Incidence of ventricular arrhythmias during transient myocardial ischemia in patients with stable coronary artery disease.

To determine the incidence of ventricular arrhythmias related to episodes of transient myocardial ischemia during ambulatory electrocardiographic (ECG) monitoring, 97 patients with stable angina pectoris, angiographically proved coronary artery disease and an abnormal exercise test were studied. A total of 573 episodes with ST segment depression were documented: in 118 episodes (21%) the patients were symptomatic and in 455 (79%) they remained asymptomatic. Ventricular arrhythmias (greater than 5 premature ventricular beats/min, bigeminy, couplets or salvos of premature ventricular beats) occurred during 27 (5%) ischemic episodes in a subset of 10 patients (10%) (group A). The other 87 patients (90%) (group B) showed exclusively ischemic episodes without ventricular arrhythmias. Comparison of patients in group A and group B showed no differences in hemodynamic, angiographic, exercise testing and ambulatory ECG monitoring data. Ischemic episodes with and without ventricular arrhythmias showed a similar duration and amplitude of ST segment depression and a comparable heart rate at the onset of ischemia. Both types of ischemic episodes, with and without arrhythmias, occurred predominantly during the morning hours between 6:00 AM and noon, and both types remained asymptomatic to within similar percentages. The data demonstrate that ventricular arrhythmias are related to transient myocardial ischemia in only a few patients with stable angina pectoris; these arrhythmias are related neither to the degree of ischemia during ambulatory ECG monitoring nor to the occurrence of anginal symptoms.

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.

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.

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.

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.

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)

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)

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.

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.

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.

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.

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.

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.

[Pseudostabilization of unstable angina pectoris: disappearance of symptoms in persistence of silent myocardial ischemia]. / Pseudostabilisation einer instabilen Angina pectoris: Verschwinden der Symptome bei Persistieren der stummen Myokardischämie.

We studied a patient hospitalized with unstable angina pectoris; ST-segment analysis during Holter ECG revealed several silent ischemic attacks despite complete disappearance of anginal symptoms under medical treatment. Prior to cardiac catheterization the patient went into acute myocardial infarction. Immediate intravenous thrombolysis and subsequent angioplasty of a high-grade stenosis abolished the ischemic events. ST-segment analysis during Holter ECG offers a method to detect ischemic events despite the disappearance of anginal symptoms in the clinical course of unstable angina pectoris. This technique might therefore identify patients with unstable angina pectoris at higher risk for further cardiac events.

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).

[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.

[M-mode echocardiography determination of the severity of aortic stenosis: is the assumption of constant wall stress a realistic approach?]. / M-Mode-echokardiographische Bestimmung des Schweregrades einer Aortenstenose: Ist die Zugrundelegung einer konstanten Wandspannung ein realistischer Ansatz?

We reevaluated a previously described M-mode echocardiographic method for the assessment of the hemodynamic severity of an isolated or predominant, advanced aortic stenosis in 89 adult patients without significant associated coronary artery disease. Endsystolic left ventricular wall thickness and diameters were measured using the echocardiogram and left ventricular systolic pressure was calculated under the assumption of a constant left ventricular wall stress (235 mm Hg); the results were compared with the pressure values measured during catheterization. The correlation between the echocardiographic and the invasively determined pressure values was poor and without any clinical relevance; r-values ranged between 0.14 and 0.46. Calculated left ventricular wall stress showed a large scatter with values between 126 mm Hg and 468 mm Hg. Our data indicate that in adults with aortic stenosis, M-mode echocardiographic determination of the hemodynamic severity is not possible, and the assumption of a constant left ventricular wall stress in these patients is misleading.

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.

[High-dose single administration of isosorbide dinitrate: effect on diurnal distribution of transitory myocardial ischemia in patients with stable angina pectoris]. / Hochdosierte Einmalgabe Isosorbiddinitrat: Einfluss auf die tageszeitliche Verteilung von transitorischen Myokardischämien bei Patienten mit stabiler Angina pectoris.

We studied the effect of a monotherapy of isosorbiddinitrate on symptomatic and asymptomatic ischemic episodes in 15 ambulatory patients with chronic stable angina pectoris, positive exercise test, and coronary stenosis greater than 70%. Transient ST-segment depression (greater than 0.1 mV for at least 1 min) was documented by 48-h Holter monitoring during a control period without anti-ischemic therapy and at the end of 14 days of treatment with 120 mg o.d. isosorbiddinitrate slow-release. In the control period, 68 asymptomatic and 28 symptomatic ischemic episodes were detected; most of the episodes occurred in the morning between 6.00h and 12.00h (41 episodes) and in the afternoon between 12.00h and 18.00h (36 episodes). Under anti-ischemic therapy the number of episodes and the total duration of ischemia was reduced by 46% and 53%, respectively (p less than 0.01). The anti-ischemic effect was most evident during the morning and the afternoon; the ischemic episodes during the evening and the night were not significantly diminished. It is concluded that in patients with stable angina pectoris a single high-dose of isosorbiddinitrate significantly reduces the number and duration of transient ischemic episodes during daily life.