Physiological flow simulation in residual human stenoses after coronary angioplasty

To evaluate the local hemodynamic implications of coronary artery balloon angioplasty, computational fluid dynamics (CFD) was applied in a group of patients previously reported by [Wilson et al. (1988), 77, pp. 873-885] with representative stenosis geometry post-angioplasty and with measured values of coronary flow reserve returning to a normal range (3.6 +/- 0.3). During undisturbed flow in the absence of diagnostic catheter sensors within the lesions, the computed mean pressure drop delta p was only about 1 mmHg at basal flow, and increased moderately to about 8 mmHg for hyperemic flow. Corresponding elevated levels of mean wall shear stress in the midthroat region of the residual stenoses, which are common after angioplasty procedures, increased from about 60 to 290 dynes/cm2 during hyperemia. The computations (Ree approximately equal to 100-400; alpha e = 2.25) indicated that the pulsatile flow field was principally quasi-steady during the cardiac cycle, but there was phase lag in the pressure drop-mean velocity (delta p - u) relation. Time-averaged pressure drop values, delta p, were about 20 percent higher than calculated pressure drop values, delta ps, for steady flow, similar to previous in vitro measurements by Cho et al. (1983). In the throat region, viscous effects were confined to the near-wall region, and entrance effects were evident during the cardiac cycle. Proximal to the lesion, velocity profiles deviated from parabolic shape at lower velocities during the cardiac cycle. The flow field was very complex in the oscillatory separated flow reattachment region in the distal vessel where pressure recovery occurred. These results may also serve as a useful reference against catheter-measured pressure drops and velocity ratios (hemodynamic endpoints) and arteriographic (anatomic) endpoints post-angioplasty. Some comparisons to previous studies of flow through stenoses models are also shown for perspective purposes.     

Effects of diagnostic guidewire catheter presence on translesional hemodynamic measurements across significant coronary artery stenoses

This study gains insight on the nature of flow blockage effects of small guidewire catheter sensors in measuring mean trans-stenotic pressure gradients Deltap across significant coronary artery stenoses. Detailed pulsatile hemodynamic computations were made in conjunction with previously reported clinical data in a group of patients with clinically significant coronary lesions before angioplasty. Results of this study ascertain changes in hemodynamic conditions due to the insertion of a guidewire catheter (di=0.46 mm) across the lesions used to directly determine the mean pressure gradient (Deltap) and fall in distal mean coronary pressure (pr). For the 32 patient group of Wilson et al. [1988] (minimal lesion diameter dm=0.95 mm; 90% mean area stenosis; proximal measured coronary flow reserve (CFR) of 2.3 in the abnormal range) the diameter ratio of guidewire catheter to minimal lesion was 0.48, causing a tighter "artifactual" mean area stenosis of 92.1%. The results of the computations indicated a significant shift in the Deltap-Q relation due to guidewire induced increases in flow resistances (R=Deltap/Q) of 110% for hyperemic flow, a 35% blockage in hyperemic flow (Qh) and a phase shift of the coronary flow waveform to systolic predominance. These alterations in flow resulted in a fall in distal mean coronary pressure (at lower mean flow rates) below the patho-physiological range of prh approximately 55 mmHg, which is known to cause ischemia in the subendocardium (Brown et al. [1984]) and coincides with symptomatic angina. Transient wall shear stress levels in the narrow throat region (with flow blockage) were of the order of levels during hyperemic conditions for patho-physiological flow. In the separated flow region along the distal vessel wall, vortical flow cells formed periodically during the systolic phase when instantaneous Reynolds numbers Ree(t) exceeded about 110. For patho-physiological flow without the presence of the guidewire these vortical flow cells were much stronger than in the more viscous flow regime with the guidewire present. The non-dimensional pressure data given in tabular form may be useful in interpretation of guidewire measurements done clinically for lesions of similar geometry and severity.     

Systemic nitric oxide synthase inhibition improves coronary flow reserve to adenosine in patients with significant stenoses

We studied the impact of systemic infusion of the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine (L-NMMA) on coronary flow reserve (CFR) in patients with coronary artery disease (CAD). We have previously demonstrated that CFR to adenosine was significantly increased after systemic infusion of L-NMMA in normal volunteers but not in recently transplanted denervated hearts. At baseline, myocardial blood flow (MBF; ml x min(-1) x g(-1)) was measured at rest and during intravenous administration of adenosine (140 microg x kg(-1) x min(-1)) in 10 controls (47 +/- 5 yr) and 10 CAD patients (58 +/- 8 yr; P < 0.01 vs. controls) using positron emission tomography and (15)O-labeled water. Both MBF measurements were repeated during intravenous infusion of 10 mg/kg L-NMMA. CFR was calculated as the ratio of MBF during adenosine to MBF at rest. CFR was significantly higher in healthy volunteers than in CAD patients and increased significantly after L-NMMA in controls (4.00 +/- 1.10 to 6.15 +/- 1.35; P < 0.0001) and in patients, both in territories subtended by stenotic coronary arteries (>70% luminal diameter; 2.06 +/- 1.13 to 3.21 +/- 1.07; P < 0.01) and in remote segments (3.20 +/- 1.23 to 3.92 +/- 1.62; P < 0.05). In conclusion, CFR can be significantly increased in CAD by a systemic infusion of L-NMMA. Similarly to our previous findings in normal volunteers, this suggests that adenosine-induced hyperemia in CAD patients is constrained by a mechanism that can be relieved by systemic NOS inhibition with L-NMMA.     

Influence of arterial wall compliance on the pressure drop across coronary artery stenoses under hyperemic flow condition

Hemodynamic endpoints such as flow and pressure drop are often measured during angioplasty procedures to determine the functional severity of a coronary artery stenosis. There is a lack of knowledge regarding the influence of compliance of the arterial wall-stenosis on the pressure drop under hyperemic flows across coronary lesions. This study evaluates the influence in flow and pressure drop caused by variation in arterial-stenosis compliance for a wide range of stenosis severities. The flow and pressure drop were evaluated for three different severities of stenosis and tested for limiting scenarios of compliant models. The Mooney-Rivlin model defined the non-linear material properties of the arterial wall and the plaque regions. The non-Newtonian Carreau model was used to model the blood flow viscosity. The fluid (blood)-structure (arterial wall) interaction equations were solved numerically using the finite element method. Irrespective of the stenosis severity, the compliant models produced a lower pressure drop than the rigid artery due to compliance of the plaque region. A wide variation in the pressure drop was observed between different compliant models for significant (90% area occlusion) stenosis with 41.0, 32.1, and 29.8 mmHg for the rigid artery, compliant artery with calcified plaque, and compliant artery with smooth muscle cell proliferation, respectively. When compared with the rigid artery for significant stenosis the pressure drop decreased by 27.7% and 37.6% for the calcified plaque and for the smooth muscle cell proliferation case, respectively. These significant variations in pressure drop for the higher stenosis may lead to misinterpretation and misdiagnosis of the stenosis severity.     

Estimated flow resistance increase in a spiral human coronary artery segment

Coronary flow estimates were made for a spiral coronary artery segment (identified from a post-mortem replica casting) by using a modified Dean number based on the approximate coil radius of curvature, as suggested earlier. The estimates were found to correlate experimental pressure drop data for helical coiled tubes. Over a physiological range of mean Reynolds numbers from 100 to 400 for blood flow through main coronary arteries, estimates of the flow resistance increase relative to a straight lumen segment ranged from about 20 to 80 percent, and were of similar magnitude to those found in a flow study in a sinuous coronary vessel segment with no spiral.     

Proteomic analysis of circulating human monocytes in coronary artery disease

Monocytes play an important role in inflammation and atherosclerosis; however, the molecular details underlying these diverse functions are not completely understood. Proteomic analysis of monocytes can provide new insights into their biological role in coronary artery disease (CAD). Twenty angiographically confirmed male, CAD patients (≥50% stenosis) attending cardiology clinic of Nehru Hospital, PGIMER, Chandigarh, and who were not receiving any lipid lowering therapy and 20 TMT negative subjects who served as controls were enrolled in the study. Circulating monocytes isolated from overnight fasting blood samples were analyzed by 2D gel electrophoresis (pH 4-7), and differentially expressed protein spots were subjected to mass spectrometry and identification of proteins. We observed 333 ± 40 protein spots in monocytes from patients and 312 ± 20 in controls; out of which 63 protein spots showed altered intensity in CAD patients. Thirteen spots showed fivefold increased and two protein spots showed fivefold decreased expression in CAD group as compared to control group, respectively. Two proteins showing decreased expression in monocytes from CAD patients were identified as: (i) glutathione transferase and (ii) heat shock protein 70 KDa. Proteins showing increased expression in CAD patients were identified as: (i) vimentin, (ii) mannose binding lectin receptor protein, and (iii) S100A8 calcium-binding protein. The results of our study offer identification of several proteins in monocytes which can provide new perspectives in role of monocytes in pathogenesis of atherosclerosis.     

Steady flow through a double converging-diverging tube model for mild coronary stenoses

Velocity profiles and the pressure drop across two mild (62 percent) coronary stenoses in series have been investigated numerically and experimentally in a perspex-tube model. The mean flow rate was varied to correspond to a Reynolds number range of 50-400. The pressure drop across two identical (62 percent) stenoses show that for low Reynolds numbers the total effect of two stenoses equals that of two single stenoses. A reduction of 10 percent is found for the higher Reynolds numbers investigated. Numerical and experimental results obtained for the velocity profiles agree very well. The effect of varying the converging angle of a single mild (62 percent) coronary stenosis on the fluid flow has been determined numerically using a finite element method. Pressure-flow relation, especially with respect to relative short stenoses, is discussed.     

An intergral method for the analysis of flow in arterial stenoses

An approximate solution is presented to the problem of incompressible flow through an axisymmetric constriction. The geometry is intended to simulate an arterial stenosis, and the solution is applicable to both mild and severe stenoses for Reynolds numbers below transition. Theoretical results obtained for specific geometries are given for the velocity distribution, pressure drop, wall shearing stress, and separation phenomena. These results reveal the significant alterations in flow caused by a stenosis. Experiments using model stenoses are described and compared with the theoretical results. Theoretical predictions of pressure drop and separation characteristics are in reasonably good agreement with the experimental observations.     

CTCA for detection of significant coronary artery disease in routine TAVI work-up

Transcatheter aortic valve implantation (TAVI) has evolved to standard treatment of severe aortic stenosis in patients with an intermediate to high surgical risk. Computed tomography coronary angiography (CTCA) could partially replace invasive coronary angiography to diagnose significant coronary artery disease in the work-up for TAVI. A literature search was performed in MEDLINE and EMBASE for papers comparing CTCA and coronary angiography in TAVI candidates. The primary endpoint was the diagnostic accuracy of CTCA, compared to coronary angiography, for detection of significant (>50% diameter stenosis) coronary artery disease, measured as sensitivity, specificity, positive—(PPV) and negative predictive value (NPV). Seven studies were included, with a cumulative sample size of 1,275 patients. The patient-based pooled sensitivity, specificity, PPV and NPV were 95, 65, 71 and 94% respectively. Quality assessment revealed excellent and good quality in terms of applicability and risk of bias respectively, with the main concern being patient selection. In conclusion, on the basis of a significance cut-off value of 50% diameter stenosis, CTCA provides acceptable diagnostic accuracy for the exclusion of coronary artery disease in patients referred for TAVI. Using the routinely performed preoperative computed tomography scans as a gatekeeper for coronary angiography could decrease additional coronary angiographies by 37% in this high-risk and fragile population.     

Patterns of flow in the left coronary artery

The purpose of this investigation is to describe our preliminary observations of the overall pattern of flow in a mold of the left coronary artery of a pig. Flow in the coronary mold was visualized by the injection of dye into the sinus of Valsalva. Studies were performed during steady flow at rates of 100, 200, 300, 400, and 500 mL/min. Studies were also performed during pulsatile flow, using a pulse duplicator that simulated the magnitude and phasic pattern of coronary flow at rest and during reactive hyperemia. At conditions that simulated rest, mean coronary flow was adjusted to 121 mL/min of which 24 mL/min (20 percent) was systolic. During simulated reactive hyperemia, mean flow was 440 mL/min. Visualization of flow revealed the absence of disturbances of turbulence during both steady and pulsatile flow in the left anterior descending (LAD) and left circumflex (CIRC) coronary arteries throughout the entire range of flow studied. Prominent spiraling of flow occurred during steady and pulsatile flow. Spiraling of flow was not observed in the LAD at rest during pulsatile flow, but developed during simulated reactive hyperemia. Helical flows were observed in the CIRC both during simulated rest and reactive hyperemia. These observations suggest that helical flows may be characteristic features of flow in the left coronary artery; whereas turbulence may not be a feature of this flow field. Whether the spiraling of flow that we observed related to the spiral distribution of early atheroma reported by others, is undetermined.     

Minimal effect of collateral flow on coronary microvascular resistance in the presence of intermediate and noncritical coronary stenoses

Depending on stenosis severity, collateral flow can be a confounding factor in the determination of coronary hyperemic microvascular resistance (HMR). Under certain assumptions, the calculation of HMR can be corrected for collateral flow by incorporating the wedge pressure (P(w)) in the calculation. However, although P(w) > 25 mmHg is indicative of collateral flow, P(w) does in part also reflect myocardial wall stress neglected in the assumptions. Therefore, the aim of this study was to establish whether adjusting HMR by P(w) is pertinent for a diagnostically relevant range of stenosis severities as expressed by fractional flow reserve (FFR). Accordingly, intracoronary pressure and Doppler flow velocity were measured a total of 95 times in 29 patients distal to a coronary stenosis before and after stepwise percutaneous coronary intervention. HMR was calculated without (HMR) and with P(w)-based adjustment for collateral flow (HMR(C)). FFR ranged from 0.3 to 1. HMR varied between 1 and 5 and HMR(C) between 0.5 and 4.2 mmHg·cm(-1)·s. HMR was about 37% higher than HMR(C) for stenoses with FFR < 0.6, but for FFR > 0.8, the relative difference was reduced to 4.4 ± 3.4%. In the diagnostically relevant range of FFR between 0.6 and 0.8, this difference was 16.5 ± 10.4%. In conclusion, P(w)-based adjustment likely overestimates the effect of potential collateral flow and is not needed for the assessment of coronary HMR in the presence of a flow-limiting stenosis characterized by FFR between 0.6 and 0.8 or for nonsignificant lesions.     

冠心病患者运动致QRS延长的临床意义

为探讨冠心病病人由于急性心肌缺血对ＱＲＳ持续时间变化的影响及其意义。本文收集了５３例病人,均进行运动试验和冠脉造影,其中２０例经冠脉造影排除心病,其他３３例经冠脉造影确定为冠心病。结果运动使冠脉正常者ＱＲＳ持续时间缩短,而使冠心病者ＱＲＳ持续时间延长。     

Measurement of the flow in coronary artery bypass grafts

The aim of our study was to measure the flow in coronary artery bypass grafts and to compare the flow between two groups of patients. In group A the arterial revascularization was performed with both internal thoracic arteries using as a Y graft and in group B conventional revascularization using left internal thoracic artery (ITA) attached to the left anterior descending artery (LAD) and venous grafts to the other branches of the left coronary artery was performed. The flow in all grafts was measured at six time points during the operation. The cumulative flow at the end of the operation in the group A (arterial Y graft) was 51.8 +/- 24.5 ml/min and in group B (conventional technique) it was 96.8 +/- 41.1 ml/min (p < 0.05). The flow in left ITA to LAD was similar in both groups (27.3 +/- 15.9 ml/min and 26.3 +/- 16.1 ml/min in group A and B). The flow in right ITA (25.2 +/- 18.4 ml/min) was significantly lower than in venous grafts (72.5 +/- 45.5 ml/min). The calculated flow reserve was 2.2 in group A and 2.1 in group B. We found that the cumulative flow in arterial Y graft was lower in comparison with conventional revascularization. This is due to the lower flow in the right ITA branch of the Y graft compared to venous grafts. However based on clinical results, we can postulate that the flow in the Y graft is sufficient to meet the demand of the myocardium originally supplied by the left coronary artery.     

Localization of bypass-induced changes in flow in coronary artery models

Right coronary artery bypass restores blood flow through heart tissues. This also induces changes in flow leading to its failure. By this work the sites which are prone to such changes are localized. The bypass models are developed from transparent silicon rubber of elastic properties similar to arterial tissues. Flow visualization is carried out by photoelasticity technique by using dilute solution of vanadium pentoxide. This analysis carried out under pulsatile flow conditions shows that the proximal stenotic region continues to contribute to the alteration in flow in the hood region of the bypass. Thus making its proximal and distal regions prone to flow-induced changes, which may lead to its blockage over the long duration.     

Preoperative prediction of significant coronary artery disease in patients with valvular heart disease.

A prognostic index for predicting significant coronary artery disease was established using multiple logistic regression analysis of clinical data from 643 patients with valvular heart disease who had undergone routine coronary arteriography before valve replacement. The index or equation obtained incorporated the presence of angina, a family history of ischaemic heart disease, age, cigarette smoking habits, mitral valve disease, sex, and electrocardiographic evidence of myocardial infarction. The equation was validated using prospective data from 387 patients with valvular disease and shown to enable almost a third of routine coronary arteriograms to be omitted while maintaining 95% sensitivity for patients with coronary artery disease. Similar analysis of the more detailed prospective data produced a second discriminant function incorporating diastolic blood pressure, total cigarettes smoked in life, the severity of angina, family history of ischaemic heart disease, age, current cigarette smoking habits, and the ratio of total to high density lipoprotein cholesterol. This method improved the discrimination between patients with and without coronary artery disease, allowing omission of 30% of routine coronary arteriograms with 100% sensitivity for patients with coronary disease and omission of 41% with a 96% sensitivity level.     

Pulsatile flow in a coronary artery using multiphase kinetic theory

Pulsatile flow in a model of a right coronary artery (RCA) was previously modeled as a single-phase fluid and as a two-phase fluid using experimental rheological data for blood as a function of hematocrit and shear rate. Here we present a multiphase kinetic theory model which has been shown to compute correctly the viscosity of red blood cells (RBCs) and their migration away from vessel walls: the Fahraeus–Lindqvist effect. The computed RBC viscosity decreases with shear rate and vessel size, consistent with measurements. The pulsatile computations were performed using a typical cardiac waveform until a limit cycle was well established. The RBC volume fractions, shear stresses, shear stress gradients, granular temperatures, viscosities, and phase velocities varied with time and position during each cardiac cycle. Steady-state computations were also performed and were found to compare well with time-averaged transient results. The wall shear stress and wall shear stress gradients (both spatial and temporal) were found to be highest on the inside area of maximum curvature. Potential atherosclerosis sites are identified using these computational results.     

Multiphase hemodynamic simulation of pulsatile flow in a coronary artery

A multiphase transient non-Newtonian three-dimensional (3-D) computational fluid dynamics (CFD) simulation has been performed for pulsatile hemodynamics in an idealized curved section of a human coronary artery. We present the first prediction, to the authors' knowledge, of particulate buildup on the inside curvature using the multiphase theory of dense suspension hemodynamics. In this study, the particulates are red blood cells (RBCs). The location of RBC buildup on the inside curvature correlates with lower wall shear stress (WSS) relative to the outside curvature. These predictions provide insight into how blood-borne particulates interact with artery walls and hence, have relevance for understanding atherogenesis since clinical observations show that atherosclerotic plaques generally form on the inside curvatures of arteries. The buildup of RBCs on the inside curvature is driven by the secondary flow and higher residence times. The higher viscosity in the central portion of the curved vessel tends to block their flow, causing them to migrate preferentially through the boundary layer. The reason for this is the nearly neutrally buoyant nature of the dense two-phase hemodynamic flow. The two-phase non-Newtonian viscosity model predicts greater shear thinning than the single-phase non-Newtonian model. Consequently, the secondary flow induced in the curvature is weaker. The waveforms for computed hemodynamic parameters, such as hematocrit, WSS, and viscosity, follow the prescribed inlet velocity waveforms. The lower oscillatory WSS produced on the inside curvature has implications for understanding thickening of the intimal layer.