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Evaluation of left atrial filling using systolic pulmonary venous flow velocity measurements in patients with atrial fibrillation.

BACKGROUND: The pattern of pulmonary venous flow velocity is useful for understanding the hemodynamic relationship between the left atrium and left ventricle in patients with a variety of diseases, and the systolic flow wave, in particular, is considered a clinically important parameter that reflects left atrial filling. HYPOTHESIS: The study was undertaken to determine whether systolic pulmonary venous flow velocity patterns can be used to evaluate left atrial filling in patients with atrial fibrillation. METHODS: We performed transesophageal pulsed Doppler echocardiography and cardiac catheterization in 34 patients with chronic atrial fibrillation (10 with hypertrophic cardiomyopathy, 5 with dilated cardiomyopathy, 7 with previous myocardial infarction, and 12 with isolated atrial fibrillation) and 15 normal controls in sinus rhythm. RESULTS: Mean pulmonary capillary wedge pressure, V-wave height in the pulmonary capillary wedge pressure curve, and left ventricular end-diastolic pressure were significantly higher in the hypertrophic cardiomyopathy and dilated failing heart (previous myocardial infarction and dilated cardiomyopathy) groups than in the isolated atrial fibrillation and normal groups. The peak velocity and time-velocity integral of the systolic pulmonary venous flow velocity, and percent left atrial emptying fraction were significantly lower in the dilated failing heart group than in the isolated atrial fibrillation, hypertrophic cardiomyopathy, and normal groups. The peak velocity and time-velocity integral of the systolic pulmonary venous flow velocity, percent left atrial emptying fraction, and V-wave height were comparatively constant when the preceding R-R intervals were relatively stable in the isolated atrial fibrillation group and in 4 of the 10 patients with hypertrophic cardiomyopathy. However, changes in these variables correlated with the preceding R-R interval in all patients with dilated failing hearts and in 6 of the 10 patients with hypertrophic cardiomyopathy. CONCLUSION: Transesophageal pulsed Doppler echocardiographic measurements of systolic pulmonary venous flow velocity are valid indicators of left atrial filling in patients with atrial fibrillation.

Adult↗

Time-course of recovery of atrial contraction after cardioversion of chronic atrial fibrillation.

We aimed to study the time-course of recovery of atrial contraction after cardioversion of chronic atrial fibrillation (duration of more than 3 months) to sinus rhythm. Using M-mode, two-dimensional and pulsed Doppler echocardiography, we determined left atrial (LA) and ventricular (LV) dimensions, peak velocities, and velocity-time integrals of early and atrial filling velocity-time profiles in both LV and right ventricular (RV) inflows (peak E and peak A, Ea and Aa). Results of the LA and LV functions in seven elderly patients (an initial study group) were as follows. The extent of the LA dimensional reduction resulting from atrial contraction was significantly increased up to 5-8 weeks compared with values 0-1 day after cardioversion [from 1.3 +/- 0.8 (mean +/- SD) mm to 3.9 +/- 1.1, P < 0.01]. In conjunction with the progressive increase in peak A, the ratio of peak E to peak A (peak E/A) was significantly decreased and reached a plateau at 5-8 weeks (from 1.93 +/- 0.59 to 0.67 +/- 0.11, P < 0.01). LV fractional shortening was increased significantly 5-8 weeks after cardioversion (from 0.20 +/- 0.06 to 0.29 +/- 0.05, P < 0.01). Since a large part of the improvement in LA contraction was expected to occur in an early stage after cardioversion, we studied eight additional patients more frequently in the early stage (an additional study group). Furthermore, we studied the time course of LA and right atrial (RA) contractions.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

The pulmonary venous systolic flow pulse--its origin and relationship to left atrial pressure.

OBJECTIVES: The purpose of this study was to determine the origin of the pulmonary venous systolic flow pulse using wave-intensity analysis to separate forward- and backward-going waves. BACKGROUND: The mechanism of the pulmonary venous systolic flow pulse is unclear and could be a "suction effect" due to a fall in atrial pressure (backward-going wave) or a "pushing effect" due to forward-propagation of right ventricular (RV) pressure (forward-going wave). METHODS: In eight patients during coronary surgery, pulmonary venous flow (flow probe), velocity (microsensor) and pressure (micromanometer) were recorded. We calculated wave intensity (dP x dU) as change in pulmonary venous pressure (dP) times change in velocity (dU) at 5 ms intervals. When dP x dU > 0 there is a net forward-going wave and when dP x dU < 0 there is a net backward-going wave. RESULTS: Systolic pulmonary venous flow was biphasic. When flow accelerated in early systole (S1), pulmonary venous pressure was falling, and, therefore, dP x dU was negative, -0.6 +/- 0.2 (x +/- SE) W/m2, indicating a net backward-going wave. When flow accelerated in late systole (S2), pressure was rising, and, therefore, dP x dU was positive, 0.3 +/- 0.1 W/m2, indicating a net forward-going wave. CONCLUSIONS: Pulmonary venous flow acceleration in S1 was attributed to a net backward-going wave secondary to a fall in atrial pressure. However, flow acceleration in S2 was attributed to a net forward-going wave, consistent with propagation of the RV systolic pressure pulse across the lungs. Pulmonary vein systolic flow pattern, therefore, appears to be determined by right- as well as left-sided cardiac events.

Aged↗

Monitoring the effect of anticoagulants on left atrial thrombi in patients with rheumatic heart disease: assessment with 111In-oxine-labelled platelet heart scintigraphy and transoesophageal echocardiography.

111In-oxine-labelled platelet heart scintigraphy (In-plt) was used to evaluate the activity of left atrial thrombi detected by transoesophageal echocardiography (TEE) in 16 cases of rheumatic heart disease. The effect of anticoagulants on the therapeutic intervention of these patients was evaluated by In-plt and TEE. In-plt was performed in all patients in serial pre- and post-anticoagulant therapy studies with anterior, 45 degrees left anterior oblique and left lateral views taken daily from the second to sixth day after injection of labelled platelets. After discontinuing anticoagulants for at least 1 week, only nine cases of left atrial thrombi were detected among the 16 cases by initial In-plt. After anticoagulants were again used for at least 3 weeks, all nine positive cases became negative on repeat In-plt. These results suggest that the diagnostic sensitivity of In-plt is lower than that of TEE. However, In-plt is more suitable and useful for evaluating the activity of left atrial thrombi after antithrombotic agent therapy and for monitoring the effect of anticoagulant therapy on left atrial thrombi in patients with rheumatic heart disease.

Adult↗

Fuzzy logic and continuous cellular automata in warfarin dosing of stroke patients.

"Evidence-based" recommendations for warfarin prescription in patients with history of ischemic stroke limit its use to prevention of stroke due to atrial fibrillation. Warfarin is also prescribed by the authors to prevent thrombosis in stroke patients with thrombophilia and potential cardiac or arterial source for thromboembolism. These potential conditions, in the face of thrombophilia, include, but may not be limited to, dilated cardiomyopathy, decreased left ventricular function, atrial septal aneurysm with or without patent foramen ovale (PFO), PFO with evidence of pelvic or lower extremity deep venous thrombosis or with clear thrombophilia, spontaneous echocardiographic contrast, intracardiac or intra-arterial thrombus, intra-aortic arch thrombus, high degree of stenosis of large- and medium-sized cerebrovascular arteries, and arterial dissection. Commonly diagnosed thrombophilic states in our population currently include protein S or C deficiency, antiphospholipid antibodies, and less commonly ATIII deficiency, factor V Leiden mutation, G20210A PT mutation, and plasminogen activator inhibitor-1 mutation. Thrombophilic states often occur in combination. The occurrence of combined arterial, cardiac, and thrombophilic sources of thromboembolism poignantly describes the complexity of causation of ischemic stroke in any one patient. Our practice of treating the complex interaction of thromboembolic sources is based on scientific evidence, which is not arbitrarily limited to probability-based statistics. Warfarin is well known in the clinical setting to interact with many different contextual factors of the individual patient, making its dosing and response unique to that patient. We have shown why the indications for warfarin use and its dosing cannot be directly extrapolated to the individual patient from the results of large, double-blind, randomized trials. In practice, the unique patient and his or her context must be considered by the expert physician who makes the therapeutic decision. The context includes, but is not limited to, known pathologies that contribute to thrombus formation according to the accepted pathophysiologic model of thrombosis based on Virchow's triad of altered flow, endothelium, and blood components.

Journal Article↗

Cardiac resynchronization therapy restores optimal atrioventricular mechanical timing in heart failure patients with ventricular conduction delay.

We characterized the relationship between systolic ventricular function and left ventricular (LV) end-diastolic pressure (LVEDP) in patients with heart failure (HF) and baseline asynchrony during ventricular stimulation. The role of preload in the systolic performance improvement that can be obtained in HF patients with LV stimulation is uncertain.We measured the maximum rate of increase of LV pressure, LVEDP, aortic pulse pressure (PP) and the atrioventricular mechanical latency (AVL) between left atrial systole and LV pressure onset in 39 patients with HF. Two subgroups were identified: "responder" if PP improved, or "nonresponder."Maximum hemodynamic improvement occurred at an atrioventricular (AV) delay that did not decrease LVEDP. Left ventricular and biventricular (BV) stimulation increased systolic hemodynamics significantly, despite no significant increase in LVEDP. All parameters decreased when the LVEDP was decreased by shorter AV delay. Left ventricular and BV stimulation provided better hemodynamics than right ventricular (RV) stimulation. For the nonresponder subgroup, systolic hemodynamics only worsened during AV delay shortening. For the responder subgroup, optimum PP was achieved when AVL was near zero. Restoration of optimal left atrial-ventricular mechanical timing partly contributes to the hemodynamic improvements observed in this patient subgroup. However, preload alone cannot explain the differences seen between RV and BV stimulation and the contradictory PP decreases even at maximal preload in the nonresponder subgroup. These results may be explained by a site-dependent mechanism such as the degree of ventricular synchrony. Caution should be taken in these patients when optimizing AV delays using echocardiography techniques that focus on LV inflow.

Atrial Function, Left↗

Transesophageal echocardiographic guidance of cardioversion in patients with atrial fibrillation.

The role of TEE in the guidance of cardioversion of atrial fibrillation was studied. Thirty-seven (18%) of 206 patients had left atrial thrombus. Cardioversion was attempted in 153 patients receiving no (n = 107) or < 7 days (n = 46) of anticoagulation prophylaxis, in 27 patients after > or = 3 weeks of anticoagulation, and was cancelled in 26 patients, primarily on the basis of TEE findings. Left atrial thrombus was observed in 37 (18%) of 206 patients. No embolic complications occurred over a 4-week follow-up period. In 7 (41%) of 17 patients new left atrial appendage spontaneous echocardiographic contrast developed immediately after electric cardioversion. In this group, significant decreases occurred in the left atrial appendage maximal emptying shear rate (11.1 +/- 11.1 sec-1 vs 5.0 +/- 5.1 sec-1; p < 0.05), maximal filling shear rate (6.7 +/- 5.9 sec-1 vs 3.7 +/- 3.5 sec-1; p < 0.05), and peak emptying velocity (0.38 +/- 0.29 cm/sec vs 0.19 +/- 0.14 cm/sec; p < 0.05). In one patient a left atrial appendage thrombus formed after electric cardioversion. Left atrial thrombus resolved in 1 (5%) of 21 patients and became immobile in 0 (0%) of 16 patients after 3 to 5 weeks of anticoagulation but resolved (n = 9) or became immobile (n = 6) in 15 (71%) of 21 patients after > 5 weeks of anticoagulation. TEE-guided cardioversion was safely done without or with < 7 days of anticoagulation prophylaxis in selected patients, but the potential for left atrial thrombus to form after electric cardioversion makes anticoagulation advisable in all patients. The conventional recommendation of 3 to 4 weeks of anticoagulation prophylaxis before cardioversion is usually inadequate for left atrial thrombus to resolve or to become immobile.

Adult↗

[Cerebral infarction, pseudolupic syndrome and myxoma of the left atrium].

Left atrial myxomas are a rare stroke etiology (0.4%). They frequently present general symptoms such as fever, weight loss and an inflammatory syndrome, but the pseudolupic syndrome with cutaneous features and vasomotor symptoms is rarely described. We report the case of a 38-year old man who presented in March 1995 a stroke caused by a left atrial myxoma. There was also pseudolupic clinical and biological manifestations which disappeared after ablation of the myxoma. Cerebral angiography showed a small carotid aspect which evoked carotid dissection or carotid siphon occlusion. The authors discuss neurologic and pseudolupic manifestations of left atrial myxomas, and their physiopathologic mechanism.

Adult↗

Prediction of outcome of electrical cardioversion by left atrial appendage flow velocities in atrial fibrillation.

We evaluated the usefulness of left atrial appendage (LAA) flow velocity during atrial fibrillation as an objective measure for prediction of the outcome of electrical cardioversion. Left atrial appendage peak velocities were measured by transesophageal echocardiography before cardioversion in 56 patients. Left atrial thrombus was demonstrated in 6 (11%) of these patients. Cardioversion was then performed in the 50 patients who did not have a thrombus and in 1 patient whose left atrial thrombus disappeared after anticoagulant therapy (n = 51). Thirty-eight patients converted to sinus rhythm which remained stable until discharge (initial success group). Of these, long-term (> 6 months) maintenance of sinus rhythm was achieved in 31 patients (82%). Five patients with almost no detectable appendage contractions during atrial fibrillation were classified in the initial failure group. The peak LAA flow velocity was significantly higher in patients with the initial success group compared with the patients in the initial failure group (25.6 +/- 12.0 vs 15.3 +/- 10.7 cm/s, respectively; p < 0.01). Left atrial appendage flow velocity during atrial fibrillation may be useful for identifying candidates for electrical cardioversion.

Adult↗

beta-Adrenoceptors potentiate alpha1-adrenoceptor-mediated inotropic response in rat left atria.

AIM: To investigate whether stimulation of beta-adrenoceptor (AR) and its subtypes augment alpha1-AR-evoked positive inotropic response and inositol phosphate (InsP) accumulation in isolated rat left atria. METHODS: Inotropic response was determined by contractile function experiment in isolated electrically driven rat left atria. 3H-InsP accumulations were measured by 3H-inositol incorporation and column chromatography. RESULTS: (1) Stimulation of alpha1-AR by phenylephrine (PE) or norepinephrine (NE) in the presence of propranolol (Prop) evoked positive inotropic response and 3H-InsP accumulations, while stimulation of beta-AR by isoprenaline (ISO) or NE in the presence of phentolamine (Phen) only evoked positive inotropic response, but not 3H-InsP accumulations. (2) Simultaneous stimulation of alpha1- and beta-AR by NE or ISO plus PE significantly shifted the concentration-dependent inotropic response curves and 3H-InsP accumulation curves to the left and upward compared with individual alpha1-AR stimulation by PE or NE in the presence of Prop. (3) In the presence of ICI118551 (selective beta2-AR antagonist) or CGP12177 (selective beta1-AR antagonist), stimulation of either beta1- or beta2-AR did not change alpha1-AR-evoked inotropic response and 3H-InsP accumulations. CONCLUSION: Stimulation of beta1-AR and beta2-AR potentiates alpha1-AR-mediated positive inotropic response and InsP accumulation in isolated rat left atria.

Adrenergic alpha-1 Receptor Agonists↗

Impaired cardiac performance relating to delayed left atrial activation after atrial compartment operation for chronic atrial fibrillation.

In the presence of a normal atrial systole and optimal AV delay, atrial kick contributes to a significant fraction of the stroke volume. This atrial contribution may be lost during atrial asystole or mismatch in the timing of atrial and ventricular contraction. A patient received atrial compartment operation for his chronic AF. Although the AF was successfully converted to sinus rhythm, the conduction from the right to left atrium was markedly delayed so that the left atrial and ventricular activations occurred almost simultaneously. This delay in left atrial activation resulted in impaired cardiac performance.

Atrial Fibrillation↗

Regional left atrial coagulation and fibrinolytic activities in patients with mitral stenosis.

Systemic thromboembolism is a major complication of mitral stenosis (MS), especially in those patients having atrial fibrillation (AF). Recent evidence has suggested that regional left atrial coagulation activity may be increased in MS and may contribute to the pathophysiology of left atrial thrombus. However, the relation of left atrial coagulation activity to factors that predispose to left atrial thrombus formation is unknown. Also, the relations between left atrial and systemic coagulation activity, fibrinolysis, and platelet activation remain unresolved. Left atrial and peripheral venous levels of fibrinogen, antithrombin III, factor VII and factor VIII for coagulation, D-dimer, tPA and PAI-I, plasmin and antiplasmin for fibrinolysis, and platelet factor 4 and vWF for platelet activation, and endothelial dysfunction were measured in 46 patients with MS and normal clotting times who were undergoing percutaneous mitral valvuloplasty. Left atrial tPA, plasmin, PAI-I, antiplasmin, PF4, and vWF levels exceeded the corresponding peripheral venous levels (P < 0.05) in patients with MS, being more significant in the AF subgroup. There were no significant differences between left atrial and peripheral venous levels of fibrinogen, D-dimer, factor VII, and factor VIII within the patient group (P > 0.05). The results suggest that there are significant variations in the indices of coagulation, fibrinolytic system and platelet activation, and endothelial dysfunction between left atrial and peripheral venous blood samples of patients with MS that may be due to limited spillover from the left atrium to the systemic circulation.

Adult↗

Left atrial dilatation in constrictive pericarditis: a pre and post-operative echocardiographic study.

Thirty-three surgically proven cases of constrictive pericarditis were studied pre-operatively by echocardiography for left atrial dilatation and 18 of them underwent post-operative study at a mean follow-up period of 229 +/- 105 days. The degree of left atrial dilatation in these patients was compared with patients of restrictive cardiomyopathy (n = 8) and sex matched controls of similar age (n = 33). Significant left atrial dilatation was present in patients of constrictive pericarditis compared to controls and it was of a similar or greater degree compared to patients of restrictive cardiomyopathy (the left atrium to aorta ratio was 1.7 +/- 0.31, 1.53 +/- 0.18 and 1.07 +/- 0.1, in constrictive pericarditis, restrictive cardiomyopathy and controls, respectively, P = NS for constrictive pericarditis vs. restrictive cardiomyopathy and P < 0.001 for constrictive pericarditis vs. controls). There was no correlation of degree of left atrial dilatation with clinical and hemodynamic variables. Postoperatively, there was regression of left atrial size in patients with normal hemodynamics (n = 12, pre- vs. post-operative left atrium to aorta ratio 1.65 +/- 0.23 vs. 1.32 +/- 0.14, P < or = 0.001) and persisting or increasing left atrial dilatation in patients with persisting hemodynamic abnormality (n = 6, left atrium to aorta ratio 1.66 +/- 0.23 vs. 1.82 +/- 0.15, P = NS). We conclude that significant left atrial dilatation is a consistent echocardiographic feature of constrictive pericarditis. Hemodynamic normalization following successful pericardiectomy is associated with regression of atrial size.

Adolescent↗

Left atrial filling volume can be used to reliably estimate the regurgitant volume in mitral regurgitation.

OBJECTIVES: The objective was to analyze the accuracy and diagnostic value of the estimated regurgitant volume of mitral regurgitation using 1) left atrial volume variation during ventricular systole (left atrial filling volume) and 2) the percent of systolic pulmonary vein velocity integral compared with its total. BACKGROUND: Left atrial filling volume (LAfill), which represents the atrial volume variation during ventricular systole, has been used for the assessment of mitral regurgitation severity. A good correlation with invasive semiquantitative evaluation was found, but with an unacceptable overlapping among grades. The reason could be the absence of information concerning the contribution of blood entering into the left atrium from the pulmonary veins. METHODS: Doppler regurgitant volume (Dpl-RVol) (mitral stroke volume - aortic stroke volume) was measured in 30 patients with varying degrees and etiological causes of mitral regurgitation. In each patient atrial volumes were measured from the apical view, using the biplane area-length method. The systolic time-velocity integral of pulmonary vein flow was expressed as a percentage of the total (systolic-diastolic) time-velocity integral (PVs%). These parameters were used in this group of patients to obtain an equation whose reliability in estimating Dpl-RVol was tested in a second group of patients. RESULTS: In the initial study group, with linear regression analysis the following parameters correlated with Dpl-RVol: end-systolic left atrial volume (R2=0.37, p=0.0004); LAfill (R2=0.45, p < 0.0001); PVs% (R2=0.56, p < 0.0001). In multiple regression analysis the combination of LAfill and the percent of the systolic pulmonary vein velocity integral (PVs%) provided a more accurate estimate of regurgitant volume (R2=0.88; SEE 10.6; p < 0.0001; Dpl-RV=6.18 + (1.01 x LAfill) - (0.783 x PVs%). The equation was subsequently tested in 54 additional patients with mitral regurgitation with a mean Dpl-RVol 27+/-37 ml. Estimated regurgitant volume and Dpl-RVol correlated well with each other (R2=0.90; SEE 12.1; p < 0.0001). In the test population, the equation was 100% sensitive and 98% specific in detecting a regurgitant volume higher than 55 ml. CONCLUSIONS: Left atrial filling volume and pulmonary vein flow give a reliable estimate of regurgitant volume in mitral regurgitation.

Adult↗

Stunning of the left atrium after pharmacological cardioversion of atrial fibrillation.

INTRODUCTION: Stunning of the left atrium and atrial appendage is a well known but not fully clarified phenomenon observed during the cardioversion of atrial fibrillation regardless of the cardioversion method attempted. AIM: To assess the effects of propafenone and amiodarone on left atrium and left atrial appendage contractility. METHODS: Forty patients with paroxysmal atrial fibrillation (20 females, 20 males), aged 60-83 (mean 72.0+/-10.1) years, were enrolled into the study. Half of these patients had sinus rhythm restored by the administration of oral propafenone (150-300 mg) and the remaining 20 patients were treated with intravenous amiodarone (150-450 mg). The control group consisted of 20 patients (10 females, 10 males) aged 52-78 (mean 61.2+/-9.3) years with sinus rhythm and no history of atrial fibrillation. All the patients had a transthoracic (TTE) and transesophageal (TEE) echocardiography performed while still in the AF, before drug administration and 1 hour after sinus rhythm restoration. RESULTS: All haemodynamic parameters of the left atrium measured after the sinus rhythm restoration were significantly worse when compared with the control group. Left atrial fractional shortening and total atrial fraction were significantly lower after propafenone than amiodarone (8.6+/-3.6% vs 11.7+/-5.5%, p<0.05; and LA FC 16.2+/-5.3% vs 23.3 (+/-6.3)% respectively, p<0.05). Doppler echocardiographic parameters included in the analysis such as mitral flow and superior left pulmonary vein flow were significantly lower in the sinus rhythm restoration group than in the control group. Among them the end-diastolic mitral flow velocity amplitude and flow velocity integral as well as the maximum pulmonary retrograde velocity were significantly worse in the group treated with propafenone than in patients receiving amiodarone. All the atrial appendage Doppler velocity parameters were significantly reduced after the sinus rhythm restoration in both groups. In the patients treated with propafenone, values of these parameters were significantly decreased compared with the patients receiving amiodarone. CONCLUSIONS: Successful pharmacological cardioversion of atrial fibrillation causes the left atrium and left atrial appendage contractility impairment similar to that observed with other methods of the sinus rhythm restoration. Following the AF cardioversion the level of left atrial stunning is higher in the patients treated with propafenone than in subjects receiving amiodarone.

Aged↗

[The frequency of left atrial spontaneous echo contrast and its clinical significance in mitral valve insufficiency].

The authors investigated the frequency of left atrial spontaneous echo contrast in mitral valve disease. They also tested whether there was any correlation between the presence of left atrial spontaneous echo contrast and the severity of the mitral valve disease. Echocardiographic investigations were performed using both transthoracal and transesophageal echocardiographic methods employing monoplane transducer. The authors carried out 273 transesophageal investigations over a period of 2 years and found left atrial spontaneous echo contrast in 85 patients, who had mitral valve disease. Of this, in 18 cases thrombi were also detected in the left atrium and/or auricula. The diagnoses of mitral stenosis were made in 24 patients, of whom in 12 cases the stenosis were found to be severe, whilst in 12 cases to be moderate. Furthermore insufficiency of the mitral valve was detected in 35 cases. 20 patients had artificial mitral valve implanted, they received long term anticoagulant treatment. 59 patients had no spontaneous echo contrast. 14 patients had previous embolic events of which 9 were cerebral and in other cases arteries of the kidney, eye and extremities were affected. 71 patients had no history of embolism. The authors concluded that mitral valve disease, particularly mitral stenosis is frequently associated with left atrial spontaneous echo contrast. It has been also observed, that the more severe the mitral valve disease, the greater the probability of left atrial spontaneous echo contrast. In all cases where thrombi were found, left atrial echo contrast were demonstrated and the risk of embolism is high. In these cases anticoagulant therapy is suggested.

Adolescent↗