Peter Nikutta

Left Atrial Spontaneous Echo Contrast in Mitral Valve Disease: An Indicator for an Increased Thromboembolic Risk

The incidence of left atrial spontaneous echo contrast was evaluated in 52 patients with isolated or predominant mitral valve stenosis (Group 1) and 70 other patients who had undergone mitral valve replacement (Group 2). All patients were studied by conventional transthoracic and transesophageal two-dimensional echocardiography. Spontaneous echo contrast could be visualized within the left atrium in 35 Group 1 patients (67.3%) (including 7 patients with sinus rhythm) and 26 Group 2 patients (37.1%) (all with atrial fibrillation). Patients with spontaneous echo contrast had a significantly larger left atrial diameter and a greater incidence of both left atrial thrombi and a history of arterial embolic episodes than did patients without spontaneous echo contrast. Association between spontaneous echo contrast and left atrial thrombi and a history of arterial embolization (considered individually or in combination) showed a high sensitivity and negative predictive value. It is concluded that spontaneous echo contrast is a helpful finding for identification of an increased thromboembolic risk in patients with mitral stenosis and after mitral valve replacement.

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.

BackgroundAt 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 ResultsWe 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 ≥20% including occlusions or as formation of new stenoses ≥20% and new occlusions in previously angiographically “normal” segments. At first angiography, we found 838 stenoses ≥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 ≥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. ConclusionsIn 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 (<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).

Progression of coronary artery disease is dependent on anatomic location and diameter

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.

Circadian Variation of Myocardial Ischemia in Patients with Stable Coronary Artery Disease

The circadian variation of myocardial ischemia detected during 24-h ambulatory electrocardiographic monitoring (AEM) was analyzed in 123 patients with stable angina pectoris, positive exercise test, and angiographically proven coronary artery disease. A total of 437 ischemic episodes (ST-segment depression greater than or equal to 1 mm and duration greater than or equal to 1 min) were observed; 333 (76%) episodes remained asymptomatic, and only 104 (24%) episodes were accompanied by anginal pain. Ischemic episodes predominantly occurred during the morning hours, between 6 a.m. and noon, and another smaller peak was observed in the afternoon, between 4 and 5 p.m.; this diurnal pattern was influenced neither by the extent of coronary artery disease nor the degree of left ventricular dysfunction. The circadian variation was restricted to the 345 (78%) ischemic episodes preceded by increases in heart rate; the 92 (22%) episodes without prior heart rate changes occurred randomly throughout the day. The morning peak in ischemic episodes was not associated with less myocardial oxygen supply; in contrast, heart rate profile showed parallel increases during the morning and afternoon hours, indicating elevated myocardial demand during these periods. Ischemia-related ventricular arrhythmias were concentrated during the morning hours, but their overall prevalence was low--28 (6%) of 437 ischemic episodes. These findings may provide further insight into the pathomechanisms of acute clinical events in patients with coronary artery disease, since the circadian variation of myocardial ischemia is very similar to that observed for the onset of myocardial infarction and sudden cardiac death.

Risk of Bacteremia Induced by Transesophageal Echocardiography: Analysis of 100 Consecutive Procedures

The incidence of bacteremia induced by transesophageal echocardiography (TEE) and, consequently, the need for an antibiotic prophylaxis before TEE is still controversial. Therefore, we studied the incidence of bacteremia associated with TEE prospectively in 100 consecutive patients without clinical or laboratory signs of bacterial infection. Blood samples were drawn immediately before and at 0, 5, and 15 minutes after TEE. In addition, swabs were taken from the pharyngeal region before TEE and from the distal part of the TEE-probe before and after TEE. All blood cultures taken before TEE remained sterile. After TEE, three positive blood cultures were found in two patients: the first patient had two different species of coagulase-negative staphylococci in cultures taken at 0 minutes (Staphylococcus capitis) and 15 minutes (Staphylococcus cohnii) after TEE, whereas the sample taken after 5 minutes remained sterile. In the second patient, Propionibacterium species appeared after 7 days of processing in a culture taken immediately after TEE, but not in the samples taken after 5 and 15 minutes. None of the three microorganisms found in the blood were simultaneously isolated in pharyngeal specimens or TEE-probe specimens of the same patient. Thus positive blood cultures in both patients were considered contaminated. This study demonstrates that TEE, when performed by an experienced investigator, is not associated with an increased risk of bacteremia. Accordingly, it is justified to perform TEE examinations (also in high-risk patients) without antibiotic prophylaxis.

Circadian distribution of the characteristics of ischemic episodes in patients with stable coronary artery disease

To determine the circadian distribution of episodes of myocardial ischemia, studies were performed in 111 patients with chronic stable angina pectoris, positive exercise test results and angiographically proven coronary artery disease. During 24 hours of ambulatory electrocardiographic monitoring, 101 symptomatic and 298 asymptomatic ischemic episodes (ST-segment depression greater than 1 mm, duration greater than 1 minute) were observed. The number of ischemic episodes and the cumulative duration of ischemia showed a circadian variation with the highest values between 8 and 10 A.M. and between 4 and 5 P.M. associated with a similar circadian variation of heart rate. Mean duration of ischemic episodes, maximal amplitude of ST-segment depression during ischemic episodes and increase in heart rate before the onset of ischemic episodes showed no significant circadian variation. Heart rate at the onset of ischemic episodes and maximal heart rate during ischemic episodes were lower between midnight and A.M. than during other times of the day. The morning and afternoon increase in ischemic activity is not paralleled by changes reflecting a decrease in myocardial oxygen supply during these periods (heart rate at onset of ischemia, heart rate increase before onset of ischemia), but is paralleled by a similar circadian variation of heart rate. The circadian variation in ischemic activity is predominantly based on a comparable variation in myocardial oxygen requirements.

Usefulness of a new automatic boundary detection system (acoustic quantification) for assessing stiffness of the descending thoracic aorta by transesophageal echocardiography

Abstract Increasing attention has been concentrated on the noninvasive assessment of aortic wall stiffness. 1 Aortic stiffness was found to correlate with age, hypercholesterolemia, arterial hypertension and degree of atherosclerosis. 1,2 It has been proposed that aortic stiffness may identify patients at risk for rapid progression of coronary artery disease. 2 Aortic stiffness is usually measured in terms of Youngs modulus or the β index. 3 Both parameters are calculated from the relation between systemic blood pressure and arterial diameter. Arterial diameter may be measured by angiography 4,5 or transcutaneous ultrasonic systems. 2,3,5 The latter technique appears to be more practicable than angiography, but analysis based on this technique is strongly dependent on sufficient image quality. Furthermore, measurement of systolic-diastolic changes of arterial diameter by ultrasonography at 1 given point of the aortic circumference may not be representative for the distensibility of the entire arterial wall. In the present study, stiffness of the descending thoracic aorta was assessed by transesophageal echocardiography (TEE) in patients with various cardiac diseases. Ultrasonic assessment of the descending thoracic aorta from the esophagus provides optimal image quality in virtually all patients. In contrast to previous studies, systolic-diastolic changes of aortic areas were measured, rather than changes in aortic diameters, using a new, commercially available automatic boundary detection system (acoustic quantification [AQ]). AQ permits online tracking of borders between endocardium and blood based on integrated backscatter analysis. 6 These automatically detected borders are displayed in real-time on the 2-dimensional echocardiogram. Furthermore, AQ software enables continuous analysis of areas on a beatby-beat basis.

International nifedipine trial on anti-atherosclerotic therapy (INTACT) - methodologic implications and results of a coronary angiographic follow-up study using computer-assisted film analysis

Animal experiments demonstrated a significant suppressive effect of various calcium channel blockers on the formation of atherosclerotic lesions. Therefore, a prospective, placebo-controlled, randomized, double blind multicenter study was performed to investigate the inhibitory influence of the calcium channel blocker nifedipine (80 mg/day) on the progression of coronary artery disease in man. Study endpoints were changes of coronary morphology documented by coronary angiography with particular respect to the formation of new coronary stenoses. In 348 out of 425 patients included in the study, coronary angiograms were repeated after three years. The angiograms were standardized by induction of a maximal coronary vasodilation with high doses of nitrates and by using absolutely identical angiographic projections. Quantitative analysis of coronary cineangiograms was performed with the computer-assisted contour detection system CAAS. Parameters were mean and minimal diameter of all segments and minimal stenosis diameter, percent diameter stenosis, length and plaque area of all stenoses.Continuous intake of study medication was registered in 282 patients, 134 on nifedipine and 148 patients on placebo. In these patients, a total of 3808 coronary segments with 893 stenoses (⩾ 20% diameter reduction in at least one angiographic projection) were compared on the baseline and follow-up cineangiograms. The changes in all angiographic parameters analyzed averaged over all patients by considering all angiographic projections analyzed, indicated significant progression of the disease (p < 0.006). The average changes in all parameters were even about three times more profound, when in the individual patients only the respective projections indicating the maximal changes were considered for the calculation (p < 0.001). However, with neither of these two analysis modes, the differences in progression between the treatment groups were statistically significant.In the follow-up angiograms, a total of 196 new coronary lesions (185 stenoses, 11 occlusions) were found at previously normal arterial sites. In patients on nifedipine, an average of only 0.58 new lesions per patient were detected versus 0,80 lesions per patient on placebo (−27%; p=0.031).INTACT is the first prospective angiographic trial on the progression of coronary artery disease using computer-assisted quantitative coronary angiography in such a high number of patients. All parameters analyzed indicated significant progression of coronary artery sclerosis. Nifedipine had no influence on the progression of preexisting coronary stenoses, but inhibited significantly the formation of new angiographically recognizable lesions. Further prospective coronary angiographic trials with calcium channel blockers using a comparably exact method are needed to confirm the results of this study.

Influence of the selection of angiographic projections on the results of coronary angiographic follow-up trials

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.

Anginal symptoms without ischemic electrocardiographic changes during ambulatory monitoring in men with coronary artery disease

Episodes of angina pectoris without electrocardiographic (ECG) signs of myocardial ischemia during 24-hour ambulatory monitoring were studied in 128 patients with a history of stable angina, angiographically proven coronary artery disease and positive exercise test results. In all, 341 episodes of ischemic ECG changes (ST-segment depression greater than 1 mm for greater than 1 minute) and 190 episodes of angina pectoris were observed: 86 episodes consisted of both ECG changes and angina pectoris, 255 episodes consisted only of ECG changes, and 104 episodes only of angina pectoris. Duration and magnitude of ST-segment deviation and heart rate at the onset of ischemia were similar in the 86 symptomatic and the 255 asymptomatic episodes with ECG changes. The 104 episodes of angina pectoris without ECG changes were detected in 44 patients (34%) (group A); 29 of them had only episodes with angina pectoris and 15 patients had both--episodes of angina pectoris with and without ECG changes. In 84 patients (66%) (group B) angina pectoris without ECG changes was not observed; all episodes were accompanied by ischemic ECG changes in these patients. No differences in the angiographic extent of coronary artery disease and in exercise test data were seen in both groups A and B; however, maximal ST-segment depression during exercise testing was significantly greater in group B than in group A patients (2.4 +/- 0.8 mm vs 1.9 +/- 0.9 mm; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)