Dilatation of the entire thoracic aorta in patients with bicuspid aortic valve: a magnetic resonance angiography study.

BACKGROUND: The presence of a bicuspid aortic valve (BAV) might be associated with a progressive dilatation of the aortic root and ascending aorta. However, involvement of the aortic arch and descending aorta has not yet been elucidated. PATIENTS AND METHODS: Magnetic resonance angiography (MRA) was used to assess the diameter of the ascending aorta, aortic arch, and descending aorta in 28 patients with bicuspid aortic valves (mean age 30 +/- 9 years). RESULTS: Patients with BAV, but without significant aortic stenosis or regurgitation (n = 10, mean age 27 +/- 8 years, n.s. versus control) were compared with controls (n = 13, mean age 33 +/- 10 years). In the BAV-patients, aortic root diameter was 35.1 +/- 4.9 mm versus 28.9 +/- 4.8 mm in the control group (p < 0.01). The diameter of the ascending aorta was also significantly increased at the level of the pulmonary artery (35.5 +/-5.6 mm versus 27.0 +/- 4.8 mm, p < 0.001). BAV-patients with moderate or severe aortic regurgitation (n = 18, mean age 32 +/- 9 years, n.s. versus control) had a significant dilatation of the aortic root, ascending aorta at the level of the pulmonary artery (41.7 +/- 4.8 mm versus 27.0 +/- 4.8 mm in control patients, p < 0.001) and, furthermore, significantly increased diameters of the aortic arch (27.1 +/- 5.6 mm versus 21.5 +/- 1.8 mm, p < 0.01) and descending aorta (21.8 +/- 5.6 mm versus 17.0 +/- 5.6 mm, p < 0.01). CONCLUSIONS: The whole thoracic aorta is abnormally dilated in patients with BAV, particularly in patients with moderate/severe aortic regurgitation. The maximum dilatation occurs in the ascending aorta at the level of the pulmonary artery. Thus, we suggest evaluation of the entire thoracic aorta in patients with BAV.

Sixty-minute alteplase protocol: a new accelerated recombinant tissue-type plasminogen activator regimen for thrombolysis in acute myocardial infarction.

OBJECTIVES: Our aim was to design and evaluate a new and easily administered recombinant tissue-type plasminogen activator (rt-PA) regimen for thrombolysis in acute myocardial infarction (AMI) based on established pharmacokinetic data that improve the reperfusion success rate. BACKGROUND: Rapid restoration of Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow is a primary predictor of mortality after thrombolysis in AMI. However, TIMI grade 3 patency rates 90 min into thrombolysis of only 50% to 60% indicate an obvious need for improved thrombolytic regimens. METHODS: Pharmacokinetic simulations were performed to design a new rt-PA regimen. We aimed for a plateau tissue-type plasminogen activator (t-PA) plasma level similar to that of the first plateau of the Neuhaus regimen. These aims were achieved with a 20-mg rt-PA intravenous (i.v.) bolus followed by an 80-mg i.v. infusion over 60 min (regimen A). This regimen was tested in a consecutive comparative trial in 80 patients versus 2.25 10(6) IU of streptokinase/60 min (B), and 70 mg (C) or 100 mg (D) of rt-PA over 90 min. Subsequently, a confirmation trial of regimen A in 254 consecutive patients was performed with angiographic assessment by independent investigators of patency at 90 min. RESULTS: The comparative phase of the trial yielded, respectively, TIMI grade 3 and total patency (TIMI grades 2 and 3) of 80% and 85% (regimen A), 35% and 50% (B), 50% and 55% (C) and 60% and 70% (D). In the confirmation phase of the trial, regimen A yielded 81.1% TIMI grade 3 and 87.0% total patency. At follow-up angiography 7 (4.1%) of 169 vessels had reoccluded. In-hospital mortality rate was 1.2%. Nadir levels of fibrinogen, plasminogen and alpha2-antiplasmin were 3.6 +/- 0.8 mg/ml, 60 +/- 21% and 42 +/- 16%, respectively (mean +/- SD). Fifty-seven patients (22.4%) suffered from bleeding; 3.5% needed blood transfusions. CONCLUSIONS: The 60-min alteplase thrombolysis in AMI protocol achieved a TIMI grade 3 patency rate of 81.1% at 90 min with no indication of an increased bleeding hazard; it was associated with a 1.2% overall mortality rate. These results are substantially better than those reported from all currently utilized regimens. Head to head comparison with established thrombolytic regimens in a large-scale randomized trial is warranted.

Angiographically undetected plaque in the left main coronary artery. Findings of intravascular ultrasound imaging.

The absence of angiographic findings despite significant coronary artery disease has been previously described. Possible explanations for the limitation of plaque detection by angiography include compensatory vessel enlargement in face of intracoronary plaque formation, the lack of reference segments in diffuse atherosclerosis as well as technical limitations. Intracoronary ultrasound (ICUS) imaging provides the possibility of direct plaque visualization. We studied angiographically normal left main coronary arteries (LMCA) in 72 patients prior to diagnostic angiography or therapeutic interventions using ICUS (30 MHz). ICUS images were continuously recorded and recalled from memory for morphometric analysis. Lumen area, plaque area and the total vessel area were determined by computer software. ICUS imaging revealed atherosclerotic plaque in 55 of the 72 patients with angiographically normal LMCA (76%). The average plaque area stenosis was 22 +/- 12% (range 3-44%). Total vessel area showed a significant direct correlation with plaque area, indicating compensation of coronary plaque formation. The average percent change in plaque area (difference between maximal and minimal plaque area within the LMCA) was 11 +/- 19%, indicating a diffuse pattern. Measurement of change in lumen area (difference between maximal and minimal lumen area within the LMCA) revealed an average value of 6 +/- 7%. Lumen area of the LMCA was 15.9 +/- 3.2 mm2 in patients with and 17.2 +/- 1.9 mm2 without atherosclerotic plaque (n.s.). Thus, the lack of angiographic changes despite advanced plaque formation in the LMCA could be explained by compensatory vessel enlargement and by diffuse distribution of plaque in the vessel; true lumen narrowings overlooked by angiography seem not to account for the failure of angiography to detect plaque.

Anti-atherosclerotic properties of nifedipine. Benefit of early intervention to prevent cardiovascular complications.

Early stages of the atherosclerotic plaque are considered to be responsible for about 2/3 of all acute coronary syndromes. Therefore, suppression of this initial stage of plaque formation constitutes a major target to reduce the incidence of the disease itself as well as its complications. Ca antagonists, like Nifedipine, interfere with Ca++ ions crucially involved in atherogenesis. Consequently, interval angiographic trials with Nifedipine in patients afflicted with coronary artery disease assessed a significant reduction of coronary lesions. Clinical outcome trials will establish the prognostic importance of the anti-atherosclerotic properties of Nifedipine.

Influence of the selection of angiographic projections on the results of coronary angiographic follow-up trials. International Nifedipine Trial on Antiatherosclerotic Therapy Investigators.

In recent years follow-up trials on coronary artery disease with angiographic end points analyzed quantitatively have gained increasing relevance and popularity. There is no consensus, however, on the method of calculation of progression or regression from multiple angiographic projections. Therefore the influence of the selection of angiographic projections on the outcomes of such trials was investigated with the data of the International Nifedipine Trial on Antiatherosclerotic Therapy. In 348 patients with coronary artery disease, repeated coronary angiograms were compared in multiple identical angiographic projections. Changes in angiographic parameters were averaged over the 1063 stenoses analyzed. Five methods of evaluation of multiple projections in the individual stenoses were applied, resulting in different extents of overall progression, or even regression of coronary artery disease (p < 0.01). It is concluded that in quantitative coronary angiographic follow-up trials changes should be averaged over all angiographic projections available for a stenosis to avoid overestimation of progression or regression.

Vascular responses to 17 beta-oestradiol in postmenopausal women.

The vascular responses to 17 beta-oestradiol were examined in 23 postmenopausal women (59 +/- 7 years [mean +/- SD]) using a placebo-controlled double-blind crossover design. All women received 1 mg 17 beta-oestradiol or placebo (P) sublingually on consecutive days in random order. Axial diameters and blood flow rates of the left common femoral arteries were determined before and 60-80 min after application of verum or placebo as well as 10-30 min after 10 mg isosorbide dinitrate (ISDN) with a quantitative duplex ultrasound technique. Oestradiol induced a vasodilation of femoral arteries (+6.4 +/- 4.1% of basal, P < 0.001 vs. basal and P), the vessel diameter was unchanged with placebo (+0.7 +/- 2.1%). The blood flow rate increased significantly after oestradiol application (+30 +/- 28%, P < 0.05 vs. basal and P), but not after placebo (+11 +/- 21%). Mean blood pressure and heart rate remained constant with both drugs. Despite its vasodilatory effect, ISDN significantly reduced the arterial blood flow after pretreatment with oestradiol and placebo, probably through cardiac preload reduction. In conclusion, 17 beta-oestradiol alters the vascular tone of systemic arteries resulting in a vasodilation and increase of blood flow. We suggest that these direct vascular actions may contribute to the preventive properties of oestrogens on cardiovascular diseases in postmenopausal women.

Evolution of coronary stenoses is related to baseline severity--a prospective quantitative angiographic analysis in patients with moderate coronary disease. INTACT Investigators. International Nifedipine Trial on Antiatherosclerotic Therapy.

A correlation of the angiographic evolution of coronary stenoses (stenosis diameter > or = 20%) with morphological stenosis parameters at baseline could help to identify the risk of progressive stenoses. Therefore, the data of the prospective INTACT study (International Nifedipine Trial on Antiatherosclerotic Therapy) were reviewed. In 348 patients with moderate coronary artery disease, standardized coronary angiograms were taken 3 years apart and were quantitatively analysed. Changes in the minimal diameter of the 1063 preexisting coronary stenoses compared between both angiograms were set in relation to a number of conventional stenosis parameters at baseline. Regression analysis demonstrated a significant correlation of the changes in minimal diameter with baseline % diameter stenosis (r = 0.30; P < 0.001), minimal diameter (r = -0.28; P < 0.001) and reference diameter of stenoses (r = -0.14; P < 0.001). The changes were not correlated with stenosis length and plaque area. The baseline parameters of 22 preexisting stenoses progressing to occlusions differed from those remaining patent only with regard to the % diameter stenosis (43 +/- 9% vs 39 +/- 11%; P < 0.05). Additional progression of coronary disease became manifest through development of 228 stenoses and 19 occlusions at arterial sites free from definitive stenoses in the baseline angiograms. Thus, progression of atherosclerosis predominantly occurred in mild preexisting coronary stenoses and developed at previously angiographically normal sites. Since the conventional angiographic parameters analysed in this study failed to identify individual arterial sites with an increased risk for progression, definition of new angiographic parameters or application of new techniques seem mandatory to this end.

Hypertension treatment and prevention of new atherosclerotic plaque formation.

The effect of hypertension on the arterial vascular wall is characterised primarily by morphological changes to the endothelium and hypertrophy of smooth muscle cells within the arterial media. Endothelial dysfunction is manifest through increased permeability to high molecular weight compounds as well as mitogenic and vasoactive substances. At the same time, denudation of the vascular endothelium promotes platelet aggregation and subsequent release of platelet-derived growth factor (PDGF). In conjunction with endothelium- and monocyte-derived growth factors, this mitogen stimulates subintimal smooth muscle cell proliferation and migration and arterial wall thickening, resulting in a haemodynamically important increase in vascular resistance, particularly at the precapillary level. In addition, focal endothelial dysfunction allows entry of lipids into the vascular wall, thereby promoting formation of a lipid-rich fatty streak, the primary 'early' atherosclerotic lesion. Most of these changes, including endothelial injury, subintimal lipid-binding, cellular proliferation and migration, platelet aggregation and PDGF release are common to both hypertensive and early atherosclerotic processes and involve the participation of calcium ions as 'second messengers'. Thus, antihypertensive treatment with calcium antagonists may not only lead to a protective decrease in wall shear stress through a reduction in blood pressure, but may also inhibit those cellular processes within the vascular wall that are responsible for initiating atherosclerosis. Indeed, experimental as well as human studies have demonstrated a beneficial suppressant effect of calcium antagonists on the early stages of atherosclerosis.

[Adverse effects of a new non-ionic contrast medium in heart catheterization]. / Verträglichkeit eines neuen nichtionischen Kontrastmittels bei Herzkatheteruntersuchungen.

Tolerance of a New Non-ionic Contrast Medium during Heart Catheterization The new non-ionic contrast medium iomeprol (CAS 78649-41-9) was investigated for adverse reactions and diagnostic quality in 75 patients undergoing heart catheterization. Blood pressure and ECG were continuously registered. The patients were asked for subjective complaints by using a standardized questionnaire. Experienced cardiologists assessed the diagnostic quality of the angiograms. With iomeprol neither fatal nor severe reactions were observed. The dye had only little influence on diastolic and systolic blood pressure; heart rate was not significantly influenced. Minor and partly moderate adverse reactions all being completely reversible were observed in 14 patients (18.7%). One patient complained of strong heat sensation after dye injection into the left ventricle. The diagnostic quality of the angiograms allowed to make a definitive diagnosis in all cases. Thus, iomeprol proved to be a suitable and safe contrast medium for heart catheterization.

Usefulness of quantitative and qualitative angiographic lesion morphology, and clinical characteristics in predicting major adverse cardiac events during and after native coronary balloon angioplasty. CARPORT and MERCATOR Study Groups.

Major, adverse cardiac events (death, myocardial infarction, bypass surgery and reintervention) occur in 4 to 7% of all patients undergoing coronary balloon angioplasty. Prospectively collected clinical data, and angiographic quantitative and qualitative lesion morphologic assessment and procedural factors were examined to determine whether the occurrence of these events could be predicted. Of 1,442 patients undergoing balloon angioplasty for native primary coronary disease in 2 European multicenter trials, 69 had major, adverse cardiac procedural or in-hospital complications after > or = 1 balloon inflation and were randomly matched with patients who completed an uncomplicated in-hospital course after successful angioplasty. No quantitative angiographic variable was associated with major adverse cardiac events in univariate and multivariate analyses. Univariate analysis showed that major adverse cardiac events were associated with the following preprocedural variables: (1) unstable angina (odds ratio [OR] 3.11; p < 0.0001), (2) type C lesion (OR 2.53; p < 0.004), (3) lesion location at a bend > 45 degrees (OR 2.34; p < 0.004), and (4) stenosis located in the middle segment of the artery dilated (OR 1.88; p < 0.03); and with the following postprocedural variable: angiographically visible dissection (OR 5.39; p < 0.0001). Multivariate logistic analysis was performed to identify variables independently correlated with the occurrence of major adverse cardiac events. The preprocedural multivariate model entered unstable angina (OR 3.77; p < 0.0003), lesions located at a bend > 45 degrees (OR 2.87; p < 0.0005), and stenosis located in the middle portion of the artery dilated (OR 1.95; p < 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Update on cardiac catheterization and coronary arteriography.

Indications for cardiac catheterization--including coronary angiography--have substantially broadened with the advent of nonsurgical therapeutic interventions performed in the catheterization laboratory. Consequently, the increasing number of facilities performing these procedures require clear and unmistakable guidelines regarding the indications for and the safety and ethical aspects of the procedure. Technical developments in image acquisition and evaluation, such as quantitative analysis, allow the exact, reproducible assessment of minute changes in cardiac morphology and function, the evaluation of which becomes increasingly important in prognosis-related clinical trials.

Ovarian sex steroids and atherosclerosis.

Estrogens have been found to protect against atherosclerosis in a variety of animal models, and these antiatherogenic properties have been confirmed by epidemiological and clinical studies in women as well. Since the estrogen-induced changes of plasma lipid and lipoprotein levels do not fully account for the prevention of atherosclerosis, additional effects must be assumed. Experimental studies suggest various direct vascular actions. Estrogens enhance the endothelial degradation of low-density lipoprotein cholesterol, and preliminary data indicate antioxidative actions on low-density lipoprotein particles in macrophages. They suppress intimal proliferation and extracellular matrix production in the arterial wall and induce marked vasodilatation in systemic and coronary arteries. Adverse effects on hemostatic factors described with high doses and synthetic compounds are not evident during hormonal replacement in postmenopausal women, in whom an estradiol-induced inhibition of platelet aggregation may even have beneficial clinical effects. The role of progesterone and other progestogens in the progression of atherosclerosis is controversial. Despite a partial antagonism to estrogen-induced changes of plasma lipids, their addition to estrogens does not alter the anti-atherosclerotic properties, at least in animal experiments. The direct vascular actions of progestogens-although not as well documented-seem to be less pronounced than those of estrogens. The experimental data indicate that direct vascular effects play an important role in the antiatherogenic properties of ovarian sex steroids. However, the underlying cellular and molecular mechanisms remain largely unknown.

Progression of coronary artery disease is dependent on anatomic location and diameter. The INTACT investigators.

OBJECTIVES: This study represents the first prospective, quantitative analysis of the association of progression of coronary atherosclerosis with anatomic site and diameter. BACKGROUND: The progressive course of coronary artery disease has been documented in many angiographic follow-up trials. METHODS: The data of 348 patients with coronary artery disease from the International Nifedipine Trial on Antiatherosclerotic Therapy (INTACT) were reviewed. Standardized coronary angiograms were taken 3 years apart and were analyzed quantitatively. The coronary tree was subdivided into 25 segments. The progression of 1,063 preexisting coronary stenoses and the appearance of 247 newly formed stenoses was assessed in relation to the mean diameter of segments (< 2 mm, 2 to 3 mm, > 3 mm) and to their position in the coronary tree (proximal, mid, distal) and in the three major coronary arteries. RESULTS: Decreases in the minimal diameter of preexisting stenoses were largest in segments that were > 3 mm in diameter (mean +/- SD 0.23 +/- 0.5 mm vs. 0.10 +/- 0.4 mm and 0.02 +/- 0.3 mm, p < 0.001), in a proximal position (0.14 +/- 0.5 mm vs. 0.09 +/- 0.4 mm and 0.06 +/- 0.3 mm, p = 0.081) and in the right coronary artery (0.14 +/- 0.4 mm vs. 0.07 +/- 0.4 mm and 0.07 +/- 0.3 mm, p < 0.01). Changes in percent diameter stenosis of preexisting stenoses were lowest in segments that were < 2 mm in diameter and in a distal position (p = NS). The number of new stenoses/segment was lowest in segments that were < 2 mm in diameter (44 of 1,756 vs. 139 of 1,967 and 64 of 1,125, p < 0.001) and in a distal position (77 of 2,370 vs. 84 of 1,193 and 86 of 1,285, p < 0.001) and was highest in segments of the right coronary artery (100 of 1,546 vs. 66 of 1,496 and 72 of 1,492, p = 0.044). CONCLUSIONS: Progression of coronary artery disease occurs most frequently in coronary segments that are > 2 mm in diameter, in a proximal or midartery position and in the right coronary artery.

Quantitative angiographic follow-up studies on the development of coronary artery disease: which coronary segments should be analyzed? Experience from INTACT.

Angiographic follow-up studies on the evolution of coronary artery disease are of increasing relevance. It has still to be evaluated which coronary segments are predominantly involved in the process of atherosclerosis and, thus, should be preferably included in the analysis. Therefore, the correlation of progression and regression of coronary disease with the diameter and location (proximal, mid or distal) of coronary segments was investigated from the data of the INTACT-study, in which 25 different coronary segments were defined including anatomic variants of rather distal segments. In 348 patients with coronary artery disease, standardized coronary angiograms were repeated within 3 years and were quantitatively analyzed (CAAS). In 1063 coronary stenoses (% diameter stenosis > 20%) compared from both angiograms, progression and regression were not influenced by diameter nor location of arterial segments. In the follow-up angiograms, the number of new lesions (stenoses and occlusions) per coronary segment differed with regard to segment diameter (> 3 mm: 64/1125 (6%); 2-3 mm: 139/1967 (7%); < 2 mm: 44/1756 (2%); p < 0.001) and location of segments (proximal: 86/1285 (7%); mid: 84/1193 (7%); distal: 77/2370 (3%); p < 0.001). Out of 77 distal new lesions, only 25 (32%) were found in segments < 2 mm in diameter. Since the absolute number of new lesions was high in distal coronary segments, but low in segments with diameters < 2 mm, angiographic follow-up studies should analyze coronary segments at any location, but may neglect segments with diameters smaller than 2 mm.

Anatomical progression of coronary artery disease in humans as seen by prospective, repeated, quantitated coronary angiography. Relation to clinical events and risk factors. The INTACT Study Group.

BACKGROUND: At present, there is extensive knowledge on the clinical course of coronary artery disease (CAD), whereas data on the underlying anatomical changes and their relation to clinical events are still limited. METHODS AND RESULTS: We investigated progression and regression of CAD prospectively over 3 years in 230 patients (average age, 53.2 years) with mild to moderate disease by applying quantitated, repeated coronary angiography. Minimal stenotic diameters, segment diameters, and percent stenosis were analyzed by the computer-assisted Coronary Angiography Analysis System (CAAS). Progression was defined either as an increase in percent stenosis of preexisting stenoses by greater than or equal to 20% including occlusions or as formation of new stenoses greater than or equal to 20% and new occlusions in previously angiographically "normal" segments. At first angiography, we found 838 stenoses greater than or equal to 20% (average degree, 39.3%) and 135 occlusions in the four major coronary branches (4.23 lesions per patient). At second angiography, 82 (9.8%) of the preexisting stenoses had progressed, 15 of them up to occlusion (1.8%; preocclusion degree averaging 46.6%; 29.7-65.6%). In addition, there were 144 newly formed stenoses (average degree, 39.2%) and 10 new occlusions. Hence, 25 (2.6%) of all stenoses had become occluded. Altogether, 129 patients (56.1%) showed progression: 68 (29.6%) with new lesions only, 27 (11.7%) with preexisting lesions, and 34 (14.8%) with both types. Regression (decrease in degree of stenoses greater than or equal to 20%) was present in 29 stenoses (3.6%) and 28 patients (12%). The incidence of new myocardial infarctions was low, with three originating from occluding preexisting stenoses and one from new stenoses; hence, only four (16%) of the 25 new occlusions led to myocardial infarctions. Risk factor analysis showed that cigarette smoking correlated significantly with the formation of new lesions (p = 0.001), whereas total cholesterol correlated with the further progression of preexisting stenoses (p = 0.017) but not with the incidence of new lesions. CONCLUSIONS: In patients with mild to moderate CAD, the angiographic progression is slow (in this study 18.7% of patients and 7% of stenoses per year) but exceeds regression (4.1% of patients and 1.2% of stenoses per year). Progression is predominantly seen in the formation of new coronary stenoses and less in growth of preexisting ones. Most of the stenoses were of a low degree (less than 50%), clinically not manifest including those going into occlusion and leading to myocardial infarction. Progression was influenced by risk factors, especially cigarette smoking (formation of new lesions) and high cholesterol levels (progression of preexisting stenoses).