George E. Parcharidis

Spatial and phasic oscillation of non-newtonian wall shear stress in human left coronary artery bifurcation : an insight to atherogenesis

ObjectiveTo investigate the wall shear stress oscillation in a normal human left coronary artery bifurcation computational model by applying non-Newtonian blood properties and phasic flow. MethodsThe three-dimensional geometry of the investigated model included the left main coronary artery along with its two main branches, namely the left anterior descending and the left circumflex artery. For the computational analyses a pulsatile non-Newtonian flow was applied. To evaluate the cyclic variations in wall shear stress, six characteristic time-points of the cardiac cycle were selected. The non-Newtonian wall shear stress variation was compared with the Newtonian one. ResultsThe wall shear stress varied remarkably in time and space. The flow divider region encountered higher wall shear stress values than the lateral walls throughout the entire cardiac cycle. The wall shear stress exhibited remarkably lower and oscillatory values in systole as compared with that in diastole in the entire bifurcation region, especially in the lateral walls. Although the Newtonian wall shear stress experienced consistently lower values throughout the entire cardiac cycle than the non-Newtonian wall shear stress, the general pattern of lower wall shear stress values at the lateral walls, particularly during systole, was evident regardless of the blood properties. ConclusionsThe lateral walls of the bifurcation, where low and oscillating wall shear stress is observed, are more susceptible to atherosclerosis. The systolic period, rather than the diastolic one, favors the development and progression of atherosclerosis. The blood viscosity properties do not seem to qualitatively affect the spatial and temporal distribution of the wall shear stress.

In-vivo validation of spatially correct three-dimensional reconstruction of human coronary arteries by integrating intravascular ultrasound and biplane angiography

ObjectivesThe in-vivo validation of geometrically correct three-dimensional reconstruction of human coronary arteries by integrating intravascular ultrasound and biplane coronary angiography has not been adequately investigated. The purpose of this study was to describe the reconstruction method and investigate its in-vivo feasibility and accuracy. MethodsIn 17 coronary arteries (mean length, 85.7±17.1 mm) from nine patients, an intravascular ultrasound procedure along with a biplane coronary angiography was performed. From each angiographic projection, a single end-diastolic frame was selected in order to reconstruct the intravascular ultrasound catheter trajectory in space. In each end-diastolic intravascular ultrasound image, the lumen and media–adventitia contours were detected semi-automatically by an active contour algorithm. Each pair of contours was located on the catheter trajectory appropriately and interpolated with the adjacent pairs creating a three-dimensional volume of the arterial lumen and wall. The reconstructed lumen was back-projected onto both angiographic planes and the agreement between the back-projected and the angiographic luminal outlines was calculated. ResultsThe angiogram-derived catheter length showed very high correlation (y=0.97x+1.8, P<0.001) and agreement with the corresponding pullback-derived values. Accordingly, the semi-automated segmentation of intravascular ultrasound images was also in significant correlation (r≥0.96, P<0.001) and agreement with the reference manual tracing. The back-projected luminal borders showed good overall association with the corresponding angiographic ones (r=0.78, P<0.001) as well as remarkable agreement. ConclusionsSpatially correct three-dimensional reconstruction of human coronary arteries constitutes an imaging method with considerably high in-vivo feasibility and accuracy.

Total Cholesterol Content of Erythrocyte Membranes and Coronary Atherosclerosis: An Intravascular Ultrasound Pilot Study

Background: Increasing evidence suggests that erythrocytes may participate in atherogenesis. We sought to investigate the relationship between total cholesterol content in erythrocyte membranes (CEM) and coronary atheroma burden in patients with coronary artery disease (CAD). Methods: We prospectively enrolled 28 participants: 11 patients with angiographically significant CAD and 17 controls. Intravascular ultrasound (IVUS) and 3-dimensional reconstruction of coronary arteries was performed in the patient subgroup. Results: Cholesterol content of erythrocyte membranes was higher in patients compared to controls (P < .01). Cholesterol content of erythrocyte membranes correlated with total atheroma volume (r = .82, P < .01) and with percentage plaque area at the vessel site with minimal lumen area (r = .75, P < .05). On multivariate analysis, CEM was the only variable independently predicting total atheroma volume (P = .05). Conclusions: This pilot study is the first to demonstrate a significant relation between CEM and coronary atherosclerotic burden, suggesting a possible role of erythrocyte membrane—derived lipids in the expansion of atheromata. The results merit validation in larger studies.

Low-Density Lipoprotein concentration in the normal Left Coronary Artery tree.

BackgroundThe blood flow and transportation of molecules in the cardiovascular system plays a crucial role in the genesis and progression of atherosclerosis. This computational study elucidates the Low Density Lipoprotein (LDL) site concentration in the entire normal human 3D tree of the LCA.MethodsA 3D geometry model of the normal human LCA tree is constructed. Angiographic data used for geometry construction correspond to end-diastole. The resulted model includes the LMCA, LAD, LCxA and their main branches. The numerical simulation couples the flow equations with the transport equation applying realistic boundary conditions at the wall.ResultsHigh concentration of LDL values appears at bifurcation opposite to the flow dividers in the proximal regions of the Left Coronary Artery (LCA) tree, where atherosclerosis frequently occurs. The area-averaged normalized luminal surface LDL concentrations over the entire LCA tree are, 1.0348, 1.054 and 1.23, for the low, median and high water infiltration velocities, respectively. For the high, median and low molecular diffusivities, the peak values of the normalized LDL luminal surface concentration at the LMCA bifurcation reach 1.065, 1.080 and 1.205, respectively. LCA tree walls are exposed to a cholesterolemic environment although the applied mass and flow conditions refer to normal human geometry and normal mass-flow conditions.ConclusionThe relationship between WSS and luminal surface concentration of LDL indicates that LDL is elevated at locations where WSS is low. Concave sides of the LCA tree exhibit higher concentration of LDL than the convex sides. Decreased molecular diffusivity increases the LDL concentration. Increased water infiltration velocity increases the LDL concentration. The regional area of high luminal surface concentration is increased with increasing water infiltration velocity. Regions of high LDL luminal surface concentration do not necessarily co-locate to the sites of lowest WSS. The degree of elevation in luminal surface LDL concentration is mostly affected from the water infiltration velocity at the vessel wall. The paths of the velocities in proximity to the endothelium might be the most important factor for the elevated LDL concentration.

In-vivo accuracy of geometrically correct three-dimensional reconstruction of human coronary arteries: is it influenced by certain parameters?

ObjectiveThe geometrically correct three-dimensional reconstruction of human coronary arteries by integrating intravascular ultrasound (IVUS) and biplane angiography constitutes a promising imaging method for coronaries with broad clinical potential. The determinants of the accuracy of the method, however, have not been investigated before. MethodsIn total, 17 arterial segments (right coronary artery, n=7; left anterior descending, n=4; left circumflex, n=6) derived from nine patients were three-dimensionally reconstructed by applying three-dimensional intravascular ultrasound. The degree of matching between the reconstructed lumen back-projected onto each angiographic plane and the actual lumen in each plane was used as a measure of methods accuracy. The investigated factors that could potentially affect the reliability of the method included the type of the artery (left anterior descending, left circumflex, right coronary artery) and several geometrical and morphological characteristics of the reconstructed arteries. ResultsThe correlation between the back-projected reconstructed lumens and the actual angiographic ones was found to be high (r=0.78, P<0.001). Neither the category of the reconstructed arteries nor their particular geometrical and morphological characteristics influenced the accuracy of the reconstruction method significantly. Nonetheless, the method exhibited slightly less accuracy in the reconstruction of right coronary arteries, an observation that could be attributed to the more intense pulsatile motion that this artery experiences during the cardiac cycle compared to the left anterior descending and left circumflex artery. ConclusionsThe in-vivo accuracy of three-dimensional intravascular ultrasound (3D IVUS) is significantly high regardless of the type of the coronary arteries or their particular geometrical and morphological characteristics. This finding further supports the applicability of the method for either diagnostic or investigational purposes.

Molecular Viscosity in the Normal Left Coronary Arterial Tree. Is It Related to Atherosclerosis

The purpose of this study is to elucidate, probably for the first time, the distribution of molecular viscosity in the entire left coronary artery (LCA) tree. The governing mass, momentum, and energy flow equations were solved by using a previously validated 3-dimensional numerical (finite-element analysis) code. High-molecular-viscosity regions occur at bifurcations in regions opposite the flow dividers, which are anatomic sites predisposed for atherosclerotic development. Furthermore, high-molecular-viscosity values appear in the proximal regions of the LCA tree, where atherosclerosis frequently occurs. The effect of blood flow resistance, due to increased blood viscosity, gives rise to increased contact time between the atherogenic particles of the blood and the endothelium, probably promoting atherosclerosis. Observations suggest that, whole viscosity distribution within the coronary artery tree may represent a risk factor for the resulting atherosclerosis. This distribution can become a possible tool for the location of atherosclerotic lesions.

Idiopathic left ventricular aneurysm causing ventricular tachycardia with 1:1 ventriculoatrial conduction and intermittent wenckebach block.

Left ventricular aneurysms (LVAs) can be congenital or acquired. They develop most frequently after myocardial infarction. Other causes include hypertrophic cardiomyopathy, arrythmogenic right ventricular cardiomyopathy, myocarditis, chest trauma, sarcoidosis or Chagas disease [1, 2]. LVAs without identifiable cause are considered as idiopathic. Most of LVAs are asymptomatic and are occasionally identified during routine diagnostic procedures. However, in rare cases LVAs may be associated with life-threatening ventricular tachyarrhythmias (mostly ventricular tachycardia, VT) and sudden cardiac death, even as a first manifestation [3]. In most of the cases VT has right bundle branch block morphology consistent with left ventricular origin. Idiopathic LVAs are anatomically distinguished from congenital diverticula, which are characterized by a narrow communication with the ventricle [2, 4]. In this report we describe an interesting and rare case of idiopathic LVA associated with sustained monomorphic VT, ventriculoatrial conduction and intermittent Wenckebach block. Management strategies are discussed and our treatment approach is presented. Case Report A 72-year old woman was admitted to our hospital with palpitations, dizziness and fatigue from a few hours ago. The patient had a history of heart failure (NYHA II) from three years ago and also an episode of paroxysmal atrial flutter two years ago. She was free of angina and had no cardiovascular disease risk factors. The family history was unremarkable with respect to cardiac arrest, unexplained syncope, ventricular tachyarrhythmias, or cardiomyopathy. At the time of presentation to the emergency department the patient was receiving carvedilol, valsartan, and furosemide. The baseline 12-lead ECG revealed a sustained monomorphic VT with RBBB morphology and left axis deviation (Fig. ​1A1A). Since tachycardia was poorly tolerated with systolic blood pressure of 80 mmHg an electrical cardioversion was applied and the rhythm was restored to sinus (Fig. ​1B1B). The ECG, physical examination and laboratory tests after the cardioversion were unremarkable. Fig. (1A) ECG on admission showing the ventriculat tachycardia (VT) with RBBB morphology, (B). Restoration of VT to sinus rhythm with electrical cardioversion, (C). Induced VT with LBBB morphology during the electrophysiology study, (D). Electrogram during the ... The chest X-ray revealed an increased cardiothoracic index. The transthoracic echocardiogram showed dilated left ventricle with a lateral wall aneurysm, left ventricular ejection fraction of 40% and mild mitral regurgitation (Fig. ​2A2A). The coronary angiography revealed normal coronary arteries, whereas the left ventriculography further confirmed the lateral wall aneurysm (Fig. ​2B2B). Magnetic resonance imaging further confirmed the presence of the LVA (Fig. ​2C2C). Fig. (2A) Echocardiogram showing the left ventricular aneurysm (arrows), (B). Left ventriculography further depicting the lateral wall aneurysm (arrows), (C). Magnetic resonance imaging further confirmed the presence of an aneurysm with wall thinning (arrows). The patient was started on amiodarone per os and after two weeks an electrophysiology study was performed. The programmed ventricular stimulation in the right ventricular apex with 500/230-240 msec basic drive cycle and two extrastimuli reproducibly induced sustained monomorphic VT of 160 bpm associated with hemodynamic instability. That tachycardia, however, had different characteristics from the one at the emergency department as it was associated with left branch bundle block (LBBB) morphology and normal cardiac axis and was terminated by overdrive pacing (Fig. ​1C1C). The LBBB morphology was consistent with septal origin of the VT. Of note, during the inducible VT a 1:1 ventriculoatrial conduction with intermittent Wenckebach block was recorded (Fig. ​1D1D). A cardioverter defibrillator (ICD) was implanted for the secondary prevention of VT and the patient was discharged 2 days after ICD implantation on treatment with carvedilol, amiodarone and angiotensin converting enzyme inhibitor. During a follow-up period of six months no ventricular arrhythmias occurred.

Parathyroid hormone-related protein is reduced in severe chronic heart failure

In the cardiovascular system, parathyroid hormone-related peptide (PTHrP) is expressed in various cells such as cardiac vascular smooth muscle cells, coronary endothelial cells and cardiomyocytes and acts as an autocrine/paracrine substance. We compared PTHrP levels in 35 consecutive patients with severe CHF (33 male, mean age 66.2 +/- 8.9 years) with 26 normal controls (24 male, mean age 63.1 +/- 8.6 years). PTHrP levels were reduced in severe CHF patients (11.10 +/- 1.37 fmol/ml) compared with the controls (20.62 +/- 3.30 fmol/ml, p = 0.005). PTHrP values decreased as a function of New York Heart Association classification. These results suggest that PTHrP levels decrease in proportion to the severity of heart failure and could potentially be used to monitor progression of disease non-invasively.

In Vivo Comparative Study of Linear Versus Geometrically Correct Three-Dimensional Reconstruction of Coronary Arteries

Although conventional linear 3-dimensional (3D) reconstruction of coronary arteries by intravascular ultrasound has been widely used for the assessment of plaque volume and progression; the volumetric error (VE) that is produced has not been adequately studied. Linear and geometrically correct 3D reconstruction was applied in 16 coronary arterial segments from 9 patients. Using geometrically correct reconstruction as reference, VE was assessed in 1-mm-long arterial slices. Although for the entire length of the coronary arteries VEs for lumen, external elastic membrane (EEM), and intima-media volumes were minimal (lumen VE 0.4%, -0.8 to 1.8; EEM VE 0.3%, -0.9 to 1.9; intima-media VE 0.4%, -1.4 to 2.2), the VE in each arterial slice exhibited a large variation from -15.6% to 36.2% for lumen volume, from -12.9% to 33.1% for EEM volume, and from -17.2% to 46.7% for intima-media volume, suggesting that linear reconstruction over- or underestimates the true arterial volumes. Lumen VE, EEM VE, and intima-media VE were also significantly higher in curved arterial subsegments than in relatively straight arterial subsegments (p <0.05). In conclusion, in highly curved arterial subsegments, the VE that is produced by linearly stacking the intravascular ultrasound images may be not negligible. Geometrically correct reconstruction of coronary arteries provides more reliable arterial reconstructions and plaque volume measurements. It is anticipated that clinical application of this technique will contribute to more accurate follow-up of the progression of atherosclerosis and assessment of arterial remodeling.

Sex-related differences in the angiographic results of 14 500 cases referred for suspected coronary artery disease

ObjectiveTo investigate sex differences of angiographic results in patients undergoing coronary angiography for suspected coronary artery disease (CAD). MethodsWe retrospectively assessed the coronary angiograms of 2840 women and 11 610 men from 1984 to 2003. We examined sex differences regarding the extent and topography of significant stenoses (SS) (i.e. ≥50% of the luminal diameter), the age of presentation, and the variation of the annual frequency of the angiographic findings across the study period. ResultsSS were recorded in 1817 women and 9984 men (64 vs. 86%, P<0.001). Women were more likely to present with nonsignificant stenoses (i.e. <50% of the luminal diameter) or angiographically normal coronaries (P<0.001). In patients with SS, women had a higher chance to present with one-vessel (P<0.001) or peripheral branches (P<0.05) disease, whereas men were more likely to have two-vessel disease (P<0.005). Compared with men, women were less likely to exhibit SS in the right coronary artery (P<0.001), left circumflex (P<0.01), intermediate artery (P<0.01) and first obtuse marginal branch (P<0.01). No significant sex differences were recorded in the frequency of SS in the left anterior descending artery. In patients aged from 31 to 60 years, SS were more common in men, whereas in patients 61–80 years of age SS were more common in women. The annual frequency of SS in women gradually increased throughout the study period. ConclusionSS were less common in women, were found later in life, and were less likely to involve the right coronary artery, left circumflex, intermediate artery and first obtuse marginal branch than in men.