Lampros Michalis

Coronary stents have revolutionized the treatment of coronary artery disease. Improvement in clinical outcomes requires detailed evaluation of the performance of stent biomechanics and the effectiveness as well as safety of biomaterials aiming at optimization of endovascular devices. Stents need to harmonize the hemodynamic environment and promote beneficial vessel healing processes with decreased thrombogenicity. Stent design variables and expansion properties are critical for vessel scaffolding. Drug-elution from stents, can help inhibit in-stent restenosis, but adds further complexity as drug release kinetics and coating formulations can dominate tissue responses. Biodegradable and bioabsorbable stents go one step further providing complete absorption over time governed by corrosion and erosion mechanisms. The advances in computing power and computational methods have enabled the application of numerical simulations and the in silico evaluation of the performance of stent devices...

Cardiovascular disease (CVD) is the leading cause of death in predialysis chronic kidney disease (CKD) and dialysis patients as well as in renal transplant recipients (RTRs). Left ventricular hypertrophy (LVH) starts early during the course of CKD and is a strong predictor of CVD in this population. Regression of LVH after a successful renal transplantation remains a debatable issue among investigators, whereas there is little data comparing echocardiographic measurements between patients with predialysis CKD and RTRs. The aim of this study was to compare echocardiographic measurements of LV structure and function between predialysis CKD patients and RTRs of similar renal function level. We conducted a case control study with individual (1:2) matching from the Renal Transplant and the predialysis CKD Outpatient Clinic. For each of the 36 RTRs, two matched for gender, age and estimated glomerular filtration rate (eGFR) predialysis CKD outpatients (72 patients) were included. All pati...

The management of abdominal aortic aneurysm with endovascular repair (EVAR) requires extended exposure to ionizing radiation, before, during and after the intervention. The aim of this study was to quantify the radiological risks to patients and operating team, and to develop strategies to assess and reduce them. EVAR was carried out in 97 patients using either a low-power mobile or a high-power stationary fluoroscopic unit. Empirically determined relationships between the indicated dose area product (DAP) and peak skin dose, obtained by direct in vivo dosimetry in a subgroup of patients, were used to predict the peak skin dose. Individual worker monitoring was used to assess personnel radiological burden. The probability for radiation induced biological effects due to the repair itself and the preoperative and life-long surveillance, as carried out, was about 2.4 10-3. The peak skin dose of repairs was linearly correlated with the DAP and did not exceed 1.2 Gy. The collective effec...

We investigated the effects of coronary rotational atherectomy (PTCRA) on plasma levels of endothelin-1 (ET-1), atrial natriuretic peptide (ANP), and cyclic adenosine monophosphate (cAMP). We studied 14 patients undergoing PTCRA and compared them with 14 patients undergoing plain balloon angioplasty. Blood samples were taken from the femoral vein at baseline, after the end of the atherectomy, after the first balloon inflation, after the end of the procedure, and 4 hours later. ET-1 increased in the angioplasty group from 6.3 +/- 3.2 pmol/L at baseline to 8.5 +/- 3.9 pmol/L at the end of the procedure (F = 3.83, P = .02), whereas it did not change in the PTCRA group. ANP increased in the PTCRA group from 78.1 +/- 15.7 pmol/L at baseline to 89.7 +/- 24.0 pmol/L at the end of the procedure (F = 6.75, P = .0001), whereas it did not change in the angioplasty group. cAMP decreased in the PTCRA group, whereas it did not change in the angioplasty group. In conclusion, ET-1 increases less, A...

Macrophages that uptake modified lipoproteins are activated and may initially behave as endotoxin-stimulated macrophages. This study was undertaken in order to determine whether signal transduction pathways controlling endotoxin-mediated activation may also influence the lipoprotein-mediated activation of macrophages. Rat peritoneal macrophages were incubated for 16 hours with acetylated low-density lipoprotein and certain agents that modify the phosphoinositide/calcium- and cyclic AMP-mediated pathways, such as 2-[4-morpholinyl]-8-phenyl-1[4H]-benzopyran-4-one (LY-294002), autocamtide 2-related inhibitory peptide (AIP), N-(2-[p-bromocinnamylamino]-ethyl)-5-isoquinolinesulfonamide hydrochloride (H-89) and actinomycin D. The production of nitric oxide and the intracellular and extracellular activities of acid phosphatase were assayed. Macrophages incubated with acetylated low-density lipoprotein showed an increased production of nitric oxide and intracellular acid phosphatase activit...

The purpose of this article is to report the initial experience with endovascular repair of thoracic aortic disease in a single tertiary vascular unit in northwestern Greece. Between 2003 and 2005, 16 patients were treated with endovascular techniques for various pathologies of the descending thoracic aorta. Twelve patients were treated electively and four emergently. Operative and follow-up data for a mean time of 18.4 months were retrospectively collected and analyzed. Primary technical success was obtained in 14 (87.5%) cases. No early or late deaths occurred, and there was no major operation-related complication. No paraplegia was observed in our patients. Stent graft-related complications occurred in 18.75% (one type 2 and two type 3 endoleaks), but they all had a favorable outcome. No further problems have been reported in any of our patients. Endovascular stent graft repair for diseases of the thoracic aorta seems to be a promising alternative to open surgery, especially for ...

During reperfusion of ischemic myocardium, oxygen-derived free radicals are produced and can cause deleterious effects, known as reperfusion injury. We aimed to determine if a combination of the antioxidant ascorbic acid and an iron-chelating agent desferrioxamine, which reduces the production of the hydroxyl radical via ferrum-catalyzed reactions, can exert a protective action against reperfusion injury. Twenty-two young male farm pigs were anesthetized and subjected to 45 mins of ischemia and 3 and a half hours of reperfusion, in the left circumflex coronary artery territory, via the inflation and deflation of an angioplasty balloon. Animals were randomly assigned to receive either an intravenous infusion of 100 mg/ kg ascorbic acid and 60 mg/kg desferrioxamine (treatment group, TG) or an equal amount of normal saline (control group, CG). The I/R ratio, the ratio of the infarcted (necrotic) zone (I) to the myocardial area at risk (R) after 3 and a half hours of reperfusion, was ca...

Despite the exposure of the entire vasculature to the atherogenic effects of systemic risk factors, atherosclerotic plaques preferentially develop at sites with disturbed flow. This study aimed at exploring in vivo the relationship between local endothelial shear stress (ESS) and coronary plaque characteristics in humans using computational fluid dynamics and frequency-domain optical coherence tomography. Three-dimensional coronary artery reconstruction was performed in 21 patients (24 arteries) presenting with acute coronary syndrome using frequency-domain optical coherence tomography and coronary angiography. Each coronary artery was divided into sequential 3-mm segments and analyzed for the assessment of local ESS and plaque characteristics. A total of 146 nonculprit segments were evaluated. Compared with segments with higher ESS [≥1 Pascal (Pa)], those with low ESS (<1 Pa) showed higher prevalence of lipid-rich plaques (37.5% versus 20.0%; P=0.019) and thin-cap fibroatheroma ...

To develop a simplified approach of virtual functional assessment of coronary stenosis from routine angiographic data and test it against fractional flow reserve using a pressure wire (wire-FFR). Three-dimensional quantitative coronary angiography (3D-QCA) was performed in 139 vessels (120 patients) with intermediate lesions assessed by wire-FFR (reference standard: ≤0.80). The 3D-QCA models were processed with computational fluid dynamics (CFD) to calculate the lesion-specific pressure gradient (ΔP) and construct the ΔP-flow curve, from which the virtual functional assessment index (vFAI) was derived. The discriminatory power of vFAI for ischaemia- producing lesions was high (area under the receiver operator characteristic curve [AUC]: 92% [95% CI: 86-96%]). Diagnostic accuracy, sensitivity and specificity for the optimal vFAI cut-point (≤0.82) were 88%, 90% and 86%, respectively. Virtual-FAI demonstrated superior discrimination against 3D-QCA-derived % area stenosis (AUC: 78% [95% CI: 70- 84%]; p<0.0001 compared to vFAI). There was a close correlation (r=0.78, p<0.0001) and agreement of vFAI compared to wire-FFR (mean difference: -0.0039±0.085, p=0.59). We developed a fast and simple CFD-powered virtual haemodynamic assessment model using only routine angiography and without requiring any invasive physiology measurements/hyperaemia induction. Virtual-FAI showed a high diagnostic performance and incremental value to QCA for predicting wire-FFR; this "less invasive" approach could have important implications for patient management and cost.

Coronary angioplasty was successfully carried out with an activated guidewire technique in 33 of 47 patients who had undergone a failed attempt at conventional angioplasty for the treatment of chronic coronary artery occlusion. 80% of these occlusions were stump-like occlusions. This technique involves the attachment of a hand-held battery-driven motorised device to standard angioplasty equipment and can be used at any time during the procedure. The device generates complex vibratory movement in the guidewire to facilitate crossing of occluded vessels.

The platelet integrin receptor alpha(IIb)beta(3) plays a critical role in thrombosis. We have shown previously that the octapeptide YMESRADR, corresponding to sequences 313 to 320 of the human alpha(IIb) subunit, inhibits human platelet activation and fibrinogen binding to alpha(IIb)beta(3), possibly interacting with the ligand. We investigated the effect of YMESRADR on electrically induced carotid artery thrombosis in New Zealand white rabbits. Peptide was administered via the femoral vein, starting 60 min before and continuing for 90 min after the electrical stimulation. Carotid blood flow was monitored for 90 min after the electrical stimulation. The peptide effects on platelet aggregation, in vitro and ex vivo, and on various coagulation, bleeding, and hemostatic parameters were evaluated. YMESRADR significantly inhibited rabbit platelet aggregation in vitro in a dose-dependent manner. It is important that peptide administration in vivo, at doses ranging from 3 to 15 mg/kg, prolonged the duration of the patency of the carotid artery, and no artery occlusion was observed until the end of the study (90 min after electrical stimulation). Furthermore, YMESRADR administration reduced platelet aggregation ex vivo and thrombus weight; however, these reductions reached statistical significance, compared with the control group, at the peptide doses of 12 and 15 mg/kg. YMESRADR did not affect any coagulation parameter studied and the hemostatic response observed in control animals. Thus, YMESRADR represents a novel antiplatelet agent that can inhibit thrombus formation effectively and carotid artery occlusion without causing hemorrhagic complications in a rabbit model of arterial thrombosis.

The need for antiarrhythmic drugs (AAD) after a first episode of atrial fibrillation (AF) is determined by the probability of recurrence. The aim of this study was to asses the probability of relapse and the predictors of recurrence in patients with idiopathic AF. A cohort of 98 consecutive patients younger than 65 years admitted at the emergency room because of an episode of symptomatic idiopathic (lone) AF was included in this study. On admission, a complete medical history was taken, and an echocardiogram and 24-h Holter monitoring were performed. Patients were seen at 3 and 6 months after the index episode. There were 35 (35.7%) patients with a new-onset AF episode and 63 (64.3%) with a recurrent AF episode. A majority of them were male (71%), with a mean age of 48+/-11 years. Patients with new-onset AF episodes did not receive AAD. At 6 month follow-up, 57% of all patients suffered at least one symptomatic AF relapse. Patients with AF relapses belong more often to the recurrent group vs. new-onset group of AF (65.1 vs. 34.9%, respectively, P = 0.03); they had larger LA diameter indexed for body surface area (BSA) (22.6+/-3.7 vs. 19.8+/-3.2 mm/m(2), P = 0.001), larger left ventricular end-systolic diameter (18.4+/-3.1 vs. 17.2+/-2.5 mm/m(2), P = 0.05) and a tendency towards a higher proportion of atrial tachycardia runs on Holter (66.7 vs. 50%, P = 0.09). Logistic regression analysis showed that the presence of previous episodes of AF (OR: 3.2; 95% CI; 1.0-8.0, P = 0.04) and a larger anteroposterior LA diameter (OR: 1.3; 95% CI; 1.1-1.6, P = 0.001) were independent predictors of AF recurrences at 6 months. The recurrence rate in lone AF patients is high. The presence of previous episodes and a mildly enlarged anteroposterior LA diameter increase the probability of relapse of lone AF.

The incidence of cardiovascular disease is low in healthy premenopausal women and increases with age especially after the menopause; this difference has been attributed to the loss of endogenous estrogen. Atherosclerosis is a chronic inflammatory condition of the vascular wall that may result in an acute clinical event by inducing plaque rupture/erosion leading to thrombosis. A growing body of evidence suggests that the spectrum of the effects of estrogen on vascular pathophysiology is complex and may depend largely on the state of vascular pathology. In relatively healthy vessels, estrogen prevents the development and progression of atherosclerotic lesions, while in the presence of established atherosclerotic plaques, estrogen fails to inhibit the progression of atherosclerosis or may even trigger cardiovascular events. The mechanisms responsible for this are not yet fully elucidated. It is possible that postmenopausal estrogen/progestogen therapy may be beneficial in perimenopausal and early menopausal women prior to atherosclerotic plaque formation, but it may not prevent progression of atherosclerotic plaques and acute cardiovascular events in older women with cardiovascular risk factors or women with established atherosclerosis. Various formulations, doses and routes of hormone therapy administration as well as the genetic background of women should also be taken into account when considering the benefit-to-risk ratio of hormone therapy use.

Low folate levels are related to increased risk for coronary artery disease in humans, while experimental work has shown that folate deficiency is thrombogenic. We hypothesized that relatively low folate levels are related to the development of acute coronary syndromes in patients with previously stable coronary artery disease. One hundred and forty-one men were studied: 53 consecutive patients with acute coronary syndromes, 41 with stable coronary artery disease and 47 control participants. Known clinical and lipid risk factors were identified in all subjects and in addition plasma B12, plasma and red cell folate levels were measured. Red cell folate levels were significantly lower in patients with acute coronary syndromes (510+/-178 nmol/l) than in both stable coronary artery disease patients (638+/-264 nmol/l, P< 0.005) and controls (615+/-193 nmol/l, P< 0.05 respectively). Plasma folate and B12 levels were similar in all three groups. Multiple logistic regression analysis identified red cell folate levels as the only independent predictor of acute coronary events in the whole population of patients with known coronary artery disease and in the subgroup of non-smokers (P=0.010 and P=0.031). The present study suggests that relatively low red cell folate levels are associated with acute coronary syndromes and are an independent predictor of acute coronary events.

Increased levels of plasma brain natriuretic peptide (BNP) are observed in patients with congestive heart failure, hypertension, left ventricular hypertrophy, and acute myocardial infarction. However, there are no data on serial changes in plasma levels of BNP in patients undergoing coronary angioplasty. The study was undertaken to examine plasma concentrations of BNP together with those of atrial natriuretic peptide (ANP) in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). Plasma concentrations of BNP and ANP were examined in 13 patients with stable angina pectoris and good left ventricular function undergoing PTCA. Blood samples were taken from the femoral vein at baseline, after the first balloon inflation, after the end of the procedure, and 4 h thereafter. Plasma BNP levels were 14 +/- 4 at baseline, 22 +/- 10 after the first balloon inflation, 28 +/- 12 at the end of the procedure, and 15 +/- 4 pgr/ml 4 h thereafter (F = 13.05, p < 0.00001). Plasma ANP levels were 80 +/- 15, 86 +/- 14, 90 +/- 24, and 75 +/- 6 fmol/l (F = 5.95, p = 0.002), respectively. The increase of BNP at the end of the procedure was related to the increase of ANP (r = 0.78, p = 0.002). Plasma BNP levels increase acutely and much more prominently than those of plasma ANP during coronary angioplasty; however, plasma BNP levels return to baseline values shortly after the end of the procedure.

Since increases in blood pressure may be effectively controlled by hydraulic feedback by reducing the venous return through the inferior vena cava in proportion to the blood pressure this principle was applied using a totally implantable extravascular system consisting of a periaortic blood pressure sensor and a pericaval cuff around the inferior vena cava. The two cuffs were supported externally by hard skeletons, filled with water, and connected directly to each other. The two devices were tested separately and together in 10 anaesthetised mongrel dogs with normal and high blood pressure induced by a metaraminol infusion. With the periaortic sensor an increase in blood pressure of 100 mmHg caused a mean(SD) isotonic volume displacement of 0.41(0.11) ml, and an increase in the pericaval balloon energy content of 100 ml.mmHg-1 caused a fall in blood pressure of 37.8(18.3)%. The whole system prevented an excessive rise in blood pressure when metaraminol was infused, with a feedback gain of about 2.8. It is concluded that blood pressure can be maintained at acceptable levels despite strong hypertensive stimuli, by this system, without additional treatment with drugs or an external energy source. The system is totally implantable and is applied extravascularly so that no anticoagulation is needed.

To investigate the influence that measurement of balloon volume as a controlled variable in addition to balloon pressure has on the outcome of balloon angioplasty in an experimental model. One hundred and three segments of explanted normal porcine carotid arteries were obtained. Five were used as controls, and the remaining 98 were subjected to balloon angioplasty with simultaneous measurement of balloon volume and pressure. These arteries were randomized into two groups. In one group the endpoint of the angioplasty was determined by balloon pressure (pressure-limited group, PLG) and in the other group by balloon volume (volume-limited group, VLG). Pressure/volume curves for each procedure were constructed by continuous measurement of both parameters by a purpose-designed computer-controlled inflation device. The diameter of each arterial segment was measured by intravascular ultrasound (IVUS) and the ratio of the inflated balloon to arterial diameter calculated. Arterial appearances after angioplasty were recorded using IVUS. The balloon volumes measured at the endpoint of angioplasty were significantly smaller in the PLG compared with the VLG (p < 0.001). Three types of pressure/volume curves were identified: A, B, and C. In the type A curves, IVUS identified fissures in 28% (17/60) and the examination was normal in 72% (43/60). In the type B curves, IVUS identified fissures in 44% (4/9), dissections in 22% (2/9), and the examination was normal in 33% (3/9). In the type C curves, IVUS identified fissures in 44% (4/9) and dissection in 56% (5/9) with no normal examinations. In undamaged arterial segments a very high correlation was achieved between balloon volume and the balloon/artery ratio (Pearson correlation = -0.979, R(2) = 0.957, p < 0.0001, n = 27). The measurement of pressure and volume during angioplasty enabled the construction of pressure/volume curves that showed deviations from the curves obtained in air. The balloon volume results, and significant deviation of the curve shape from the control curve shape, predicted vessel damage, which was confirmed by the IVUS appearance of the vessel after angioplasty. When pressure was used as the endpoint of balloon inflation the balloons were significantly underdilated compared with the manufacturer's nominal sizes. These data indicate that monitoring of pressure and volume during angioplasty may provide an alternative method of predicting vessel damage.

The aim of this work was to evaluate a new semi-automated intravascular ultrasound (IVUS) border detection method. The method was used to identify the lumen and the external elastic membrane or the borders of stents in 80 IVUS images, randomly selected from 10 consecutive human coronary arteries. These semi-automated results were compared with observations of two experts. Several indices in each case were obtained in order fully to evaluate the method. The time required for identification of the borders was also recorded. The interobserver variability of the method ranged from 1.21% to 5.61%, the correlation coefficient from 0.98 to 0.99, the slope was close to unity (0.94-1.03), the y intercept close to zero and the Williams index value was close to unity (range 0.67-0.91). The time (mean+/-SD) required for the method to identify the borders of the different vessel layers for the whole IVUS sequence was 5.2+/-0.2 min. The results demonstrate that the method is reliable and capable of identifying rapidly and accurately the different vessel layers depicted in IVUS images.

Chronic inflammatory diseases in adults have been associated with increased cardiovascular risk and impaired vascular function. We aimed to assess the presence of early vascular dysfunction in patients with juvenile idiopathic arthritis (JIA) and investigate the role of inherent inflammatory process of JIA in vascular health. Thirty patients with JIA (age range 7-18 years) were compared to 33 age- and sex-matched controls. Endothelial function (brachial artery flow-mediated dilation [FMD]), carotid intima-media thickness (IMT), and arterial stiffness were examined. Endothelial inflammation was assessed by intercellular adhesion molecule 1 (ICAM-1) and P-selectin measurements. Patients with JIA showed decreased FMD compared to controls (P = 0.001), independent of age (P = 0.9 among age subgroups). Baseline differences in erythrocyte sedimentation rate, ICAM-1, and glucose between the 2 groups accounted for the difference in FMD. The presence of systemic JIA was associated with greater IMT compared to patients with oligoarticular disease, polyarticular disease, or controls (P = 0.014, P = 0.069, and P = 0.046, respectively). The difference in IMT between systemic versus oligoarticular/polyarticular JIA was attributed to the following risk factors: age, body mass index, blood pressure, disease activity, and corticosteroids use. There were no differences in arterial stiffness indices between JIA patients and controls or between patients with systemic versus nonsystemic disease. Endothelial function is impaired in patients with JIA at a very young age, while IMT is increased only in the presence of systemic JIA. Vascular dysfunction may be partly attributed to the effects of disease-related characteristics (inflammation, disease activity, and medications).

Coronary artery ectasia (CAE) is an uncommon form of coronary artery disease. It has been reported in association with a variety of pathological conditions, such as isolated congenital heart disease and Kawasaki disease. CAE is more relevant in young adults with multiple predisposing risk factors, especially familial hypercholesterolemia, and is usually considered a form of atherosclerotic coronary artery disease. A case of CAE is reported with familial hypercholesterolemia and diffuse ectasia of the coronary vessels in association with anomalous origin of the left circumflex coronary artery, which lacked ectatic segments. This combination has not been reported previously.

Optical Coherence Tomography (OCT) is a new invasive technology for performing high-resolution cross-sectional imaging of the coronary arteries. In OCT images only Calcified plaque (CA) components can be accurately depicted as light penetrates hard tissue. In this work we present an automated method for detecting CA in OCT images. The method is fully automated as no user intervention is needed and includes three steps. In the first step the region between the lumen and the maximum penetration depth of OCT from the lumen border is determined. In the second step the region is classified into 3 clusters using the K-means algorithm. CA is identified using the results of k-means. The method was validated using experts' annotations on 27 images. The sensitivity of the method is 83% with Positive predictive value (PVV) 74 %.