Chronic Nonrheumatic Atrial Fibrillation Research Articles

Role of video-assisted thoracoscopy in the management of stroke

To evaluate the role of surgery (anterior thoracotomy versus video-assisted thoracoscopy) in avoidance of stroke by obliteration of the left atrial appendage in patients with chronic nonrheumatic atrial fibrillation. In a prospective study, 58 patients (35 men and 23 women, aged 62 ± 13.2 years) with chronic nonrheumatic atrial fibrillation were divided into 2 groups: group A was 29 patients who underwent an anterior thoracotomy, and group B was 29 patients who had video-assisted thoracoscopic obliteration of the left atrial appendage. All patients were followed up for at least 2 years. The 2 groups were well matched for age, sex, and comorbidities. No stroke was observed in either group. Operative time was significantly longer in group B. There was no intraoperative or postoperative complication, except for 2 cases of superficial wound infection in group A. In chronic atrial fibrillation, prophylactic left atrial appendage exclusion is suggested to prevent occurrence of stroke, which can be achieved by a surgical or thoracoscopic approach, but a video-assisted thoracoscopic approach is effective, less invasive, and avoids the complications of a surgical approach.

Is thrombogenesis in atrial fibrillation related to matrix metalloproteinase-1 and its inhibitor, TIMP-1?

Decreased matrix metalloproteinase-1 (MMP-1) and increased levels of its inhibitor, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), reflect impaired matrix degradation with an increase in fibrosis. A prothrombotic state has been described in atrial fibrillation (AF), increasing the risk of stroke and thromboembolism. Because structural abnormalities and remodeling of atria have been observed in AF, we hypothesized that the prothrombotic state in AF may be related to abnormal indexes of matrix degradation. We studied 48 consecutive patients (30 men; age, 70.5+/-9.0 years) with chronic nonrheumatic AF who were not on anticoagulation. Plasma levels of MMP-1, TIMP-1, and prothrombin fragment 1+2 (F1+2, an index of thrombogenesis) were measured by enzyme-linked immunosorbent assay. M-mode, 2-dimensional, and Doppler echocardiographic studies were performed in all patients. Research indexes were compared with data from 32 control subjects in sinus rhythm who were of similar age and sex. Patients with AF had lower levels of MMP-1 (P=0.011) but increased levels of TIMP-1 (P=0.033) and F1+2 (P<0.001) and a higher ratio of TIMP-1 to MMP-1 (P=0.009) compared with control subjects. After adjustment for sex, age, hypertension, and diabetes, TIMP-1 levels and the ratio of TIMP-1 to MMP-1 correlated with F1+2 levels (r=0.24, P=0.038; and r=0.26, P=0.023, respectively). In multivariate analysis, there was no independent relationship between MMP-1, TIMP-1, or ratio of TIMP-1 to MMP-1 and the presence of AF. Patients with AF have evidence of impaired matrix degradation, but this was not independently associated with the presence of AF on multivariate analysis. However, an independent relationship was found between the MMP/TIMP system and prothrombotic state (assessed by F1+2 levels).

Factor V Leiden mutation and its relation to left atrial thrombus in chronic nonrheumatic atrial fibrillation.

The genetic defect of coagulation factor V, known as factor V Leiden, produces a resistance to degradation by activated protein C and increased venous thrombosis. However, the role of factor V Leiden in the formation of left atrial thrombus with nonrheumatic atrial fibrillation has not been studied. We investigated whether factor V Leiden is a risk factor for left atrial thrombus in patients with nonrheumatic atrial fibrillation. We analyzed clinical, echocardiographic, and biochemical data in 105 consecutive patients with nonrheumatic atrial fibrillation. These patients were divided into two groups: group A (n = 37) with left atrial thrombus and group B (n = 68) without left atrial thrombus. The study also included 42 control subjects. Left atrial thrombus was investigated by using both transthoracic echocardiography and transesophageal echocardiography. Blood samples from the patients and controls were analyzed for the factor V Leiden mutation by DNA analysis, using the polymerase chain reaction. There was no significant difference in the prevalence of factor V Leiden between the patients and control subjects. The prevalence of factor V Leiden mutation was 8.1% (3/37) in patients with left atrial thrombus, and 8.8% (6/68) in patients without left atrial thrombus. The prevalence of factor V Leiden was 7.1% (3/42) in control subjects. The prevalance of factor V Leiden was 10% (2/20) in patients with spontaneous echo contrast and 8% (7/85) in patients without spontaneous echo contrast. Multivariate analyses showed that left ventricular ejection fraction was an independent predictor of left atrial thrombus. Factor V Leiden mutation is not a risk factor for left atrial thrombus formation and spontaneous echo contrast in patients with nonrheumatic atrial fibrillation.

Relation of fibrillatory wave amplitude with hemostatic abnormality and left atrial appendage dysfunction in patients with chronic nonrheumatic atrial fibrillation.

Large left atrium (LA) and LA appendage (LAA) dysfunction are known to relate to cardiogenic thromboembolism, so the present study investigated the relation of the atrial fibrillatory wave (F wave) amplitude to hemostatic markers and LAA function. Transthoracic and transesophageal echocardiographic studies were performed in 82 consecutive patients with chronic, nonrheumatic atrial fibrillation (AF). Patients were divided into 2 groups according to F wave amplitude in lead V1 on the 12-lead ECG: coarse AF (the greatest amplitude of F wave > or =1 mm, n=44) and fine AF (<1 mm, n=38). Plasma levels of thrombin-antithrombin III complex, D-dimer, platelet factor 4 and beta-thromboglobulin were determined. Compared with patients with coarse AF, those with fine AF had lower LAA peak flow velocity (p<0.05) and higher prevalence of embolic cerebral infarction (50% vs 27%, p<0.05). Platelet activity did not differ between the 2 groups; however, plasma levels of thrombin-antithrombin III complex and D-dimer were significantly higher in patients with fine AF than in those with coarse AF (p<0.05). Multiple logistic regression analysis showed that fine AF was independently associated with cerebral embolism. Therefore, the presence of fine F wave in V1 would be a useful marker of LAA dysfunction and hypercoagulability, and indicate a risk for cerebral embolism in patients with chronic, nonrheumatic AF.

Correlation between left atrial size, prothrombotic state and markers of endothelial dysfunction in patients with lone chronic nonrheumatic atrial fibrillation

Atrial fibrillation is associated with a prothrombotic state and endothelial dysfunction. To understand whether the prothrombotic state was correlated with endothelial dysfunction and whether the latter was related to atrial dimension (endocardial damage), we studied systemic hemocoagulative activity and markers of endothelial dysfunction in 45 patients with chronic nonrheumatic atrial fibrillation and in 35 controls. We assessed fibrinogen, antithrombin III, protein C, markers of platelet activation (platelet factor 4 and β-thromboglobulin) as markers of fibrinolysis, and D-dimer, tissue plasminogen activator, plasminogen activator inhibitor, von Willebrand’s factor and soluble thrombomodulin as endothelial dysfunction. Plasma fibrinogen ( P<0.005), platelet factor 4 ( P<0.001), thromboglobulin ( P<0.001), D-dimer ( P<0.03), tissue plasminogen activator ( P<0.006), plasminogen activator inhibitor ( P<0.04) and both von Willebrand’s factor ( P<0.0001) and soluble thrombomodulin ( P<0.03) were significantly higher in the patients than in the controls. Positive significant linear correlations were found between fibrinogen and markers of endothelial dysfunction and left atrial volume and fibrinogen or markers of endothelial dysfunction. These findings confirm that chronic nonrheumatic atrial fibrillation is associated with a prothrombotic state but also suggest that there is a correlation between endothelial dysfunction, coagulation factors and left atrial dimension.

Atrial fibrillation and cognitive disorders in older people.

To find a correlation between chronic nonrheumatic atrial fibrillation (CNRAF) and cognitive impairment in a group of older, nondemented patients. Acute Care Unit for the Elderly, Poliambulanza Hospital, Brescia (Italy). Two hundred fifty-five hospital in-patients older than 70 years (42 with CNRAF and 213 controls with normal sinus rhythm) were assessed by complete clinical history, physical examination, ECG, serum albumin levels, APACHE II score, mental status (Mini-Mental State Exam [MMSE] and Geriatric Depression Score [GDS]), functional status (Barthel Index and instrumental activities of daily living [IADL]), number of prescribed drugs, and comorbidity (Charlson Index). The group of patients with CNRAF had MMSE scores significantly lower than that of the reference group with normal sinus rhythm. Chronic nonrheumatic atrial fibrillation retained an independent relation to cognitive impairment also after adjusting for those variables associated with mental decline in univariate models (GDS, IADL, and APACHE II scores). The results of this study support the relationship between nonrheumatic atrial fibrillation and impaired cognitive function. Independent of etiopathogenetic mechanisms (thromboembolic or hemodynamic hypotheses), prevention of cognitive impairment in older persons should take into account the treatment of atrial fibrillation and its consequences.

Association of Follow-up Change of Left Atrial Appendage Blood Flow Velocity With Spontaneous Echo Contrast in Nonrheumatic Atrial Fibrillation

To evaluate the time-related change of left atrial (LA) appendage flow velocity in chronic atrial fibrillation (AF) by follow-up transesophageal echocardiography (TEE) and to investigate its association with the occurrence of LA spontaneous echo contrast. Prospective follow-up study. University-based, tertiary referral medical center. Forty-seven patients with chronic nonrheumatic AF. All studied patients underwent both a baseline and follow-up TEE during a mean period of 13 +/- 7 months. Baseline TEE revealed that LA spontaneous echo contrast was present in 28 patients (group 1) and was absent in 19 patients (group 2). The LA appendage flow velocity profiles at baseline were significantly lower in group 1 than in group 2; on follow-up, the appendage flow velocities decreased significantly in group 2, but were not significantly changed in group 1. Follow-up TEE revealed that spontaneous echo contrast was persistent in all group 1 patients. In group 2, LA spontaneous echo contrast was newly observed in 9 patients (group 2A) but was persistently absent in 10 patients (group 2B). In group 2A, all of the LA appendage flow velocity profiles decreased significantly at the follow-up study. In group 2B, however, only LA appendage inflow velocity integral showed significant decrease on follow-up; there were no significant changes in LA appendage outflow velocity indexes and peak inflow velocity. LA appendage flow velocity may decrease with time in some patients with AF, and this change is associated with a new occurrence of LA spontaneous echo contrast. For patients without LA spontaneous echo contrast, serial follow-up of the LA appendage flow velocity profiles may be useful for predicting future development of spontaneous echo contrast. Once LA spontaneous echo contrast occurs in AF patients, it tends to persist with time and the LA appendage is usually under a persistently low flow state.

The relationship between left atrial thrombus and hematological markers in patients with chronic non-rheumatic atrial fibrillation

We examined the relationship between left atrial thrombus and hematological variables in patients with chronic non-rheumatic atrial fibrillation (NRAf). This study consisted of 122 patients, 76 men and 46 women with a mean age of 73. Transesophageal echocardiography was performed to detect left atrial thrombi, and at the same time hematological variables including hematocrit, platelet count, fibrinogen level, thrombin-antithrombin III complex (TAT), D-dimer (DD) and fibrin degradation product E (FDP-E) levels were measured. Left atrial thrombi were detected in 28 (23%) of the 122 chronic NRAf patients. The serum fibrinogen was significantly higher in thrombus-positive patients than thrombus-negative patients (400 +/- 140 mg/dl vs. 274 +/- 69 mg/dl, p < 0.0001). The patients with left atrial thrombi had significantly higher levels of serum DD (302 +/- 200 vs. 157 +/- 101 ng/ml, p < 0.0001) and FDP-E (169 +/- 129 vs. 85 +/- 68 ng/ml, p < 0.0001) than the patients without. Scoring was made based on the levels of fibrinogen, DD and FDP-E as follows: 0 points if fibrinogen was under 380 mg/dl and 1 points if was 380 mg/dl or over, 0 points if DD was under 150 ng/ml, 1 points if 150 ng/ml or over and under 250 ng/ml, 2 points if 250 ng/ml or over, 0 points if FDP-E was under 70 ng/ml, 1 points if 70 ng/ml or over and under 140 ng/ml, 2 points if 140 ng/ml or over. According to the combined scores for these 3 markers, the prevalence of positive left atrial thrombi was 4% in 46 patients with 0 points, 18% in 38 patients with 1 or 2 points, 38% in 26 patients with 3 or 4 points and 75% in 12 patients with 5 points.

649 Restoration of sinus rhythm decreases the incidence of left atrial spontaneous echocardiographic contrast in patients with chronic nonrheumatic atrial fibrillation: An echocardiographic study

649 Restoration of sinus rhythm decreases the incidence of left atrial spontaneous echocardiographic contrast in patients with chronic nonrheumatic atrial fibrillation: An echocardiographic study

Relation of Left Atrial Spontaneous Echo Contrast With Prethrombotic State in Atrial Fibrillation Associated With Systemic Hypertension, Idiopathic Dilated Cardiomyopathy, or No Identifiable Cause (Lone)

To investigate the association of left atrial (LA) spontaneous echo contrast with the hemostatic state in nonrheumatic atrial fibrillation (AF), we examined the plasma levels of prothrombin fragment 1+2 and fibrinopeptide A in 73 patients with chronic nonrheumatic AF undergoing transesophageal echocardiography and 38 age-matched normal subjects. The results support the theory that LA spontaneous echo contrast in nonrheumatic AF is associated with a hypercoagulable state, especially in patients with marked LA spontaneous echo contrast.

Natural History of Left Atrial Spontaneous Echo Contrast in Nonrheumatic Atrial Fibrillation

A prospective study was designed to investigate potential changes of left atrial (LA) spontaneous echo contrast with time and the effects of antithrombotic therapy on its presence in 77 patients with chronic nonrheumatic atrial fibrillation (AF), using serial transesophageal echocardiography (TEE). During a mean follow-up period of 20 ± 15 months (range 6 to 77), a total of 197 TEE studies were performed in these patients. Baseline TEE revealed that LA spontaneous echo contrast was absent in 43 patients (group 1) and present in 34 (group 2). LA thrombus was found in 8 of group 2 but in none of the group 1 patients. During the follow-up period, only 2 of the group 1 patients were receiving antithrombotic agents; the patients in group 2 without LA thrombus were treated with either warfarin or aspirin, whereas those with LA thrombus were treated with warfarin. On the latest TEE study, LA spontaneous echo contrast was observed in 19 of the group 1 patients (44%) and was persistently found in all of the group 2 patients. During the study period, no patient was found to develop new LA thrombus formation and only 4 episodes of transient ischemic attack were recorded in 4 patients (embolic event rate = 3.1% per year). Of these, 2 were observed in group 1 and the remaining 2 were from group 2 and under aspirin therapy (event rate = 2.2% and 4.7% per year, respectively). In the subgroup of patients with LA thrombus receiving warfarin therapy, follow-up TEE revealed complete resolution of the thrombi in 6 and partial resolution in the remaining 2 in spite of the persistence of LA spontaneous echo contrast; none of these patients developed clinical thromboembolic events during the study period. Thus, future occurrence of LA spontaneous echo contrast could be observed by serial TEE at a substantial rate in patients with nonrheumatic AF who have no LA spontaneous echo contrast; follow-up TEE should be recommended for these patients to detect early the potential occurrence of LA spontaneous echo contrast if preventive antithrombotic therapy is not considered. Although warfarin therapy is associated with resolution of LA thrombus, neither warfarin nor aspirin is effective for suppressing the presence of LA spontaneous echo contrast in nonrheumatic AF.

Antithrombotic treatment in chronic non-rheumatic atrial fibrillation

Antithrombotic treatment in chronic non-rheumatic atrial fibrillation

Prevalence and clinical significance of left atrial thrombus in nonrheumatic atrial fibrillation

The prevalence and clinical significance of left atrial thrombus were prospectively investigated in a consecutive series of 219 patients with chronic nonrheumatic atrial fibrillation using transesophageal echocardiography. Fifteen left atrial thrombi were detected in 15 of the 219 patients (6.8%); 12 of these thrombi (80%) were confined to the left atrial appendage. Left atrial spontaneous echo contrast was visualized in 85 patients (39%). All the thrombi were found in the left atria with spontaneous echo contrast. Patients with left atrial thrombus had significantly lower left ventricular ejection fraction than those without (49±14% vs. 59±14%; P<0.05). Multivariate analysis among clinical and transthoracic echocardiographic variables showed that left ventricular ejection fraction <50% was the only independent predictor for the presence of left atrial thrombus. A history of thromboembolism was significantly more frequent in patients with left atrial thrombus than in those without (73% vs. 32%; P<0.005). The presence of left atrial thrombus was more specific than spontaneous echo contrast for predicting history of thromboembolism (97% vs. 80%), but its sensitivity was significantly lower (14% vs. 73%). We conclude that: (1) Transesophageal echo-detected left atrial thrombus is not uncommon in patients with chronic nonrheumatic atrial fibrillation and is exclusively observed in those with left atrial spontaneous echo contrast. (2) Impaired left ventricular systolic function may predispose the left atrial thrombus formation. (3) Left atrial thrombus is a highly specific but insensitive predictor for thromboembolic events.

Influence of left ventricular diastole on left atrial appendage blood flow in patients with nonrheumatic atrial fibrillation.

The function of the left atrial appendage (LAA) reflected by the Doppler flow velocity at the outlet of the left atrial appendage has been reported to be correlated with spontaneous echo contrast and thrombus formation. To evaluate the influence of left ventricular diastole on LAA flow during atrial fibrillation (AF), 81 patients with chronic nonrheumatic AF were studied by transesophageal echocardiography. The peak outflow velocity of LAA during ventricular diastole was higher than that during ventricular systole (0.23 +/- 0.14 vs. 0.15 +/- 0.13 m/s, p < 0.001). The peak inflow velocity of LAA during ventricular diastole was also higher than that during ventricular systole (0.22 +/- 0.15 vs. 0.18 +/- 0.11 m/s, p < 0.01). Patients with a good left ventricular ejection fraction have a significantly higher peak LAA outflow velocity and a larger diastolic augmentation of LAA outflow (defined by the difference of LAA outflow between systolic and diastolic phases) than patients with an impaired left ventricular function. Thus, left ventricular diastole might have an influence on LAA flow during AF. In addition, the left ventricular function might be considered a predictor of subsequent thromboembolism from the viewpoint of its effect on LAA flow in patients with nonrheumatic AF.

Clinical, adrenergic and heart endocrine measures in chronic atrial fibrillation as predictors of conversion and maintenance of sinus rhythm after direct current cardioversion.

The aim of this study was to evaluate clinical, adrenergic and endocrine factors that could predict sinus rhythm maintenance after direct current cardioversion in chronic atrial fibrillation. Nineteen patients with chronic non-rheumatic atrial fibrillation (mean duration 6 +/- 5 months) were studied. They were exercised 24 h before cardioversion at maximum effort with the Naughton protocol. Heart rate and blood pressure at rest and exercise were recorded and blood samples were taken for the assessment of adrenergic activity, by measuring cyclic adenosine monophosphate, heart endocrine function, atrial natriuretic peptide and its second messenger, cyclic guanosine monophosphate. Fifteen of the 19 patients were initially converted to sinus rhythm (eight patients with external and seven patients with internal DC shocks). After 3 months eight patients remained in sinus rhythm and 11 had relapsed, most of them within the first month. On exercise the chronotropic response was lower in the group who remained in sinus rhythm than in the group in atrial fibrillation (peak heart rate 147 +/- 11 beats.min-1 vs 165 +/- 24 beats.min-1 P = 0.02). During exercise, the systolic blood pressure in the sinus group reached higher values than in the group who relapsed (192 +/- 17 mmHg vs 176 +/- 18 mmHg, P = 0.03). Cyclic adenosine monophosphate increased significantly from rest to peak exercise in the sinus rhythm group (from 23 +/- 9 pmol.ml-1 to 31 +/- 15 mol.ml-1, P = 0.02) while it remained unchanged in the atrial fibrillation group (25 +/- 10 pmol.ml-1 to 24 +/- 8 pmol.ml-1, P = 0.02). For all 19 patients the difference in cyclic adenosine monophosphate between rest and exercise was negatively correlated with maximum heart rate (r = 0.58, P = 0.009). Atrial natriuretic peptide increased from rest to peak exercise in the sinus rhythm group (from 129 +/- 58 fmol.ml-1 to 140 +/- 66 fmol.ml-1) while it remained unchanged in the group in which atrial fibrillation persisted or recurred (from 112 +/- 58 fmol.ml-1 to 111 +/- 53 fmol.ml-1, P = 0.002). A significant correlation between atrial natriuretic peptide and cyclic guanosine monophosphate levels at exercise before cardioversion was found for the sinus rhythm group only (r = 0.76, P = 0.02). In patients with non-rheumatic chronic atrial fibrillation evaluation of clinical parameters such as heart rate and blood pressure changes during maximal exercise can be useful in the choice of suitable therapy. An inadequate increase in plasma cyclic-adenosine monophosphate and atrial natriuretic peptide on exercise could predict patients with more severe underlying disease, where cardioversion should not be recommended.

Role of transesophageal echocardiography in the detection of left atrial thrombus in patients with chronic nonrheumatic atrial fibrillation

Transesophageal echocardiography was used to assess cardiac abnormalities associated with embolization in patients who had completed the Department of Veterans Affairs Cooperative Study of Stroke Prevention in Nonrheumatic Atrial Fibrillation at the Minneapolis and West Haven Department of Veterans Affairs Medical Centers without an embolic event. Patients were men, 71 ± 7 years old, with atrial fibrillation of 6.2 ± 4.3 years' duration who had received warfarin ( n = 32) or placebo ( n = 23) for 2 years. Thrombi were found in 5 of 55 patients (warfarin 4 and placebo 1; p = 0.39); spontaneous echo contrast was seen in 4 of 5 patients. Other abnormalities identified included spontaneous echo contrast (47%), patent foramen ovale (54%), atrial septal aneurysm (7.3%), and left ventricular thrombus (3.6%). During 34 months of posttreatment follow-up, 5 patients had a stroke (1 fatal), and 10 died. Potential sources of emboli did not predict subsequent outcome. Thus warfarin therapy did not preclude the presence of thrombi. Stroke reduction likely involves the prevention of emboli from sources in addition to the atrial appendage.

Clinical Significance of Fibrillatory Wave Amplitude: A Clue to Left Atrial Appendage Function in Nonrheumatic Atrial Fibrillation

Seventy-eight patients with chronic nonrheumatic atrial fibrillation were studied by transesophageal echocardiography with regard to the left atrial appendage function and its relation to the coarseness of atrial fibrillation on electrocardiogram. These 78 patients (52 men and 26 women; mean age, 66 +/- 10 years; range, 40 to 94 years) were classified into two groups according to the presence of coarse (group 1, n = 46; those with the greatest amplitude of fibrillatory wave in lead V1 > or = 1 mm) or fine (group 2, n = 32; those without the coarse fibrillatory wave in lead V1) atrial fibrillation on a standard 12-lead electrocardiogram within 1 month of echocardiographic studies. There were no significant differences in age, sex, mean duration of atrial fibrillation, left ventricular end-diastolic dimension, left ventricular end-systolic dimension, left ventricular ejection fraction, and left atrial dimension between the two groups. In group 1, however, the left atrial appendage ejection fraction (24.4 +/- 14.2% vs 32.6 +/- 14.8%; p < 0.05) and the peak emptying velocity (21.7 +/- 12.6 cm/s vs 30.4 +/- 14.3 cm/s; p < 0.01) were lower than those in group 2. There were higher incidences of left atrial appendage spontaneous echo contrast (26/46 vs 7/32; p < 0.005) and thrombus (8/46 vs 0/32; p < 0.05) in group 1 patients. The coarse atrial fibrillation revealed a sensitivity of 80.0%, a specificity of 58.1%, a positive predictive value of 60.9%, and a negative predictive value of 78.1% for the presence of left atrial appendage spontaneous echo contrast and/or thrombus formation. In conclusion, in patients with coarse nonrheumatic atrial fibrillation, the left atrial appendage function is usually poor and the incidence of spontaneous echo contrast and thrombus formation appears to be higher in these patients.

Clinical Implications of Left Atrial Appendage Flow Patterns in Nonrheumatic Atrial Fibrillation

Left atrial appendage (LAA) function and flow patterns in 29 patients with chronic nonrheumatic atrial fibrillation were studied by transesophageal echocardiography. These 29 patients (16 men and 13 women; mean age, 63.8 years; range, 38 to 77 years) were classified into two groups according to different LAA flow patterns. Seventeen patients (group 1) had well-defined LAA emptying and filling Doppler flow signals, and the other 12 patients (group 2) had very low LAA flow signals. No significant differences were found in age, sex, mean duration of atrial fibrillation, left ventricular end diastolic dimension, and left ventricular ejection fraction between the two groups. However, group 2 patients had larger left atrial diameter (42.8 +/- 4.2 mm vs 36.6 +/- 8.8 mm; p < 0.05), lower LAA ejection fraction (26.4 +/- 15.2 percent vs 42.6 +/- 14.1 percent; p < 0.05), and lower LAA peak emptying velocity (0.13 +/- 0.03 m/s vs 0.36 +/- 0.16 m/s; p < 0.001). Higher incidence of LAA spontaneous echocardiographic contrast formation in group 2 patients (8/12 vs 1/17; p < 0.001) was noted. In conclusion, a subset of patients with nonrheumatic atrial fibrillation were found to have lower LAA blood flow and poorer LAA function. These patients had higher incidence of left atrial or LAA spontaneous echo contrast formation which had been proved previously to be a marker for future systemic thromboembolism.

Clinical implications of left atrial spontaneous echo contrast in nonrheumatic atrial fibrillation

The prevalence and clinical significance of left atrial (LA) spontaneous echo contrast were investigated in 103 consecutive patients with chronic nonrheumatic atrial fibrillation (AF) using transesophageal echocardiography. LA spontaneous echo contrast was visualized in 25 of 103 patients (24.3%). Age, sex, LA diameter, left ventricular diastolic and systolic dimensions, left ventricular ejection fraction, and the percentage of lone AF were not significantly different between patients with and without LA spontaneous echo contrast; however, those with LA spontaneous echo contrast were less likely to have moderate or severe mitral regurgitation. LA thrombi were observed in 7 patients (6.8%), and all 7 thrombi were found in the atria with spontaneous echo contrast. History of cerebral ischemia or peripheral embolism, or both, was significantly more frequent in patients with than without LA spontaneous echo contrast (84 vs 18%; p < 0.001). The presence of LA spontaneous echo contrast was highly specific (94%) and predictive for thromboembolic events (positive and negative predictive values of 84 and 82%, respectively). Thus, transesophageal echo-detected LA spontaneous echo contrast is frequently found in patients with chronic nonrheumatic AF. This phenomenon may represent a precursor of thrombus formation, and its presence is associated with an increased thromboembolic risk.

PLACEBO-CONTROLLED, RANDOMISED TRIAL OF WARFARIN AND ASPIRIN FOR PREVENTION OF THROMBOEMBOLIC COMPLICATIONS IN CHRONIC ATRIAL FIBRILLATION: The Copenhagen AFASAK Study

From November, 1985,to June, 1988, 1007 outpatients with chronic non-rheumatic atrial fibrillation (AF) entered a randomised trial; 335 received anticoagulation with warfarin openly, and in a double-blind study 336 received aspirin 75 mg once daily and 336 placebo. Each patient was followed up for 2 years or until termination of the trial. The primary endpoint was a thromboembolic complication (stroke, transient cerebral ischaemic attack, or embolic complications to the viscera and extremities). The secondary endpoint was death. The incidence of thromboembolic complications and vascular mortality were significantly lower in the warfarin group than in the aspirin and placebo groups, which did not differ significantly. 5 patients on warfarin had thromboembolic complications compared with 20 patients on aspirin and 21 on placebo. 21 patients on warfarin were withdrawn because of non-fatal bleeding complications compared with 2 on aspirin and none on placebo. Thus, anticoagulation therapy with warfarin can be recommended to prevent thromboembolic complications in patients with chronic non-rheumatic AF.