George E. Louridas

The Sympathetic Nervous System in Heart Failure Physiology, Pathophysiology, and Clinical Implications

Heart failure is a syndrome characterized initially by left ventricular dysfunction that triggers countermeasures aimed to restore cardiac output. These responses are compensatory at first but eventually become part of the disease process itself leading to further worsening cardiac function. Among these responses is the activation of the sympathetic nervous system (SNS) that provides inotropic support to the failing heart increasing stroke volume, and peripheral vasoconstriction to maintain mean arterial perfusion pressure, but eventually accelerates disease progression affecting survival. Activation of SNS has been attributed to withdrawal of normal restraining influences and enhancement of excitatory inputs including changes in: 1) peripheral baroreceptor and chemoreceptor reflexes; 2) chemical mediators that control sympathetic outflow; and 3) central integratory sites. The interface between the sympathetic fibers and the cardiovascular system is formed by the adrenergic receptors (ARs). Dysregulation of cardiac beta(1)-AR signaling and transduction are key features of heart failure progression. In contrast, cardiac beta(2)-ARs and alpha(1)-ARs may function in a compensatory fashion to maintain cardiac inotropy. Adrenergic receptor polymorphisms may have an impact on the adaptive mechanisms, susceptibilities, and pharmacological responses of SNS. The beta-AR blockers and the inhibitors of the renin-angiotensin-aldosterone axis form the mainstay of current medical management of chronic heart failure. Conversely, central sympatholytics have proved harmful, whereas sympathomimetic inotropes are still used in selected patients with hemodynamic instability. This review summarizes the changes in SNS in heart failure and examines how modulation of SNS activity may affect morbidity and mortality from this syndrome.

State-of-the-Art PaperThe Sympathetic Nervous System in Heart Failure: Physiology, Pathophysiology, and Clinical Implications

Heart failure is a syndrome characterized initially by left ventricular dysfunction that triggers countermeasures aimed to restore cardiac output. These responses are compensatory at first but eventually become part of the disease process itself leading to further worsening cardiac function. Among these responses is the activation of the sympathetic nervous system (SNS) that provides inotropic support to the failing heart increasing stroke volume, and peripheral vasoconstriction to maintain mean arterial perfusion pressure, but eventually accelerates disease progression affecting survival. Activation of SNS has been attributed to withdrawal of normal restraining influences and enhancement of excitatory inputs including changes in: 1) peripheral baroreceptor and chemoreceptor reflexes; 2) chemical mediators that control sympathetic outflow; and 3) central integratory sites. The interface between the sympathetic fibers and the cardiovascular system is formed by the adrenergic receptors (ARs). Dysregulation of cardiac beta(1)-AR signaling and transduction are key features of heart failure progression. In contrast, cardiac beta(2)-ARs and alpha(1)-ARs may function in a compensatory fashion to maintain cardiac inotropy. Adrenergic receptor polymorphisms may have an impact on the adaptive mechanisms, susceptibilities, and pharmacological responses of SNS. The beta-AR blockers and the inhibitors of the renin-angiotensin-aldosterone axis form the mainstay of current medical management of chronic heart failure. Conversely, central sympatholytics have proved harmful, whereas sympathomimetic inotropes are still used in selected patients with hemodynamic instability. This review summarizes the changes in SNS in heart failure and examines how modulation of SNS activity may affect morbidity and mortality from this syndrome.

Model-based morphological segmentation and labeling of coronary angiograms

A method for extraction and labeling of the coronary arterial tree (CAT) using minimal user supervision in single-view angiograms is proposed. The CAT structural description (skeleton and borders) is produced, along with quantitative information for the artery dimensions and assignment of coded labels, based on a given coronary artery model represented by a graph. The stages of the method are: (1) CAT tracking and detection; (2) artery skeleton and border estimation; (3) feature graph creation; and (iv) artery labeling by graph matching. The approximate CAT centerline and borders are extracted by recursive tracking based on circular template analysis. The accurate skeleton and borders of each CAT segment are computed, based on morphological homotopy modification and watershed transform. The approximate centerline and borders are used for constructing the artery segment enclosing area (ASEA), where the defined skeleton and border curves are considered as markers. Using the marked ASEA, an artery gradient image is constructed where all the ASEA pixels (except the skeleton ones) are assigned the gradient magnitude of the original image. The artery gradient image markers are imposed as its unique regional minima by the homotopy modification method, the watershed transform is used for extracting the artery segment borders, and the feature graph is updated. Finally, given the created feature graph and the known model graph, a graph matching algorithm assigns the appropriate labels to the extracted CAT using weighted maximal cliques on the association graph corresponding to the two given graphs. Experimental results using clinical digitized coronary angiograms are presented.

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.

N-Terminal Pro-Brain Natriuretic Peptide Levels Are Elevated in Patients with Acute Ischemic Stroke

Brain natriuretic peptide (BNP) is a counterregulatory hormone released by the ventricles of the heart. Its main actions are natriuresis and vasodilation. The authors studied N-terminal pro-brain natriuretic peptide (NT-proBNP) levels soon after an acute ischemic stroke. They compared plasma NT-proBNP concentrations in 30 patients with an acute ischemic stroke with those of 30 controls. The 2 groups were adjusted for age and gender, and there were no significant differences in vascular risk factors and left ventricular systolic and diastolic function. Venous samples were collected within the first 11.8 ±1.2 hours after the onset of symptoms and again on day 6. Brain computed tomography/magnetic resonance imaging (CT/MRI) was performed on the same days (day 0 and day 6) in order to assess the site (carotid or vertebrobasilar), cause (atherothrombotic, cardioembolic, or lacunar), and size (large, medium, or small) of the brain infarct. NT-proBNP levels were elevated in patients with acute stroke (129.9 ±9.9 fmol/mL) compared with the controls (90.8 ±6.3 fmol/mL, p<0.05). These levels remained elevated at day 6 (113.5 ±13.0 fmol/mL). NT-proBNP at admission was significantly higher in cardioembolic compared with atherothrombotic infarctions. There was no correlation between circulating NT-proBNP and stroke topography, infarct size, or severity as assessed by the National Institutes of Health Stroke Scale (NIHSS) at any of the 2 time points (admission and day 6). NT-proBNP levels were raised in patients with acute ischemic stroke; this effect persisted until day 6. The authors suggest that neurohumoral activation occurs in patients with acute ischemic stroke, either reflecting a counterbalancing vasodilating response to the cerebral ischemia or direct myocardial dysfunction.

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.

Wall shear stress gradient topography in the normal left coronary arterial tree: possible implications for atherogenesis

SUMMARY Objective: Wall shear stress gradient (WSSG) in vitro has shown its importance in atherogenesis, probably as a local modulator of endothelial gene expression.The purpose of this study is to numerically analyse the WSSG distribution over the normal human left coronary artery (LCA) tree. Research design and methods: A three-dimensional computer generated model of the LCA tree, based on an averaged human data set extracted from angiographies, was adopted for finite-element analysis. The LCA tree includes the left main coronary artery (LMCA), the left anterior descending (LAD), the left circumflex artery (LCxA) and their major branches. Results: In proximal LCA tree regions where atherosclerosis frequently occurs, low WSSG appears. At distal segments, the WSSG increases substantially due to increased velocity resulting from increased vessel tapering. Low WSSG occurs at bifurcations in regions opposite the flow dividers, which are anatomic sites predisposed for atherosclerotic development. Conclusions: This computational work determines, probably for the first time, the topography of the WSSG in the normal human LCA tree. Spatial WSSG differentiation indicates that low values of this parameter probably correlate to atherosclerosis localization. However, further studies are needed to clarify the role of WSSG in atherogenesis.

Coronary vessel perforation during balloon angioplasty: A case report

Coronary perforation can be managed with prolonged balloon inflations, covered stents, or embolization of the vessel. We report on a case of a balloon-induced perforation of the distal left anterior descending artery, that was sealed by injecting preclotted autologous blood through the balloon catheter lumen at the site of the perforation. The patency of the distal vessel was maintained.

Trimetazidine Administration Minimizes Myocardial Damage and Improves Left Ventricular Function after Percutaneous Coronary Intervention

Background and objectiveThe aim of this study was to evaluate whether the administration of trimetazidine, a piperazine derivative, to patients before and after percutaneous coronary intervention (PCI) minimizes the PCI-induced myocardial damage and improves left ventricular function 1 and 3 months after the procedure.MethodsFifty-two patients hospitalized for acute coronary syndromes (ACS) were included in this study. Patients were randomized into two groups: group A (trimetazidine group; n = 27) and group B (placebo group; n = 25). All patients received conventional antianginal therapy. In addition, group A patients received oral trimetazidine 20mg every 8 hours, starting 15 days before PCI and continuing for 3 months after the procedure. For each patient, serum troponin I and creatinine kinase (CK)-MB levels were measured before PCI, then at 6, 24, and 48 hours after the procedure; a 2D cardiac echocardiogram was performed before PCI and at 1 and 3 months after the procedure.ResultsTwenty-four hours after PCI, troponin I levels were >1 ng/mL in 7 of 27 patients (26%) of group A and 11 of 25 patients (44%) in group B. Fourty-eight hours after revascularization troponin levels remained elevated in 15% of patients in group A and in 32% of patients in group B. Twenty-two percent of patients in group A had CK-MB levels >5 ng/mL, 24 hours after PCI, compared with 40% of patients in group B; four patients of group A had high CK-MB levels prior to PCI procedure.Echocardiographic measurements before revascularization revealed that 11 of 27 patients (40%) in group A had an ejection fraction <50% versus 8 of 24 patients (33%) in group B. The number of patients with an ejection fraction <50% was significantly reduced in group A compared with group B at 1 and 3 months after PCI, i.e. 11 % versus 16% (p = 0.046) at 1 month and 4% versus 16% (p = 0.017) at 3 months.A significant improvement in regional wall motion was noted after treatment with trimetazidine compared with placebo. One month after PCI, inferior left ventricular (LV) wall hypokinesia had improved in 4 of 6 trimetazidine recipients and in 4 of 14 placebo recipients (p = 0.014, group A vs group B). After 3 months inferior wall hypokinesia improved in four patients in group A versus six patients in group (p = 0.05). Similarly, anterior LV wall motion improved in 3 of 11 patients in group A and in 1 of 6 patients in group B at 1 month. After 3 months anterior wall hypokinesia had improved in eight patients in group A and in two patients in group B (p = 0.04, group A vs group B).ConclusionThe metabolic agent trimetazidine appears to minimize myocardial reperfusion injury during PCI and improves global and regional wall motion at 1 and 3 months after PCI. This study was limited by small patient numbers and further studies are necessary to evaluate exact mechanisms of action and clinical implications of using trimetazidine in conjunction with PCI.

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.