Electrocardiographic characteristics in patients with nonrheumatic atrial fibrillation and their relation to echocardiographic parameters.

The aim of this study was to determine the relation between (1) ECG fibrillatory wave amplitude and left atrial diameter and left atrial appendage (LAA) flow velocity using different ECG recording techniques, and (2) ECG fibrillatory frequency and frequency of LAA contractions in patients with nonrheumatic AF. In 36 patients (22 men, 14 women, mean age 61 +/- 11 years) with persistent AF, ECG recordings were performed using a standard 12-lead EGG and an orthogonal EGG lead system using a high gain, high resolution ECG. AF was classified as coarse (fibrillatory amplitude > or = 1 mm) orfine (fibrillatory amplitude < 1 mm) in leads I, aVF, V1 and corresponding leads X, Y, and Z. Fibrillatory frequency from the ECG was determined by subtracting averaged QRST complexes and applying a Fourier analysis to the resulting signal. Doppler flow was obtained from LAA during transesophageal echocardiography and LAA emptying velocity was determined. Fourier analysis was also applied to the Doppler signal generating the frequency of LAA contractions. Coarse AF was observed in 0, 9, and 18 patients in leads I, aVF, and V, respectively. It was more often (P < 0.05) detected in corresponding leads X (n = 13), Y (n = 31), and Z (n = 23). Fine AF in lead X was associated with a reduced LAA velocity (33 +/- 16 cm/s in coarse AF vs 22 +/- 13 cm/s in fine AF, P = 0.05). There was neither a relation between AF coarseness in any other ECG lead and LAA flow velocity, left atrial diameter, or echo contrast. In 25 patients with an active LAA flow, the mean frequency of LAA contractions was 6.8 +/- 0.8 Hz. The corresponding mean frequency obtainedfrom the EGG was 6.7 +/- 0.7 Hz (r = 0.85, P < 0.001). The mean difference between these two measures was 0.04 Hz, and the 95% confidence limits were 0.90 and- 0.82 Hz using the Bland-Altman method. In conclusion, AF coarseness and its relation to LAA flow velocity depend on the ECG recording technique used. LAA contractions represent one mechanical correlate of the electrical fibrillatory activity in AF.

Left atrial appendage flow in nonrheumatic atrial fibrillation : relationship with pulmonary venous flow and ECG fibrillatory wave amplitude.

OBJECTIVE: This study was conducted (1) to examine the relationship between left atrial appendage (LAA) flow velocity and pulmonary venous flow (PVF) variables during nonrheumatic atrial fibrillation (AF), and (2) to determine whether a reduction in LAA flow is reflected by the fibrillatory wave amplitude on the surface ECG. BACKGROUND: Although LAA Doppler echocardiographic signals provide information regarding the velocity and direction of flow only for a localized narrow sample, systolic PVF represents in part the global left atrial function, mainly relaxation. Controversy exists about whether the amplitude of fibrillatory waves recorded on the surface ECG correlates with LAA flow velocity during AF. MEASUREMENTS AND RESULTS: Thirty-three patients (20 men, 13 women; mean [+/- SD] age, 61 +/- 11 years) with nonrheumatic AF undergoing transthoracic and transesophageal echocardiography were studied. A correlation between LAA flow velocity and systolic PVF variables (peak systolic velocity, R: = 0.450, p = 0.009; velocity-time integral of systolic flow, R = 0.491, p = 0.004; systolic fraction of PVF, R: = 0.627, p < 0.0001) was observed. Patients with a low LAA flow profile (< 25 cm/s) had a reduced systolic PVF. Longer AF duration and the occurrence of moderate mitral regurgitation were related to reduced LAA flow. AF was subdivided into coarse (peak-to-peak fibrillatory amplitude > or = 1 mm) or fine (< 1 mm) in standard ECG lead V1. There was no association between the coarseness of AF and the LAA flow profile. CONCLUSION: In patients with nonrheumatic AF, a reduction in LAA flow velocity correlates with a reduction in systolic PVF. These hemodynamic changes are not reflected by the ECG fibrillatory wave amplitude.

Association between coronary angiograms and cardiac events--a prospective 3-year follow-up. INTACT-Investigators. International Nifedipine Trial on Antiatherosclerotic Therapy.

The correlation between extent and severity of coronary artery disease as documented by quantitative coronary angiography and the incidence of cardiac events within 3 years was analyzed from a prospective study. In 73 out of 419 patients, 89 events occurred comprising 10 cardiac deaths, 15 non-fatal myocardial infarcts, 26 cases of unstable angina, and 38 coronary revascularization procedures (bypass graft operation or angioplasty). The incidence of any event correlated with the baseline number of all stenoses and high-grade stenoses (> or =20% and > or =50% diameter stenosis, respectively) (P<0.05). With respect to specific events, non-fatal myocardial infarcts and revascularization procedures were correlated with the number of all stenoses (P<0.05), but not with high-grade stenoses. Specification of coronary arteries revealed correlation of non-fatal myocardial infarcts and revascularization procedures with the number of high-grade stenoses in the left anterior descending artery. Finally, baseline left ventricular ejection fraction was found to be lower in patients who died of cardiac causes than in the remaining patients (49 +/- 10% vs. 67 +/- 13%; P<0.001). In conclusion, the total coronary stenosis burden seems to predict the incidence of subsequent cardiac events even better than the number of high-grade stenoses. Only in the left anterior descending artery high-grade stenoses seem to cause myocardial infarcts within a relatively short period of time justifying short-term revascularization in these patients.

Association between coronary occlusions and myocardial infarcts. The INTACT investigators. International Nifedipine Trial on Antiatherosclerotic Therapy.

The number of angiographically documented coronary occlusions and the incidence of Q-wave myocardial infarcts were retrospectively compared in 348 patients with moderate coronary artery disease from the INTACT study (International Nifedipine Trial on Antiatherosclerotic Therapy). In only 68 out of 118 infarcts (58%) an occlusion of the respective coronary artery was found, suggesting a spontaneous recanalization rate of 42%. On the other hand, only 68 out of 150 coronary occlusions (45%) had resulted in a Q-wave infarct. Considering the high spontaneous recanalization rate of the occlusions, it seemed possible that roughly only every fourth coronary occlusion might result in a myocardial infarct. This hypothesis was confirmed in the prospective 3 years follow-up of the identical patients during which 41 new occlusions developed causing only 10 myocardial infarcts (24%). These findings might contribute to explain the relatively low incidence of clinically apparent coronary heart disease in the general population despite a high prevalence of coronary artery disease.

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.

Transesophageal echocardiographic assessment of superior vena cava thrombosis in patients with long-term central venous hemodialysis catheters.

In some patients with end-stage renal failure, arteriovenous fistulas cannot be created due to poor vessel conditions. Alternatively, hemodialysis (HD) can be performed using long-term central venous catheters. However, these dialysis catheters are associated with a presently unknown risk of superior vena cava (SVC) thrombosis. We examined 20 patients (11 female, 9 male, age 29-83 years) 1-48 (mean 15) months after transjugular insertion of a permanent single lumen silicone rubber HD catheter. All patients underwent both transthoracic (TTE) and biplane transesophageal (TEE) echocardiography. TTE visualized the catheter only when its tip was localized in the right atrium (2 patients), but did not succeed in adequate imaging of the SVC. In contrast, TEE allowed high quality imaging of the SVC in all patients and detected a SVC thrombosis in 6 patients; in 3 of them, caval thrombosis was subtotal. One additional patient showed a thrombus attached to the catheter tip alone. Dwelling time of catheters since insertion in the SVC was not significantly different in patients with and without thrombosis. Reduced blood flow during HD was observed in 5 of 7 patients with catheter-associated thrombi but also in 4 of 13 patients without evidence for caval thrombosis by TEE. It is concluded that thrombotic occlusion of the SVC is frequent in patients with long-term central venous access; it does not necessarily correlate with clinical signs but can easily be detected by TEE. Patients with long-term central venous hemodialysis catheters should undergo transesophageal echocardiography at regular intervals.

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.

Assessment of left atrial appendage function by biplane transesophageal echocardiography in patients with nonrheumatic atrial fibrillation: identification of a subgroup of patients at increased embolic risk.

OBJECTIVES: This study was conducted to identify a subgroup of patients with nonrheumatic atrial fibrillation with an increased risk for cardiogenic embolism by assessing left atrial appendage function. BACKGROUND: Patients with nonrheumatic atrial fibrillation have an increased risk for thromboembolic complications. The left atrial appendage is the most likely source for thrombus formation. It is likely that the appendage function (contraction, filling dynamics) is related to the pathogenesis of thrombus formation. METHODS: Twenty-nine patients with nonrheumatic atrial fibrillation (group I) underwent biplane transesophageal echocardiography. The maximal and minimal areas during a cardiac cycle and the peak emptying and filling velocities of the appendage were measured in both scan planes. For comparison, two additional groups were also analyzed. Group II consisted of 12 patients with chronic atrial fibrillation due to significant mitral stenosis, and group III consisted of 30 patients who were in sinus rhythm. RESULTS: Patients with nonrheumatic atrial fibrillation showed two distinct appendage flow patterns: either well defined peak filling and emptying waves (> or = 25 cm/s) with visible fibrillatory contractions of the appendage wall ("high flow profile") or irregular, very low, peak filling and emptying waves (< 25 cm/s) associated with almost no visible appendage contractions ("low flow profile"). The left atrial appendage function in the first subgroup resembles that seen in patients with sinus rhythm, whereas the appendage function in the latter subgroup resembles more the "static pouch" seen in patients with rheumatic atrial fibrillation. Events suggestive of cardiogenic embolism occurred in six patients from group I, five of whom were in the low flow profile subgroup (p < 0.05). The spontaneous echo contrast phenomenon was observed in 80% of the low flow profile subgroup but in only 5% in the high flow profile subgroup (p < 0.05). Three thrombi confined to the left atrial appendage were detected by transesophageal echocardiography in group I; all three of the patients were in the low flow profile subgroup. CONCLUSIONS: The assessment of left atrial appendage function by transesophageal echocardiography may be helpful to identify subgroups of patients with nonrheumatic atrial fibrillation with an increased risk of thrombus formation.

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.

[Imaging of a congenital coronary fistula using biplane transesophageal color-coded echocardiography. A case report]. / Darstellung einer kongenitalen Koronarfistel mittels biplaner transösophagealer Farbdopplerechokardiographie. Eine Fallbeschreibung.

A case report of a congenital coronary artery fistula between left main stem and pulmonary artery is presented. This fistula was not detectable by conventional transthoracic color-Doppler echocardiography. In contrast, precise localization of origin and site of drainage of this fistula could be demonstrated by biplane transesophageal color-Doppler echocardiography. Subsequent coronary angiography confirmed the echocardiographic findings.

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.

Comparison of transthoracic and transesophageal echocardiography for detection of abnormalities of prosthetic and bioprosthetic valves in the mitral and aortic positions.

Two-dimensional echocardiography is the diagnostic procedure of choice for evaluation of prosthetic valve abnormalities. However, transthoracic echocardiography (TTE) may be limited owing to acoustic shadowing and poor acoustic windows. Some of these limitations may be overcome by transesophageal echocardiography (TEE). One hundred twenty-six patients with 148 prosthetic valves (113 bioprostheses and 35 mechanical devices) were studied by M-mode and 2-dimensional TTE and TEE. Prosthetic valve morphology was confirmed by surgery or autopsy in all cases; 124 prostheses were classified as diseased (33 endocarditis, 8 thrombi, and 83 degeneration defined as leaflet thickening > 3 mm with restricted motion) and 24 as normal. Prosthetic valve endocarditis and thrombi were correctly identified by TTE in 12 of 33 (36%) and 1 of 8 (13%) prostheses, respectively, but could be diagnosed by TEE in 27 of 33 (82%; p < 0.001) and 8 of 8 (100%; p < 0.01), respectively. Compared with TTE, TEE had a higher sensitivity for morphologic prosthetic valve abnormalities in patients with either bioprostheses (88 [87%] vs 66 [65%] of 101 prostheses; p < 0.01) or mechanical devices (19 [83%] vs 5 [22%] of 23 prostheses; p < 0.01) and in patients with a prosthesis in either the aortic (49 [77%] vs 32 [50%] of 64; p < 0.01) or mitral (58 [97%] vs 39 [65%] of 60; p < 0.001) position. Overall, sensitivity and specificity were 57 and 63%, respectively, for TTE, and 86 and 88%, respectively, for TEE.(ABSTRACT TRUNCATED AT 250 WORDS)

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).

Concept of an antiatherosclerotic efficacy of calcium entry blockers. INTACT Investigators.

Animal experiments suggest an inhibitory effect of calcium entry blockers on arterial calcinosis and the formation of atherosclerotic plaques. Experiments with isolated tissues suggest various mechanisms for an antiatherosclerotic effect of calcium entry blockers. INTACT, the International Nifedipine Trial on Antiatherosclerotic Therapy, is the first study investigating, with a prospective, placebo-controlled, randomized, double-blind design, the influence of a calcium entry blocker (nifedipine 80 mg/day) on the progression of coronary atherosclerosis in patients with proven coronary artery disease. Study endpoints were changes of established coronary stenoses (diameter reduction greater than or equal to 20%), as well as the formation of new stenoses as documented by coronary angiography. Standardized coronary angiograms were taken before and after a treatment period of 3 years. The angiograms were quantitatively analyzed with the computer-assisted edge detection system CAAS. Of the 425 patients included in the study, 282 patients (134 on nifedipine and 148 on placebo) revealed no protocol violations. In the inclusion angiograms of these patients, 893 coronary stenoses were detected which were not significantly influenced in their development by nifedipine. However, 196 entirely new coronary lesions, 185 stenoses and 11 occlusions, were found in the follow-up angiograms. There were 78 lesions in 54 patients (40%) on nifedipine (0.58 new lesions/patient) and 118 lesions in 73 patients (49%; n.s.) on placebo (0.8 new lesions/patient; p = 0.031). In two other studies on the inhibiting effect of dihydropyridine calcium entry blockers on the progression of coronary artery disease in man defining angiographic endpoints, the drugs were also shown to reduce the number of newly formed significant coronary lesions. If further trials in man confirm a protective role of calcium entry blockers against the formation of atherosclerotic coronary lesions, a new strategy in the prevention of coronary artery disease has to be considered.

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.

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)

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.

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.

Retardation of coronary artery disease in humans by the calcium-channel blocker nifedipine: results of the INTACT study (International Nifedipine Trial on Antiatherosclerotic Therapy).

Experimental studies have demonstrated a 30-50% reduction in the development of atheromatous lesions of the aorta in rabbits fed a diet rich in cholesterol when they were treated with nifedipine. Based on these favorable results, we designed a multicenter, placebo (PL)-controlled, randomized, double-blind study, to test the effect of 80 mg nifedipine (NIF) per day versus placebo on the progression of mild coronary artery disease (CAD) (further development of existing stenoses, especially formation of new stenoses and occlusions) over a duration of 3 years. Progression of CAD was assessed by coronary angiograms performed at entrance and at completion of the study, using a computer-assisted analysis system (CAAS) to quantitate various stenosis parameters (percent degree of stenosis and minimal stenosis diameter). Of the 425 patients enrolled, 348 (82%) underwent a second angiogram; 66 of them, however, terminated treatment prematurely after an average of 359 (placebo) and 467 days (nifedipine). A total of 282 patients (148 on placebo, 134 on nifedipine) completed the trial with full-length treatment. There were no differences between the two groups in the progression of the existing stenoses. Patients on nifedipine, however, demonstrated significantly fewer new lesions (stenoses greater than 20% or occlusions) than those on placebo: In the 282 patients undergoing the full-length treatment, there were 73 patients on placebo (49%) with 118 new lesions (0.8/patient) and 54 patients on nifedipine (40%) with 78 new lesions (0.58/patient), a difference of -27% (p = 0.031 by Cochran's linear trend test). The difference was greatest in the left anterior descending branch, with 28 patients on placebo developing 33 new lesions (0.22/patient), versus 16 patients on nifedipine with 18 new lesions (0.13/patient) (-40%; p = 0.045); and in the left circumflex branch, where 34 patients on placebo exhibited 39 new lesions (0.26/patient) versus 23 patients on nifedipine with 22 new lesions (0.16/patient) (-38%, p = 0.033). No differences were observed in the right coronary artery, the vessel with the highest number of existing and new lesions [PL] versus 0.27 [NIF] new lesions/patient) (-7.6%, p = 0.381). Hence, INTACT confirmed the previous experimental studies and demonstrates a significant reduction in newly formed coronary lesions in patients on nifedipine when compared with those on placebo, especially in the presence of early coronary artery disease.