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Interventional cardiology has contributed significantly to our understanding of coronary atherosclerosis. Interventional cardiology has allowed a correlation between the clinical picture of coronary atherosclerosis with the underlying pathology and has helped establish the evolution of atherosclerotic plaques in vivo. Better understanding of the basic mechanisms of coronary atherosclerosis, due to the contributions of interventional cardiology, will help cure and/or prevent coronary atherosclerosis in the next few decades. In this mini review, several of the remarkable contributions of interventional cardiology, which have allowed a better understanding of the pathophysiologic mechanisms related to coronary atherosclerosis, will be emphasized. In addition, certain projections for the future will be made based on current knowledge. © 2016 Hellenic Society of Cardiology

Aim: To investigate the effects of exercise on atherosclerotic plaque composition, the concentration of matrix metalloproteinases (MMPs) in the atherosclerotic plaque and the systemic circulation. Methods: Ninety apolipoprotein E-deficient (apoE-/-) mice (45 male) were randomized to the following groups (n = 15 each): control male/female; sedentary male/female; exercise male/female. Mice were kept on a 16-week high-fat diet. Subsequently, the control groups were sacrificed, while the rest of the animals were placed on a normal diet for 6 more weeks. During the latter period, the exercise groups were trained daily on treadmill. At the end of the study, mice were euthanized, and blood samples as well as aortic root specimens were obtained. Results: Compared to control and sedentary animals, exercise training reduced atherosclerotic plaques (-30%; p < 0.01) and increased elastin and collagen content in both genders (p < 0.05). Body weight or lipid profile did not change significantly. Decreased macrophages and MMP-9 as well as increased tissue inhibitor of metalloproteinases 1 (TIMP-1) levels were observed in the atherosclerotic plaques of the exercise-treated groups (p < 0.05). Plasma concentrations of MMP-9 decreased, while plasma TIMP-1 levels increased in the exercise compared to control and sedentary groups (p < 0.05). Conclusions: Exercise training had a favorable effect on the size and composition of the atherosclerotic plaque in apoE-/- mice, associated with suppressed MMP activity. Copyright © 2011 S. Karger AG.

Background: It is known that oxidative stress plays an important role in the pathogenesis of atherosclerosis and that an association exists between osteopontin (OPN) and atherosclerosis. Objectives: It was proposed that malondialdehyde (MDA), a biomarker of lipid peroxidation and oxidative stress, would be related to plasma OPN levels in patients with coronary artery disease (CAD). Methods/results: Plasma OPN and MDA levels were measured in 71 patients (60 males and 11 females; mean age 61.7 ± 10 years). Fifty-eight patients had significant CAD (group I) and 13 patients were free of CAD as defined angiographically (group II). Plasma OPN was measured by enzyme-linked immunosorbent assay (ELISA), while MDA was determined spectrophotometrically. Multivariate regression analysis revealed that In-transformed OPN levels were independently associated with MDA after adjustment for age, hypertension and diabetes mellitus (R2 = 0.278, p = 0.0004 and β regression coefficient = 0.252 [standard error = 0.0958], p = 0.011). OPN and MDA levels were higher in patients with diabetes (73.6 ± 36.2 ng/ml versus 56.1 ± 30.9 ng/ml, p = 0.02 and 2.5 ± 0.5 μM versus 2.0 ± 0.5 μM, p = 0.002, respectively). Conclusions: The association between OPN and MDA levels in patients with CAD suggests an interaction between OPN and oxidative stress. This interaction may play a role in the pathogenesis of atherosclerosis. © 2008 Informa UK Ltd.

Objective: Previous studies demonstrated that osteopontin (OPN) was increased after vascular injury, such as atherosclerosis and restenosis following angioplasty. We sought to determine the effects of percutaneous coronary intervention (PCI) on plasma OPN levels compared with coronary arteriography (CA). Methods: Plasma OPN levels were determined in 103 patients who underwent CA or PCI with stent implantation, at baseline and 24 h after the procedure. Patients were divided into three groups; group I: patients without significant coronary artery stenosis, group II: patients with coronary artery disease in whom only CA was performed, group III: patients with coronary artery disease who had PCI and stent implantation. Results: Plasma OPN levels before the procedure were similar in all three groups. OPN levels 24 h after the procedure were significantly higher only in group III compared with baseline. Among three groups, the OPN levels observed in 24 h were significantly higher in group III compared with group I. Patients in group III had significantly higher OPN values after the procedure, depending on the number of stents implanted (p = 0.03). Conclusion: The increase in OPN levels after PCI suggests that vascular injury due to PCI is responsible for this phenomenon. © 2008 Informa UK Ltd.

The objective of the study was to investigate the alterations of aortic function after interposition of a tubular graft in the descending porcine thoracic aorta. Eight healthy Landrace pigs were subjected to thoracotomy under sterile conditions. A 5-cm-long segment of descending thoracic aorta was replaced with a Dacron graft. Pulse wave velocity (PWV) was measured using simultaneous recordings of electrocardiogram and Doppler pressure waveforms, which were received from right carotid and femoral arteries. Then, the recordings were fed to a computer for analytical estimation of PWV in several occasions: right after the interposition (D0), and after 15 (D15) and 30 (D30) days time. Euthanasia was performed after the D30-recordings and the aortic graft area was removed. "Before graft" (BG) as well as "after graft" (AG) aortic regions were examined under light microscopy in order to determine the aortic thickness (T) and number of lamellar units (LU). Eight sham-operated pigs were used as controls. The results showed that PWV decreased as soon as the graft interposition took place and was maintained, until the end of experiment (P < 0.05). Aortic wall thickness was increased both at pregraft and postgraft areas (P < 0.05), and LUs were also increased at the same regions. It is concluded that the interposition of a tubular graft in the descending thoracic aorta resulted in a decrease in PWV, which may improve left ventricular performance and enhance myocardial perfusion, due to a delay in the arrival of the reflecting diastolic wave. © 2006, Copyright the Authors.

A constitutive law that includes three analytical expressions was recently proposed to approximate the low, physiologic, and high-stress parts of the aortic stress-strain relation in uniaxial tension, consistent with the biphasic nature of the aortic wall under passive conditions. This consistency, and the fact that previous phenomenological uniaxial laws have only indirectly been related to vessel wall structure, motivates the investigation of the structural basis underlying the newly proposed three-part constitutive law. For this purpose, longitudinally oriented aortic strips were fixed in Karnovsky's solution, while subjected to various pre-selected levels of uniaxial tensile stress. Light microscopy examination disclosed that the elastic lamellae gradually unfolded at low and were almost straight at physiologic and high stresses, while collagen fibers reoriented in the longitudinal axis at low, started uncoiling at physiologic, and straightened massively at high stresses. In the circumferential sections, the elastic lamellae and the circumferentially distributed collagen bundles remained wavy at all levels of longitudinally applied stress. These microstructural changes suggest that elastin becomes load-bearing at low, and collagen at physiologic but mostly at high stresses, so that the first and third parts of the constitutive law are in turn due to the presence of elastin and collagen alone, and the second due to both elastin and collagen. The structural basis of this constitutive law allows physically significant interpretation of its parameters, offering insight into how the aortic microstructure determines the macromechanical response. © 2005 Elsevier Ltd. All rights reserved.

This study assessed the long-term effect of vagotomy on the structure and passive mechanical characteristics of the thoracic aorta under a wide range of stresses in vitro. Eight healthy Landrace pigs underwent bilateral vagotomy distal to the origin of the recurrent laryngeal nerve, and 10 pigs were sham-operated. Three months post-surgery, the aorta was excised and specimens from the ascending aorta, arch, and descending thoracic aorta were subjected to histomorphometrical evaluation and uniaxial tensile-testing until failure. Elastic modulus-stress data were plotted and submitted to regression analysis. Structural remodeling after vagotomy was characterized as vascular growth in the ascending aorta and arch, and as thinning in the descending thoracic aorta. In the aortic segments of vagotomized animals, the area density of elastin and collagen was increased, but smooth muscle density was decreased. Similar differences in regression parameters and failure strength between groups were found in all aortic segments, indicating that the vessel wall was stiffer and stronger in vagotomized animals. In the clinical setting, disease states or drugs blocking the regulatory role of the vagi nerves on the aortic wall may have undesirable consequences on the mechanical performance of the thoracic aorta, and therefore on hemodynamic homeostasis. © 2005 Biomedical Engineering Society.

The passive elastic characteristics of the abdominal aorta were investigated in two experimental animal models, aiming at assessing the stress-strain relation of the aortic wall. Twenty porcine and 15 rabbit healthy abdominal aortas were subjected to uniaxial stress-strain analysis, performed on a tensile-testing device, while immersed in a physiologic saline bath at body temperature. Measured parameters included original length, width and thickness, as well as axial force and extension. Based on these data, Kirchhoff stress and Green-St. Venant strain were computed and one-dimensional constitutive equations were defined, comprising of a power function and two exponential ones, in turn, for the low, physiologic and high-stress regions. The stress-strain curves were plotted as elastic modulus versus stress, displaying nonlinear part I and linear parts II and III. These were regressed, yielding parameters k, q (part I), a, b (part II) and c, d (part III). A detailed comparison of these constitutive parameters was undertaken between the two species, demonstrating variations in d (p

The objective of this study was to evaluate multiple structural characteristics, in addition to vasa vasorum density, in different aortic regions. The aorta of healthy Landrace pigs was divided into four thoracic and three abdominal segments. Transverse sections were reserved for morphometric analysis. Image analysis showed the aortic diameter, the thickness of the media, the number of elastic lamellae and the thickness of elastic membranes being reduced with increased distance from the heart (P < 0.05). The average thickness of lamellar units remained constant in the thoracic, but increased in the abdominal aorta (P < 0.05). The number of lamellar units, contained in the avascular zone of the media, and the density of vasa vasorum decreased peripherally (P < 0.05), still the average thickness of the avascular zone was invariant. In conclusion, the anatomical properties of the vessel wall alter through the aorta, being optimal for the varying stresses to which the aorta is subjected along its length. The distinct aortic parts may exhibit inherent morphological features, responsible for the various pathological processes that affect the aorta.

Objective: To investigate the alterations of structure and mechanical properties of the aortic wall, resulting from impairment of vasa vasorum Row. Methods: Eight healthy Landrace pigs were subjected to interruption of vasa vasorum how to the upper segment of their descending thoracic aorta. Under sterile conditions, the periaortic tissue was excised and the contiguous intercostal arteries were ligated. Ten sham-operated pigs were used as controls. Fifteen days postoperatively, the animals were sacrificed and their upper descending thoracic aortas were removed. Histology, and collagen and elastin content determination by image analysis technique were performed. Mechanical analysis of aortic strips was carried out with a uniaxial tension device and stress-strain curves were obtained. Results: In contrast to normal aortic walls of the control group, histology of the avascular aortas revealed severe ischemic necrosis of the outer media along with abnormal straightening of the elastin and collagen fibers, without significant collagen and elastin content changes. The borderline between the outer ischemic and inner non-ischemic media was sharp, and an outset of dissection was observed at this point. Mechanical analysis showed that at the same level of strain, the ischemic aorta was significantly stiffer at both low (P = 0.03) and high strains (P = 0.003). Conclusions: Impairment of blood supply to the thoracic aorta leads to abnormal morphology of elastin and collagen fibers of the outer media, resulting in increased aortic stiffness under a wide range of stresses. In the clinical setting, decreased vasa vasorum flew, reportedly occurring in arterial hypertension, may increase the stiffness of the outer media of the thoracic aorta and produce interlaminar shear stresses, contributing to the development of aortic dissection. (C) 2000 Elsevier Science B.V. All rights reserved.

Background Smoking is a major risk factor for cardiovascular morbidity and mortality. Because previous studies have shown that smoking affects vasomotor response, we hypothesized that smoking may also acutely alter aortic elastic properties. Methods and Results We studied 40 male current and longterm smokers who underwent diagnostic cardiac catheterization for chest-pain evaluation. Twenty subjects (age, 48+/-2 years, mean+/-SEM) were randomly assigned to smoking and 20 (age, 47+/-2 years) to sham smoking studies. Aortic elastic properties were studied with the determination of the aortic pressure-diameter relation before smoking, every minute for the first 5 minutes after the initiation of smoking or sham smoking, and every 5 minutes for the following 15 minutes. Instantaneous diameter of the thoracic aorta was measured with a special ultrasonic dimension catheter developed in our laboratory and previously validated. Instantaneous aortic pressure was measured at the same site as was diameter with a Millar micromanometer. Smoking was associated with significant changes in the aortic pressure-diameter relation that denote deterioration of the elastic properties and were maintained during the whole study period: the slope of the pressure-diameter loop became steeper (baseline, 35.43+/-1.38; minute 1, 45.26+/-1.65; peak at minute 10, 46.36+/-1.69 mm Hg/mm; P

Mitral valve prolapse due to floppy mitral valve (MVP/FMV) is a common valvular abnormality with a variable clinical course. Flail mitral valve leaflet resulting in severe mitral regurgitation is a complication of MVP/FMV.In order to understand the structural correlates of flail mitral valve leaflet in MVP, we reviewed the morphologic characteristics of the mitral valve by transesophageal echocardiography (TEE) in 72 patients (24 normal; 26 mitral valve prolapse; 22 flail mitral valve leaflet).Compared with the normal group, the mitral valve prolapse group had greater anterior and posterior mitral valve leaflet thickness and anterior mitral valve leaflet length. Patients with flail mitral valve leaflets as a complication of FMV had greater anterior and posterior mitral valve leaflet length and posterior mitral valve leaflet thickness compared with MVP patients without flail mitral valve leaflets. Posterior mitral valve leaflet length was the only echocardiographic independent predictor of flail mitral valve leaflet. Older FMV patients with increased mitral valve leaflet length and thickness are predisposed to flail mitral valve leaflets and severe mitral regurgitation.TEE may identify patients with MVP/FMV with the greatest structural abnormalities who are at risk for complications such as flail mitral valve leaflet(s).

Background Pressure-diameter relation of the aorta provides important information about the elastic properties of the vessel. However, owing to methodological limitations, data regarding this relation are limited in conscious humans. In the present study, we assessed a new method for the direct estimation of the elastic properties of the aorta in conscious humans by simultaneous acquisition of instantaneous aortic pressure and diameter. Methods and Results With this method, instantaneous diameter of the thoracic aorta was acquired by a newly designed intravascular catheter developed in our institution that incorporates an ultrasonic displacement meter at its distal end. Instantaneous aortic pressure was acquired simultaneously at the same aortic level with a catheter-tip micromanometer. Aortic pressure-diameter loops were derived from computer analysis of data. After in vitro and animal testing, elastic properties of the aorta were investigated in coronary artery disease (CAD) patients (n=15) and compared with those of control subjects (n=10). Aortic distensibility was less in the CAD group than in the control group (1.73+/-0.33 versus 3.95+/-1.09x10(-6)Xcm(2)Xdyne(-1), P

Acute myocardial ischemia decreases conduction velocity through the ischemic myocardium and may produce QRS prolongation on the surface electrocardiogram. To investigate the effect of exercise-induced myocardial ischemia on the QRS duration, 124 patients who underwent diagnostic cardiac catheterization and exercise thallium-201 scintigraphy were studied. Seventeen patients had normal coronary arteries and 107 had coronary artery disease. QRS duration decreased with exercise in patients with normal coronary arteries (-3.7 ms, confidence interval -7.7 to 0.3) but increased in patients with coronary artery disease; exercise-induced QRS prolongation was directly related to the number of vessel disease (1.2 ms in patients with one-vessel disease; 8.7 ms in patients with two-vessel disease, and 10.5 ms in patients with three-vessel disease, p < 0.001). Likewise, exercise-induced QRS duration decreased in patients without exercise-induced reversible perfusion defects (-1.3 ms, confidence limits -2.8 to 0.2) but increased in patients with exercise-induced perfusion defects (9.7 ms in patients with one perfusion defect; 13.6 ms in patients with two perfusion defects, and 16.3 ms in patients with three perfusion defects, p < 0.001). Exercise-induced QRS prolongation was best related to the number of exercise-induced perfusion defects than to the number of vessel disease, p < 0.001. In conclusion, exercise-induced QRS prolongation in patients with coronary artery disease was directly related to the number of vessel disease and to exercise-induced perfusion defects. This QRS prolongation was better related to the number of reversible perfusion defects than to the number of vessel disease. Thus, exercise-induced QRS prolongation in patients with coronary artery disease may be a marker of exercise-induced myocardial ischemia.

To investigate whether left atrial systolic dysfunction in dilated cardiomyopathy is the result of left atrial dilatation, atrial involvement in the myopathic process, or both, 20 patients with aortic stenosis, 14 patients with idiopathic dilated cardiomyopathy, and 10 normal control subjects were studied. Left atrial volumes (cubic centimeters) were echocardiographically measured at mitral valve opening (maximal), mitral valve closure (minimal), and onset of atrial systole (P wave of the electrocardiogram) with the biplane area-length method. Atrial systolic function was assessed by calculating the active emptying fraction, equal to (volume at onset of atrial systole minus minimal volume)/volume at onset of atrial systole. Heart rate was similar in patients with aortic stenosis and dilated cardiomyopathy (83 +/- 11 vs 86 +/- 15 beats/min, respectively). Maximal volume was similar in patients with aortic stenosis (74.8 +/- 26.4 cm(3)) and dilated cardiomyopathy (79.7 +/- 25.3 cm(3)) but greater (p < 0.0001) than in control subjects (46.4 +/- 11.9 cm(3)). Active emptying fraction was inversely related to volume at onset of atrial systole and to tension at end of atrial systole (aortic stenosis r= -0.61 and r= -0.81, respectively; dilated cardiomyopathy r= -0.79 and r= -0.66, respectively). At any given level of volume at onset of atrial systole and tension at end of atrial systole, however, active emptying fraction was lower in patients with dilated cardiomyopathy compared with those with aortic stenosis. Thus left atrial systolic dysfunction in dilated cardiomyopathy is not explained by the degree of left atrial dilatation or left atrial tension at end of atrial systole; this suggests that left atrial myopathy may be involved in the dysfunction.

To study the effect of nifedipine on aortic distensibility in patients with coronary artery disease, ascending aorta distensibility was measured before and 10 min after 10 mg of nifedipine was given sublingually in 13 patients with coronary artery disease and 12 control subjects. Aortic distensibility was calculated as a function of changes in the aortic diameter and pulse pressure. Aortic diameters were measured by echocardiography and aortic pressures were measured directly by catheterization of the ascending aorta. At baseline, aortic distensibility was lower in patients with coronary artery disease compared with control (0.922 +/- 0.367 vs 2.456+/-0.588 10(-6).cm(2).dyn(-1) respectively, p

The objective of this study was to investigate the effect of myocardial ischemia on the QRS duration in patients with coronary artery disease since acute myocardial ischemia decreases conduction velocity through the ischemic myocardium and may produce QRS prolongation on the surface electrocardiogram. One hundred fifty patients who underwent cardiac catheterization and exercise radionuclide ventriculography within 1 month of each other were studied. Forty patients had normal coronary arteries and 110 had coronary artery disease. QRS duration decreased with exercise in patients with normal coronary arteries (-3.0 msec, confidence limits -6.2 to 0.2), but increased in patients with coronary artery disease; exercise-induced QRS prolongation was directly related to the number of diseased vessels (4.8 msec in patients with one, 7.8 msec in patients with two, and 13.3 msec in patients with three-vessel disease, p < 0.001). Likewise, QRS duration decreased with exercise in patients without exercise-induced segmental contraction abnormalities (-1.8 msec, confidence limits -3.7 to 0.1), but increased in patients with segmental contraction abnormalities (6.7 msec in patients with one, 13.5 msec in patients with two, and 21 msec in patients with three segmental contraction abnormalities, p < 0.0001). Exercise-induced QRS prolongation was better related to the number of segmental contraction abnormalities than to the number of diseased vessels (p < 0.01). It was concluded that exercise produces QRS prolongation in patients with coronary artery disease in direct relation to the number of diseased vessels and to exercise-induced segmental contraction abnormalities. This QRS prolongation was more closely related to the number of exercise-induced segmental contraction abnormalities than to the number of diseased vessels. Thus exercise-induced QRS prolongation in patients with coronary artery disease may be a marker of exercise-induced myocardial ischemia.

PURPOSE: The purpose of the present investigation was to study the distensibility of the ascending aorta in patients with arterial hypertension and normal subjects before and after administration of a calcium antagonist, nifedipine. PATIENTS AND METHODs: The distensibility of the ascending aorta was measured before and after nifedipine administration in 22 male hypertensive patients and 12 age-matched male normotensive subjects. Aortic distensibility was calculated as a function of changes in aortic diameter and pulse pressure, using the formula: 2 X (pulsatile change in aortic diameter)/[(diastolic aortic diameter) X (aortic pulse pressure)]. Aortic diameters were measured by echocardiography and aortic pressures were obtained by catheterization of the ascending aorta. RESULTS, In the basal state, the distensibility of the ascending aorta and aortic strain were lower in hypertensive patients than in normotensive subjects (p

Myocardial ischemia may decrease conduction velocity and produce QRS prolongation in the surface electrocardiogram. In cases with normal intraventricular conduction, areas of the myocardium contributing to the development of the S wave receive blood from all 3 major coronary arteries, whereas in left anterior hemiblock or right bundle branch block, most of the blood supply to the areas of the myocardium contributing to the development of the S wave is from the left anterior descending (LAD) coronary artery. To test the hypothesis that the S wave will be prolonged with exercise only in patients with LAD coronary artery stenosis and left anterior hemiblock or right bundle branch block, 88 patients with normal intraventricular conduction, 66 with left anterior hemiblock and 36 with right bundle branch block were studied. Sixty-four, 32 and 21 patients had LAD, right and left circumflex coronary artery stenoses, respectively. In patients with normal coronary arteries, S-wave duration decreased with exercise regardless of the status of ventricular conduction. In patients with coronary artery disease and normal intraventricular conduction, the S wave was prolonged slightly with exercise, but in those with left anterior hemiblock and right bundle branch block, it was prolonged significantly (12.5 +/- 6 and 10.4 ms, respectively) only in those with LAD, but not in those with circumflex or right coronary artery stenosis. S-wave prolongation in patients with LAD coronary artery stenosis and left anterior hemiblock or right bundle branch block most likely is related to exercise-induced ischemia in the areas of the myocardium contributing to the development of the S wave.