized that LIF expression might be altered during in-stent neointimal hyperplasia. Ossabaw miniature swine, a unique large-animal model of metabolic syndrome and cardiovascular disease, were used for these studies. Bare-metal stents were deployed in the left anterior descending and left circumflex coronary arteries. Stents were expanded to either 1.0 x luminal diameter (in accordance with current clinical practice) or 1.3 x (overexpansion). The development of in-stent neointimal hyperplasia was assessed 28-day postimplantation using intravascular ultrasound. The atherosclerotic coverage of the vessel wall was approximately five-fold higher in 1.0 x stents and approximately nine-fold higher in 1.3 x stents 4 weeks after deployment, compared with the same segments before stenting. LIF mRNA was elevated approximately 11-fold in stented segments, relative to unstented epicardial coronary arteries. LIF expression and the intima : media ratio were strongly correlated in 1.0 x stented vessels. Further studies to investigate the nature of the association between LIF and neointimal hyperplasia revealed that vascular smooth muscle cell proliferation was inhibited by LIF treatment in an in-vitro model of atherosclerosis (coronary artery organ culture). These novel and clinically relevant studies show that elevated LIF gene expression is predictive for in-stent neointimal hyperplasia, and suggest that LIF upregulation may be a compensatory mechanism in this setting.     

Direct comparison of optical coherence tomography and high-definition 60-MHz intravascular ultrasound imaging of intra-procedural stent thrombosis in a patient with acute coronary syndrome

An 80-year-old man with ST-segment elevation myocardial infraction underwent coronary stenting using an everolimus-eluting stent, which resulted in a good coronary flow with no residual stenosis. However, 10?min after final coronary angiography, the patient complained of chest discomfort and the ECG again showed ST elevation. Repeat coronary angiography revealed multiple contrast filling defects in the stent. High-definition 60-MHz intravascular ultrasound (IVUS) examination showed multiple low echoic structures inside the stent, though its visualization was not clear. We also conducted optical coherence tomography (OCT) for further investigation, which clearly delineated the outline of the thrombus. An additional balloon dilatation was performed at the site of the stented lesion, and the patient's chest discomfort was relieved, and the ECG was normalized. The clinical implication of this case is that very early phase of intra-stent thrombus is low-density and coarse, and its visualization is better in OCT than in high-definition 60?MHz IVUS.     

Directional atherectomy for treatment of restenosis within coronary stents: clinical, angiographic and histologic results.

OBJECTIVES. The safety and long-term results of directional coronary atherectomy in stented coronary arteries were determined. In addition, tissue studies were performed to characterize the development of restenosis. METHODS. Directional coronary atherectomy was performed in restenosed stents in nine patients (10 procedures) 82 to 1,179 days after stenting. The tissue was assessed for histologic features of restenosis, smooth muscle cell phenotype, markers of cell proliferation and cell density. A control (no stenting) group consisted of 13 patients treated with directional coronary atherectomy for restenosis 14 to 597 days after coronary angioplasty, directional coronary atherectomy or laser intervention. RESULTS. Directional coronary atherectomy procedures within the stent were technically successful with results similar to those of the initial stenting procedure (2.31 +/- 0.38 vs. 2.44 +/- 0.35 mm). Of five patients with angiographic follow-up, three had restenosis requiring reintervention (surgery in two and repeat atherectomy followed by laser angioplasty in one). Intimal hyperplasia was identified in 80% of specimens after stenting and in 77% after coronary angioplasty or atherectomy. In three patients with stenting, 70% to 76% of the intimal cells showed morphologic features of a contractile phenotype by electron microscopy 47 to 185 days after coronary intervention. Evidence of ongoing proliferation (proliferating cell nuclear antigen antibody studies) was absent in all specimens studied. Although wide individual variability was present in the maximal cell density of the intimal hyperplasia, there was a trend toward a reduction in cell density over time. CONCLUSIONS. Although atherectomy is feasible for the treatment of restenosis in stented coronary arteries and initial results are excellent, recurrence of restenosis is common. Intimal hyperplasia is a nonspecific response to injury regardless of the device used and accounts for about 80% of cases of restenosis. Smooth muscle cell proliferation and phenotypic modulation toward a contractile phenotype are early events and largely completed by the time of clinical presentation of restenosis. Restenotic lesions may be predominantly cellular, matrix or a combination at a particular time after a coronary procedure.     

Edge detection versus densitometry for assessing coronary stenting quantitatively

The optimal method used to analyze quantitatively the immediate angiographic results of coronary stenting in the coronary arteries has not been studied. Accordingly, minimal luminal cross-sectional area was determined by 2 methods, edge detection and densitometry, in 19 patients who underwent percutaneous transluminal coronary angioplasty (PTCA) and then coronary stent implantation for symptomatic coronary stenoses. The correlation coefficient, 0.73 before angioplasty, decreased to 0.59 after coronary angioplasty and then increased to 0.83 after stent implantation. The mean differences between edge detection and densitometric determinations of minimal luminal cross-sectional area were 0.31 +/- 0.51 mm2 before PTCA, -0.38 +/- 1.22 mm2 after angioplasty and 0.35 +/- 0.79 mm2 after coronary stenting. It is concluded that, although the correlation and variability in the measurement of minimal luminal cross-sectional area between edge detection and densitometry deteriorate after PTCA, they are improved after stenting, probably because of smoothing of the vessel contours by the stent and remodeling of the stented segment into a more circular configuration. Therefore, in the stented coronary artery, edge detection and densitometry are equally acceptable methods of analysis.     

Six-month success of intracoronary stenting for anomalous coronary arteries associated with myocardial ischemia

Fourteen patients with anomalous coronary arteries associated with objective evidence of myocardial ischemia, a group at increased risk for cardiac events, were successfully stented. This led to 6-month patency and resolution of the ischemia, which was confirmed angiographically and by stress imaging studies.