Influence of heart rate on fractional flow reserve, pressure drop coefficient, and lesion flow coefficient for epicardial coronary stenosis in a porcine model

A limitation in the use of invasive coronary diagnostic indexes is that fluctuations in hemodynamic factors such as heart rate (HR), blood pressure, and contractility may alter resting or hyperemic flow measurements and may introduce uncertainties in the interpretation of these indexes. In this study, we focused on the effect of fluctuations in HR and area stenosis (AS) on diagnostic indexes. We hypothesized that the pressure drop coefficient (CDP(e), ratio of transstenotic pressure drop and distal dynamic pressure), lesion flow coefficient (LFC, square root of ratio of limiting value CDP and CDP at site of stenosis) derived from fluid dynamics principles, and fractional flow reserve (FFR, ratio of average distal and proximal pressures) are independent of HR and can significantly differentiate between the severity of stenosis. Cardiac catheterization was performed on 11 Yorkshire pigs. Simultaneous measurements of distal coronary arterial pressure and flow were performed using a dual sensor-tipped guidewire for HR < 120 and HR > 120 beats/min, in the presence of epicardial coronary lesions of <50% AS and >50% AS. The mean values of FFR, CDP(e), and LFC were significantly different (P < 0.05) for lesions of <50% AS and >50% AS (0.88 ± 0.04, 0.76 ± 0.04; 62 ± 30, 151 ± 35, and 0.10 ± 0.02 and 0.16 ± 0.01, respectively). The mean values of FFR and CDP(e) were not significantly different (P > 0.05) for variable HR conditions of HR < 120 and HR > 120 beats/min (FFR, 0.81 ± 0.04 and 0.82 ± 0.04; and CDP(e), 95 ± 33 and 118 ± 36). The mean values of LFC do somewhat vary with HR (0.14 ± 0.01 and 0.12 ± 0.02). In conclusion, fluctuations in HR have no significant influence on the measured values of CDP(e) and FFR but have a marginal influence on the measured values of LFC. However, all three parameters can significantly differentiate between stenosis severities. These results suggest that the diagnostic parameters can be potentially used in a better assessment of coronary stenosis severity under a clinical setting.     

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 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.     

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.     

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 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.     

Pressure drop and arterial compliance – Two arterial parameters in one measurement

Coronary artery pressure-drop and distensibility (compliance) are two major, seemingly unrelated, parameters in the cardiovascular clinical setting, which are indicative of coronary arteries patency and atherosclerosis severity. While pressure drop is related to flow, and therefore serves as a functional indicator of a stenosis severity, the arterial distensibility is indicative of the arterial stiffness, and hence the arterial wall composition. In the present study, we hypothesized that local pressure drops are dependent on the arterial distensibility, and hence can provide information on both indices. The clinical significance is that a single measurement of pressure drop could potentially provide both functional and bio-mechanical metrics of lesions, and thus assist in real-time decision making prior to stenting. The goal of the current study was to set the basis for understanding this relationship, and define the accuracy and sensitivity required from the pressure measurement system. The investigation was performed using numerical fluid–structure interaction (FSI) simulations, validated experimentally using our high accuracy differential pressure measurement system. Simplified silicone mock coronary arteries with zero to intermediate size stenoses were used, and various combinations of arterial distensibility, diameter, and flow rate were simulated. Results of hyperemic flow cases were also compared to fractional flow reserve (FFR). The results indicate the potential clinical superiority of a high accuracy pressure drop-based parameter over FFR, by: (i) being more lesion-specific, (ii) the possibility to circumvent the FFR dependency on pharmacologically-induced hyperemia, and, (iii) by providing both functional and biomechanical lesion-specific information.     

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.     

Effect of simultaneous intracoronary guidewires on the predictive accuracy of functional parameters of coronary lesion severity

The aim of this study was to assess the influence of a second guidewire on the diagnostic accuracy of functional parameters of coronary lesion severity. Sixty-five patients with intermediate coronary lesions underwent myocardial perfusion scintigraphy. Fractional flow reserve (FFR), coronary flow velocity reserve (CFVR), and hyperemic stenosis resistance (HSR) index (HSR = stenosis pressure gradient / velocity) were determined in 77 lesions. Distal pressure and velocity were acquired simultaneously (dual wire) and sequentially (single wire) with two sensor-equipped guidewires. Overall, functional parameters deteriorated from single- to dual-wire assessment. In patients without ischemia, the good diagnostic performance of FFR, CFVR, and HSR deteriorated significantly (P < 0.001) when assessed by dual wires, with an increase in the number of false-positive results. This trend was more pronounced for HSR, since the presence of a second wire reduced maximal velocity and increased the pressure gradient. The presence of two guidewires, especially across a myocardial perfusion scintigraphy-induced nonsignificant lesion, is associated with overestimation of the hemodynamically assessed lesion severity and, therefore, is likely to have a major impact on clinical decision making. This underscores the advantage of a dual-sensor-equipped guidewire for the evaluation of stenosis severity by combined pressure and velocity measurements.     

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.     

Turbulence intensity measurements using particle image velocimetry in diseased carotid artery models: Effect of stenosis severity,plaque eccentricity,and ulceration

Clinical decision-making for the treatment of patients with diseased carotid artery is mainly based on the severity of the stenosis. However, stenosis severity alone is not a sensitive indicator, and other local factors for the assessment of stroke risk are required. Flow disturbance is of particular interest due to its proven association with increased thromboembolic activities. The objective of this study was to investigate the level of turbulence intensity (TI) with regards to certain geometrical features of the plaque – namely stenosis severity, eccentricity, and ulceration. A family of eight carotid-artery bifurcation models was examined using particle image velocimetry. Results showed a marked difference in turbulence intensity among these models; increasing degree of stenosis severity resulted in increased turbulence intensity, going from 0.12 m/s for mild stenosis to 0.37 m/s for severe stenosis (with concentric geometry). Moreover, independent of stenosis severity, eccentricity led to further elevations in turbulence intensity, increasing TI by 0.05–0.10 m/s over the counterpart concentric plaque. The presence of ulceration (in a 50% eccentric plaque) produced a larger portion of moderate turbulence intensity (~0.10 m/s) compared to the non-ulcerated model, more proximal to the bifurcation apex in the post-stenotic recirculation zone. The effect of plaque eccentricity and ulceration in enhancing the downstream turbulence has potential clinical implications for a more sensitive assessment of stroke risk beyond stenosis severity alone.     

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.     

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.     

Effect of changes in contractility on the index of myocardial performance in the dysfunctional left ventricle

Background

Carotid plaque severity and morphology can affect cardiovascular prognosis. We evaluate both the importance of echographically assessed carotid artery plaque geometry and morphology as predictors of death in hospitalised cardiological patients.

Methods

541 hospitalised patients admitted in a cardiological division (age = 66 ± 11 years, 411 men), have been studied through ultrasound Duplex carotid scan and successively followed-up for a median of 34 months. Echo evaluation assessed plaque severity and morphology (presence of heterogeneity and profile).

Results

361 patients showed carotid stenosis (67% with <50% stenosis, 18% with 50–69% stenosis, 9% with >70% stenosis, 4% with near occlusion and 2% with total occlusion). During the follow-up period, there were 83 all-cause deaths (15% of the total population). Using Cox's proportional hazard model, age (RR 1.06, 95% CI 1.03–1.09, p = 0.000), ejection fraction > 50% (RR = 0.62, 95% CI 0.4–0.96, p = 0.03), treatment with statins (RR = 0.52, 95% CI 0.29–0.95, p = 0.34) and the presence of a heterogeneous plaque (RR 1.6; 95% CI, 1.2 to 2.14, p = 0.002) were independent predictors of death. Kaplan – Meier survival estimates have shown the best outcome in patients without plaque, intermediate in patients with homogeneous plaques and the worst outcome in patients with heterogeneous plaques (90% vs 79% vs 73%, p = 0.0001).

Conclusion

In hospitalised cardiological patients, carotid plaque presence and morphology assessed by ultrasound are independent predictors of death.     

One-dimensional steady inviscid flow through a stenotic collapsible tube

A one-dimensional inviscid solution for flow through a compliant tube with a stenosis is presented. The model is used to represent an artery with an atherosclerotic plaque and to investigate a range of conditions for which arterial collapse may occur. The coupled equations for flow through collapsible tubes are solved using a Runge-Kutta finite difference scheme. Quantitative results are given for specific physiological parameters including inlet and outlet pressure, flow rate, stenosis size, length and stiffness. The results suggest that high-grade stenotic arteries may exhibit collapse with typical physiological pressures. Critical stenoses may cause choking of flow at the throat followed by a transition to supercritical flow with tube collapse downstream. Greater amounts of stenosis produced a linear reduction of flow rate and a shortening of the collapsed region. Changes in stenosis length created proportional changes in the length of collapse. Increasing the stiffness of the stenosis to a value greater than the nominal tube stiffness caused a greater amount of flow limitation and more negative pressures, compared to a stenosis with constant stiffness. These findings assist in understanding the clinical consequences of flow through atherosclerotic arteries.     

Computational simulation of flow-induced arterial remodeling of the pancreaticoduodenal arcade associated with celiac artery stenosis

Arterial remodeling of the pancreaticoduodenal arcade, which enables collateral flow to the liver, spleen, and stomach, is a well-recognized clinical sign of celiac artery (CA) stenosis. However, the hemodynamic changes due to remodeling are poorly understood, despite their importance in surgical procedures such as pancreaticoduodenectomy. In this study, a framework to simulate remodeling of the arterial network following pathological flow alterations was developed and applied to investigate the hemodynamic characteristics of patients with CA stenosis. A one-dimensional–zero-dimensional cardiovascular model was used for blood flow simulation. After introducing CA stenosis into the normal network, arterial remodeling was simulated by iteratively changing the diameter of each artery until time-averaged wall shear stress reached its value under normal conditions. A representative case was simulated to validate the present framework, followed by simulation cases to investigate the impact of stenosis severity on remodeling outcome. A markedly dilated arcade was observed whose diameter agreed well with the corresponding values measured in subjects with CA stenosis, confirming the ability of the framework to predict arterial remodeling. A series of simulations clarified how the geometry and hemodynamics after remodeling change with stenosis severity. In particular, the arterial remodeling and resulting blood flow redistribution were found to maintain adequate organ blood supply regardless of stenosis severity. Furthermore, it was suggested that flow conditions in patients with CA stenosis could be estimated from geometric factors, namely, stenosis severity and arcade diameter, which can be preoperatively and non-invasively measured using diagnostic medical images.     

Diagnostic Performance of First-Pass Myocardial Perfusion Imaging without Stress with Computed Tomography (CT) Compared with Coronary CT Angiography Alone,with Fractional Flow Reserve as the Reference Standard

Coronary computed tomography angiography (CCTA) in combination with first-pass CT myocardial perfusion imaging (MPI) has a better diagnostic performance than CCTA alone, compared with invasive coronary angiography as the reference standard. The aim of this study was to investigate the additional diagnostic value of first-pass CT-MPI without stress for detecting hemodynamic significance of coronary stenosis, compared with invasive fractional flow reserve (FFR). We recruited 53 patients with suspected coronary artery disease undergoing both CCTA and first-pass CT-MPI without stress and invasive FFR, and 75 vessels were analyzed. We used the same raw data for CCTA and CT-MPI. First-pass CT-MPI was reconstructed by examining the diastolic signal densities as a bull’s eye map. Invasive FFR <0.8 was considered as positive. On per-vessel analysis, the area under the receiver operating characteristic curve for CCTA plus first-pass CT-MPI and CCTA alone was 0.81 (0.73–0.90) and 0.70 (0.61–0.81), respectively (P = 0.036). CCTA plus first-pass CT-MPI without stress showed 0.73 sensitivity, 0.74 specificity, 0.53 positive predictive value, and 0.87 negative predictive value for detecting hemodynamically significant coronary stenosis. First-pass CT-MPI without stress correctly reclassified 38% of CCTA false-positive vessels as true negative. First-pass CT-MPI without stress combined with CCTA demonstrated excellent diagnostic accuracy, compared with invasive FFR as the reference standard. This technique could complement CCTA for diagnosis of coronary artery disease.     

Residual angina pectoris after percutaneous coronary intervention for acute coronary syndrome

Fractional flow reserve (FFR) is an important diagnostic tool to guide decision-making in the cardiac catheterisation laboratory and for evaluation of percutaneous coronary interventions (PCI). Especially the pressure pullback curve at maximal hyperaemia is convincing in demonstrating the exact location and severity of a coronary stenosis. This pressure pullback curve can also demonstrate the presence of diffuse disease. We present a case in which FFR with pressure pullback curve seven days after a PCI, which did not result in complete symptom relief, indicates the presence of diffuse disease. Based on this result the patient was treated medically.     

The severity of coronary artery disease and reversible ischemia revealed by N-terminal pro-brain natriuretic peptide in patients with unstable angina and preserved left ventricular function

The association between the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and the severity of coronary artery disease (CAD) diagnosed by coronary angiography and other approaches has been investigated. The clinical application of NT-proBNP is restricted by the drawbacks of these techniques now available in screening out patients who need intensive or conservative treatment. Fractional flow reserve (FFR) is superior to coronary angiography and other functional indicators. Accordingly, we designed to investigate the association between NT-proBNP and myocardial ischemia from the perspective of anatomy and physiology in patients with unstable angina and preserved left ventricular function. Plasma samples were collected from 110 patients and NT-proBNP levels were measured by radioimmunoassay. The severity of coronary artery stenosis in patients was measured by coronary angiography and FFR. Stenosis ≥50% in the left main artery or stenosis of 70%, and fractional flow reserve (FFR) ≤0.80 in one or more coronary branches with diameter ≥2 mm were defined as “positive”, which require revascularization. NT-proBNP levels increased progressively between patients with negative and positive angiographic results (p < 0.05), and between FFR-negative and FFR-positive patients (p < 0.05). A significant correlation was observed between log NT-proBNP and log GS (GS = Gensini score, p < 0.001). NT-proBNP level serves as a predictor of positive results of angiographic stenosis and FFR, with the area under the receiver operating characteristic curve being 0.697 and 0.787, respectively. NT-proBNP levels are correlated with the severity of anatomic coronary obstruction and inducible myocardial ischemia, but NT-proBNP per se is insufficient to identify clinically significant angiographic and physiological stenoses.     

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.