CLINICAL RESEARCH
Europace (2015) 17, 539–545 doi:10.1093/europace/euu347
Atrial fibrillation
Left atrial appendage morphology is closely associated with specific echocardiographic flow pattern in patients with atrial fibrillation 1 Medical Faculty, Division of Cardiology, Pulmonology and Vascular Medicine, University Duesseldorf, Moorenstraße 5, Duesseldorf 40225, Germany; and 2Department of Electrophysiology, University Heart Center, University Hospital Eppendorf, Martinistraße 52, Hamburg 20246, Germany
Received 25 August 2014; accepted after revision 8 November 2014; online publish-ahead-of-print 9 December 2014
Aims
To assess the relation between left atrial appendage (LAA) morphology and echocardiographic flow pattern of the LAA by means of two- and three-dimensional transoesophageal echocardiography (3D-TEE). ..................................................................................................................................................................................... Methods In a total of 131 patients with atrial fibrillation, LAA morphology was analyzed by 3D-TEE and classified into four types (Chicken Wing, Windsock, Cactus, Cauliflower). Left atrial appendage flow pattern as maximal LAA emptying flow veland results ocity and spontaneous echo contrast (SEC) were retrieved from 2D-TEE imaging in all patients. In patients with atrial fibrillation (AF), Chicken Wing morphology was associated with a higher LAA emptying flow velocity (difference of means ¼ 211.7, 95% CI 4.6– 19.3, P ¼ 0.003) and a reduced prevalence of SEC (OR 3.2, 95% CI 1.1 –9.3, P ¼ 0.025) compared with all other LAA types (so-called ‘Non-Chicken Wing’ LAA). These alterations were irrespective of the underlying type of AF. ..................................................................................................................................................................................... Conclusion Non-Chicken Wing LAA morphologies are associated with a specific echocardiographic flow pattern in patients with AF. Since evidence exists that LAA flow pattern are indicative of an enhanced risk of thrombus formation, 3D-TEE might be a valuable tool warranting future studies to test whether these morphological and functional characteristics permit risk stratification in AF.
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Left atrial appendage † Morphology † 3D transoesophageal echocardiography † Thrombus formation † Atrial fibrillation
Introduction Cardiac thrombus formation substantially occurs inside the left atrial appendage (LAA). Overall, one-third of thromboembolic events emanates from the heart.1 In patients with non-valvular atrial fibrillation (AF), 90% of events are attributed to thrombi originating from the LAA.2 A recent retrospective study showed an association between LAA morphology and prior thromboembolic events by applying computed tomography (CT) and magnetic resonance imaging (MRI).3 Most importantly, patients with AF and the so-called Chicken Wing LAA morphology were found to be 79% less likely to suffer from transient ischaemic attacks (TIA) or strokes, compared with patients with Non-Chicken Wing LAA morphology. Moreover, we
could lately show that 3D-TEE as an alternative imaging technique is reliable, safe, and non-inferior in the evaluation of LAA morphology compared with CT and MRI (Petersen et al., in press). Chicken Wing LAA and Non-Chicken Wing LAA could be distinguished with 100% specificity and sensitivity. Besides capturing detailed anatomic information by applying both 2D and 3D techniques, TEE allows measurement of LAA flow pattern. A reduction of maximal LAA emptying flow velocity (from here on referred to as LAA flow) and the presence of spontaneous echo contrast (SEC) are well-established parameters4 – 6 indicative of an increased risk of thrombus formation. Therefore, the aim of our study was to assess the relation between LAA morphology and flow pattern in AF patients by means of 2Dand 3D-TEE.
* Corresponding author. Tel: +49 211 81 18801; fax: +49 211 81 18812. E-mail address: [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2014. For permissions please email: [email protected].
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Margot Petersen 1, Adalbert Roehrich 1, Jan Balzer 1, Dong-In Shin 1, Christian Meyer 1,2, Malte Kelm 1, and Eva S. Kehmeier 1*
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What’s new? † Three-dimensional transoesophageal echocardiography (3D-TEE) has been validated for the assessment of LAA type. † Atrial fibrillation (AF) patients with Non-Chicken Wing LAA morphologies show a reduced LAA emptying flow velocity and an increased prevalence of spontaneous echo contrast inside the LAA compared with patients with Chicken Wing morphology. † Evaluation of LAA characteristics by 3D-TEE might emerge as a new approach in risk stratification regarding thrombus formation in the setting of both conservative and interventional AF treatment.
Study population The study cohort was enrolled retrospectively in the Department of Cardiology, Pneumology and Angiology at the University Hospital Duesseldorf, 3D-TEE studies were performed between May and October 2013. The clinical indication for 3D-TEE was detection of possible cardiac sources of emboli before electric cardioversion (n ¼ 33) or before catheter ablation for AF (n ¼ 47), and in the clarification of cryptogenic stroke (n ¼ 5). Structural heart diseases, such as patent foramen ovale, atrial septal defect, valve insufficiency, or stenosis were evaluated by 3D-TEE in the presence of insufficient transthoracic image quality and/or before preoperative surgery in 25 cases. Furthermore, 3D-TEE was applied pre-interventionally before transcatheter aortic valve implantation (n ¼ 19) and before the MitralClip procedure (n ¼ 2). During enrollment, 10 out of 141 patients were excluded due to insufficient image quality in 3D-TEE. Figure 1 delineates enrollment and analysis of the study cohort. The study complies with the Declaration of Helsinki, that the research protocol is approved by the locally appointed ethics committee and that the informed consent of the subjects (or their parents) has been obtained.
Transoesophageal three-dimensional-echocardiography Transoesophageal echocardiography studies were carried out with an iE33 echocardiography system and a X7-2t live 3D-TEE transducer (Philips Medical Systems). All patients gave written informed consent for transoesophageal 3D-echocardiography. Patients remained fasting for a minimum of 6 h before the procedure, and TEE was performed while lying in a left lateral position. Patients received mild sedation with midazolam and propofol 1% intravenously, adjusted to weight, and titrated cautiously to tolerate the TEE probe and to remain sufficiently breathing without assistance. Heart rate, blood pressure, oxygen saturation, and electrocardiogram were continuously monitored. Two-dimensional transoesophageal echocardiography was conducted in a standard protocol according to international guidelines.7 Assessment of SEC or thrombi was performed stepwise in 0–208, 45–608, 908, and 120–1358, using X-plane mode to visualize orthogonal images simultaneously. Left atrial appendage emptying flow velocity was measured with pulsed wave Doppler at the site of maximal flow velocities, determined by optimal alignment in 2D colour flow imaging, in the proximal third of the appendage, as described before.5,8 After optimization of gain settings, a pyramidal 3D zoom dataset of the entire LAA was acquired and analysed offline by QLAB version 8 (Philips Medical Systems), as in former studies (Petersen et al., in press).
Classification of left atrial appendage morphology Left atrial appendage morphology was classified into four types, as first described by Wang et al. 9 In short, the presence and extent of an obvious bend was assessed. Chicken Wing LAA was identified by an obvious bend ,1108 in the proximal or middle part of the dominate lobe or folding back of the LAA anatomy on itself at some distance from the ostium. Non-Chicken Wing LAA morphology was subclassified in Windsock, Cactus, and Cauliflower LAA.9
Statistical methods For subgroup analysis (SR/AF during TEE, Chicken Wing/Non-Chicken Wing LAA), Student’s t-test or analysis of variance was performed for continuous data. For categorical data, patient groups were compared performing x2 or Fisher’s exact test. All tests were two-sided. Predictors of LAA flow velocity were determined by standard multiple linear regression analysis. P values ,0.05 were considered statistically significant. All statistical analyses were performed using IBM SPSS version 22.0 (SPSS, Inc.).
Results Study population The study population consisted of 131 patients. Mean age was 68.1 + 11.6 years, 86 (65.6%) were men, and body mass index was 26.7 + 4.5 kg/m2. Hypertension, congestive heart failure (CHF), diabetes, and vascular disease were present in 62 (47.3%), 9 (6.9%), 23 (17.6%), and 38 (29%) patients. Sixty-six (50.4%) patients suffered from paroxysmal, 46 (35.1%) from persistent, and 19 (14%) from long-standing persistent AF. CHA2DS2-VASc-score10 was 2.3 + 1.6 implying a statistical risk of ischaemic stroke .2% per year without oral anticoagulation. One hundred and seven (81.7%) patients with known AF were treated with an effective oral anticoagulation. Among 16 patients with stroke/TIA in their past history, 2 (12.5%) took an oral anticoagulant at the time of the event, 9 (56.3%) had no oral anticoagulation, and in 5 (31.3%) anticoagulation state at the time of the event was unknown. Baseline characteristics are shown in detail in Table 1.
Left atrial appendage morphology in three-dimensional transoesophageal echocardiography The number of Chicken Wing, Windsock, Cactus and Cauliflower LAA types was 56 (42.7%), 44 (33.6%), 20 (15.3%), and 11 (8.4%), concordant with previous studies.3,9 The LAA showed single, double, and multiple lobes in 56 (42.7%), 33 (25.2%), and 42 (32%) patients. Eleven of 56 (19.7%) Chicken Wing LAA and 31 of 75 (41.3%) Non-Chicken Wing LAA were multilobed with a significant difference in means (difference of means ¼ 20.2, 95% CI 20.9 to 20.2, P ¼ 0.002). No significant difference in age, calculated CHA2DS2-VASc-score, duration and characteristics of AF, oral anticoagulation, as well as prevalence and magnitude of mitral regurgitation or stenosis was found between patients with Chicken Wing and Non-Chicken Wing LAA (see Table 1).
Left atrial appendage flow pattern in atrial fibrillation patients Overall, LAA emptying flow velocity was 44.6 + 22.4 cm/s. Patients showed typical differences in flow velocities depending on their heart
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Methods
M. Petersen et al.
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LAA morphology related to echocardiographic flow pattern
Enrollment
TEE including 3D-zoom and PW-doppler assessed for eligibility (n = 141)
Excluded (n = 10) •
Quality of 3D-images insufficient (n = 10)
Analyzed for LAA flow, SEC and thrombi
Figure 1 Consort diagram: overview of enrollment and analysis of the study cohort. Of 141 TEE examinations screened for eligibility, a total of 131 datasets were found acceptable in quality (insufficient image quality 7%).
Table 1 Baseline characteristics by LAA morphology Overall population (n 5 131)
LAA-Typ: chicken wing [n 5 56 (42.7%)]
LAA-Typ: non-chicken wing [n 5 75 (57.3%)]
LAA-Typ: windsock [n 5 44 (33.6%)]
LAA-Typ: cactus [n 5 20 (15.3%)]
LAA-Typ: cauliflower [n 5 11 (8.4%)]
Pairwise sign. chicken wing vs. non-chicken wing
67.0 + 12.5 35 (62.5%)
67.7 + 14.3 51 (68.0%)
70.1 + 9.1 33 (75.0%)
68.8 + 11.0 11 (55%)
64.6 + 15.8 7 (63.6%)
0.348 0.512
............................................................................................................................................................................... Age, years Male
68.1 + 11.6 86 (65.6%)
Paroxysmal AF
66 (50.4%)
29 (51.8%)
37 (49.3%)
21 (47.7%)
11 (55%)
5 (45.5%)
0.688
Persistent AF 46 (35.1%) Long-standing persistent AF 19 (14%)
19 (33.9%) 8 (14.3%)
27 (36%) 11 (14.7%)
16 (36.4%) 7 (15.9%)
7 (35%) 2 (10%)
4 (36.4%) 2 (18.2%)
0.815 0.991
AF duration, month
31 (0– 168)
30.2 (0– 168)
31.7 (0 –132)
31.1 (0– 132)
16.6 (0–36)
64.6 (23–120)
0.318
BMI, kg/m2 Hypertension
26.7 + 4.5 62 (47.3%)
26.8 + 5.1 23 (41.1%)
26.6 + 3.9 39 (52%)
26.8 + 3.2 25 (56.8%)
27.2 + 4.6 11 (55%)
24.6 + 4.7 3 (27.3%)
0.794 0.215
CHF
9 (6.9%)
3 (5.4%)
6 (8%)
3 (6.8%)
0 (0%)
3 (27.3%)
0.554
Diabetes Vascular Disease
23 (17.6%) 38 (29%)
9 (16.1%) 15 (26.8%)
14 (18.7%) 23 (3.7%)
10 (22.7%) 13 (29.5%)
4 (20%) 5 (25%)
0 5 (45.5%)
0.699 0.628
Prior stroke/TIA
16 (12.2%)
6 (10.7%)
10 (13.3%)
16 (13.6%)
4 (20%)
0
0.651
MS ≥ II8 MR ≥ II8
3 (2.3%) 25 (19.1%)
2 (3.6%) 8 (14.3%)
1 (1.3%) 17 (22.7%)
0 (0%) 11 (25.0%)
1 (5%) 2 (10%)
1 (9.1%) 4 (36.4%)
0.376 0.695
CHA2DS2-VASc-scorea
2.3 + 1.6
2.1 + 1.7
2.4 + 1.5
2.5 + 1.5
2.3 + 1.5
2.3 + 1.8
0.329
CHA2DS2-VASc-score 0a CHA2DS2-VASc-score 1a
21 (16.0%) 28 (21.4%)
11 (19.6%) 13 (23.2%)
10 (13.3%) 15 (20%)
5 (11.4%) 9 (20.5%)
3 (15%) 3 (15%)
2 (18.2%) 3 (27.3%)
0.330 0.657
CHA2DS2-VASc-score ≥2a 82 (62.7%)
32 (57.3%)
50 (60.7%)
30 (68.2%)
14 (70%)
6 (54.5%)
0.265
Oral anticoagulation SEC
107 (81.7%) 23 (17.6%)
42 (75%) 5 (8.9%)
65 (86,7%) 18 (24%)
39 (88.6%) 11 (25%)
16 (80%) 6 (30%)
10 (90.9%) 1 (9.1%)
0.088 0.025
Thrombus
6 (4.6%)
0 (0%)
6 (8%)
5 (11.4%)
1 (5%)
0 (0%)
0.030
LAA flow, cm/s Number of lobes
44.6 + 22.4 2.0 + 1.0
51.4 + 25.1 1.7 + 0.9
39.7 + 18.8 2.2 + 1.0
42.5 + 18.9 2 + 1.1
33.3 + 17.2 3.1 + 0.8
39.8 + 20.0 1.9 + 0.8
0.003 0.002
Values are mean + SD, n (%), or median (interquartile range). BMI, body mass index; CHA2DS2-VASc, congestive heart failure, hypertension, age .75 years, diabetes mellitus, prior stroke or transient ischaemic attack, vascular disease history (10); CHF, congestive heart failure; TIA transient ischaemic attack. a CHA2DS2-VASc-score has been calculated before any thromboembolic event.
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Analysis
Patients with eligible TEE (n = 131)
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Atrial fibrillation patients with Chicken Wing LAA had a higher LAA emptying flow (difference in means 11.7, 95% CI 4.1–19.3, P ¼ 0.003;
Maximal LAA emptying flow velocity (cm/s)
A
Difference in means 14.4, 95% Cl 6.6 to 22.1, P < 0.001 100
80
53.8 ± 25.1 39.4 ± 18.9
60
40
20
0
n = 48
n = 83
Sinus rhythm
Atrial fibrillation
B
OR 4.7, 95% Cl: 1.3 to 17.0, P = 0.010 60% 50% 40% 30% 20% 10% 0%
n=3
n = 20
Sinus rhythm
Atrial fibrillation
Heart rhythm during TEE
Heart rhythm during TEE
D
P < 0.001 100 80
51.4 ± 25.1 40.9 ± 16.3
60
29.7 ± 15.1 40 20 0
n = 66
n = 46
n = 19
Paroxysmal AF
Persistent AF
Long-standing persistent AF
Prevalence of spontaneous echo contrast
Maximal LAA emptying flow velocity (cm/s)
C
P = 0.006 60% 50% 40% 30% 20% 10% 0%
n=7
n=8
Paroxysmal AF Persistent AF
n=8 Long-standing persistent AF
Figure 2 Left atrial appendage flow and prevalence of SEC in AF Patients. Patients with AF during TEE showed a reduced LAA flow (difference in means 14.4, 95% CI 6.6 – 22.1, P , 0.001; figure A) and a reduced prevalence of SEC (OR 4.7, 95% CI 1.3 to 17.0, P ¼ 0.010; B) compared with patients with SR during TEE and a history of AF. Left atrial appendage flow decelerated (C, showed as mean + standard deviation, P , 0.001), and prevalence of SEC rise gradually among AF categories (D, P ¼ 0.006). CI, confidence interval; OR, odds ratio.
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Left atrial appendage flow pattern and morphology in atrial fibrillation patients
Figure 3A) and a 2.5-fold-reduced prevalence of SEC (OR 3.2, 95% CI 1.1–9.3, P ¼ 0.025; Figure 3B) than patients with Non-Chicken Wing LAA morphology. In sub-analysis, a higher LAA flowand a reduced prevalence of SEC were found in Chicken Wing compared with Non-Chicken Wing LAA of all AF types (see Figure 4). This difference was statistically significant for LAA flow in the subgroup of paroxysmal AF (P , 0.001). In Chicken Wing and Non-Chicken Wing LAA, the formerly observed graduation of LAA flow among the various AF categories (paroxysmal, persistent and long-standing persistent) was evident, and reached statistical significance in patients with Chicken Wing LAA morphology (P , 0.001; see Figure 4A). Likewise, the gradually rise in SEC was found from paroxysmal to persistent and long-standing persistent AF in Chicken Wing and Non-Chicken Wing LAA. Only one patient with Chicken Wing LAA and persistent AF showed less SEC than two patients with paroxysmal AF. This gradual increase in SEC was significant for NonChicken Wing LAA (P ¼ 0.019), but not for Chicken Wing LAA.
Prevalence of spontaneous echo contrast
rhythm during TEE: In patients with paroxysmal AF and SR during TEE (n ¼ 48, 36.6%), LAA flow was 53.8 + 25.1 cm/s, compared with 39.4 + 18.9 cm/s in patients with AF during TEE (n ¼ 83, 63.4%). Thus, LAA flow was significantly lower during AF (difference in means 14.4, 95% CI 6.6– 22.1, P , 0.001; Figure 2A). Moreover, LAA flow velocities gradually decreased from paroxysmal to persistent and further to long-standing persistent AF in sub-analysis (P , 0.001; Figure 2C). SEC was found in 23 out of 131 AF patients (17.6%). By subcategorizing in the various AF types, also a gradually rise in prevalence was found from paroxysmal to persistent and longstanding persistent AF (P ¼ 0.006; Figure 2D).
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LAA morphology related to echocardiographic flow pattern
100
80
51.4 ± 25.1 39.7 ± 18.8
60
40
20
0
n = 56
n = 75
OR 3.2, 95% Cl 1.1 to 9.3, P = 0.025
B Prevalence of spontaneous echo contrast
Difference in means 11.7, 95% Cl 4.1 to 19.3, P = 0.003
60% 50% 40% 30% 20% 10% n=5
0% Chicken wing
Non-chicken wing
n = 18
Chicken wing
LAA Morphology
Non-chicken wing
LAA Morphology
Figure 3 Left atrial appendage flow and prevalence of SEC in Chicken Wing vs. Non-Chicken Wing LAA. AF patients with Chicken Wing LAA showed a higher LAA flow (difference in means 11.7, 95% CI 4.1– 19.3, P ¼ 0.003; A) and a 2.5-fold-reduced prevalence of SEC (OR 3.2, 95% CI 1.1 – 9.3, P ¼ 0.025; B) compared with patients with Non-Chicken Wing LAA morphology.
Concerning the number of lobes, LAA emptying flow was reduced in patients with three or more lobes (difference in means 9.3, 95% CI 1.2– 17.5, P ¼ 0.025), whereas prevalence of SEC showed no significant difference comparing patients with single-/bilobed and multilobed LAA.
Predictors of left atrial appendage flow and left atrial appendage morphology In multivariate linear regression analysis, AF characteristic (paroxysmal, persistent, long-standing persistent) (b ¼ 20.273, SE ¼ 2.806, P ¼ 0.003), CHA2DS-VASc-score (b ¼ 20.279, SE ¼ 1.113, P ¼ 0.001), LAA morphology (Chicken Wing vs. Non-Chicken Wing; b ¼ 20.205, SE ¼ 3.493, P ¼ 0.009) and left ventricular function (b ¼ 0.167, SE ¼ 2.138, P ¼ 0.037) were identified as independent predictors of LAA flow (Table 2). The number of LAA lobes was no predictive factor for LAA flow. In binary logistic regression, no predictive association could be found between LAA morphology and age, gender, BMI, left ventricular function, AF characteristic and CHA2DS2-VASc-score.
Thrombi and thromboembolic events The rate of thrombi in our study population was low, just as thromboembolic event rate (12.2% prior stroke/TIA in the overall study population). In total, thrombi were found in six (4.6%) patients, all characterized by a Non-Chicken Wing LAA morphology. In our study collective, neither heart rhythm (SR/AF), nor LAA morphology showed a significant relation to prior stroke or TIA.
Safety of three-dimensional transoesophageal echocardiography In our study cohort, no TEE- or anaesthesia-related complications or TEE-related infections were observed.
Discussion Major finding of this study is the association of Chicken Wing LAA morphology with a higher LAA emptying flow velocity and a reduced prevalence of SEC in patients with AF. In contrast, NonChicken Wing LAA is related to both reduced LAA flow and enhanced SEC.
Left atrial appendage morphology and flow pattern in patients with atrial fibrillation By applying 2D- and 3D-TEE, we for the first time showed a relation between Non-Chicken Wing LAA and echocardiographic surrogate markers of an increased risk of thrombus formation as reduced LAA emptying flow and SEC. This relation was seen in all types of AF, and the risk delineated by our surrogates increased gradually from paroxysmal to persistent and long-standing persistent AF. Furthermore, multivariate linear regression analysis identified LAA morphology as predictor of LAA flow in patients with AF, irrespective of comorbidities, such as mitral regurgitation or stenosis, hypertension, congestive heart failure, diabetes and vascular disease, as well as administration of an oral anticoagulant. These findings might in part explain results from previous studies showing an increased rate of prior thromboembolic events in patients with Non-Chicken Wing LAA morphology.3,11 Results from our study also showed that LAA emptying flow was reduced in multilobed LAA, however, the number of lobes was no predictive parameter of LAA flow in multivariate linear regression analysis. Furthermore, no relation was found between the number of lobes and the prevalence of SEC. As multilobed LAA were more common in Non-Chicken Wing patients in our study collective, further research differentiating the role of both characteristics is desirable.
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Maximal LAA emptying flow velocity (cm/s)
A
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M. Petersen et al.
A
Chicken wing: P < 0.001, Non-Chicken wing: P = 0.152
B
*
LAA morphology Chicken wing Non-Chicken wing
80
60
40
20
0
n = 29
n = 37
Paroxysmal AF
n = 19
n = 27
Persistent AF
n=8
n = 11
Prevalence of spontaneous echo contrast
60% LAA morphology Chicken wing Non-Chicken wing
50%
40%
30%
20%
10%
0%
Long-standing persistent AF
n=2
n=5
Paroxysmal AF
n=1
n=7
Persistent AF
n=2
n=6
Long-standing persistent AF
Figure 4 Left atrial appendage flow and prevalence of SEC in various AF types and Chicken Wing vs. Non-Chicken Wing LAA. Left atrial appendage flow (A) decelerated, and prevalence of SEC (B) rise gradually from paroxysmal to persistent and long-standing persistent AF in the Chicken Wing (LAA flow: P , 0.001, SEC: P ¼ 0.223) and Non-Chicken Wing LAA group (LAA flow: P ¼ 0.152, SEC: P ¼ 0.019). In all AF types, a higher LAA flow and a reduced prevalence of SEC were found in Chicken Wing compared with Non-Chicken Wing LAA. This difference was statistically significant for LAA flow in the subgroup of paroxysmal AF (P , 0.001).
Table 2 Predictors for LAA flow identified by linear regression in patients with AF Variables
Model LAA flow in patients with AF, linear regression with enter method
.......................................................................................................... B
SE
b
t
Sig.
............................................................................................................................................................................... (constant)
89.484
10.149
8.817
0.000
Heart rate during TEE Rhythm during TEE
0.044 23.940
0.083 4.674
0.044 20.084
0.533 20.835
0.595 0.405
Paroxysmal, persistent and long-persistent AF
28.396
2.806
20.273
22.992
0.003
6.075
4.311
0.106
1.409
0.161
24.501 24.501
1.113 2.138
20.279 20.167
23.451 22.105
0.001 0.037
OAK yes/no CHA2DS-VASC-score Left ventricular function Chicken Wing vs. Non-Chicken Wing LAA
29.260
3.493
20.205
22.651
0.009
Number of Lobes R2-adjusted
21.998 0.298
1.758
20.089
21.136
0.258
R2
0.334
Atrial fibrillation characteristic (paroxysmal, persistent, or long-standing persistent), CHA2DS2-VASc-score, left ventricular function and LAA morphology (Chicken Wing vs. Non-Chicken Wing) are identified as independent predictors of LAA flow.
Our data suggest that Non-Chicken Wing LAA in the presence of AF causes reduced LAA flow rates, which might predispose to an increased risk of thrombus formation. Therefore, additional information about LAA morphology and thus, surrogates for thromboembolism might be valuable in certain clinical situations for conservatively treated AF patients, e.g. in the perioperative
management of anticoagulation therapy before non-cardiac surgery, as well as in the setting of post-interventional care of AF patients after ablation therapy. However, the high prevalence of an effective anticoagulation in the general population, as well as the rise in well-tolerated new anticoagulants with a low-risk profile makes a wide application unlikely.12 Unquestionably, future
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Maximal LAA emptying flow velocity (cm/s)
100
Chicken wing: P = 0.223, Non-Chicken wing: P = 0.109
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studies are needed to confirm the impact of this new approach in risk stratification.
Study limitations
Conclusion In our study population, Non-Chicken Wing LAA morphology was associated with reduced LAA emptying flow and a higher prevalence of SEC, in all types of AF. Hence, evaluation of LAA characteristics by 3D-TEE might emerge as a widely available, cost-efficient and radiation-free imaging approach in risk stratification regarding thrombus formation, in selected clinical situations of AF patients.
Acknowledgements The authors thank Mr Pablo Verde, Coordinating Centre for Clinical Trials, University Duesseldorf for statistical advice. Conflict of interest: none declared.
This study was supported in part with a restricted grant from the federal state government of North Rhine-Westphalia and the European Union (ERFE-Program “Med in.NRW”, support code 005-GW01-235A).
References 1. Mohr JP, Sacco RL. Classification of ischemic strokes. In: Wolf PA, Cobb JL, D’Agostino RB. Epidemiology of stroke. In: Barnett HJM, Mohr JP, Stein BM, Yatsu FM, eds. Stroke: Pathophysiology, Diagnosis, and Management, 2nd ed. New York: Churchill Livingstone, 1992:271 –83. 2. Johnson WD, Ganjoo AK, Stone CD, Srivyas RC, Howard M. The left atrial appendage: our most lethal human attachment! Surgical implications. Eur J Cardiothorac Surg 2000;17:718 –22. 3. Di Biase L, Santangeli P, Anselmino M, Mohanty P, Salvetti I, Gili S et al. Does the left atrial appendage morphology correlate with the risk of stroke in patients with atrial fibrillation? Results from a multicenter study. J Am Coll Cardiol 2012;60:531 –8. 4. Mu¨gge A, Ku¨hn H, Nikutta P, Grote J, Lopez AG, 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. 5. Fatkin D, Kelly RP, Feneley MP. Relations between left atrial appendage blood flow velocity, spontaneous echocardiographic contrast and thromboembolic risk in vivo. J Am Coll Cardiol 1994;23:961 – 9. 6. The Stroke Prevention in Atrial Fibrillation Investigators Committee on Echocardiography. Transesophageal echocardiographic correlates of thromboembolism in highrisk patients with nonvalvular atrial fibrillation. Ann Intern Med 1998;128:639–47. 7. Hahn RT, Abraham T, Adams MS, Bruce CJ, Glas KE, Lang RM et al. Guidelines for performing a comprehensive transesophageal echocardiographic examination: recommendations from the American Society of Echocardiography and the Society of Cardiovascular Anesthesiologists. J Am Soc Echocardiogr 2013;26:921 – 64. 8. Agmon Y, Khandheria BK, Gentile F, Seward JB. Echocardiographic assessment of the left atrial appendage. J Am Coll Cardiol 1999;34:1867 –77. 9. Wang Y, Di Biase L, Horton RP, Nguyen T, Morhanty P, Natale A. Left atrial appendage studied by computed tomography to help planning for appendage closure device placement. J Cardiovasc Electrophysiol 2010;21:973 – 82. 10. Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Europace 2010;12:1360 –420. 11. Kimura T, Takatsuki S, Inagawa K, Katsumata Y, Nishiyama T, Nishiyama N et al. Anatomical characteristics of the left atrial appendage in cardiogenic stroke with low CHADS2 scores. Heart Rhythm 2013;10:921 –5. 12. Meier B, Blaauw Y, Khattab AA, Lewalter T, Sievert H, Tondo C et al. EHRA/EAPCI expert consensus statement on catheter-based left atrial appendage occlusion. Europace 2014;16:1397 –416.
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In our study, we investigated a relatively low-risk population reflected by a mean CHA2DS2-VASc-score of 2.3 Additionally, the rate of anticoagulation therapy was high (.80%), which in turn lowers the rate of thromboembolic events and definite thrombus formation. Thus, our findings cannot be adapted to a high-risk population, and further prospective studies are needed to confirm our preliminary data. Lack of statistical significance in the sub-analysis of AF categories in Chicken Wing and Non-Chicken Wing LAA was presumably attributed to low patient numbers in these subgroups, which needs to be exclusively confirmed. Furthermore, the proportion of women was comparably low in our patient population (34.4%). Finally, it is important to note that until now, 3D-imaging of the LAA during TEE is not a routine procedure in AF patients and unlikely to be used for risk stratification in AF patients beyond CHA2DSVASc-score, unless clinically indicated.
Funding
Europace (2015) 17, 539–545 doi:10.1093/europace/euu347
Atrial fibrillation
Left atrial appendage morphology is closely associated with specific echocardiographic flow pattern in patients with atrial fibrillation 1 Medical Faculty, Division of Cardiology, Pulmonology and Vascular Medicine, University Duesseldorf, Moorenstraße 5, Duesseldorf 40225, Germany; and 2Department of Electrophysiology, University Heart Center, University Hospital Eppendorf, Martinistraße 52, Hamburg 20246, Germany
Received 25 August 2014; accepted after revision 8 November 2014; online publish-ahead-of-print 9 December 2014
Aims
To assess the relation between left atrial appendage (LAA) morphology and echocardiographic flow pattern of the LAA by means of two- and three-dimensional transoesophageal echocardiography (3D-TEE). ..................................................................................................................................................................................... Methods In a total of 131 patients with atrial fibrillation, LAA morphology was analyzed by 3D-TEE and classified into four types (Chicken Wing, Windsock, Cactus, Cauliflower). Left atrial appendage flow pattern as maximal LAA emptying flow veland results ocity and spontaneous echo contrast (SEC) were retrieved from 2D-TEE imaging in all patients. In patients with atrial fibrillation (AF), Chicken Wing morphology was associated with a higher LAA emptying flow velocity (difference of means ¼ 211.7, 95% CI 4.6– 19.3, P ¼ 0.003) and a reduced prevalence of SEC (OR 3.2, 95% CI 1.1 –9.3, P ¼ 0.025) compared with all other LAA types (so-called ‘Non-Chicken Wing’ LAA). These alterations were irrespective of the underlying type of AF. ..................................................................................................................................................................................... Conclusion Non-Chicken Wing LAA morphologies are associated with a specific echocardiographic flow pattern in patients with AF. Since evidence exists that LAA flow pattern are indicative of an enhanced risk of thrombus formation, 3D-TEE might be a valuable tool warranting future studies to test whether these morphological and functional characteristics permit risk stratification in AF.
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Left atrial appendage † Morphology † 3D transoesophageal echocardiography † Thrombus formation † Atrial fibrillation
Introduction Cardiac thrombus formation substantially occurs inside the left atrial appendage (LAA). Overall, one-third of thromboembolic events emanates from the heart.1 In patients with non-valvular atrial fibrillation (AF), 90% of events are attributed to thrombi originating from the LAA.2 A recent retrospective study showed an association between LAA morphology and prior thromboembolic events by applying computed tomography (CT) and magnetic resonance imaging (MRI).3 Most importantly, patients with AF and the so-called Chicken Wing LAA morphology were found to be 79% less likely to suffer from transient ischaemic attacks (TIA) or strokes, compared with patients with Non-Chicken Wing LAA morphology. Moreover, we
could lately show that 3D-TEE as an alternative imaging technique is reliable, safe, and non-inferior in the evaluation of LAA morphology compared with CT and MRI (Petersen et al., in press). Chicken Wing LAA and Non-Chicken Wing LAA could be distinguished with 100% specificity and sensitivity. Besides capturing detailed anatomic information by applying both 2D and 3D techniques, TEE allows measurement of LAA flow pattern. A reduction of maximal LAA emptying flow velocity (from here on referred to as LAA flow) and the presence of spontaneous echo contrast (SEC) are well-established parameters4 – 6 indicative of an increased risk of thrombus formation. Therefore, the aim of our study was to assess the relation between LAA morphology and flow pattern in AF patients by means of 2Dand 3D-TEE.
* Corresponding author. Tel: +49 211 81 18801; fax: +49 211 81 18812. E-mail address: [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2014. For permissions please email: [email protected].
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Margot Petersen 1, Adalbert Roehrich 1, Jan Balzer 1, Dong-In Shin 1, Christian Meyer 1,2, Malte Kelm 1, and Eva S. Kehmeier 1*
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What’s new? † Three-dimensional transoesophageal echocardiography (3D-TEE) has been validated for the assessment of LAA type. † Atrial fibrillation (AF) patients with Non-Chicken Wing LAA morphologies show a reduced LAA emptying flow velocity and an increased prevalence of spontaneous echo contrast inside the LAA compared with patients with Chicken Wing morphology. † Evaluation of LAA characteristics by 3D-TEE might emerge as a new approach in risk stratification regarding thrombus formation in the setting of both conservative and interventional AF treatment.
Study population The study cohort was enrolled retrospectively in the Department of Cardiology, Pneumology and Angiology at the University Hospital Duesseldorf, 3D-TEE studies were performed between May and October 2013. The clinical indication for 3D-TEE was detection of possible cardiac sources of emboli before electric cardioversion (n ¼ 33) or before catheter ablation for AF (n ¼ 47), and in the clarification of cryptogenic stroke (n ¼ 5). Structural heart diseases, such as patent foramen ovale, atrial septal defect, valve insufficiency, or stenosis were evaluated by 3D-TEE in the presence of insufficient transthoracic image quality and/or before preoperative surgery in 25 cases. Furthermore, 3D-TEE was applied pre-interventionally before transcatheter aortic valve implantation (n ¼ 19) and before the MitralClip procedure (n ¼ 2). During enrollment, 10 out of 141 patients were excluded due to insufficient image quality in 3D-TEE. Figure 1 delineates enrollment and analysis of the study cohort. The study complies with the Declaration of Helsinki, that the research protocol is approved by the locally appointed ethics committee and that the informed consent of the subjects (or their parents) has been obtained.
Transoesophageal three-dimensional-echocardiography Transoesophageal echocardiography studies were carried out with an iE33 echocardiography system and a X7-2t live 3D-TEE transducer (Philips Medical Systems). All patients gave written informed consent for transoesophageal 3D-echocardiography. Patients remained fasting for a minimum of 6 h before the procedure, and TEE was performed while lying in a left lateral position. Patients received mild sedation with midazolam and propofol 1% intravenously, adjusted to weight, and titrated cautiously to tolerate the TEE probe and to remain sufficiently breathing without assistance. Heart rate, blood pressure, oxygen saturation, and electrocardiogram were continuously monitored. Two-dimensional transoesophageal echocardiography was conducted in a standard protocol according to international guidelines.7 Assessment of SEC or thrombi was performed stepwise in 0–208, 45–608, 908, and 120–1358, using X-plane mode to visualize orthogonal images simultaneously. Left atrial appendage emptying flow velocity was measured with pulsed wave Doppler at the site of maximal flow velocities, determined by optimal alignment in 2D colour flow imaging, in the proximal third of the appendage, as described before.5,8 After optimization of gain settings, a pyramidal 3D zoom dataset of the entire LAA was acquired and analysed offline by QLAB version 8 (Philips Medical Systems), as in former studies (Petersen et al., in press).
Classification of left atrial appendage morphology Left atrial appendage morphology was classified into four types, as first described by Wang et al. 9 In short, the presence and extent of an obvious bend was assessed. Chicken Wing LAA was identified by an obvious bend ,1108 in the proximal or middle part of the dominate lobe or folding back of the LAA anatomy on itself at some distance from the ostium. Non-Chicken Wing LAA morphology was subclassified in Windsock, Cactus, and Cauliflower LAA.9
Statistical methods For subgroup analysis (SR/AF during TEE, Chicken Wing/Non-Chicken Wing LAA), Student’s t-test or analysis of variance was performed for continuous data. For categorical data, patient groups were compared performing x2 or Fisher’s exact test. All tests were two-sided. Predictors of LAA flow velocity were determined by standard multiple linear regression analysis. P values ,0.05 were considered statistically significant. All statistical analyses were performed using IBM SPSS version 22.0 (SPSS, Inc.).
Results Study population The study population consisted of 131 patients. Mean age was 68.1 + 11.6 years, 86 (65.6%) were men, and body mass index was 26.7 + 4.5 kg/m2. Hypertension, congestive heart failure (CHF), diabetes, and vascular disease were present in 62 (47.3%), 9 (6.9%), 23 (17.6%), and 38 (29%) patients. Sixty-six (50.4%) patients suffered from paroxysmal, 46 (35.1%) from persistent, and 19 (14%) from long-standing persistent AF. CHA2DS2-VASc-score10 was 2.3 + 1.6 implying a statistical risk of ischaemic stroke .2% per year without oral anticoagulation. One hundred and seven (81.7%) patients with known AF were treated with an effective oral anticoagulation. Among 16 patients with stroke/TIA in their past history, 2 (12.5%) took an oral anticoagulant at the time of the event, 9 (56.3%) had no oral anticoagulation, and in 5 (31.3%) anticoagulation state at the time of the event was unknown. Baseline characteristics are shown in detail in Table 1.
Left atrial appendage morphology in three-dimensional transoesophageal echocardiography The number of Chicken Wing, Windsock, Cactus and Cauliflower LAA types was 56 (42.7%), 44 (33.6%), 20 (15.3%), and 11 (8.4%), concordant with previous studies.3,9 The LAA showed single, double, and multiple lobes in 56 (42.7%), 33 (25.2%), and 42 (32%) patients. Eleven of 56 (19.7%) Chicken Wing LAA and 31 of 75 (41.3%) Non-Chicken Wing LAA were multilobed with a significant difference in means (difference of means ¼ 20.2, 95% CI 20.9 to 20.2, P ¼ 0.002). No significant difference in age, calculated CHA2DS2-VASc-score, duration and characteristics of AF, oral anticoagulation, as well as prevalence and magnitude of mitral regurgitation or stenosis was found between patients with Chicken Wing and Non-Chicken Wing LAA (see Table 1).
Left atrial appendage flow pattern in atrial fibrillation patients Overall, LAA emptying flow velocity was 44.6 + 22.4 cm/s. Patients showed typical differences in flow velocities depending on their heart
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Methods
M. Petersen et al.
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LAA morphology related to echocardiographic flow pattern
Enrollment
TEE including 3D-zoom and PW-doppler assessed for eligibility (n = 141)
Excluded (n = 10) •
Quality of 3D-images insufficient (n = 10)
Analyzed for LAA flow, SEC and thrombi
Figure 1 Consort diagram: overview of enrollment and analysis of the study cohort. Of 141 TEE examinations screened for eligibility, a total of 131 datasets were found acceptable in quality (insufficient image quality 7%).
Table 1 Baseline characteristics by LAA morphology Overall population (n 5 131)
LAA-Typ: chicken wing [n 5 56 (42.7%)]
LAA-Typ: non-chicken wing [n 5 75 (57.3%)]
LAA-Typ: windsock [n 5 44 (33.6%)]
LAA-Typ: cactus [n 5 20 (15.3%)]
LAA-Typ: cauliflower [n 5 11 (8.4%)]
Pairwise sign. chicken wing vs. non-chicken wing
67.0 + 12.5 35 (62.5%)
67.7 + 14.3 51 (68.0%)
70.1 + 9.1 33 (75.0%)
68.8 + 11.0 11 (55%)
64.6 + 15.8 7 (63.6%)
0.348 0.512
............................................................................................................................................................................... Age, years Male
68.1 + 11.6 86 (65.6%)
Paroxysmal AF
66 (50.4%)
29 (51.8%)
37 (49.3%)
21 (47.7%)
11 (55%)
5 (45.5%)
0.688
Persistent AF 46 (35.1%) Long-standing persistent AF 19 (14%)
19 (33.9%) 8 (14.3%)
27 (36%) 11 (14.7%)
16 (36.4%) 7 (15.9%)
7 (35%) 2 (10%)
4 (36.4%) 2 (18.2%)
0.815 0.991
AF duration, month
31 (0– 168)
30.2 (0– 168)
31.7 (0 –132)
31.1 (0– 132)
16.6 (0–36)
64.6 (23–120)
0.318
BMI, kg/m2 Hypertension
26.7 + 4.5 62 (47.3%)
26.8 + 5.1 23 (41.1%)
26.6 + 3.9 39 (52%)
26.8 + 3.2 25 (56.8%)
27.2 + 4.6 11 (55%)
24.6 + 4.7 3 (27.3%)
0.794 0.215
CHF
9 (6.9%)
3 (5.4%)
6 (8%)
3 (6.8%)
0 (0%)
3 (27.3%)
0.554
Diabetes Vascular Disease
23 (17.6%) 38 (29%)
9 (16.1%) 15 (26.8%)
14 (18.7%) 23 (3.7%)
10 (22.7%) 13 (29.5%)
4 (20%) 5 (25%)
0 5 (45.5%)
0.699 0.628
Prior stroke/TIA
16 (12.2%)
6 (10.7%)
10 (13.3%)
16 (13.6%)
4 (20%)
0
0.651
MS ≥ II8 MR ≥ II8
3 (2.3%) 25 (19.1%)
2 (3.6%) 8 (14.3%)
1 (1.3%) 17 (22.7%)
0 (0%) 11 (25.0%)
1 (5%) 2 (10%)
1 (9.1%) 4 (36.4%)
0.376 0.695
CHA2DS2-VASc-scorea
2.3 + 1.6
2.1 + 1.7
2.4 + 1.5
2.5 + 1.5
2.3 + 1.5
2.3 + 1.8
0.329
CHA2DS2-VASc-score 0a CHA2DS2-VASc-score 1a
21 (16.0%) 28 (21.4%)
11 (19.6%) 13 (23.2%)
10 (13.3%) 15 (20%)
5 (11.4%) 9 (20.5%)
3 (15%) 3 (15%)
2 (18.2%) 3 (27.3%)
0.330 0.657
CHA2DS2-VASc-score ≥2a 82 (62.7%)
32 (57.3%)
50 (60.7%)
30 (68.2%)
14 (70%)
6 (54.5%)
0.265
Oral anticoagulation SEC
107 (81.7%) 23 (17.6%)
42 (75%) 5 (8.9%)
65 (86,7%) 18 (24%)
39 (88.6%) 11 (25%)
16 (80%) 6 (30%)
10 (90.9%) 1 (9.1%)
0.088 0.025
Thrombus
6 (4.6%)
0 (0%)
6 (8%)
5 (11.4%)
1 (5%)
0 (0%)
0.030
LAA flow, cm/s Number of lobes
44.6 + 22.4 2.0 + 1.0
51.4 + 25.1 1.7 + 0.9
39.7 + 18.8 2.2 + 1.0
42.5 + 18.9 2 + 1.1
33.3 + 17.2 3.1 + 0.8
39.8 + 20.0 1.9 + 0.8
0.003 0.002
Values are mean + SD, n (%), or median (interquartile range). BMI, body mass index; CHA2DS2-VASc, congestive heart failure, hypertension, age .75 years, diabetes mellitus, prior stroke or transient ischaemic attack, vascular disease history (10); CHF, congestive heart failure; TIA transient ischaemic attack. a CHA2DS2-VASc-score has been calculated before any thromboembolic event.
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Analysis
Patients with eligible TEE (n = 131)
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Atrial fibrillation patients with Chicken Wing LAA had a higher LAA emptying flow (difference in means 11.7, 95% CI 4.1–19.3, P ¼ 0.003;
Maximal LAA emptying flow velocity (cm/s)
A
Difference in means 14.4, 95% Cl 6.6 to 22.1, P < 0.001 100
80
53.8 ± 25.1 39.4 ± 18.9
60
40
20
0
n = 48
n = 83
Sinus rhythm
Atrial fibrillation
B
OR 4.7, 95% Cl: 1.3 to 17.0, P = 0.010 60% 50% 40% 30% 20% 10% 0%
n=3
n = 20
Sinus rhythm
Atrial fibrillation
Heart rhythm during TEE
Heart rhythm during TEE
D
P < 0.001 100 80
51.4 ± 25.1 40.9 ± 16.3
60
29.7 ± 15.1 40 20 0
n = 66
n = 46
n = 19
Paroxysmal AF
Persistent AF
Long-standing persistent AF
Prevalence of spontaneous echo contrast
Maximal LAA emptying flow velocity (cm/s)
C
P = 0.006 60% 50% 40% 30% 20% 10% 0%
n=7
n=8
Paroxysmal AF Persistent AF
n=8 Long-standing persistent AF
Figure 2 Left atrial appendage flow and prevalence of SEC in AF Patients. Patients with AF during TEE showed a reduced LAA flow (difference in means 14.4, 95% CI 6.6 – 22.1, P , 0.001; figure A) and a reduced prevalence of SEC (OR 4.7, 95% CI 1.3 to 17.0, P ¼ 0.010; B) compared with patients with SR during TEE and a history of AF. Left atrial appendage flow decelerated (C, showed as mean + standard deviation, P , 0.001), and prevalence of SEC rise gradually among AF categories (D, P ¼ 0.006). CI, confidence interval; OR, odds ratio.
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Left atrial appendage flow pattern and morphology in atrial fibrillation patients
Figure 3A) and a 2.5-fold-reduced prevalence of SEC (OR 3.2, 95% CI 1.1–9.3, P ¼ 0.025; Figure 3B) than patients with Non-Chicken Wing LAA morphology. In sub-analysis, a higher LAA flowand a reduced prevalence of SEC were found in Chicken Wing compared with Non-Chicken Wing LAA of all AF types (see Figure 4). This difference was statistically significant for LAA flow in the subgroup of paroxysmal AF (P , 0.001). In Chicken Wing and Non-Chicken Wing LAA, the formerly observed graduation of LAA flow among the various AF categories (paroxysmal, persistent and long-standing persistent) was evident, and reached statistical significance in patients with Chicken Wing LAA morphology (P , 0.001; see Figure 4A). Likewise, the gradually rise in SEC was found from paroxysmal to persistent and long-standing persistent AF in Chicken Wing and Non-Chicken Wing LAA. Only one patient with Chicken Wing LAA and persistent AF showed less SEC than two patients with paroxysmal AF. This gradual increase in SEC was significant for NonChicken Wing LAA (P ¼ 0.019), but not for Chicken Wing LAA.
Prevalence of spontaneous echo contrast
rhythm during TEE: In patients with paroxysmal AF and SR during TEE (n ¼ 48, 36.6%), LAA flow was 53.8 + 25.1 cm/s, compared with 39.4 + 18.9 cm/s in patients with AF during TEE (n ¼ 83, 63.4%). Thus, LAA flow was significantly lower during AF (difference in means 14.4, 95% CI 6.6– 22.1, P , 0.001; Figure 2A). Moreover, LAA flow velocities gradually decreased from paroxysmal to persistent and further to long-standing persistent AF in sub-analysis (P , 0.001; Figure 2C). SEC was found in 23 out of 131 AF patients (17.6%). By subcategorizing in the various AF types, also a gradually rise in prevalence was found from paroxysmal to persistent and longstanding persistent AF (P ¼ 0.006; Figure 2D).
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LAA morphology related to echocardiographic flow pattern
100
80
51.4 ± 25.1 39.7 ± 18.8
60
40
20
0
n = 56
n = 75
OR 3.2, 95% Cl 1.1 to 9.3, P = 0.025
B Prevalence of spontaneous echo contrast
Difference in means 11.7, 95% Cl 4.1 to 19.3, P = 0.003
60% 50% 40% 30% 20% 10% n=5
0% Chicken wing
Non-chicken wing
n = 18
Chicken wing
LAA Morphology
Non-chicken wing
LAA Morphology
Figure 3 Left atrial appendage flow and prevalence of SEC in Chicken Wing vs. Non-Chicken Wing LAA. AF patients with Chicken Wing LAA showed a higher LAA flow (difference in means 11.7, 95% CI 4.1– 19.3, P ¼ 0.003; A) and a 2.5-fold-reduced prevalence of SEC (OR 3.2, 95% CI 1.1 – 9.3, P ¼ 0.025; B) compared with patients with Non-Chicken Wing LAA morphology.
Concerning the number of lobes, LAA emptying flow was reduced in patients with three or more lobes (difference in means 9.3, 95% CI 1.2– 17.5, P ¼ 0.025), whereas prevalence of SEC showed no significant difference comparing patients with single-/bilobed and multilobed LAA.
Predictors of left atrial appendage flow and left atrial appendage morphology In multivariate linear regression analysis, AF characteristic (paroxysmal, persistent, long-standing persistent) (b ¼ 20.273, SE ¼ 2.806, P ¼ 0.003), CHA2DS-VASc-score (b ¼ 20.279, SE ¼ 1.113, P ¼ 0.001), LAA morphology (Chicken Wing vs. Non-Chicken Wing; b ¼ 20.205, SE ¼ 3.493, P ¼ 0.009) and left ventricular function (b ¼ 0.167, SE ¼ 2.138, P ¼ 0.037) were identified as independent predictors of LAA flow (Table 2). The number of LAA lobes was no predictive factor for LAA flow. In binary logistic regression, no predictive association could be found between LAA morphology and age, gender, BMI, left ventricular function, AF characteristic and CHA2DS2-VASc-score.
Thrombi and thromboembolic events The rate of thrombi in our study population was low, just as thromboembolic event rate (12.2% prior stroke/TIA in the overall study population). In total, thrombi were found in six (4.6%) patients, all characterized by a Non-Chicken Wing LAA morphology. In our study collective, neither heart rhythm (SR/AF), nor LAA morphology showed a significant relation to prior stroke or TIA.
Safety of three-dimensional transoesophageal echocardiography In our study cohort, no TEE- or anaesthesia-related complications or TEE-related infections were observed.
Discussion Major finding of this study is the association of Chicken Wing LAA morphology with a higher LAA emptying flow velocity and a reduced prevalence of SEC in patients with AF. In contrast, NonChicken Wing LAA is related to both reduced LAA flow and enhanced SEC.
Left atrial appendage morphology and flow pattern in patients with atrial fibrillation By applying 2D- and 3D-TEE, we for the first time showed a relation between Non-Chicken Wing LAA and echocardiographic surrogate markers of an increased risk of thrombus formation as reduced LAA emptying flow and SEC. This relation was seen in all types of AF, and the risk delineated by our surrogates increased gradually from paroxysmal to persistent and long-standing persistent AF. Furthermore, multivariate linear regression analysis identified LAA morphology as predictor of LAA flow in patients with AF, irrespective of comorbidities, such as mitral regurgitation or stenosis, hypertension, congestive heart failure, diabetes and vascular disease, as well as administration of an oral anticoagulant. These findings might in part explain results from previous studies showing an increased rate of prior thromboembolic events in patients with Non-Chicken Wing LAA morphology.3,11 Results from our study also showed that LAA emptying flow was reduced in multilobed LAA, however, the number of lobes was no predictive parameter of LAA flow in multivariate linear regression analysis. Furthermore, no relation was found between the number of lobes and the prevalence of SEC. As multilobed LAA were more common in Non-Chicken Wing patients in our study collective, further research differentiating the role of both characteristics is desirable.
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Maximal LAA emptying flow velocity (cm/s)
A
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Chicken wing: P < 0.001, Non-Chicken wing: P = 0.152
B
*
LAA morphology Chicken wing Non-Chicken wing
80
60
40
20
0
n = 29
n = 37
Paroxysmal AF
n = 19
n = 27
Persistent AF
n=8
n = 11
Prevalence of spontaneous echo contrast
60% LAA morphology Chicken wing Non-Chicken wing
50%
40%
30%
20%
10%
0%
Long-standing persistent AF
n=2
n=5
Paroxysmal AF
n=1
n=7
Persistent AF
n=2
n=6
Long-standing persistent AF
Figure 4 Left atrial appendage flow and prevalence of SEC in various AF types and Chicken Wing vs. Non-Chicken Wing LAA. Left atrial appendage flow (A) decelerated, and prevalence of SEC (B) rise gradually from paroxysmal to persistent and long-standing persistent AF in the Chicken Wing (LAA flow: P , 0.001, SEC: P ¼ 0.223) and Non-Chicken Wing LAA group (LAA flow: P ¼ 0.152, SEC: P ¼ 0.019). In all AF types, a higher LAA flow and a reduced prevalence of SEC were found in Chicken Wing compared with Non-Chicken Wing LAA. This difference was statistically significant for LAA flow in the subgroup of paroxysmal AF (P , 0.001).
Table 2 Predictors for LAA flow identified by linear regression in patients with AF Variables
Model LAA flow in patients with AF, linear regression with enter method
.......................................................................................................... B
SE
b
t
Sig.
............................................................................................................................................................................... (constant)
89.484
10.149
8.817
0.000
Heart rate during TEE Rhythm during TEE
0.044 23.940
0.083 4.674
0.044 20.084
0.533 20.835
0.595 0.405
Paroxysmal, persistent and long-persistent AF
28.396
2.806
20.273
22.992
0.003
6.075
4.311
0.106
1.409
0.161
24.501 24.501
1.113 2.138
20.279 20.167
23.451 22.105
0.001 0.037
OAK yes/no CHA2DS-VASC-score Left ventricular function Chicken Wing vs. Non-Chicken Wing LAA
29.260
3.493
20.205
22.651
0.009
Number of Lobes R2-adjusted
21.998 0.298
1.758
20.089
21.136
0.258
R2
0.334
Atrial fibrillation characteristic (paroxysmal, persistent, or long-standing persistent), CHA2DS2-VASc-score, left ventricular function and LAA morphology (Chicken Wing vs. Non-Chicken Wing) are identified as independent predictors of LAA flow.
Our data suggest that Non-Chicken Wing LAA in the presence of AF causes reduced LAA flow rates, which might predispose to an increased risk of thrombus formation. Therefore, additional information about LAA morphology and thus, surrogates for thromboembolism might be valuable in certain clinical situations for conservatively treated AF patients, e.g. in the perioperative
management of anticoagulation therapy before non-cardiac surgery, as well as in the setting of post-interventional care of AF patients after ablation therapy. However, the high prevalence of an effective anticoagulation in the general population, as well as the rise in well-tolerated new anticoagulants with a low-risk profile makes a wide application unlikely.12 Unquestionably, future
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Maximal LAA emptying flow velocity (cm/s)
100
Chicken wing: P = 0.223, Non-Chicken wing: P = 0.109
545
LAA morphology related to echocardiographic flow pattern
studies are needed to confirm the impact of this new approach in risk stratification.
Study limitations
Conclusion In our study population, Non-Chicken Wing LAA morphology was associated with reduced LAA emptying flow and a higher prevalence of SEC, in all types of AF. Hence, evaluation of LAA characteristics by 3D-TEE might emerge as a widely available, cost-efficient and radiation-free imaging approach in risk stratification regarding thrombus formation, in selected clinical situations of AF patients.
Acknowledgements The authors thank Mr Pablo Verde, Coordinating Centre for Clinical Trials, University Duesseldorf for statistical advice. Conflict of interest: none declared.
This study was supported in part with a restricted grant from the federal state government of North Rhine-Westphalia and the European Union (ERFE-Program “Med in.NRW”, support code 005-GW01-235A).
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In our study, we investigated a relatively low-risk population reflected by a mean CHA2DS2-VASc-score of 2.3 Additionally, the rate of anticoagulation therapy was high (.80%), which in turn lowers the rate of thromboembolic events and definite thrombus formation. Thus, our findings cannot be adapted to a high-risk population, and further prospective studies are needed to confirm our preliminary data. Lack of statistical significance in the sub-analysis of AF categories in Chicken Wing and Non-Chicken Wing LAA was presumably attributed to low patient numbers in these subgroups, which needs to be exclusively confirmed. Furthermore, the proportion of women was comparably low in our patient population (34.4%). Finally, it is important to note that until now, 3D-imaging of the LAA during TEE is not a routine procedure in AF patients and unlikely to be used for risk stratification in AF patients beyond CHA2DSVASc-score, unless clinically indicated.
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