Patient-specific 3D hemodynamics modelling of left coronary artery under hyperemic conditions.

The purpose of this study is to investigate the effect of various degrees of percentage stenosis on hemodynamic parameters during the hyperemic flow condition. 3D patient-specific coronary artery models were generated based on the CT scan data using MIMICS-18. Numerical simulation was performed for normal and stenosed coronary artery models of 70, 80 and 90% AS (area stenosis). Pressure, velocity, wall shear stress and fractional flow reserve (FFR) were measured and compared with the normal coronary artery model during the cardiac cycle. The results show that, as the percentage AS increase, the pressure drop increases as compared with the normal coronary artery model. Considerable elevation of velocity was observed as the percentage AS increases. The results also demonstrate a recirculation zone immediate after the stenosis which could lead to further progression of stenosis in the flow-disturbed area. Highest wall shear stress was observed for 90% AS as compared to other models that could result in the rupture of coronary artery. The FFR of 90% AS is found to be considerably low.

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.

Feasibility and Efficacy of Herculink Elite ((TM)) Biliary Stent Implantation in Large Coronary Arteries (≥ 5 mm) and Venous Conduits: An Observational Study.

BACKGROUND AND OBJECTIVES: Percutaneous coronary intervention (PCI) in patients with lesions of large calibre coronary arteries (≥ 5 mm) and saphenous venous grafts (≥ 5 mm) can be challenging. There are no separate guidelines available to treat these vessels with PCI. Standard coronary stents of 4 mm diameter are used to treat these lesions conventionally but carry the risk of under deployment, distortion of stent architecture and future stent thrombosis even if they are subsequently expanded beyond 5 mm. METHODS AND RESULTS: Biliary stents (Herculink Elite™) provide a better alternative to standard coronary stents in these patients. These stents are of larger diameter (5-7 mm) and can be safely delivered over a 6 French sheath. In our case series, we demonstrate the use of intravascular ultrasound examination to confirm that biliary stents provide improved stent strut apposition within the coronary artery associated with extremely low repeat revascularisation rates. CONCLUSION: Our paper highlights that PCI of lesions in patients with large calibre coronary arteries can successfully be achieved using biliary stents.

Differences in thrombus structure and kinetics in patients with type 2 diabetes mellitus after non ST elevation acute coronary syndrome.

INTRODUCTION: Despite optimal secondary prevention therapy following non-ST elevation acute coronary syndrome (NSTE-ACS), recurrent thrombotic events are more frequent in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: This exploratory study was aimed to evaluate quantitative and qualitative aspects of thrombus. In 28 patients with and without T2DM treated with aspirin and clopidogrel we assessed thrombus quantity using an ex-vivo chamber, platelet reactivity, thrombus ultrastructure and thrombus kinetics one week after NSTE-ACS. RESULTS: T2DM was associated with increased thrombus [14861 (8003 to 30161) vs 8908 (6812 to 11996), µ(2)/mm, median (IQR), p=0.045] and platelet reactivity. In addition, diabetic thrombus showed lower visco-elastic tensile strength [(-0.2(-1.7 to 0.7) vs 1.0(-0.9 to 3.3), p=0.044)] and was more resistant to autolysis [(27.8(11.7 to 70.7) vs 78.8(68.5 to109.6) mm/min, p=0.002)]. On SEM, fibrin fibres in diabetes were thinner, with higher lateral interlinkage and mesh-like organisation. Thrombus quantity correlated inversely with thrombus retraction (r=-0.450 p=0.016) but not with platelet reactivity (r=0.153, p=0.544). CONCLUSIONS: Despite optimal antiplatelet therapy, T2DM patients after NSTE-ACS developed increased thrombus of lower tensile strength and slower retraction. SEM revealed loosely arranged fibrin fibres. Our data showed significant differences in the magnitude as well as structural and mechanistic characteristics of thrombus in patients with T2DM.

Effect of porous media of the stenosed artery wall to the coronary physiological diagnostic parameter: a computational fluid dynamic analysis.

Functional assessment of a coronary artery stenosis severity is generally assessed by fractional flow reserve (FFR), which is calculated from pressure measurements across the stenosis. The purpose of this study is to investigate the effect of porous media of the stenosed arterial wall on this diagnostic parameter. To understand the role of porous media on the diagnostic parameter FFR, a 3D computational simulations of the blood flow in rigid and porous stenotic artery wall models are carried out under steady state and transient conditions for three different percentage area stenoses (AS) corresponding to 70% (moderate), 80% (intermediate), and 90% (severe). Blood was modeled as a non Newtonian fluid. The variations of pressure drop across the stenosis and diagnostic parameter were studied in both models. The FFR decreased in proportion to the increase in the severity of the stenosis. The relationship between the percentage AS and the FFR was non linear and inversely related in both the models. The cut-off value of 0.75 for FFR was observed at 81.89% AS for the rigid artery model whereas 83.61% AS for the porous artery wall model. This study demonstrates that the porous media consideration on the stenotic arterial wall plays a substantial role in defining the cut-off value of FFR. We conclude that the effect of porous media on FFR, could lead to misinterpretation of the functional severity of the stenosis in the region of 81.89 %-83.61% AS.

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.

Thrombus and antiplatelet therapy in type 2 diabetes mellitus. A prospective study after non-ST elevation acute coronary syndrome and a randomised, blinded, placebo-controlled study in stable angina.

Type 2 diabetes mellitus (T2DM) is associated with higher rates of thrombotic complications in patients with coronary artery disease (CAD) despite optimal medical therapy. Thrombus area was measured in T2DM and non-diabetic patients receiving aspirin and clopidogrel 7-10 days after troponin positive Non ST-elevation acute coronary syndrome (NSTE-ACS). Secondly, we assessed response to clopidogrel in naive patients with T2DM and stable CAD in a randomised controlled trial. Thrombus area was measured by Badimon chamber and platelet reactivity by VerifyNow®. In T2DM patients presenting with NSTE-ACS, thrombus area was greater compared to non-diabetic patients (mean ± SD, 20,512 ± 12,567 [n=40] vs. 14,769 ± 8,531 [n=40] µm²/mm, p=0.02) Clopidogrel decreased thrombus area among stable CAD patients with T2DM (mean ± SD, Clopidogrel [n=45]: 13,978 ± 5,502 to 11,192 ± 3,764 µm²/mm vs. placebo [n=45]: 13,959 ± 7,038 to 14,201 ± 6,780 µm²/mm, p<0.001, delta values: clopidogrel vs. placebo, mean ± SD, 2,786 ± 4,561 vs. -249 ± 2,478, p<0.0005). Only 44% of patients with CAD and T2DM responded to clopidogrel as per VerifyNow® (cut-off PRUz value of ≥ 240). Importantly, no correlation was observed between thrombus area and VerifyNow® values (rho 0.08, p=0.49). Thrombus area values were similar among hypo-responders and good responders to clopidogrel (mean thrombus area ± SD: 12,186 ± 4,294 vs. 10,438 ± 3,401; p=0.17). Type 2 diabetes mellitus is associated with an increased blood thrombogenicity among NSTE-ACS patients on currently recommended medical therapy. Thrombus area was significantly reduced in all stable CAD patients independently of their response to clopidogrel therapy.

Increased atherothrombotic burden in patients with diabetes mellitus and acute coronary syndrome: a review of antiplatelet therapy.

Patients with diabetes mellitus presenting with acute coronary syndrome have a higher risk of cardiovascular complications and recurrent ischemic events when compared to nondiabetic counterparts. Different mechanisms including endothelial dysfunction, platelet hyperactivity, and abnormalities in coagulation and fibrinolysis have been implicated for this increased atherothrombotic risk. Platelets play an important role in atherogenesis and its thrombotic complications in diabetic patients with acute coronary syndrome. Hence, potent platelet inhibition is of paramount importance in order to optimise outcomes of diabetic patients with acute coronary syndrome. The aim of this paper is to provide an overview of the increased thrombotic burden in diabetes and acute coronary syndrome, the underlying pathophysiology focussing on endothelial and platelet abnormalities, currently available antiplatelet therapies, their benefits and limitations in diabetic patients, and to describe potential future therapeutic strategies to overcome these limitations.