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Right atrial appendage thrombosis in atrial fibrillation: its frequency and its clinical predictors
Right Atrial Appendage Thrombosis in Atrial Fibrillation: Its Frequency and Its Clinical Predictors Marcello de Divitiis, MD, Heyder Omran, MD, Rami Rabahieh, MD, Barbara Rang, Stefan Illien, Rainer Schimpf, MD, Dean MacCarter, PhD, Werner Jung, MD, Harald Becher, MD, and Berndt Lu¨deritz, MD This study assesses the incidence of right atrial (RA) chamber and appendage thrombosis in patients with atrial fibrillation (AF) in relation to RA appendage morphology and function. Transthoracic and multiplane transesophageal echocardiography were performed in 102 patients with AF to assess the incidence of RA and left atrial (LA) thrombi and spontaneous echo contrast. Both right and left ventricular sizes, atrial chamber and appendage sizes and function were measured. Twentytwo patients in sinus rhythm served as the control group (SR). Complete visualization of the RA appendage was feasible in 90 patients with AF. Patients with AF had lower tricuspid annular excursion (p ⴝ 0.008) and larger RA chamber area (p ⴝ 0.0001) than patients in SR. In addition, RA appendage areas were larger (p <0.05) and RA ejection fraction and peak emptying velocities (both p <0.0001) were lower in patients with AF patients than in those in SR. Equivalent differences
were found for the LA appendage. Six thrombi were found in the RA appendage and 11 thrombi in the LA appendage in AF patients. Spontaneous echo contrast was found in 57% and 66% in the right atrium and in the left atrium, respectively. AF patients with RA appendage thrombi had a larger RA area (p ⴝ 0.0001), and lower RA appendage ejection fraction and emptying velocities (both p ⴝ 0.0001) than patients without thrombi. Spontaneous echo contrast was detected in all patients with thrombi. Spontaneous echo contrast was the only independent predictor of RA (p ⴝ 0.03) and LA appendage thrombosis (p ⴝ 0.036). In conclusion, multiplane transesophageal echocardiography allows the assessment of RA appendage morphology and function. RA spontaneous echo contrast is the only independent predictor of RA appendage thrombosis. 䊚1999 by Excerpta Medica, Inc. (Am J Cardiol 1999;84:1023–1028)
trial fibrillation (AF) is associated with an increased risk of atrial thrombosis, cerebral stroke, A and peripheral embolism compared with sinus rhythm
geal echocardiography were included in this study. Of these, we selected 90 patients (88%) in whom visualization of both RA and LA appendages was adequate to perform detailed measurements. Twenty-two patients in SR served as control group. All patients underwent both transthoracic and multiplane transesophageal echocardiographic study. The reasons for transesophageal echocardiography in patients with AF were: (1) no atrial thrombi in patients with cerebral ischemic insult (n ⫽ 10), or pulmonary (n ⫽ 2) or peripheral (n ⫽ 4) embolism of unclear origin; (2) before cardioversion for the exclusion of thrombi (n ⫽ 22); and (3) for a more accurate study of the underlying disease and better choice of anticoagulation therapy. In patients with SR, the indications were: cerebral ischemic insult of unclear origin (n ⫽ 18), and fever of unknown origin (n ⫽ 4). No patient in SR had echocardiographic signs of cardiac disease. Written informed consent was obtained from all patients. Echocardiography: All studies were conducted with commercially available equipment (Vingmed 800 C, Vingmed Sound, Horton, Norway). To allow off-line quantitative analysis of the echocardiographic data, studies were recorded on videotape with selected cine loops and velocity spectra digitally transferred to a MacIntosh PowerPC computer for subsequent analysis. Transthoracic echocardiography: The studies were performed with a 3.25-MHz transthoracic transducer
(SR).1,2 Systemic embolic risk is determined by echocardiographic factors such as left atrial (LA) size,3 spontaneous echo-contrast phenomenon,4,5 absence of mitral regurgitation,6 and impaired LA appendage function.7,8 Although right atrial (RA) appendage thrombosis has been reported in patients with AF9 –11 and although pulmonary embolism was recognized as a life-threatening complication of electrical and pharmacologic cardioversion of AF,12–15 there are no data available about RA appendage morphology and function and the incidence of RA thrombi in patients with AF.9,15 This prospective study evaluates the incidence of RA thrombosis in patients with AF and its relation to clinical and echocardiographic parameters.
METHODS
Patients: One hundred two consecutive patients with AF (on the basis of clinical history and of a 12-lead electrocardiogram) referred for transesopha-
From the Department of Cardiology, University of Bonn, Bonn, Germany. This study was supported by a grant from the Italian Society of Cardiology, Rome, Italy. Manuscript received February 23, 1999; revised manuscript received May 26, 1999, and accepted May 27. Address for reprints: Heyder Omran, MD, Department of Medicine—Cardiology, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany. E-mail: [email protected]. ©1999 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 84 November 1, 1999
0002-9149/99/$–see front matter PII S0002-9149(99)00492-0
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FIGURE 1. Visualization of RA appendage and measurement of maximal RA appendage area (see text).
FIGURE 2. LA appendage (LAA) with pulsed Doppler sample volume (upper left) and Doppler velocities (upper right) in a patient with AF. RA appendage (RAA) with pulsed Doppler sample volume (lower left) and Doppler velocities (lower right) in the same patient.
with patients in the left lateral decubitus position. A single-lead electrocardiogram was continously recorded. M-mode LA dimension was measured at endsystole in the parasternal long-axis view and left ventricular ejection fraction was measured according to the guidelines of the American Society of Echocardiography.16 Both the transverse and longitudinal diameters of the RA and LA chambers were measured by means of 2-dimensional echocardiography in the apical 4-chamber view; RA and LA area were calculated as the products of transverse and longitudinal diameters.17,18 The right ventricle was visualized in the apical 4-chamber view and its size assessed by the measurement of long-axis, maximal short-axis, and right ventricular area by the method described by Weyman.18 Tricuspidal annular excursion in the apical 4-chamber view was measured according to Kaul et al.19 as measurement of right ventricular function. Right ventricular free wall thickness was measured by M-mode in the parasternal short-axis view.20 Pulmo1024 THE AMERICAN JOURNAL OF CARDIOLOGY姞
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nary artery systolic pressure was determined by the sum of the right ventricular RA pressure gradient and an assumed RA pressure.21 Tricuspid regurgitation was graded by measurement of the regurgitant jet size according to Miyatake et al.22 Transesophageal echocardiography: Transesophageal echocardiography was performed using a 5-MHz multiplane transducer. Topical lidocaine spray and viscous lidocaine solution were used to anesthetize the oropharynx before the investigation. Cine loops of the RA and LA chambers and appendages were recorded and stored. The LA appendage was imaged in the basal short-axis view using a transverse scan. RA visualization was performed as suggested by Seward et al.23 The multiplane probe was placed posterior to the atria and the 4-chamber view was visualized; the probe was rotated to achieve visualization of the right heart chambers. The scanning plane was rotated from 90° to 20° to obtain a long-axis view of the right atrium. The junction of the superior vena cava and NOVEMBER 1, 1999
were examined for thrombi and spontaneous echo contrast. The degree of spontaneous echo contrast AF SR was classified by 2 independent observers, and by a (n ⫽ 90) (n ⫽ 22) third observer in case of disagreement, as absent (0), mild (1⫹), mild to moderate (2⫹), moderate (3⫹), or Men/women 69/21 15/7 Age (yrs) 60 ⫾ 13 58 ⫾ 17 severe (4⫹) according to Fatkin et al.24 EchocardioUnderlying disease (no.) graphic evaluations were performed in a singleCoronary heart disease 20 0 blinded manner, with the results confirmed by 2 indeArterial hypertension 19 1 pendent observers after the original examination. Mitral stenosis 8 0 Mitral regurgitation 6 0 Statistical analysis: All data are expressed as Aortic stenosis 4 0 mean ⫾ 1 SD. An unpaired Student t test was used to Aortic regurgitation 3 0 compare echocardiographic parameters between the 2 Dilated cardiomyopathy 10 0 groups. Subgroup analysis of patients with AF was Myocarditis 5 0 performed by an unpaired Mann-Whitney test, None 21 19 Neurologic deficit 10 18 whereas linear regression analysis between all paramAcute peripheral ischemia 4 0 eters in the AF group was performed by a Pearson test. Pulmonary embolism 2 0 Interobserver variability of the measurements of maxAnticoagulation therapy 50 7 imal and minimal areas and emptying velocities of RA appendage were evaluated by linear regression analysis and by the mean coefficient of variation using the forTABLE II Comparison of Echocardiographic Parameters Between Patients With AF mula: ⌺[(Observer 1 ⫺ Observer 2)/ and SR Observer 1]/n, expressed as percentAF SR p Value age. The interobserver variability regarding measurements of the same Transthoracic echocardiography RA area (cm2) 20 ⫾ 4 14 ⫾ 3 0.0001 parameters in the LA appendage in Right ventricular area (cm2) 19 ⫾ 4 19 ⫾ 6 NS our laboratory has been already reRight ventricular long axis (mm) 75 ⫾ 8 72 ⫾ 7 NS ported.25,26 Logistic regression analRight ventricular short axis (mm) 36 ⫾ 6 31 ⫾ 13 0.009 ysis was performed using the presRight ventricular wall thickness (mm) 2.9 ⫾ 0.6 2.5 ⫾ 0.6 0.05 Tricuspid annular excursion (mm) 15 ⫾ 0.4 20 ⫾ 7 0.008 ence of thrombi in the RA appendage Pulmonary artery pressure (mm Hg) 30 ⫾ 13 24 ⫾ 7 0.07 as a function of the duration of AF, LA diameter (mm) 43 ⫾ 6 35 ⫾ 4 0.0001 tricuspid annular excursion, pulmo2 LA area (cm ) 23 ⫾ 5 16 ⫾ 3 0.005 nary artery pressure, RA appendage, Left ventricular ejection fraction (%) 50 ⫾ 11 58 ⫾ 5 0.002 peak emptying velocities, and the deTransesophageal echocardiography RA appendage maximal area (cm2) 5.6 ⫾ 1.9 4.7 ⫾ 1.6 0.05 gree of spontaneous echo contrast. RA appendage ejection fraction (%) 29 ⫾ 15 49 ⫾ 13 0.0001 The same analysis was performed for RA appendage emptying velocity (m/s) 0.30 ⫾ 0.14 0.44 ⫾ 0.14 0.0001 the presence of thrombi in the LA 2 LA appendage maximal area (cm ) 5.0 ⫾ 2.1 3.5 ⫾ 1.0 0.0001 appendage as a function of age, LA LA appendage ejection fraction (%) 29 ⫾ 15 54 ⫾ 14 0.0001 LA appendage emptying velocity (m/s) 0.36 ⫾ 0.21 0.65 ⫾ 0.22 0.0001 area, LA appendage area, ejection fraction, peak emptying velocities, and spontaneous echo contrast. The right atrium was also visualized. In this view, the RA degree of spontaneous echo contrast was considered appendage was imaged inferior to the insertion of the as continuous variable. A p value ⬍0.05 was considsuperior vena cava (Figure 1). ered significant. Transesophageal data analysis: Evaluation of LA appendage size and function was performed as previously described.7,8,24 –26 RA appendage maximal and RESULTS Patients: Characteristics of the study population are minimal areas were measured and the ejection fraction calculated according to the following formula: (RA described in Table I. The duration of the last episode appendage maximal area ⫺ RA appendage minimal of AF was 534 ⫾ 1,019 days. Eleven patients had area)/RA appendage maximal area. RA appendage paroxysmal AF and showed AF at the time of the areas were measured by tracing a line starting from the study. Echocardiography: Patients with AF had a higher superior aspect of the limbus of the superior vena cava along the entire appendage endocardial border (Figure heart rate than SR patients during transthoracic (94 ⫾ 1). Peak emptying and filling velocities were evalu- 28 vs 71 ⫾ 13 beat/min; p ⫽ 0.0003) and transesophated on 7 to 10 consecutive cardiac cycles by placing ageal echocardiography (103 ⫾ 31 vs 86 ⫾ 25 beats/ the Doppler sample volume at the orifice of the RA min; p ⫽ 0.02). Transthoracic echocardiography: Table II lists reappendage (Figure 2). Because of the correlations between peak emptying and filling velocities both in sults of transthoracic measurements. Tricuspid regurthe RA (r ⫽ 0.83, p ⬍0.0001) and LA (r ⫽ 0.81, p gitation was present in 41 patients with AF. Of those ⬍0.0001) appendage, only peak emptying velocities patients, 36 had a grade 1⫹ regurgitation and 5 paare reported. RA and LA chambers and appendages tients a grade 2⫹ regurgitation. TABLE I Characteristics of Study Patients With AF and SR
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echo contrast. Spontaneous echo contrast was not detected in the LA or RA appendages of patients in SR. Comparison of patients with and without thrombi:
Results regarding RA appendage thrombosis are listed in Table III. All patients with RA thrombi had spontaneous echo contrast. In contrast, only 42 patients (55%) without RA thrombi had spontaneous echo contrast. Five of 6 patients (83 %) with RA appendage thrombi had spontaneous echo contrast grade 4⫹, which was found in 9 (11%) without RA appendage thrombi. Patients with LA appendage thrombi were older in age (68 ⫾ 1 vs 59 ⫾ 12 years, p ⫽ 0.028), had larger LA area (28 ⫾ 7 vs 21 ⫾ 5 cm2, p ⫽ 0.003), larger maximal LA appendage area (6.4 ⫾ 2.8 vs FIGURE 3. Imaging of a large RA appendage (RAA) thrombus in 4.8 ⫾ 1.9 cm2, p ⫽ 0.042), lower LA appendage a patient with dilated cardiomyopathy and AF with spontaneous ejection fraction (20 ⫾ 10 vs 36 ⫾ 18%, p ⫽ 0.003), echo contrast (SEC) grade 4ⴙ. and lower peak emptying velocities (0.25 ⫾ 0.26 vs 0.39 ⫾ 0.19 m/s, p ⬍0.001) compared to patients withTABLE III Comparison of Clinical and Echocardiographic Data Between Patients out LA thrombi. All patients with LA in AF With and Without RA Thrombi appendage thrombi had spontaneous RA Thrombi echo contrast, which was found in 46 patients without thrombi (57%). Ten ⫹ ⫺ p Value of 11 patients with LA appendage n⫽6 n ⫽ 84 thrombi (91%) had grade 4⫹ conMen/women 5/1 64/20 trast effect, and 9 patients (12%) Age (yrs) 65 ⫾ 11 60 ⫾ 13 NS Duration of AF (d) 1,670 ⫾ 1,596 480 ⫾ 924 0.05 without LA thrombi had grade 4⫹ RA area (cm2) 21 ⫾ 2.8 20 ⫾ 4.4 NS echo contrast (p ⬍0.01). Eight of 12 2 Right ventricular area (cm ) 19 ⫾ 2.3 19 ⫾ 4.2 NS patients with evidence of LA and/or Right ventricular long axis (mm) 71 ⫾ 4 75 ⫾ 8 NS RA appendage thrombi were not takRight ventricular short axis (mm) 40 ⫾ 4 36 ⫾ 6 NS Right ventricular wall thickness (mm) 2.6 ⫾ 0.6 2.9 ⫾ 0.6 NS ing anticoagulant therapy. Tricuspid annular excursion (mm) Pulmonary artery pressure (mm) RA appendage maximal area (cm2) RA appendage ejection fraction (%) RA appendage emptying velocity (m/s) Anticoagulation (no.)
9 39 6.2 17.6 0.18
⫾4 ⫾ 11 ⫾ 1.5 ⫾ 5.0 ⫾ 0.16 2
16 29 5.6 30.0 0.31
⫾5 ⫾ 13 ⫾ 2.0 ⫾ 15.0 ⫾ 0.13 46
Transesophageal echocardiography: Measurements of RA and LA appendage size and function are described in Table II. In patients with AF, 17 thrombi were found in 12 patients: 6 in the RA appendage (6.7%) and 11 in the LA appendage (12.2%). Five patients had both RA and LA appendage thrombi (Figure 3). One patient had a thrombus in the RA but not in the LA appendage (Figure 4). Thrombi were not found in patients with SR. One patient with RA appendage thrombus was examined after an episode of angiographically diagnosed pulmonary embolism. Of the 11 patients with LA appendage thrombi, 2 were examined after an acute cerebral ischemic insult, and 1 after an episode of acute lower limb ischemia. RA appendage spontaneous echo contrast was detected in 51 patients with AF (56.6%) The degree of spontaneous echo contrast was 4⫹ in 14 patients, 3⫹ in 3 patients, 2⫹ in 13 patients, and 1⫹ in 18 patients. All patients with RA thrombi had spontaneous echo contrast. Spontaneous echo contrast was detected in the left atrium in 57 patients with AF (63.3%); of these, 19 had 4⫹ contrast effect, 7 patients a 3⫹ effect, 13 patients a 2⫹ effect, and 18 patients a 1⫹ effect. All patients with LA thrombi had spontaneous 1026 THE AMERICAN JOURNAL OF CARDIOLOGY姞
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0.01 0.04 NS 0.018 0.008
Correlations of echocardiographic parameters in patients with atrial fibrillation: RA area was correlated
positively to right ventricular long axis (r ⫽ 0.35; p ⬍0.003), short axis (r ⫽ 0.49; p ⬍0.0001), and wall thickness (r ⫽ 0.24; p ⬍0.05), and to pulmonary artery pressure (r ⫽ 0.3; p ⫽ 0.02), and negatively to RA appendage ejection fraction (r ⫽ ⫺0.4; p ⬍0.01) and emptying velocity (r ⫽ ⫺0.5; p ⬍0.001). The latter 2 parameters were related to each other (r ⫽ 0.4; p ⫽ 0.0002) and were both inversely correlated to tricuspid excursion (r ⫽ ⫺0.34 [p ⫽ 0.05] and r ⫽ ⫺0.38 [p ⫽ 0.002], respectively). The degree of spontaneous echo contrast was correlated positively to AF duration (r ⫽ 0.3; p ⫽ 0.004) and pulmonary pressure (r ⫽ 0.5; p ⬍0.0001) and negatively to RA ejection fraction (r ⫽ ⫺0.3; p ⬍0.004), tricuspid annulus excursion, and RA appendage emptying velocities (both r ⫽ ⫺0.5; p ⬍0.0001). Pulmonary artery pressure and tricuspid annular excursion were inversely correlated (r ⫽ ⫺0.36; p ⫽ 0.04).
Relations between right and left heart chambers size and function: In patients with AF, RA area was smaller
than LA area (p ⫽ 0.004). In the same group, positive correlations were found between RA and LA areas (r ⫽ 0.66; p ⫽ 0.001), RA and LA appendage maximal areas (r ⫽ 0.3; p ⫽ 0.005), RA and LA appendage ejection fractions (r ⫽ 0.28; p ⫽ 0.009), and RA and LA appendage emptying velocities (r ⫽ 0.40; p ⫽ 0.0001). Left ventricular ejection fraction correlated NOVEMBER 1, 1999
FIGURE 4. Patient with mitral stenosis and AF showing thrombi and grade 4ⴙ spontaneous echo contrast (SEC) in both LA (LAA, upper left) and RA (RAA, lower left) appendages with corresponding low Doppler velocities (upper and lower right).
positively with tricuspid annulus excursion (r ⫽ 0.37, p ⫽ 0.003) and negatively with pulmonary artery pressure (r ⫽ ⫺0.25; p ⫽ 0.048).
Independent predictors of right atrial and left atrial appendage thrombosis: Logistic regression analysis
showed that the degree of spontaneous echo contrast in the RA appendage was the only independent predictor of the presence of thrombi in the RA appendage (p ⬍0.03; odds ratio 3.18; 95% confidence intervals 1.11 to 9.11). LA appendage spontaneous echo contrast was the only significant predictor for LA appendage thrombosis (p ⬍0.036, odds ratio 4.99; 95% confidence intervals 1.1 to 22.5). Interobserver variability: A significant interobserver reproducibility was found for RA maximal area (r ⫽ 0.95; mean absolute difference 0.18 ⫾ 0.14 cm2; mean coefficient of variation 2.3%), RA appendage minimal area (r ⫽ 0.95; mean absolute difference 0.18 ⫾ 0.14 cm2; mean coefficient of variation 4.8%), and RA appendage Doppler emptying velocity (r ⫽ 0.98; absolute difference ⫽ 0.01 ⫾ 0.01 ms; mean coefficient of variation 1.2%).
DISCUSSION The primary findings of this prospective study are (1) adequate visualization of the RA appendage is highly feasible by multiplane transesophageal echocardiography and allows morphologic and functional evaluation in a high percentage of patients; (2) RA appendage thrombosis may occur in patients with AF; and (3) RA appendage dysfunction and spontaneous
echo contrast predispose to thrombosis in patients with AF. According to our results, patients with AF have larger RA chamber and appendage sizes and a reduced RA appendage function than patients in SR. Equivalent observations were made for the LA chamber and appendage in accordance with previous results that showed depressed LA appendage function and enlargement in patients with AF.7,8,24 A possible explanation for enlargement of the RA appendage and its dysfunction may be the presence of AF itself. However, RA enlargement and appendage dysfunction also correlated well with increased right ventricular dimensions, depressed right ventricular systolic function, and increased systolic pulmonary artery pressure. Thus, right ventricular and RA chamber enlargement and dysfunction may predispose to RA appendage enlargement and dysfunction. The positive correlation between RA and LA chamber and appendage size and function parameters suggests that enlargement and dysfunction of the atrial chambers and appendages occur in parallel, although in our patients LA area was larger than RA area. In our study, no patient in SR had RA or LA thrombosis. The incidence of thrombosis was higher in the LA appendage (12%) than in the RA appendage (7%) in patients with AF, in agreement with previous studies.9 –11 Almost all patients with RA thrombosis also had LA thrombus, but, according to our data and in agreement with previous reports,10,11 isolated RA
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thrombosis may occur. Of 2 patients with acute pulmonary embolism, 1 had a thrombus in the RA appendage, and the other had grade 4⫹ spontaneous echo contrast in the RA appendage and impaired appendage function; both had no history of deep vein thrombosis or other possible causes of pulmonary embolism. This suggests that cardiogenic RA appendage thrombi developing in patients with AF may be a source of pulmonary embolism.27 The few patients treated with anticoagulants supports the role of anticoagulant therapy in the prevention of atrial thrombosis in AF. In this respect, disappearance of RA thrombi with continued warfarin therapy has been described.10,11,28 Patients with RA thrombi had significantly reduced right ventricular and RA appendage function, and higher pulmonary artery pressure than patients without thrombi. This suggests an increasing predisposition to RA appendage thrombosis in patients with advanced ventricular and atrial appendage dysfunction. In addition, patients with thrombi has a longer duration of AF than patients without thrombi. Equivalent results were found in patients with LA thrombi, in agreement with results reported by other investigators.7,8 Spontaneous echo contrast consists of an echogenic swirling pattern of blood flow that has been associated, both in vivo and in vitro, with parameters describing blood flow stasis.5,6,24 It has been shown that LA appendage spontaneous echo contrast is associated with reduced LA appendage function, LA thrombosis, and increased embolic risk.24 Although subjective, the diagnosis of spontaneous echo contrast has shown a low interobserver variability.29 RA echo contrast was detected in all 6 patients with RA thrombi (5 had a grade 4⫹ phenomenon). More than one third of patients (36%) with 4⫹ echo contrast had RA thrombus. Thrombi were not found in patients without spontaneous echo contrast. Furthermore, the strong correlations of both univariate and logistic regression analyses, which showed that spontaneous echo contrast is the only independent predictor of RA and LA appendage thrombosis, emphasize the predictive role of this phenomenon for both RA and LA thrombosis. 1. Kannel EB, Abbott RD, Savage DD, McNamara PM. Coronary heart disease and atrial fibrillation: the Framingham Study. Am Heart J 1983;104:389 –396. 2. Petersen P. Thromboembolic complications in atrial fibrillation. Stroke 1990; 21:4 –13. 3. Caplan LR, D’Cruz I, Hier DB, Reddy H, Shah S. Atrial size, atrial fibrillation and stroke. Ann Neurol 1986;19:158 –161. 4. Daniel WG, Nellesen U, Schroeder E, Nonnast-Daniel B, Bednarski P, Nikutta P, Lichtlen PR. Left atrial spontaneous echo contrast in mitral valve disease: an indicator for an increased thromboembolic risk. J Am Coll Cardiol 1988;11: 1204 –1211. 5. Black IW, Hopkins AP, Lee LC, Walsh WF, Jacobson BM. Left atrial
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spontaneous echo contrast: a clinical and echocardiographic analysis. J Am Coll Cardiol 1991;18:398 – 404. 6. Movsowitz C, Movsowitz HD, Jacobs LE, Meyerowitz CB, Podolski LA, Kotler MN. Significant mitral regurgitation is protective against left atrial spontaneous echo contrast and thrombus as assessed by transesophageal echocardiography. J Am Soc Echocardiogr 1993;6:107–114. 7. Muegge A, Kuehn H, Nikutta P, Grote J, Lopez JAG, Daniel WG. 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. J Am Coll Cardiol 1994;23:599 – 607. 8. Pollick C, Taylor D. Assessement of left atrial appendage function by transesophageal echocardiography. Circulation 1991;83:70 –78. 9. Silverman DI, Manning JM. Role of echocardiography in patients undergoing electric cardioversion of atrial fibrillation. Circulation 1998; 98:479 – 486. 10. Manning WJ, Silverman DI, Gordon SPF, Krumholz HM, Douglas PS. Cardioversion from atrial fibrillation without prolonged anticoagulation with use of transesophageal echocardiography to exclude the presence of atrial thrombi. N Engl J Med 1993;328:750 –755. 11. Klein AL, Grimm RA, Black IW, Leung DY, Chung MK, Vaughn SE, Murray RD, Miller DP, Arehart KL, for the ACUTE Investigators. Cardioversion guided by transesophageal echocardiography: the ACUTE Pilot Study. A randomized controlled trial. Ann Intern Med 1997;126:200 –209. 12. Lown B. Electrical reversion of cardiac arrhytmias. Br Heart J 1967;29:469 – 489. 13. Carr B, Hawley K, Channer KS. Cardioversion of atrial fibrillation of recent onset with Flecainide. Postgrad Med J 1991;67:659 – 662. 14. Oram S, Davies JPH. Further experience of electrical conversion of atrial fibrillation to sinus rhythm: analysis of 100 patients. Lancet 1964;1:1294 –1298. 15. Manning WJ. Echocardiographic aspects of atrial fibrillation. In: Falk RH, Podrid PJ, eds. On Atrial Fibrillation: Mechanisms and Management. 2nd ed. Philadelphia: Lippincot Raven, 1997:241–298. 16. Henry WL. Report of the American Society of Echocardiography on nomenclature and standards in two-dimensional echocardiography. Circulation 1980; 62:212–217. 17. Triulzi MO, Gillan LD, Gentile F, Newell JB, Weymann AE. Normal adult cross-sectional echocardiographic values: linear dimensions and chamber areas. Echocardiography 1984;1:403– 408. 18. Weyman EA. Principles and Practice of Echcardiography. 2nd ed. Philadelphia: Lea & Febiger, 1994:901–906. 19. Kaul S, Tei C, Hopkins JM, Shah PM. Assessement of right ventricular function using two-dimensional echocardiography. Am Heart J 1984;107:526 – 531. 20. Tsuda T, Sawayama T, Kawai N, Katoh K, Nezuo S, Kikawa K. Echocardiographic measurement of right ventricular wall thickness in adults by anterior approach. Br Heart J 1980;44:55– 61. 21. Yock PG, Popp RL. Noninvasive estimation of right ventricular systolic pressure by Doppler ultrasound in patients with tricuspid regurgitation. Circulation 1984:70:657– 662. 22. Miyatake K, Okamoto M, Kinoshita N, Ohta M, Kozuka T, Sakakibara H, Nimura Y. Evaluation of tricuspid regurgitation by pulsed Doppler and twodimensional echocaradiography. Circulation 1982;66:777–784. 23. Seward JB, Khandheria BK, Freeman WK, Oh JK, Enriquez-Sarano M, Miller FA, Edwards WD, Tajik A. Multiplane transesophageal echocardiography: image orientation, examination technique, anatomic correlation, and clinical applications. Mayo Clin Proc 1993;68:523–551. 24. Fatkin D, Kelly RP, Feneley MP. Relations between left atrial appendage flow velocity, spontaneous echocardiographic contrast, and thromboembolic risk in vivo. J Am Coll Cardiol 1994;23:961–969. 25. Omran H, Jung W, Rabahieh R, Schimpf R, Wolpert C, Hagendorff A, Fehske W, Luederitz B. Left atrial chamber and appendage function after internal atrial defibrillation: a prospective and serial transesophageal echocardiographic study. J Am Coll Cardiol 1997;29:131–138. 26. Omran H, Jung W, Rabahieh R, MacCarter D, Illien S, Rang B, Hagendorff A, Schimpf R, Luederitz B. Left atrial appendage function in patients with atrial flutter. Heart 1997;78:250 –254. 27. Kronik G. The European Cooperative Study of the clinical significance of right heart thrombi. Eur Heart J 1989;10:1046 –1059. 28. Collins LJ, Silverman DI, Douglas PS, Manning WJ. Cardioversion of non-rheumatic atrial fibrillation: reduced thromboembolic complications with 4 weeks of precardioversion anticoagulation are related to atrial thrombus resolution. Circulation 1995; 92:160 –163. 29. Kronik G, Stoellberger C, Schuh M, Abzieher F, Slany J, Schneider B. Interobserver variability in the detection of spontaneous echo contrast, left atrial thrombi, and left atrial appendage thrombi by transesophageal echocardiography. Br Heart J 1995;74:80 – 83.
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were found for the LA appendage. Six thrombi were found in the RA appendage and 11 thrombi in the LA appendage in AF patients. Spontaneous echo contrast was found in 57% and 66% in the right atrium and in the left atrium, respectively. AF patients with RA appendage thrombi had a larger RA area (p ⴝ 0.0001), and lower RA appendage ejection fraction and emptying velocities (both p ⴝ 0.0001) than patients without thrombi. Spontaneous echo contrast was detected in all patients with thrombi. Spontaneous echo contrast was the only independent predictor of RA (p ⴝ 0.03) and LA appendage thrombosis (p ⴝ 0.036). In conclusion, multiplane transesophageal echocardiography allows the assessment of RA appendage morphology and function. RA spontaneous echo contrast is the only independent predictor of RA appendage thrombosis. 䊚1999 by Excerpta Medica, Inc. (Am J Cardiol 1999;84:1023–1028)
trial fibrillation (AF) is associated with an increased risk of atrial thrombosis, cerebral stroke, A and peripheral embolism compared with sinus rhythm
geal echocardiography were included in this study. Of these, we selected 90 patients (88%) in whom visualization of both RA and LA appendages was adequate to perform detailed measurements. Twenty-two patients in SR served as control group. All patients underwent both transthoracic and multiplane transesophageal echocardiographic study. The reasons for transesophageal echocardiography in patients with AF were: (1) no atrial thrombi in patients with cerebral ischemic insult (n ⫽ 10), or pulmonary (n ⫽ 2) or peripheral (n ⫽ 4) embolism of unclear origin; (2) before cardioversion for the exclusion of thrombi (n ⫽ 22); and (3) for a more accurate study of the underlying disease and better choice of anticoagulation therapy. In patients with SR, the indications were: cerebral ischemic insult of unclear origin (n ⫽ 18), and fever of unknown origin (n ⫽ 4). No patient in SR had echocardiographic signs of cardiac disease. Written informed consent was obtained from all patients. Echocardiography: All studies were conducted with commercially available equipment (Vingmed 800 C, Vingmed Sound, Horton, Norway). To allow off-line quantitative analysis of the echocardiographic data, studies were recorded on videotape with selected cine loops and velocity spectra digitally transferred to a MacIntosh PowerPC computer for subsequent analysis. Transthoracic echocardiography: The studies were performed with a 3.25-MHz transthoracic transducer
(SR).1,2 Systemic embolic risk is determined by echocardiographic factors such as left atrial (LA) size,3 spontaneous echo-contrast phenomenon,4,5 absence of mitral regurgitation,6 and impaired LA appendage function.7,8 Although right atrial (RA) appendage thrombosis has been reported in patients with AF9 –11 and although pulmonary embolism was recognized as a life-threatening complication of electrical and pharmacologic cardioversion of AF,12–15 there are no data available about RA appendage morphology and function and the incidence of RA thrombi in patients with AF.9,15 This prospective study evaluates the incidence of RA thrombosis in patients with AF and its relation to clinical and echocardiographic parameters.
METHODS
Patients: One hundred two consecutive patients with AF (on the basis of clinical history and of a 12-lead electrocardiogram) referred for transesopha-
From the Department of Cardiology, University of Bonn, Bonn, Germany. This study was supported by a grant from the Italian Society of Cardiology, Rome, Italy. Manuscript received February 23, 1999; revised manuscript received May 26, 1999, and accepted May 27. Address for reprints: Heyder Omran, MD, Department of Medicine—Cardiology, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany. E-mail: [email protected]. ©1999 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 84 November 1, 1999
0002-9149/99/$–see front matter PII S0002-9149(99)00492-0
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FIGURE 1. Visualization of RA appendage and measurement of maximal RA appendage area (see text).
FIGURE 2. LA appendage (LAA) with pulsed Doppler sample volume (upper left) and Doppler velocities (upper right) in a patient with AF. RA appendage (RAA) with pulsed Doppler sample volume (lower left) and Doppler velocities (lower right) in the same patient.
with patients in the left lateral decubitus position. A single-lead electrocardiogram was continously recorded. M-mode LA dimension was measured at endsystole in the parasternal long-axis view and left ventricular ejection fraction was measured according to the guidelines of the American Society of Echocardiography.16 Both the transverse and longitudinal diameters of the RA and LA chambers were measured by means of 2-dimensional echocardiography in the apical 4-chamber view; RA and LA area were calculated as the products of transverse and longitudinal diameters.17,18 The right ventricle was visualized in the apical 4-chamber view and its size assessed by the measurement of long-axis, maximal short-axis, and right ventricular area by the method described by Weyman.18 Tricuspidal annular excursion in the apical 4-chamber view was measured according to Kaul et al.19 as measurement of right ventricular function. Right ventricular free wall thickness was measured by M-mode in the parasternal short-axis view.20 Pulmo1024 THE AMERICAN JOURNAL OF CARDIOLOGY姞
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nary artery systolic pressure was determined by the sum of the right ventricular RA pressure gradient and an assumed RA pressure.21 Tricuspid regurgitation was graded by measurement of the regurgitant jet size according to Miyatake et al.22 Transesophageal echocardiography: Transesophageal echocardiography was performed using a 5-MHz multiplane transducer. Topical lidocaine spray and viscous lidocaine solution were used to anesthetize the oropharynx before the investigation. Cine loops of the RA and LA chambers and appendages were recorded and stored. The LA appendage was imaged in the basal short-axis view using a transverse scan. RA visualization was performed as suggested by Seward et al.23 The multiplane probe was placed posterior to the atria and the 4-chamber view was visualized; the probe was rotated to achieve visualization of the right heart chambers. The scanning plane was rotated from 90° to 20° to obtain a long-axis view of the right atrium. The junction of the superior vena cava and NOVEMBER 1, 1999
were examined for thrombi and spontaneous echo contrast. The degree of spontaneous echo contrast AF SR was classified by 2 independent observers, and by a (n ⫽ 90) (n ⫽ 22) third observer in case of disagreement, as absent (0), mild (1⫹), mild to moderate (2⫹), moderate (3⫹), or Men/women 69/21 15/7 Age (yrs) 60 ⫾ 13 58 ⫾ 17 severe (4⫹) according to Fatkin et al.24 EchocardioUnderlying disease (no.) graphic evaluations were performed in a singleCoronary heart disease 20 0 blinded manner, with the results confirmed by 2 indeArterial hypertension 19 1 pendent observers after the original examination. Mitral stenosis 8 0 Mitral regurgitation 6 0 Statistical analysis: All data are expressed as Aortic stenosis 4 0 mean ⫾ 1 SD. An unpaired Student t test was used to Aortic regurgitation 3 0 compare echocardiographic parameters between the 2 Dilated cardiomyopathy 10 0 groups. Subgroup analysis of patients with AF was Myocarditis 5 0 performed by an unpaired Mann-Whitney test, None 21 19 Neurologic deficit 10 18 whereas linear regression analysis between all paramAcute peripheral ischemia 4 0 eters in the AF group was performed by a Pearson test. Pulmonary embolism 2 0 Interobserver variability of the measurements of maxAnticoagulation therapy 50 7 imal and minimal areas and emptying velocities of RA appendage were evaluated by linear regression analysis and by the mean coefficient of variation using the forTABLE II Comparison of Echocardiographic Parameters Between Patients With AF mula: ⌺[(Observer 1 ⫺ Observer 2)/ and SR Observer 1]/n, expressed as percentAF SR p Value age. The interobserver variability regarding measurements of the same Transthoracic echocardiography RA area (cm2) 20 ⫾ 4 14 ⫾ 3 0.0001 parameters in the LA appendage in Right ventricular area (cm2) 19 ⫾ 4 19 ⫾ 6 NS our laboratory has been already reRight ventricular long axis (mm) 75 ⫾ 8 72 ⫾ 7 NS ported.25,26 Logistic regression analRight ventricular short axis (mm) 36 ⫾ 6 31 ⫾ 13 0.009 ysis was performed using the presRight ventricular wall thickness (mm) 2.9 ⫾ 0.6 2.5 ⫾ 0.6 0.05 Tricuspid annular excursion (mm) 15 ⫾ 0.4 20 ⫾ 7 0.008 ence of thrombi in the RA appendage Pulmonary artery pressure (mm Hg) 30 ⫾ 13 24 ⫾ 7 0.07 as a function of the duration of AF, LA diameter (mm) 43 ⫾ 6 35 ⫾ 4 0.0001 tricuspid annular excursion, pulmo2 LA area (cm ) 23 ⫾ 5 16 ⫾ 3 0.005 nary artery pressure, RA appendage, Left ventricular ejection fraction (%) 50 ⫾ 11 58 ⫾ 5 0.002 peak emptying velocities, and the deTransesophageal echocardiography RA appendage maximal area (cm2) 5.6 ⫾ 1.9 4.7 ⫾ 1.6 0.05 gree of spontaneous echo contrast. RA appendage ejection fraction (%) 29 ⫾ 15 49 ⫾ 13 0.0001 The same analysis was performed for RA appendage emptying velocity (m/s) 0.30 ⫾ 0.14 0.44 ⫾ 0.14 0.0001 the presence of thrombi in the LA 2 LA appendage maximal area (cm ) 5.0 ⫾ 2.1 3.5 ⫾ 1.0 0.0001 appendage as a function of age, LA LA appendage ejection fraction (%) 29 ⫾ 15 54 ⫾ 14 0.0001 LA appendage emptying velocity (m/s) 0.36 ⫾ 0.21 0.65 ⫾ 0.22 0.0001 area, LA appendage area, ejection fraction, peak emptying velocities, and spontaneous echo contrast. The right atrium was also visualized. In this view, the RA degree of spontaneous echo contrast was considered appendage was imaged inferior to the insertion of the as continuous variable. A p value ⬍0.05 was considsuperior vena cava (Figure 1). ered significant. Transesophageal data analysis: Evaluation of LA appendage size and function was performed as previously described.7,8,24 –26 RA appendage maximal and RESULTS Patients: Characteristics of the study population are minimal areas were measured and the ejection fraction calculated according to the following formula: (RA described in Table I. The duration of the last episode appendage maximal area ⫺ RA appendage minimal of AF was 534 ⫾ 1,019 days. Eleven patients had area)/RA appendage maximal area. RA appendage paroxysmal AF and showed AF at the time of the areas were measured by tracing a line starting from the study. Echocardiography: Patients with AF had a higher superior aspect of the limbus of the superior vena cava along the entire appendage endocardial border (Figure heart rate than SR patients during transthoracic (94 ⫾ 1). Peak emptying and filling velocities were evalu- 28 vs 71 ⫾ 13 beat/min; p ⫽ 0.0003) and transesophated on 7 to 10 consecutive cardiac cycles by placing ageal echocardiography (103 ⫾ 31 vs 86 ⫾ 25 beats/ the Doppler sample volume at the orifice of the RA min; p ⫽ 0.02). Transthoracic echocardiography: Table II lists reappendage (Figure 2). Because of the correlations between peak emptying and filling velocities both in sults of transthoracic measurements. Tricuspid regurthe RA (r ⫽ 0.83, p ⬍0.0001) and LA (r ⫽ 0.81, p gitation was present in 41 patients with AF. Of those ⬍0.0001) appendage, only peak emptying velocities patients, 36 had a grade 1⫹ regurgitation and 5 paare reported. RA and LA chambers and appendages tients a grade 2⫹ regurgitation. TABLE I Characteristics of Study Patients With AF and SR
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echo contrast. Spontaneous echo contrast was not detected in the LA or RA appendages of patients in SR. Comparison of patients with and without thrombi:
Results regarding RA appendage thrombosis are listed in Table III. All patients with RA thrombi had spontaneous echo contrast. In contrast, only 42 patients (55%) without RA thrombi had spontaneous echo contrast. Five of 6 patients (83 %) with RA appendage thrombi had spontaneous echo contrast grade 4⫹, which was found in 9 (11%) without RA appendage thrombi. Patients with LA appendage thrombi were older in age (68 ⫾ 1 vs 59 ⫾ 12 years, p ⫽ 0.028), had larger LA area (28 ⫾ 7 vs 21 ⫾ 5 cm2, p ⫽ 0.003), larger maximal LA appendage area (6.4 ⫾ 2.8 vs FIGURE 3. Imaging of a large RA appendage (RAA) thrombus in 4.8 ⫾ 1.9 cm2, p ⫽ 0.042), lower LA appendage a patient with dilated cardiomyopathy and AF with spontaneous ejection fraction (20 ⫾ 10 vs 36 ⫾ 18%, p ⫽ 0.003), echo contrast (SEC) grade 4ⴙ. and lower peak emptying velocities (0.25 ⫾ 0.26 vs 0.39 ⫾ 0.19 m/s, p ⬍0.001) compared to patients withTABLE III Comparison of Clinical and Echocardiographic Data Between Patients out LA thrombi. All patients with LA in AF With and Without RA Thrombi appendage thrombi had spontaneous RA Thrombi echo contrast, which was found in 46 patients without thrombi (57%). Ten ⫹ ⫺ p Value of 11 patients with LA appendage n⫽6 n ⫽ 84 thrombi (91%) had grade 4⫹ conMen/women 5/1 64/20 trast effect, and 9 patients (12%) Age (yrs) 65 ⫾ 11 60 ⫾ 13 NS Duration of AF (d) 1,670 ⫾ 1,596 480 ⫾ 924 0.05 without LA thrombi had grade 4⫹ RA area (cm2) 21 ⫾ 2.8 20 ⫾ 4.4 NS echo contrast (p ⬍0.01). Eight of 12 2 Right ventricular area (cm ) 19 ⫾ 2.3 19 ⫾ 4.2 NS patients with evidence of LA and/or Right ventricular long axis (mm) 71 ⫾ 4 75 ⫾ 8 NS RA appendage thrombi were not takRight ventricular short axis (mm) 40 ⫾ 4 36 ⫾ 6 NS Right ventricular wall thickness (mm) 2.6 ⫾ 0.6 2.9 ⫾ 0.6 NS ing anticoagulant therapy. Tricuspid annular excursion (mm) Pulmonary artery pressure (mm) RA appendage maximal area (cm2) RA appendage ejection fraction (%) RA appendage emptying velocity (m/s) Anticoagulation (no.)
9 39 6.2 17.6 0.18
⫾4 ⫾ 11 ⫾ 1.5 ⫾ 5.0 ⫾ 0.16 2
16 29 5.6 30.0 0.31
⫾5 ⫾ 13 ⫾ 2.0 ⫾ 15.0 ⫾ 0.13 46
Transesophageal echocardiography: Measurements of RA and LA appendage size and function are described in Table II. In patients with AF, 17 thrombi were found in 12 patients: 6 in the RA appendage (6.7%) and 11 in the LA appendage (12.2%). Five patients had both RA and LA appendage thrombi (Figure 3). One patient had a thrombus in the RA but not in the LA appendage (Figure 4). Thrombi were not found in patients with SR. One patient with RA appendage thrombus was examined after an episode of angiographically diagnosed pulmonary embolism. Of the 11 patients with LA appendage thrombi, 2 were examined after an acute cerebral ischemic insult, and 1 after an episode of acute lower limb ischemia. RA appendage spontaneous echo contrast was detected in 51 patients with AF (56.6%) The degree of spontaneous echo contrast was 4⫹ in 14 patients, 3⫹ in 3 patients, 2⫹ in 13 patients, and 1⫹ in 18 patients. All patients with RA thrombi had spontaneous echo contrast. Spontaneous echo contrast was detected in the left atrium in 57 patients with AF (63.3%); of these, 19 had 4⫹ contrast effect, 7 patients a 3⫹ effect, 13 patients a 2⫹ effect, and 18 patients a 1⫹ effect. All patients with LA thrombi had spontaneous 1026 THE AMERICAN JOURNAL OF CARDIOLOGY姞
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0.01 0.04 NS 0.018 0.008
Correlations of echocardiographic parameters in patients with atrial fibrillation: RA area was correlated
positively to right ventricular long axis (r ⫽ 0.35; p ⬍0.003), short axis (r ⫽ 0.49; p ⬍0.0001), and wall thickness (r ⫽ 0.24; p ⬍0.05), and to pulmonary artery pressure (r ⫽ 0.3; p ⫽ 0.02), and negatively to RA appendage ejection fraction (r ⫽ ⫺0.4; p ⬍0.01) and emptying velocity (r ⫽ ⫺0.5; p ⬍0.001). The latter 2 parameters were related to each other (r ⫽ 0.4; p ⫽ 0.0002) and were both inversely correlated to tricuspid excursion (r ⫽ ⫺0.34 [p ⫽ 0.05] and r ⫽ ⫺0.38 [p ⫽ 0.002], respectively). The degree of spontaneous echo contrast was correlated positively to AF duration (r ⫽ 0.3; p ⫽ 0.004) and pulmonary pressure (r ⫽ 0.5; p ⬍0.0001) and negatively to RA ejection fraction (r ⫽ ⫺0.3; p ⬍0.004), tricuspid annulus excursion, and RA appendage emptying velocities (both r ⫽ ⫺0.5; p ⬍0.0001). Pulmonary artery pressure and tricuspid annular excursion were inversely correlated (r ⫽ ⫺0.36; p ⫽ 0.04).
Relations between right and left heart chambers size and function: In patients with AF, RA area was smaller
than LA area (p ⫽ 0.004). In the same group, positive correlations were found between RA and LA areas (r ⫽ 0.66; p ⫽ 0.001), RA and LA appendage maximal areas (r ⫽ 0.3; p ⫽ 0.005), RA and LA appendage ejection fractions (r ⫽ 0.28; p ⫽ 0.009), and RA and LA appendage emptying velocities (r ⫽ 0.40; p ⫽ 0.0001). Left ventricular ejection fraction correlated NOVEMBER 1, 1999
FIGURE 4. Patient with mitral stenosis and AF showing thrombi and grade 4ⴙ spontaneous echo contrast (SEC) in both LA (LAA, upper left) and RA (RAA, lower left) appendages with corresponding low Doppler velocities (upper and lower right).
positively with tricuspid annulus excursion (r ⫽ 0.37, p ⫽ 0.003) and negatively with pulmonary artery pressure (r ⫽ ⫺0.25; p ⫽ 0.048).
Independent predictors of right atrial and left atrial appendage thrombosis: Logistic regression analysis
showed that the degree of spontaneous echo contrast in the RA appendage was the only independent predictor of the presence of thrombi in the RA appendage (p ⬍0.03; odds ratio 3.18; 95% confidence intervals 1.11 to 9.11). LA appendage spontaneous echo contrast was the only significant predictor for LA appendage thrombosis (p ⬍0.036, odds ratio 4.99; 95% confidence intervals 1.1 to 22.5). Interobserver variability: A significant interobserver reproducibility was found for RA maximal area (r ⫽ 0.95; mean absolute difference 0.18 ⫾ 0.14 cm2; mean coefficient of variation 2.3%), RA appendage minimal area (r ⫽ 0.95; mean absolute difference 0.18 ⫾ 0.14 cm2; mean coefficient of variation 4.8%), and RA appendage Doppler emptying velocity (r ⫽ 0.98; absolute difference ⫽ 0.01 ⫾ 0.01 ms; mean coefficient of variation 1.2%).
DISCUSSION The primary findings of this prospective study are (1) adequate visualization of the RA appendage is highly feasible by multiplane transesophageal echocardiography and allows morphologic and functional evaluation in a high percentage of patients; (2) RA appendage thrombosis may occur in patients with AF; and (3) RA appendage dysfunction and spontaneous
echo contrast predispose to thrombosis in patients with AF. According to our results, patients with AF have larger RA chamber and appendage sizes and a reduced RA appendage function than patients in SR. Equivalent observations were made for the LA chamber and appendage in accordance with previous results that showed depressed LA appendage function and enlargement in patients with AF.7,8,24 A possible explanation for enlargement of the RA appendage and its dysfunction may be the presence of AF itself. However, RA enlargement and appendage dysfunction also correlated well with increased right ventricular dimensions, depressed right ventricular systolic function, and increased systolic pulmonary artery pressure. Thus, right ventricular and RA chamber enlargement and dysfunction may predispose to RA appendage enlargement and dysfunction. The positive correlation between RA and LA chamber and appendage size and function parameters suggests that enlargement and dysfunction of the atrial chambers and appendages occur in parallel, although in our patients LA area was larger than RA area. In our study, no patient in SR had RA or LA thrombosis. The incidence of thrombosis was higher in the LA appendage (12%) than in the RA appendage (7%) in patients with AF, in agreement with previous studies.9 –11 Almost all patients with RA thrombosis also had LA thrombus, but, according to our data and in agreement with previous reports,10,11 isolated RA
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thrombosis may occur. Of 2 patients with acute pulmonary embolism, 1 had a thrombus in the RA appendage, and the other had grade 4⫹ spontaneous echo contrast in the RA appendage and impaired appendage function; both had no history of deep vein thrombosis or other possible causes of pulmonary embolism. This suggests that cardiogenic RA appendage thrombi developing in patients with AF may be a source of pulmonary embolism.27 The few patients treated with anticoagulants supports the role of anticoagulant therapy in the prevention of atrial thrombosis in AF. In this respect, disappearance of RA thrombi with continued warfarin therapy has been described.10,11,28 Patients with RA thrombi had significantly reduced right ventricular and RA appendage function, and higher pulmonary artery pressure than patients without thrombi. This suggests an increasing predisposition to RA appendage thrombosis in patients with advanced ventricular and atrial appendage dysfunction. In addition, patients with thrombi has a longer duration of AF than patients without thrombi. Equivalent results were found in patients with LA thrombi, in agreement with results reported by other investigators.7,8 Spontaneous echo contrast consists of an echogenic swirling pattern of blood flow that has been associated, both in vivo and in vitro, with parameters describing blood flow stasis.5,6,24 It has been shown that LA appendage spontaneous echo contrast is associated with reduced LA appendage function, LA thrombosis, and increased embolic risk.24 Although subjective, the diagnosis of spontaneous echo contrast has shown a low interobserver variability.29 RA echo contrast was detected in all 6 patients with RA thrombi (5 had a grade 4⫹ phenomenon). More than one third of patients (36%) with 4⫹ echo contrast had RA thrombus. Thrombi were not found in patients without spontaneous echo contrast. Furthermore, the strong correlations of both univariate and logistic regression analyses, which showed that spontaneous echo contrast is the only independent predictor of RA and LA appendage thrombosis, emphasize the predictive role of this phenomenon for both RA and LA thrombosis. 1. Kannel EB, Abbott RD, Savage DD, McNamara PM. Coronary heart disease and atrial fibrillation: the Framingham Study. Am Heart J 1983;104:389 –396. 2. Petersen P. Thromboembolic complications in atrial fibrillation. Stroke 1990; 21:4 –13. 3. Caplan LR, D’Cruz I, Hier DB, Reddy H, Shah S. Atrial size, atrial fibrillation and stroke. Ann Neurol 1986;19:158 –161. 4. Daniel WG, Nellesen U, Schroeder E, Nonnast-Daniel B, Bednarski P, Nikutta P, Lichtlen PR. Left atrial spontaneous echo contrast in mitral valve disease: an indicator for an increased thromboembolic risk. J Am Coll Cardiol 1988;11: 1204 –1211. 5. Black IW, Hopkins AP, Lee LC, Walsh WF, Jacobson BM. Left atrial
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spontaneous echo contrast: a clinical and echocardiographic analysis. J Am Coll Cardiol 1991;18:398 – 404. 6. Movsowitz C, Movsowitz HD, Jacobs LE, Meyerowitz CB, Podolski LA, Kotler MN. Significant mitral regurgitation is protective against left atrial spontaneous echo contrast and thrombus as assessed by transesophageal echocardiography. J Am Soc Echocardiogr 1993;6:107–114. 7. Muegge A, Kuehn H, Nikutta P, Grote J, Lopez JAG, Daniel WG. 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. J Am Coll Cardiol 1994;23:599 – 607. 8. Pollick C, Taylor D. Assessement of left atrial appendage function by transesophageal echocardiography. Circulation 1991;83:70 –78. 9. Silverman DI, Manning JM. Role of echocardiography in patients undergoing electric cardioversion of atrial fibrillation. Circulation 1998; 98:479 – 486. 10. Manning WJ, Silverman DI, Gordon SPF, Krumholz HM, Douglas PS. Cardioversion from atrial fibrillation without prolonged anticoagulation with use of transesophageal echocardiography to exclude the presence of atrial thrombi. N Engl J Med 1993;328:750 –755. 11. Klein AL, Grimm RA, Black IW, Leung DY, Chung MK, Vaughn SE, Murray RD, Miller DP, Arehart KL, for the ACUTE Investigators. Cardioversion guided by transesophageal echocardiography: the ACUTE Pilot Study. A randomized controlled trial. Ann Intern Med 1997;126:200 –209. 12. Lown B. Electrical reversion of cardiac arrhytmias. Br Heart J 1967;29:469 – 489. 13. Carr B, Hawley K, Channer KS. Cardioversion of atrial fibrillation of recent onset with Flecainide. Postgrad Med J 1991;67:659 – 662. 14. Oram S, Davies JPH. Further experience of electrical conversion of atrial fibrillation to sinus rhythm: analysis of 100 patients. Lancet 1964;1:1294 –1298. 15. Manning WJ. Echocardiographic aspects of atrial fibrillation. In: Falk RH, Podrid PJ, eds. On Atrial Fibrillation: Mechanisms and Management. 2nd ed. Philadelphia: Lippincot Raven, 1997:241–298. 16. Henry WL. Report of the American Society of Echocardiography on nomenclature and standards in two-dimensional echocardiography. Circulation 1980; 62:212–217. 17. Triulzi MO, Gillan LD, Gentile F, Newell JB, Weymann AE. Normal adult cross-sectional echocardiographic values: linear dimensions and chamber areas. Echocardiography 1984;1:403– 408. 18. Weyman EA. Principles and Practice of Echcardiography. 2nd ed. Philadelphia: Lea & Febiger, 1994:901–906. 19. Kaul S, Tei C, Hopkins JM, Shah PM. Assessement of right ventricular function using two-dimensional echocardiography. Am Heart J 1984;107:526 – 531. 20. Tsuda T, Sawayama T, Kawai N, Katoh K, Nezuo S, Kikawa K. Echocardiographic measurement of right ventricular wall thickness in adults by anterior approach. Br Heart J 1980;44:55– 61. 21. Yock PG, Popp RL. Noninvasive estimation of right ventricular systolic pressure by Doppler ultrasound in patients with tricuspid regurgitation. Circulation 1984:70:657– 662. 22. Miyatake K, Okamoto M, Kinoshita N, Ohta M, Kozuka T, Sakakibara H, Nimura Y. Evaluation of tricuspid regurgitation by pulsed Doppler and twodimensional echocaradiography. Circulation 1982;66:777–784. 23. Seward JB, Khandheria BK, Freeman WK, Oh JK, Enriquez-Sarano M, Miller FA, Edwards WD, Tajik A. Multiplane transesophageal echocardiography: image orientation, examination technique, anatomic correlation, and clinical applications. Mayo Clin Proc 1993;68:523–551. 24. Fatkin D, Kelly RP, Feneley MP. Relations between left atrial appendage flow velocity, spontaneous echocardiographic contrast, and thromboembolic risk in vivo. J Am Coll Cardiol 1994;23:961–969. 25. Omran H, Jung W, Rabahieh R, Schimpf R, Wolpert C, Hagendorff A, Fehske W, Luederitz B. Left atrial chamber and appendage function after internal atrial defibrillation: a prospective and serial transesophageal echocardiographic study. J Am Coll Cardiol 1997;29:131–138. 26. Omran H, Jung W, Rabahieh R, MacCarter D, Illien S, Rang B, Hagendorff A, Schimpf R, Luederitz B. Left atrial appendage function in patients with atrial flutter. Heart 1997;78:250 –254. 27. Kronik G. The European Cooperative Study of the clinical significance of right heart thrombi. Eur Heart J 1989;10:1046 –1059. 28. Collins LJ, Silverman DI, Douglas PS, Manning WJ. Cardioversion of non-rheumatic atrial fibrillation: reduced thromboembolic complications with 4 weeks of precardioversion anticoagulation are related to atrial thrombus resolution. Circulation 1995; 92:160 –163. 29. Kronik G, Stoellberger C, Schuh M, Abzieher F, Slany J, Schneider B. Interobserver variability in the detection of spontaneous echo contrast, left atrial thrombi, and left atrial appendage thrombi by transesophageal echocardiography. Br Heart J 1995;74:80 – 83.
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