Yiannis S. Chatzizisis

The syndrome of rhabdomyolysis: Complications and treatment

Rhabdomyolysis is a syndrome of skeletal muscle cell damage that leads to the release of toxic intracellular material into the systemic circulation. The pathogenesis of rhabdomyolysis is based on an increase in free ionized calcium in the cytoplasm. Its main complications include (a) acute renal failure, which is triggered by renal vasoconstriction and ischemia, (b) myoglobin cast formation in the distal convoluted tubules, and (c) direct renal toxic effect of myoglobin on the epithelial cells of proximal convoluted tubules. Other major complications include electrolyte disorders, such as hyperkalemia, which may cause cardiac arrhythmias, metabolic acidosis, hyperphosphatemia, early hypocalcemia, and late hypercalcemia. Compartmental syndrome and disseminated intravascular coagulopathy may also emerge. The management of myoglobinuric acute renal failure includes aggressive fluid administration to restore the hypovolemia and urine alkalization. The concomitant electrolyte and metabolic disorders should also be treated appropriately; hemodialysis should be considered when life-threatening hyperkalemia and metabolic acidosis exist. In the case of compartmental syndrome, it is important to monitor the intra-compartmental pressure and to perform fasciotomy, if required. When diagnosed early and if the appropriate treatment is initiated promptly, the complications of rhabdomyolysis are preventable and the syndrome has a good prognosis.

IMAGE ANALYSIS TECHNIQUES FOR AUTOMATED IVUS CONTOUR DETECTION

Intravascular ultrasound (IVUS) constitutes a valuable technique for the diagnosis of coronary atherosclerosis. The detection of lumen and media-adventitia borders in IVUS images represents a necessary step towards the reliable quantitative assessment of atherosclerosis. In this work, a fully automated technique for the detection of lumen and media-adventitia borders in IVUS images is presented. This comprises two different steps for contour initialization: one for each corresponding contour of interest and a procedure for the refinement of the detected contours. Intensity information, as well as the result of texture analysis, generated by means of a multilevel discrete wavelet frames decomposition, are used in two different techniques for contour initialization. For subsequently producing smooth contours, three techniques based on low-pass filtering and radial basis functions are introduced. The different combinations of the proposed methods are experimentally evaluated in large datasets of IVUS images derived from human coronary arteries. It is demonstrated that our proposed segmentation approaches can quickly and reliably perform automated segmentation of IVUS images.

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.

Predicting the Risk of Rupture of Abdominal Aortic Aneurysms by Utilizing Various Geometrical Parameters: Revisiting the Diameter Criterion

The authors estimated noninvasively the wall stress distribution for actual abdominal aortic aneurysms (AAAs) in vivo on a patient-to-patient basis and correlated the peak wall stress (PWS) with various geometrical parameters. They studied 39 patients (37 men, mean age 73.7 ± 8.2 years) with an intact AAA (mean diameter 6.3 ± 1.7 cm) undergoing preoperative evaluation with spiral computed tomography (CT). Real 3-dimensional AAA geometry was obtained from image processing. Wall stress was determined by using a finite-element analysis. The aorta was considered isotropic with linear material properties and was loaded with a static pressure of 120.0 mm Hg. Various geometrical parameters were used to characterize the AAAs. PWS and each of the geometrical characteristics were correlated by use of Pearsons rank correlation coefficients. PWS varied from 10.2 to 65.8 N/cm2 (mean value 37.1 ± 9.9 N/cm2). Among the geometrical parameters, the PWS was well correlated with the mean centerline curvature, the maximum centerline curvature, and the maximum centerline torsion of the AAAs. The correlation of PWS with maximum diameter was nonsignificant. Multiple regression analysis revealed that the mean centerline curvature of the AAA was the only significant predictor of PWS and subsequent rupture risk. This noninvasive computational approach showed that geometrical parameters other than the maximum diameter are better indicators of AAA rupture.

Common cardiovascular medications in cancer therapeutics

Cardiac glycosides, statins, β-blockers, angiotensin-I converting enzyme inhibitors (ACEIs), and angiotensin II type 1 receptor blockers (ARBs) are widely used cardiovascular medications with pleiotropic properties. Many of these medications have been investigated in other diseases, including cancer. Cardiac glycosides and statins have advanced to clinical trial testing in cancer therapeutics, with variable success. Early observations in breast cancer were consistent with a more benign histologic phenotype among women taking digitalis compared to their counterparts who did not receive cardiac glycosides. Cardiac glycosides can induce apoptosis in cancer cells through various mechanisms and sensitize them to the effects of antitumor therapy. By blocking the generation of prenyl units, statins impair prenylation, an important posttranslational modification of proteins whose function depends on membrane anchoring. Statins also impair protein folding and N-glycosylation and inhibit the upregulation of cholesterol synthesis associated with chemotherapy resistance. Stress and catecholamine release promote tumor growth and angiogenesis, effects that can be mitigated by β-blockers. Components of the renin-angiotensin-aldosterone system are expressed in various cancers and are involved in carcinogenesis and tumor progression. Angiotensin II has potent mitogenic and angiogenic properties that can be blocked with ACEIs and ARBs. Although it is unclear whether the promising preclinical activity of many cardiovascular medications has clinically meaningful implications beyond the benefit in cardiovascular morbidity and mortality, the prevention or improvement of prognosis of common malignancies with medications known to reduce cardiovascular morbidity and mortality is encouraging and deserves further clinical investigation.

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±17.1u2009mm) 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.

Drug-eluting stent restenosis: Effect of drug type, release kinetics, hemodynamics and coating strategy

Restenosis following stent implantation diminishes the procedures efficacy influencing long-term clinical outcomes. Stent-based drug delivery emerged a decade ago as an effective means of reducing neointimal hyperplasia by providing localized pharmacotherapy during the acute phase of the stent-induced injury and the ensuing pathobiological mechanisms. However, drug-eluting stent (DES) restenosis may still occur especially when stents are used in complex anatomical and clinical scenarios. A DES consists of an intravascular metallic frame and carriers which allow controlled release of active pharmaceutical agents; all these components are critical in determining drug distribution locally and thus anti-restenotic efficacy. Furthermore, dynamic flow phenomena characterizing the vascular environment, and shear stress distribution, are greatly influenced by stent implantation and play a significant role in drug deposition and bioavailability within local vascular tissue. In this review, we discuss the performance of DES and the interaction of the different DES components with the hemodynamic milieu emphasizing on the inhibition of clinical restenosis.

Effect of HMG-CoA reductase inhibitors on vascular cell apoptosis: Beneficial or detrimental?

Vascular cell apoptosis, an active form of programmed cell death, plays an integral role in atherosclerosis and in-stent restenosis after angioplasty, thus promoting the precipitation of acute cardiovascular events. Beyond their cholesterol-lowering effects, HMG-CoA reductase inhibitors, or statins, have been persistently reported to influence the apoptotic process. In this review we discuss the effect of statin treatment on vascular cell apoptosis, and therefore on atherosclerosis development, plaque rupture and in-stent restenosis, based on the results of up-to-date experimental and clinical studies. Lipophilic statins have been shown to induce apoptosis in a variety of cell types, including vascular smooth muscle cells and endothelial cells, whereas hydrophilic statins (rosuvastatin and pravastatin) have not. The clinical importance of statin induced apoptosis remains controversial, as it may blunt vascular wall thickening in the early stages of atherosclerosis or reduce the neointimal response to injury on the one hand, but on the other hand it may also promote destabilization of vulnerable plaques precipitating acute cardiovascular events. Current data support the initiation of statin treatment early enough to inhibit both the formation of atherosclerotic plaques (primary prevention) and in-stent restenosis (secondary prevention).

Flow and atherosclerosis in coronary bifurcations

Coronary bifurcations are among the most frequent sites affected by atherosclerosis. In these regions, complex haemodynamic conditions prevail and local flow disturbances dictate the localisation and progression of atheroma. Endothelial shear stress (ESS) is the main flow-related factor affecting the distribution of atherosclerosis in a bifurcation. Plaques are more prevalent in low ESS areas, such as the lateral walls of the main vessel and side branches, while they are less common in the flow divider or carina, which is characterised by high ESS. However, the carina is not free of atheroma and is affected in up to one third of cases, but never in isolation. Lesions in the carina are likely to develop at a later stage of atherosclerosis, as result of circumferential expansion of plaques from the lateral wall. Pulsatile flow augments the local atherogenic environment by inducing low and oscillatory ESS. The geometrical configuration is also important as increased curvature and wide angles between the side branches of the bifurcation intensify flow perturbations, and highly curved segments show low ESS in the inner aspect of curvatures. Further research on the flow conditions which determine the initiation and progression of atherosclerosis in bifurcations will allow for more efficient prevention and management strategies.

Association of reduced zinc status with angiographically severe coronary atherosclerosis: a pilot study.

In vitro studies attribute antiatherogenic and insulin-like properties to zinc (Zn). However, only a few conflicting clinical data exist concerning the relationship between Zn and coronary artery disease (CAD) as well as glycemic indices. We studied 72 patients without prior history of myocardial infarction or revascularization procedures, who underwent coronary angiography for evaluation of chest pain. Coronary artery disease severity was estimated using 3 angiographic scores. Zn in serum and 24-hour urine, as well as serum Zn/24-hour urine Zn ratio were determined. Serum Zn was not associated with CAD prevalence and severity. However, urinary Zn loss was significantly higher among patients with CAD and showed a positive association with CAD severity. Serum Zn/24-hour urine Zn ratio was inversely associated with CAD, as well as with diabetes mellitus prevalence, fasting glucose, and glycated hemoglobin levels. Low serum Zn/24-hour urine Zn ratio is associated with angiographically severe atherosclerosis and impaired glucose homeostasis.