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.

BOLLMANN, A., et al.: 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 ECG and an orthogonal ECG lead system using a high gain, high resolution ECG. AF was classified as coarse (fibrillatory amplitude ≥ 1 mm) or fine (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 obtained from the ECG 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.

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 (≥20% and ≥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.

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.

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.

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.

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.

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.

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 (greater than or equal to 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 how 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 how 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.

It has yet to be established whether substantial reduction of plasma lipids will lead to retardation, and to what extent and how quickly, of diffuse and focal coronary atheroma.The Multicentre Anti-Atheroma Study (MAAS) is randomised double-blind clinical trial of 381 patients with coronary heart disease assigned to treatment with diet and either simvastatin 20 mg daily or placebo for 4 years. Patients on simvastatin had a 23% reduction in serum cholesterol, a 31% reduction in low-density lipoprotein cholesterol, and a 9% increase in high-density lipoprotein cholesterol compared with placebo over 4 years. Quantitative coronary angiography was done at baseline, and after 2 and 4 years. 167 patients (89%) on placebo and 178 (92%) on simvastatin had baseline and follow-up angiograms. In the placebo group there were reductions in mean lumen diameter (-0.08 mm) and in minimum lumen diameter (-0.13 mm). Treatment effects were + 0.06 (95% Cl 0.02 to 0.10) and + 0.08 mm (0.03 to 0.14) for mean and minimum lumen diameter, respectively (combined p = 0.006). Patients on placebo had an increase in mean diameter stenosis of 3.6% and the treatment effect of simvastatin was - 2.6% (- 4.4 to - 0.8). Treatment effects were observed regardless of diameter stenosis at baseline. On a per-patient basis, angiographic progression occurred less often in the simvastatin group, 41 versus 54 patients; and regression was more frequent, 33 versus 20 patients (combined p = 0.02). Significantly more new lesions and new tote I occlusions developed in the placebo group, 48 versus 28, and 18 versus 8, respectively. There was no difference in clinical outcome. The numbers of patients who died or had a myocardial infarction were 16 and 14 in the placebo and simvastatin groups, respectively. In the placebo group more patients underwent coronary angioplasty or re-vascularisation, 34 versus 23 on simvastatin.The trial showed that 20 mg simvastatin daily over 4 years reduces hyperlipidaemia and slows progression of diffuse and focal coronary atherosclerosis.

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.

In 166 patients with stable angina pectoris, positive exercise test and angiographically proven coronary artery disease, determinants for the absence or presence of myocardial ischemia during 24-hour ambulatory electrocardiographic (ECG) monitoring were analyzed. Variables were derived from clinical history, electrocardiogram at rest, exercise testing, ambulatory ECG monitoring as well as from cardiac catheterization and were compared in 103 patients with (group A) and 63 patients without (group B) ambulatory myocardial ischemia. In a multiple stepwise discriminant analysis, the most powerful determinants for the presence of ambulatory myocardial ischemia were: (1) R-wave amplitude during ambulatory ECG monitoring (17.2 +/- 5.3 vs. 13.8 +/- 4.6 mm in group A vs. group B; p < 0.001); (2) heart rate at onset of S-T-segment depression during exercise testing (112 +/- 17 vs. 121 +/- 16 beats/min; p < 0.001), and (3) presence of a stenosis >70% in the left anterior descending coronary artery (76 vs. 59% of the patients; p < 0.05). Furthermore, heart rates during ambulatory ECG monitoring were significantly higher in group A as compared to group B during the morning hours and in the late afternoon; during these periods, ambulatory myocardial ischemia showed a parallel increase. This study shows that the absence or presence of myocardial ischemia during ambulatory ECG monitoring is influenced by the ischemic threshold during exercise testing and involvement of the left anterior descending artery; however, R-wave amplitude and circadian heart rate profile during ambulatory ECG monitoring also play important roles.

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.

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)

INTACT is a study on the progression of coronary artery disease based on quantitated coronary angiography, applying the CAAS-system to assess the diameters of segments and stenoses and their changes over time. 348 of 425 patients (82%) underwent 2 angiograms after 3 years (175 on placebo, 173 on nifedipine, 80 mg per day). The analysis followed the intention to treat principle, as 66 patients stopped the trial medication for the last 12-18 months. Progression was defined either as an increase in the degree of stenosis by ≥20% or transition to occlusion, or as development of new stenoses (narrowings ≥20%) or new occlusions in coronary segments or sections previously angiographically normal. New lesions were selected both visually and by computer assessment. After 3 years no differences were found between groups with regard to pro- and regression of existing stenoses; however, there were fewer new lesions on nifedipine (144 on placebo versus 103 on nifedipine, -28%, p = 0.034) and also a trend to fewer patients with new lesions on nifedipine (-17%, n.s.). Hence, the calcium-antagonist significantly reduced the appearance of new stenoses and occlusions. There were interesting insights into the progression of CAD in general. Only 11.3% of existing stenoses showed progression and even fewer (4.3%) regression over 3 years, only few stenoses went into occlusion (2% of existing and 7.7% of new stenoses) (p = 0.000). Altogether, 56% of patients showed progression, 30.5% only in new stenoses, 11.8% only in old ones, and 14.1% in both. Hence, the strongest manifestation of progression of CAD was found in the development of new lesions (44.6% of all patients or 79% of all progressing patients showed new lesions). Conclusions: Repeated coronary angiography on a quantitative basis offers an excellent opportunity to study the progression of coronary artery disease, especially also during preventive interventions. A limitation is the angiographic definition of progression, which has to be based on sound statistical criteria as data from direct comparisons with the abnormal anatomy are not available as of yet.

Objectives. This study represents the first prospective, quantitative analysis of the association of progression of corona 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.