Effect of heart rate on hemodynamic endpoints under concomitant microvascular disease in a porcine model

Diagnosis of the ischemic power of epicardial stenosis with concomitant microvascular disease (MVD) is challenging during coronary interventions, especially under variable hemodynamic factors like heart rate (HR). The goal of this study is to assess the influence of variable HR and percent area stenosis (%AS) in the presence of MVD on pressure drop coefficient (CDP; ratio of transstenotic pressure drop to the distal dynamic pressure) and lesion flow coefficient (LFC; ratio of %AS to the CDP at the throat region). We hypothesize that CDP and LFC are independent of HR. %AS and MVD were created using angioplasty balloons and 90-μm microspheres, respectively. Simultaneous measurements of pressure drop (DP) and velocity were done in 11 Yorkshire pigs. Fractional flow reserve (FFR), CDP, and LFC were calculated for the groups HR < 120 and HR > 120 beats/min, %AS < 50 and %AS > 50, and additionally for DP < 14 and DP > 14 mmHg, and analyzed using regression and ANOVA analysis. Regression analysis showed independence between HR and the FFR, CDP, and LFC while it showed dependence between %AS and the FFR, CDP, and LFC. In the ANOVA analysis, for the HR < 120 beats/min and HR > 120 beats/min groups, the values of FFR (0.82 ± 0.02 and 0.82 ± 0.02), CDP (83.15 ± 26.19 and 98.62 ± 26.04), and LFC (0.16 ± 0.03 and 0.15 ± 0.03) were not significantly different (P > 0.05). However, for %AS < 50 and %AS > 50, the FFR (0.89 ± 0.02 and 0.75 ± 0.02), CDP (35.97 ± 25.79.10 and 143.80 ± 25.41), and LFC (0.09 ± 0.03 and 0.22 ± 0.03) were significantly different (P < 0.05). A similar trend was observed between the DP groups. Under MVD conditions, FFR, CDP, and LFC were not significantly influenced by changes in HR, while they can significantly distinguish %AS and DP groups.     

Influence of coronary collateral flow on coronary diagnostic parameters: An in vitro study

Functional severity of coronary stenosis is often assessed using diagnostic parameters. These parameters are evaluated from the combined pressure and/or flow measurements taken at the site of the stenosis. However, when there are functional collaterals operating downstream to the stenosis, the coronary flow-rate increases, and the pressure in the stenosed artery is altered. This effect of downstream collaterals on different diagnostic parameters is studied using a physiological representative in vitro coronary flow-loop.The three diagnostic parameters tested are fractional flow reserve (FFR), lesion flow coefficient (LFC), and pressure drop coefficient (CDP). The latter two were discussed in recent publications by our group (Banerjee et al., 2008, Banerjee et al., 2007, 2009). They are evaluated for three different severities of stenosis and tested for possible misinterpretation in the presence of variable collateral flows. Pressure and flow are measured with and without downstream collaterals. The diagnostic parameters are then calculated from these readings.In the case of intermediate stenosis (80% area blockage), FFR and LFC increased from 0.74 to 0.77 and 0.58 to 0.62, respectively, for no collateral to fully developed collateral flow. Also, CDP decreased from 47 to 42 for no collateral to fully developed collateral flow. These changes in diagnostic parameters might lead to erroneous postponement of coronary intervention. Thus, variability in diagnostic parameters for the same stenosis might lead to misinterpretation of stenosis severity in the presence of operating downstream collaterals.     

Influence of arterial wall-stenosis compliance on the coronary diagnostic parameters

Functional diagnostic parameters such as Fractional Flow Reserve (FFR), which is calculated from pressure measurements across stenosed arteries, are often used to determine the functional severity of coronary artery stenosis. This study evaluated the effect of arterial wall-stenosis compliance, with limiting scenarios of stenosis severity, on the diagnostic parameters. The diagnostic parameters considered in this study include an established index, FFR and two recently developed parameters: Pressure Drop Coefficient (CDP) and Lesion Flow Coefficient (LFC). The parameters were assessed for rigid artery (RR; signifying high plaque elasticity), compliant artery with calcified plaque (CC; intermediate plaque elasticity) and compliant artery with smooth muscle cell proliferation (CS; low plaque elasticity), with varying degrees of epicardial stenosis. A hyperelastic Mooney-Rivlin model was used to model the arterial wall and plaque materials. Blood was modeled as a shear thinning, non-Newtonian fluid using the Carreau model. The arterial wall compliance was evaluated using the finite element method. The present study found that, with an increase in stenosis severity, FFR decreased whereas CDP and LFC increased. The cutoff value of 0.75 for FFR was observed at 78.7% area stenosis for RR, whereas for CC and CS the cutoff values were obtained at higher stenosis severities of 81.3% and 82.7%, respectively. For a fixed stenosis, CDP value decreased and LFC value increased with a decrease in plaque elasticity (RR to CS). We conclude that the differences in diagnostic parameters with compliance at intermediate stenosis (78.7-82.7% area blockage) could lead to misinterpretation of the stenosis severity.     

Influence of newly designed monorail pressure sensor catheter on coronary diagnostic parameters: An in vitro study

The decision to perform intervention on a patient with coronary stenosis is often based on functional diagnostic parameters obtained from pressure and flow measurements using sensor-tipped guidewire at maximal vasodilation (hyperemia). Recently, a rapid exchange Monorail Pressure Sensor catheter of 0.022″ diameter (MPS22), with pressure sensor at distal end has been developed for improved assessment of stenosis severity. The hollow shaft of the MPS22 is designed to slide over any standard 0.014″ guidewire (G14). Hence, influence of MPS22 diameter on coronary diagnostic parameters needs investigation. An in vitro experiment was conducted to replicate physiologic flows in three representative area stenosis (AS): mild (64% AS), intermediate (80% AS), and severe (90% AS), for two arterial diameters, 3 mm (N2; more common) and 2.5 mm (N1). Influence of MPS22 on diagnostic parameters: fractional flow reserve (FFR) and pressure drop coefficient (CDP) was evaluated both at hyperemic and basal conditions, while comparing it with G14. The FFR values decreased for the MPS22 in comparison to G14, (Mild: 0.87 vs 0.88, Intermediate: 0.68 vs 0.73, Severe: 0.48 vs 0.56) and CDP values increased (Mild: 16 vs 14, Intermediate: 75 vs 56, Severe: 370 vs 182) for N2. Similar trend was observed in the case of N1. The FFR values were found to be well above (mild) and below (intermediate and severe) the diagnostic cut-off of 0.75. Therefore, MPS22 catheter can be used as a possible alternative to G14. Further, irrespective of the MPS22 or G14, basal FFR (FFR_b) had overlapping ranges in close proximity for clinically relevant mild and intermediate stenoses that will lead to diagnostic uncertainty under both N1 and N2. However, CDP_b had distinct ranges for different stenosis severities and could be a potential diagnostic parameter under basal conditions.     

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.     

The diastolic flow velocity-pressure gradient relation and dpv50 to assess the hemodynamic significance of coronary stenoses

To evaluate the hemodynamic impact of coronary stenoses, the fractional (FFR) or coronary flow velocity reserve (CFVR) usually is measured. The combined measurement of instantaneous flow velocity and pressure gradient (v-dp relation) is rarely used in humans. We derived from the v-dp relation a new index, dp(v50) (pressure gradient at flow velocity of 50 cm/s), and compared the diagnostic performance of dp(v50), CFVR, and FFR. Before coronary angiography was performed, patients underwent noninvasive stress testing. In all coronary vessels with an intermediate or severe stenosis, the flow velocity, aortic, and distal coronary pressure were measured simultaneously with a Doppler and pressure guidewire after induction of hyperemia. After regression analysis of all middiastolic flow velocity and pressure gradient data, the dp(v50) was calculated. With the use of the results of noninvasive stress testing, the dp(v50) cutoff value was established at 22.4 mmHg. In 77 patients, 124 coronary vessels with a mean 39% (SD 19) diameter stenosis were analyzed. In 43 stenoses, ischemia was detected. We found a sensitivity, specificity, and accuracy of 56%, 86%, and 76% for CFVR; 77%, 99%, and 91% for FFR; and 95%, 95%, and 95% for dp(v50). To establish that dp(v50) is not dependent on maximal hyperemia, dp(v50) was recalculated after omission of the highest quartile of flow velocity data, showing a difference of 3%. We found that dp(v50) provided the highest sensitivity and accuracy compared with FFR and CFVR in the assessment of coronary stenoses. In contrast to CFVR and FFR, assessment of dp(v50) is not dependent on maximal hyperemia.     

The influence of artery wall curvature on the anatomical assessment of stenosis severity derived from fractional flow reserve: a computational fluid dynamics study

This study aims to investigate the influence of artery wall curvature on the anatomical assessment of stenosis severity and to identify a region of misinterpretation in the assessment of per cent area stenosis (AS) for functionally significant stenosis using fractional flow reserve (FFR) as standard. Five artery models of different per cent AS severity (70, 75, 80, 85 and 90%) were considered. For each per cent AS severity, the angle of curvature of the arterial wall varied from straight to an increasingly curved model (0°, 30°, 60°, 90° and 120°). Computational fluid dynamics was performed under transient physiologic hyperemic flow conditions to investigate the influence of artery wall curvature on the pressure drop and the FFR. The findings in this study may be useful in in vitro anatomical assessment of functionally significant stenosis. The FFR decreased with increasing stenosis severity for a given curvature of the artery wall. Moreover, a significant decrease in FFR was found between straight and curved models discussed for a given severity condition. These findings indicate that the curvature effect was included in the FFR assessment in contrast to minimum lumen area (MLA) or per cent AS assessment. The MLA or per cent AS assessment may lead to underestimation of stenosis severity. From this numerical study, an uncertainty region could be evaluated using the clinical FFR cutoff value of 0.8. This value was observed at 81.98 and 79.10% AS for arteries with curvature angles of 0° and 120° respectively. In conclusion, the curvature of the artery should not be neglected in in vitro anatomical assessment.     

Influence of hemodynamic conditions on fractional flow reserve: parametric analysis of underlying model

Pressure-based fractional flow reserve (FFR) is used clinically to evaluate the functional severity of a coronary stenosis, by predicting relative maximal coronary flow (Q(s)/Q(n)). It is considered to be independent of hemodynamic conditions, which seems unlikely because stenosis resistance is flow dependent. Using a resistive model of an epicardial stenosis (0-80% diameter reduction) in series with the coronary microcirculation at maximal vasodilation, we evaluated FFR for changes in coronary microvascular resistance (R(cor) = 0.2-0.6 mmHg. ml(-1). min), aortic pressure (P(a) = 70-130 mmHg), and coronary outflow pressure (P(b) = 0-15 mmHg). For a given stenosis, FFR increased with decreasing P(a) or increasing R(cor). The sensitivity of FFR to these hemodynamic changes was highest for stenoses of intermediate severity. For P(b) > 0, FFR progressively exceeded Q(s)/Q(n) with increasing stenosis severity unless P(b) was included in the calculation of FFR. Although the P(b)-corrected FFR equaled Q(s)/Q(n) for a given stenosis, both parameters remained equally dependent on hemodynamic conditions, through their direct relationship to both stenosis and coronary resistance.     

Increase in Ultrasonic Intensity of Blood Speckle across Moderate Coronary Artery Stenosis Is an Independent Predictor of Functional Coronary Artery Stenosis Measured by Fractional Flow Reserve: Pilot Study

Background and Aims

The degree of coronary artery stenosis should be assessed both anatomically and functionally. We observed that the intensity of blood speckle (IBS) on intravascular ultrasound (IVUS) is low proximal to a coronary artery stenosis, and high distal to the stenosis. We defined step-up IBS as the distal minus the proximal IBS, and speculated that this new parameter could be used for the functional evaluation of stenosis on IVUS. The aims of this study were to assess the relationships between step-up IBS and factors that affect coronary blood flow, and between step-up IBS and fractional flow reserve (FFR).

Methods and Results

This study enrolled 36 consecutive patients with angina who had a single moderate stenosis in the left anterior descending artery. All patients were evaluated by integrated backscatter IVUS and intracoronary pressure measurements. FFR was calculated from measurements using a coronary pressure wire during hyperemia. Conventional gray-scale IVUS images were recorded, and integrated backscatter was measured in three cross-sectional slices proximal and distal to the stenosis. Step-up IBS was calculated as (mean distal integrated backscatter value) − (mean proximal integrated backscatter value). Stepwise multiple linear regression analysis showed that the heart rate (r = 0.45, P = 0.005), ejection fraction (r = −0.39, P = 0.01), and hemoglobin level (r = −0.32, P = 0.04) were independently correlated with step-up IBS, whereas proximal and distal IBS were not associated with these factors. There was a strong inverse correlation between step-up IBS and FFR (r = −0.84, P < 0.001), which remained significant on stepwise multiple linear regression analysis.

Conclusions

The newly defined parameter of step-up IBS is potentially useful for the functional assessment of coronary artery stenosis.     

Increased basal coronary blood flow as a cause of reduced coronary flow reserve in diabetic patients

A reduced coronary flow reserve (CFR) has been demonstrated in diabetes, but the underlying mechanisms are unknown. We assessed thermodilution-derived CFR after 5-min intravenous adenosine infusion through a pressure-temperature sensor-tipped wire in 30 coronary arteries without significant lumen reduction in 30 patients: 13 with and 17 without a history of diabetes. We determined CFR as the ratio of basal and hyperemic mean transit times (T(mn)); fractional flow reserve (FFR) as the ratio of distal and proximal pressures at maximal hyperemia to exclude local macrovascular disease; and an index of microvascular resistance (IMR) as the distal coronary pressure at maximal hyperemia divided by the inverse of the hyperemic T(mn). We also assessed insulin resistance by the homeostasis model assessment (HOMA) index. FFR was normal in all investigated arteries. CFR was significantly lower in diabetic vs. nondiabetic patients [median (interquartile range): 2.2 (1.4-3.2) vs. 4.1 (2.7-4.4); P = 0.02]. Basal T(mn) was lower in diabetic vs. nondiabetic subjects [median (interquartile range): 0.53 (0.25-0.71) vs. 0.64 (0.50-1.17); P = 0.04], while hyperemic T(mn) and IMR were similar. We found significant correlations at linear regression analysis between logCFR and the HOMA index (r(2) = 0.35; P = 0.0005) and between basal T(mn) and the HOMA index (r(2) = 0.44; P < 0.0001). In conclusion, compared with nondiabetic subjects, CFR is lower in patients with diabetes and epicardial coronary arteries free of severe stenosis, because of increased basal coronary flow, while hyperemic coronary flow is similar. Basal coronary flow relates to insulin resistance, suggesting a key role of cellular metabolism in the regulation of coronary blood flow.     

Percutaneous Coronary Intervention Enhances Accelerative Wave Intensity in Coronary Arteries

Background

The systolic forward travelling compression wave (sFCW) and diastolic backward travelling decompression waves (dBEW) predominantly accelerate coronary blood flow. The effect of a coronary stenosis on the intensity of these waves in the distal vessel is unknown. We investigated the relationship between established physiological indices of hyperemic coronary flow and the intensity of the two major accelerative coronary waves identified by Coronary Wave Intensity analysis (CWIA).

Methodology / Principal Findings

Simultaneous intracoronary pressure and velocity measurement was performed during adenosine induced hyperemia in 17 patients with pressure / Doppler flow wires positioned distal to the target lesion. CWI profiles were generated from this data. Fractional Flow Reserve (FFR) and Coronary Flow Velocity Reserve (CFVR) were calculated concurrently. The intensity of the dBEW was significantly correlated with FFR (R = -0.70, P = 0.003) and CFVR (R = -0.73, P = 0.001). The intensity of the sFCW was also significantly correlated with baseline FFR (R = 0.71, p = 0.002) and CFVR (R = 0.59, P = 0.01). Stenting of the target lesion resulted in a median 178% (interquartile range 55–280%) (P<0.0001) increase in sFCW intensity and a median 117% (interquartile range 27–509%) (P = 0.001) increase in dBEW intensity. The increase in accelerative wave intensity following PCI was proportionate to the baseline FFR and CFVR, such that stenting of lesions associated with the greatest flow limitation (lowest FFR and CFVR) resulted in the largest increases in wave intensity.

Conclusions

Increasing ischemia severity is associated with proportionate reductions in cumulative intensity of both major accelerative coronary waves. Impaired diastolic microvascular decompression may represent a novel, important pathophysiologic mechanism driving the reduction in coronary blood flow in the setting of an epicardial stenosis.     

Physiological flow analysis in significant human coronary artery stenoses

To evaluate the local hemodynamics in flow limiting coronary lesions, computational hemodynamics was applied to a group of patients previously reported by Wilson et al. (1988) with representative pre-angioplasty stenosis geometry (minimal lesion size d(m)=0.95 mm; 68% mean diameter stenosis) and with measured values of coronary flow reserve (CFR) in the abnormal range (2.3+/-0.1). The computations were at mean flow rates (Q) of 50, 75 and 100 ml/min (the limit of our converged calculations). Computed mean pressure drops Deltap were approximately 9 mmHg for basal flow (50 ml/min), approximately 27 mmHg for elevated flow (100 ml/min) and increased to an extrapolated value of approximately 34 mmHg for hyperemic flow (115 ml/min), which led to a distal mean coronary pressure p(rh) of approximately 55 mmHg, a level known to cause ischemia in the subendocardium (Brown et al., 1984), and consistent with the occurrence of angina in the patients. Relatively high levels of wall shear stress were computed in the narrow throat region and ranged from about 600 to 1500 dyn/cm(2), with periodic (phase shifted) peak systolic values of about 3500 dyn/cm(2). In the distal vessel, the interaction between the separated shear layer wave, convected downstream by the core flow, and the wall shear layer flow, led to the formation of vortical flow cells along the distal vessel wall during the systolic phase where Reynolds numbers Re(e)(t) were higher. During the phasic vortical mode observed at both basal and elevated mean flow rates, wide variations in distal wall shear stress occurred, distal transmural pressures were depressed below throat levels, and pressure recovery was larger farther along the distal vessel. Along the constriction (convergent) and throat segments of the lesion the pulsatile flow field was principally quasi-steady before flow separation occurred. The flow regimes were complex in the narrow mean flow Reynolds number range Re(e)=100-230 and a frequency parameter of alphae=2.25. The shear layer flow disturbances diminished in strength due to viscous damping along the distal vessel at these relatively low values of Re(e), typical of flow through diseased epicardial coronary vessels. The distal hyperemic flow field was likely to be in an early stage of turbulent flow development during the peak systolic phase.     

Quantification of absolute coronary flow reserve and relative fractional flow reserve in a swine animal model using angiographic image data

Coronary flow reserve (CFR) and fractional flow reserve (FFR) are important physiological indexes for coronary disease. The purpose of this study was to validate the CFR and FFR measurement techniques using only angiographic image data. Fifteen swine were instrumented with an ultrasound flow probe on the left anterior descending artery (LAD). Microspheres were gradually injected into the LAD to create microvascular disruption. An occluder was used to produce stenosis. Contrast material injections were made into the left coronary artery during image acquisition. Volumetric blood flow from the flow probe (Q(q)) was continuously recorded. Angiography-based blood flow (Q(a)) was calculated by using a time-density curve based on the first-pass analysis technique. Flow probe-based CFR (CFR(q)) and angiography-based CFR (CFR(a)) were calculated as the ratio of hyperemic to baseline flow using Q(q) and Q(a), respectively. Relative angiographic FFR (relative FFR(a)) was calculated as the ratio of the normalized Q(a) in LAD to the left circumflex artery (LC(X)) during hyperemia. Flow probe-based FFR (FFR(q)) was measured from the ratio of hyperemic flow with and without disease. CFR(a) showed a strong correlation with the gold standard CFR(q) (CFR(a) = 0.91 CFR(q) + 0.30; r = 0.90; P < 0.0001). Relative FFR(a) correlated linearly with FFR(q) (relative FFR(a) = 0.86 FFR(q) + 0.05; r = 0.90; P < 0.0001). The quantification of CFR and relative FFR(a) using angiographic image data was validated in a swine model. This angiographic technique can potentially be used for coronary physiological assessment during routine cardiac catheterization.     

Influence of zero flow pressure on fractional flow reserve

Fractional flow reserve (FFR) is a commonly used index to assess the functional severity of a coronary artery stenosis. It is conventionally calculated as the ratio of the pressure distal (P_d) and proximal (P_a) to the stenosis (FFR=P_d/P_a). We hypothesize that the presence of a zero flow pressure (P _zf), requires a modification of this equation. Using a dynamic hydraulic bench model of the coronary circulation, which allows one to incorporate an adjustable P _zf, we studied the relation between pressure-derived FFR=P_d/P_a, flow-derived true FFR_Q=Q_S/Q_N (=ratio of flow through a stenosed vessel to flow through a normal vessel), and the corrected pressure-derived FFR_C=(P_d–P_zf)/(P_a–P_zf) under physiological aortic pressures (70 mmHg, 90 mmHg, and 110 mmHg). Imposed P_zf values varied between 0 mmHg and 30 mmHg. FFR_C was in good agreement with FFR_Q, whereas FFR consistently overestimated FFR_Q. This overestimation increased when P_zf increased, or when P_a decreased, and could be as high as 56% (P_zf=30 mmHg and P_a=70 mmHg). According to our experimental study, calculating the corrected FFR_C instead of FFR, if P_zf is known, provides a physiologically more accurate evaluation of the functional severity of a coronary artery stenosis.     

Characterizing momentum change and viscous loss of a hemodynamic endpoint in assessment of coronary lesions

Myocardial fractional flow reserve (FFR(myo)) and coronary flow reserve (CFR), measured with guidewire, and quantitative angiography (QA) are widely used in combination to distinguish ischemic from non-ischemic coronary stenoses. Recent studies have shown that simultaneous measurements of FFR(myo) and CFR are recommended to dissociate conduit epicardial coronary stenoses from distal resistance microvascular disease. In this study, a more comprehensive diagnostic parameter, named as lesion flow coefficient, c, is proposed. The coefficient, c, which accounts for mean pressure drop, Delta p, mean coronary flow, Q, and percentage area stenosis, can be used to assess the hemodynamic severity of a coronary artery stenoses. Importantly, the contribution of viscous loss and loss due to momentum change for several lesion sizes can be distinguished using c. FFR(myo), CFR and c were calculated for pre-angioplasty, intermediate and post-angioplasty epicardial lesions, without microvascular disease. While hyperemic c decreased from 0.65 for pre-angioplasty to 0.48 for post-angioplasty lesion with guidewire of size 0.35 mm, FFR(myo) increased from 0.52 to 0.87, and CFR increased from 1.72 to 3.45, respectively. Thus, reduced loss produced by momentum change due to lower percentage area stenosis decreased c. For post-angioplasty lesion, c decreased from 0.55 to 0.48 with the insertion of guidewire. Hence, increased viscous loss due to the presence of guidewire decreased c compared with a lesion without guidewire. Further, c showed a linear relationship with FFR(myo), CFR and percentage area stenosis for pre-angioplasty, intermediate and post-angioplasty lesion. These baseline values of c were developed from fluid dynamics fundamentals for focal lesions, and provided a single hemodynamic endpoint to evaluate coronary stenosis severity.     

Hemodynamic characteristics of flow around a deformable stenosis

Clinical studies reported that some vulnerable stenoses deformed their shape in a blood vessel based on flow condition. However, the effects of shape variation on flow characteristics remain unclear. The flow characteristics are known to affect vulnerable stenosis rupture and fractional flow reserve (FFR) value which has been widely used as a diagnostic tool for stenosis. Vulnerable stenosis rupture occurs when the structural stress exerted on a fibrous cap exceeds its tolerable threshold. The stress magnitude is determined from the spatial distribution of static pressure around the stenosis. In the present study, the static pressure distribution and the FFR value in deformable stenosis were investigated with related other flow characteristics. Two phantom models were fabricated to mimic deformable and nondeformable stenoses using polydimethylsiloxane. The flow characteristics were observed under a steady-flow condition at three Reynolds numbers (Re = 500, 1000, 1500) using a particle image velocimetry. The pressure drop across the stenosis models were measured using a pressure sensor to determine effects of shape deformation on FFR value. Shape variations and jet deflections were clearly observed in the deformable stenosis model, and the effective severity of the stenosis increased up to 17.2%. The shape variations of deformable stenosis model increased the static pressure difference at the upstream and downstream sides of the stenosis. The pressure drop across the deformable stenosis model was significantly higher than that of the nondeformable stenosis model. The present results substantiate that stenosis deformability should be carefully considered to diagnose the rupture of vulnerable stenosis.     

A head-to-head comparison between CT- and IVUS-derived coronary blood flow models

The goal of this work is to compare coronary hemodynamics as predicted by computational blood flow models derived from two imaging modalities: coronary computed tomography angiography (CCTA) and intravascular ultrasound integrated with angiography (IVUS). Criteria to define boundary conditions are proposed to overcome the dissimilar anatomical definition delivered by both modalities. The strategy to define boundary conditions is novel in the present context, and naturally accounts for the flow redistribution induced by the resistance of coronary vessels. Hyperemic conditions are assumed to assess model predictions under stressed hemodynamic environments similar to those encountered in Fractional Flow Reserve (FFR) calculations. As results, it was found that CCTA models predict larger pressure drops, higher average blood velocity and smaller FFR. Concerning the flow rate at distal locations in the major vessels of interest, it was found that CCTA predicted smaller flow than IVUS, which is a consequence of a larger sensitivity of CCTA models to coronary steal phenomena. Comparisons to in-vivo measurements of FFR are shown.     

Evaluation of functional severity of coronary artery disease and fluid dynamics' influence on hemodynamic parameters: A review

Coronary Artery Disease (CAD) is responsible for most of the deaths in patients with cardiovascular diseases. Diagnostic coronary angiography analysis offers an anatomical knowledge of the severity of the stenosis. The functional or physiological significance is more valuable than the anatomical significance of CAD. Clinicians assess the functional severity of the stenosis by resorting to an invasive measurement of the pressure drop and flow. Hemodynamic parameters, such as pressure wire assessment fractional flow reserve (FFR) or Doppler wire assessment coronary flow reserve (CFR) are well-proven techniques to evaluate the physiological significance of the coronary artery stenosis in the cardiac catheterization laboratory. Between the two techniques mentioned above, the FFR is seen as a very useful index. The presence of guide wire reduces the coronary flow which causes the underestimation of pressure drop across the stenosis which leads to dilemma for the clinicians in the assessment of moderate stenosis. In such condition, the fundamental fluid mechanics is useful in the development of new functional severity parameters such as pressure drop coefficient and lesion flow coefficient. Since the flow takes place in a narrowed artery, the blood behaves as a non-Newtonian fluid. Computational fluid dynamics (CFD) allows a complete coronary flow simulation to study the relationship between the pressure and flow. This paper aims at explaining (i) diagnostic modalities for the evaluation of the CAD and valuable insights regarding FFR in the evaluation of the functional severity of the CAD (ii) the role of fluid dynamics in measuring the severity of CAD.     

Feasibility of coronary blood flow simulations using mid-fidelity numeric and geometric models

Biomechanics and Modeling in Mechanobiology - The fractional flow reserve index (FFR) is currently used as a gold standard to quantify coronary stenosis’s functional relevance. Due to its...     

Coronary physiology before and after chronic total occlusion treatment: what does it tell us?

Studies performed in the last two decades demonstrate that after successful percutaneous coronary intervention (PCI) of a chronically occluded coronary artery, the physiology of the chronic total occlusion (CTO) vessel and dependent microvasculature does not normalise immediately but improves significantly over time. Generally, there is an increase in fractional flow reserve (FFR) in the CTO artery, a decrease in collateral blood supply and an increase in FFR in the donor artery accompanied by an increase in blood flow and decrease in microvascular resistance in the myocardium supplied by the CTO vessel. Analogous to these physiological changes, positive remodelling of the distal CTO artery also occurs over time, and intravascular imaging can be helpful for analysing distal vessel parameters. Follow-up coronary angiography with physiological measurements after several weeks to months can be helpful and informative in a subset of patients in order to decide upon the necessity for treatment of residual coronary artery stenosis in the vessel distal to the CTO or in the contralateral donor artery, as well as in deciding whether stent optimisation is indicated. We suggest that such physiological guidance of CTO procedures avoids unnecessary overtreatment during the initial procedure, guides interventions at follow-up, and improves our understanding of what PCI in CTO means.