Lambros K. Michalis

Serum Lipoprotein(a) Concentrations and Apolipoprotein(a) Isoforms: Association with the Severity of Clinical Presentation in Patients with Coronary Heart Disease:

Objective The aim of this study was to investigate the possible associations between lipoprotein(a) [Lp(a)] concentrations or apolipoprotein(a) isoforms and the mode of clinical presentation of coronary heart disease (CHD) (acute thrombotic event or not). Methods A total of 131 CHD patients and 71 age- and gender-matched individuals without known CAD (free of symptoms of heart disease) were enrolled in the study. CHD patients were classified into patients with a history of an acute coronary syndrome (ACS, n=94) and patients with stable angina (SA, n=37). Lp(a) levels were measured with an ELISA method, whereas apolipoprotein(a) isoform analysis was performed (in all patients and 33 controls) by electrophoresis in 1.5% SDS-agarose gels followed by immunoblotting. Isoform size was expressed as the number of kringle 4 (K4) repeats. Results ACS patients had higher Lp(a) plasma levels [21.9 (0.8–84.1) mg/dl] and a greater proportion of elevated (≥ 30 mg/dl) Lp(a) concentrations (25.5%) compared with SA patients [9.2 (0.8–50.5) mg/dl, P < 0.01 and 10.8%, P < 0.05] and controls [8.0 (0.8–55.0) mg/dl, P < 0.01 and 11.2%, P < 0.05], while there were no differences between SA patients and controls. The median apolipoprotein(a)-isoform size was 26 K4. In 17 (10%) patients we could not detect any apolipoprotein(a) isoform bands by immunoblotting. ACS patients had a higher proportion of isoforms < 26 K4 (low molecular weight) than SA patients (56/85 vs. 12/33, P < 0.005) and controls (10/29, P < 0.005). Conclusions CAD patients with a history of ACS have higher Lp(a) plasma levels and a significantly higher proportion of low molecular weight apolipoprotein(a) isoforms compared with patients with SA or to controls.

Alarming atrioventricular block and mitral valve prolapse in the Kearns–Sayre syndrome

Kearns-Sayre syndrome (KSS) is a multisystem mitochondrial disorder characterized by the invariant triad: onset before 20, progressive external ophthalmoplegia and pigmentary retinal degeneration, plus at least one of the following: complete (or not) heart block, cereberal dysfunction and CSF protein above 100 mg/dl. Autopsies from patients with KSS revealed widespread tissue distribution mtDNA deletions. These deletions result in significantly lower activities of the enzymes of the respiratory chain. The same deletion of mitochondrial DNA present in skeletal muscle is found in myocardial tissue. An 18-year-old girl diagnosed with the KSS was admitted to our hospital because of an upper respiratory tract infection and dysphagia. ECG showed cardiac conduction defects. The patient had no history of syncope. At her surface ECG there was a complete RBBB (QRS duration approximately 130 ms), a clockwise rotation with an axis of approximately 90 degrees and a slight QT prolongation (420 ms). Echocardiography showed prolapse with thickening and degeneration of both mitral valve leaflets but without mitral regurgitation. The patient was started on a diet rich in potassium and pharmaceutical therapy with magnesium oxide (240 mg of elemental Mg p.o. per day), 1 g of calcium carbonate t.i.d., vitamin D (calcitriol 0.25 microg p.o. per day) and coenzyme Q(10) 100 mg daily and discharged 6 days later with slightly improved biochemical profile but apparent clinical improvement. Urgent pacemaker implantation was decided but unfortunately the patient died due to acute cardiac arrest 10 days later.

Effect of acute hypertension on the cardiac rhythm. Experimental observations.

An acute increase in blood pressure (BP) may be associated with the genesis of ventricular ectopy. Fourteen anesthetized dogs were examined to find out whether the critical pressure that causes an arrhythmia may be an index of the tendency of the myocardium to generate ectopic rhythms. An acute change in BP was produced 321 times using an arterial pressure reservoir or aortic obstruction or a metaraminol infusion or, inversely, arterial bleeding. Each time the BP was increased, cardiac arrhythmias appeared and each time the BP was decreased the cardiac arrhythmias disappeared. The most common type of arrhythmia was ventricular ectopy (123/167 acute BP increases), usually in a form of bigeminy. The next most common rhythm disturbance was atrioventricular block (32/167 acute BP increases), especially when a constant rate was achieved by atrial pacing. The BP above which an arrhythmia appeared varied greatly among different animals (189.0 +/- 55.1 mmHg, means +/- SD). It was significantly (p less than 0.01) reduced (-29.0 +/- 17.1 mmHg) following coronary ligation and significantly (p less than 0.05) raised (+/- 41.6 +/- 38.7 mmHg) following lidocaine administration. The incidence of ventricular ectopy on increasing the BP was significantly higher at low heart rates in ten experiments, lower in two and not significantly different in 14. The incidence of premature ventricular complexes, the degree of atrioventricular block and the PR interval in first-degree atrioventricular block, whenever these rhythm disorders appeared, were a function of the BP level. It is concluded that an acute increase in BP may cause rhythm disturbances, usually in the form of ventricular ectopy and/or atrioventricular block.(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet aggregatory response to platelet activating factor (PAF), ex vivo, and PAF-acetylhydrolase activity in patients with unstable angina: effect of c7E3 Fab (abciximab) therapy.

OBJECTIVE Platelet activation and aggregation is a dominant feature in the pathophysiology of unstable angina. The final step of platelet aggregation is mediated through the platelet integrin glycoprotein IIb/IIIa (GP IIb/IIIa), while abciximab (ReoPro) is one of the most potent inhibitors of this receptor. Platelet-activating factor (PAF) is a potent platelet agonist which is degraded and inactivated by PAF-acetylhydrolase (PAF-AH). The plasma form of PAF-AH is associated with lipoproteins. We studied the platelet response to the aggregatory effect of PAF, ex vivo, in relation to the plasma PAF-AH activity in 32 patients with unstable angina, as well as the effect of abciximab therapy on the above parameters. METHODS Thirty two patients with unstable angina and 25 sex- and age-matched healthy controls participated in the study. On the day of admission (day 1) 17 patients received a bolus of abciximab (0.25 mg/kg) followed by a 12-h infusion (10 micrograms/min). Platelet aggregation to both PAF and ADP, in platelet rich plasma, was successively studied in both patients receiving abciximab or remaining untreated. The plasma and HDL-associated PAF-AH activity was also determined at the same times. RESULTS In the untreated patients, the PAF EC50 values were significantly lower on the day of admission, whereas the maximal percentage of aggregation was significantly higher compared to controls (p < 0.01 for both comparisons). Similar behaviour of the platelets was observed in the aggregatory effect of ADP. This aggregatory response was not significantly altered 4 days, 7 days or 1 month afterwards. In the 17 patients who received abciximab, platelet aggregation to both PAF and ADP was inhibited by 90 +/- 5 and 96 +/- 3%, respectively, 1 h after bolus. At 2 and 3 days after treatment, platelet aggregation to both agonists was significantly recovered being similar to controls. However, it was fully restored 6 days after bolus, still being significantly higher compared to controls (p < 0.01 for PAF and p < 0.003 for ADP). The total plasma PAF-AH activity in both patient groups was not different from that of controls, whereas the HDL-associated PAF-AH activity was significantly lower. The total plasma or HDL-associated enzyme activity was not altered at any time interval studied, and it was not influenced by abciximab. CONCLUSIONS The increased aggregatory response of platelets to PAF and the low plasma levels of HDL-cholesterol and HDL-associated PAF-AH activity in patients with unstable angina may contribute to the severe atherosclerosis and to acute thrombosis found in these patients. Abciximab therapy may protect platelets from PAF action in vivo the first days after drug administration, but it fails to permanently restore the enhanced aggregatory response observed.

Modeling stent deployment in realistic arterial segment geometries: The effect of the plaque composition

Stents are medical devices used in cardiovascular intervention for unblocking the diseased arteries and restoring blood flow. During stent implantation the deformation of the arterial wall as well as the resulted stresses caused in the arterial morphology are studied. In this paper we study the effect of the composition of the atherosclerotic plaque during the stent deployment procedure, using Finite Element modeling. The stenting procedure is simulated for two different cases; in the first the presence of the plaque is ignored whereas in the second a three dimensional (3D) stiff calcified plaque is located in the stenotic area of the artery. Results indicate that in the second case the von Mises stresses in the arterial wall are higher than the stresses occurred in the first case. In addition, the distribution of the arterial von Mises stress depends on the plaque composition.

Quantification of the effect of Percutaneous Coronary Angioplasty on a stenosed Right Coronary Artery

Atherosclerosis is the most prevalent cardiovascular disease which affects millions of people globally each year. The development of atheroma is directly connected to the interaction of blood flow with the arterial wall. Therefore, the modeling of this interaction is of critical importance for the study of arterial blood flow mechanics and the progression of atherosclerosis. In this study, we use a patient-specific 3-dimensional model of a stenosed Right Coronary Artery (RCA). A revascularization procedure (Percutaneous Coronary Angiography-PCA) is virtually performed to the stenosed model. The distribution of the Wall Shear Stress (WSS) as well as the wall deformation are compared on the two models after solving the coupled mechanical system using the Finite Element Method (FEM). Results concerning areas of low WSS (0–2 Pa) as well as minimum and maximum wall deformation are presented, quantifying the effect of the revascularization process of the artery.

A Multiscale Approach for Modeling Atherosclerosis Progression

Progression of atherosclerotic process constitutes a serious and quite common condition due to accumulation of fatty materials in the arterial wall, consequently posing serious cardiovascular complications. In this paper, we assemble and analyze a multitude of heterogeneous data in order to model the progression of atherosclerosis (ATS) in coronary vessels. The patients medical record, biochemical analytes, monocyte information, adhesion molecules, and therapy-related data comprise the input for the subsequent analysis. As indicator of coronary lesion progression, two consecutive coronary computed tomography angiographies have been evaluated in the same patient. To this end, a set of 39 patients is studied using a twofold approach, namely, baseline analysis and temporal analysis. The former approach employs baseline information in order to predict the future state of the patient (in terms of progression of ATS). The latter is based on an approach encompassing dynamic Bayesian networks whereby snapshots of the patients status over the follow-up are analyzed in order to model the evolvement of ATS, taking into account the temporal dimension of the disease. The quantitative assessment of our work has resulted in 93.3% accuracy for the case of baseline analysis, and 83% overall accuracy for the temporal analysis, in terms of modeling and predicting the evolvement of ATS. It should be noted that the application of the SMOTE algorithm for handling class imbalance and the subsequent evaluation procedure might have introduced an overestimation of the performance metrics, due to the employment of synthesized instances. The most prominent features found to play a substantial role in the progression of the disease are: diabetes, cholesterol and cholesterol/HDL. Among novel markers, the CD11b marker of leukocyte integrin complex is associated with coronary plaque progression.

Transient Intraventricular Conduction Delay Associated with Concurrent Intake of Propafenone and Antineoplastic Agents

An 82-year old man was admitted with acute pulmonary edema. Myocardial ischemia and electrolyte abnormalities were excluded and he responded promptly to frusemide, nitrates and morphine. On admission, the duration of the QRS interval was markedly abnormal at 240 ms with a nonspecific intraventricular conduction defect pattern, of left bundle branch block type. This finding was not present three weeks prior to his admission, and was felt to be the result of drug interaction between propafenone and antineoplastic agents, as evidenced by resolution of the clinical and electrocardiographic picture after discontinuation of these agents.