- Email: [email protected]
Prevalence and Management of Atrial Thrombi in Patients With Atrial Fibrillation Before Pulmonary Vein Isolation
JACC: CLINICAL ELECTROPHYSIOLOGY
VOL.
-, NO. -, 2019
ª 2019 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER
Prevalence and Management of Atrial Thrombi in Patients With Atrial Fibrillation Before Pulmonary Vein Isolation Tobias Göldi, MD,a,b,* Philipp Krisai, MD,a,b,* Sven Knecht, PHD,a,b Stefanie Aeschbacher, PHD,a,b Florian Spies, MSC,a,b Ivan Zeljkovic, MD,c Beat A. Kaufmann, MD,a,b Beat Schaer, MD,a,b David Conen, MD, MPH,b,d Tobias Reichlin, MD,e Stefan Osswald, MD,a,b Christian Sticherling, MD,a,b Michael Kühne, MDa,b
ABSTRACT OBJECTIVES This study aimed to investigate the prevalence and management of left atrial (LA) thrombi detected by transesophageal echocardiography (TEE) in patients with atrial fibrillation undergoing pulmonary vein isolation (PVI). BACKGROUND Little data are available on LA thrombi before PVI. METHODS All patients scheduled for PVI between April 2010 and April 2018 undergoing pre-procedural TEE were analyzed. Management of LA thrombus was at the discretion of the treating physician. RESULTS In this study, 1,753 pre-procedural TEE from 1,358 patients (mean age 61 10 years, 28% female) were included. Anticoagulation was used in 86% of all TEE (51% with direct oral anticoagulants [DOAC], 35% with vitamin K antagonists [VKA]). Thrombi were found in 11 TEE (0.6%), all in the LA appendage. Of the 11 patients with a thrombus, 5 (46%) had paroxysmal atrial fibrillation, 2 (18%) had a CHA2DS2-VASc (Congestive Heart Failure, Hypertension, Age $75 Years, Diabetes Mellitus, Prior Stroke or Transient Ischemic Attack or Thromboembolism, Vascular Disease, Age 65 to 74 Years, Sex) score of 1, and 5 (46%) were in sinus rhythm at the time of TEE. Of the 8 patients (72%) on anticoagulation therapy, 5 were treated with DOAC and 3 with VKA. Starting anticoagulation (n ¼ 3), switching to VKA with a target international normalized ratio of 2.5 to 3 (n ¼ 3), or switching to a DOAC (n ¼ 1) or a different DOAC (n ¼ 4) resulted in thrombus resolution in 9 of 11 patients (82%). CONCLUSIONS In patients with atrial fibrillation scheduled for PVI, LA thrombi are rare and present in <1%. Thrombi were found in patients on VKA and DOAC, in low-risk patients, and despite sinus rhythm. Thrombus resolution was achieved in the majority of patients by changing the anticoagulation regimen. (J Am Coll Cardiol EP 2019;-:-–-) © 2019 by the American College of Cardiology Foundation.
From the aDepartment of Cardiology, University Hospital of Basel, Basel, Switzerland; bCardiovascular Research Institute Basel, University Hospital Basel, Basel, Switzerland; cSestre Milosrdnice University Hospital, Zagreb, Croatia;
d
Population Health
Research Institute, McMaster University and Department of Cardiology, Hamilton Health Sciences, Hamilton, Ontario, Canada; and the eDepartment of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. Dr. Schaer serves on the Speakers Bureau of Medtronic. Dr. Conen has received speaker honoraria from Servier, Canada. Dr. Kühne has received grants from Bayer, Pfizer-BMS, the Swiss National Science Foundation, and the Swiss Heart Foundation; and lecture or consulting fees from Daiichi-Sankyo, Boehringer Ingelheim, Bayer, Pfizer-BMS, AstraZeneca, Sanofi, Novartis, Merck Sharp & Dohme, Medtronic, Boston Scientific, St. Jude Medical, Biotronik, Sorin, Zoll, Biosense Webster, and Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. *Drs. Göldi and Krisai contributed equally to this work and are joint first authors. The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page. Manuscript received May 30, 2019; revised manuscript received September 5, 2019, accepted September 6, 2019.
ISSN 2405-500X/$36.00
https://doi.org/10.1016/j.jacep.2019.09.003
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JACC: CLINICAL ELECTROPHYSIOLOGY VOL.
A
ABBREVIATIONS AND ACRONYMS AF = atrial fibrillation
trial fibrillation (AF) is the most com-
management of LA thrombi before PVI, remain due to
mon arrhythmia and its incidence is
the
increasing (1,2). Patients with AF
associated thromboembolic stroke.
are at increased risk of death and cardiovas-
CI = confidence interval
cular
DOAC = direct oral anticoagulants
ECG = electrocardiogram INR = international normalized ratio
events,
especially
LVEF = left ventricular ejection fraction
SEC = spontaneous echo
clinical risk factors associated with a high risk for LA thrombi.
minimize the risk of thromboembolic stroke
3 weeks or a pre-procedural transesophageal echocardiography (TEE) in sinus rhythm
anticoagulation (7). Adhering to these recomrary studies investigating catheter ablation
TEE = transesophageal
for AF was shown to be as low as 0.3% (8).
echocardiography
VKA = vitamin K antagonists
Previous
studies
investigating
pre-
procedural TEE in patients with sufficient
anticoagulation have shown conflicting results with LAA thrombus prevalence ranging from 0.2% to 3.6% (9–16).
The aim of this study was to analyze the prevalence
and subsequent stroke occurrence (5,6). To
mendations, the risk of stroke in contempo-
contrast
PVI-
cohort of patients undergoing PVI and to investigate
TEE is recommended even with sufficient
PVI = pulmonary vein isolation
of
stroke (3,4). The left atrial appendage (LAA)
(6,7). For patients in AF, a pre-procedural
OR = odds ratio
consequences
plays a crucial role in LA thrombus formation
a sufficient anticoagulation for at least
LAA = left atrial appendage
detrimental
and management of LA thrombi in an unselected
(PVI), current guidelines recommend either
LA = left atrium
possible
thromboembolic
associated with pulmonary vein isolation
IQR = interquartile range
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Thrombus on TEE Before PVI
Some
studies
suggested
omitting
pre-
procedural TEE in patients without risk factors including a normal left ventricular ejection fraction (LVEF) (12,16), normally sized LA (11,16), a CHADS2 (Congestive Heart Failure, Hypertension History, Age $75 Years, Diabetes Mellitus History, Stroke or Transient Ischemic Attack Symptoms Previously) score of 0 points (10), or a CHA 2DS2-VASc (Congestive Heart Failure, Hypertension, Age $75 Years, Diabetes Mellitus, Prior Stroke or Transient Ischemic Attack or Thromboembolism, Vascular Disease, Age 65 to 74 Years, Sex) score #1 (17) in patients taking direct oral
METHODS STUDY POPULATION. All 7,541 TEE performed be-
tween April 2010 and April 2018 at the University Hospital Basel, a tertiary health care institution, were screened for eligibility. Only fully completed TEE prior to scheduled first and redo PVI were included. Follow-up TEE for verification of thrombus resolution and TEE for other indications were excluded. Two TEE were not successful due to esophageal resistance and were also excluded. During this time period, no PVI was performed without a prior TEE. Anticoagulation prior to scheduled PVI was performed according
to
current
guidelines
based
on
the
CHA 2DS2-VASc score (21). In all patients with an indication for anticoagulation, OAC therapy was prescribed for at least 3 weeks prior to PVI. The type of anticoagulation was left to the discretion of the treating physician. For anticoagulation with a VKA, the target INR was 2.0 to 3.0. In patients on VKA, PVI was performed without interrupting anticoagulation. In patients on DOACs, the morning dose before the PVI procedure was withheld. In patients on a singledose regimen (rivaroxaban, edoxaban) and a medication intake in the evening, anticoagulation was not interrupted for PVI.
anticoagulants (DOAC) with paroxysmal AF (9).
TRANSESOPHAGEAL
However, other studies showed presence of LAA
was performed using an iE33 or EPIQ 7 (Philips Med-
ECHOCARDIOGRAPHY. TEE
thrombi
(14,15).
ical Systems, Andover, Massachusetts) ultrasound
Furthermore, a study investigating sufficiently anti-
system with X7-2t and X8-2t transducers by experi-
coagulated patients before electrical cardioversion for
enced echocardiographers not involved in the abla-
also
in
these
patient
groups
AF found LAA thrombi in up to 7.7% of all performed
tion procedure. Specifically, the LA and LAA were
TEE (18). Treatment options for an LAA thrombus
scanned in multiple mid-esophageal imaging planes
including initiation of vitamin K antagonists (VKA) in
from 0 to 180 . LAA thrombus was defined as a
non-anticoagulated patients and increasing interna-
localized echo mass distinct to the LAA pectinate
tional normalized ratio (INR) targets to 2.5 to 3.5 in
muscles (Figure 1). As both LAA sludge and sponta-
previously anticoagulated patients are based on
neous echo contrast (SEC) have been shown to be
expert opinion and retrospective studies only and
high-risk markers for thromboembolic events and
lead to resolution rates close to 90% (19). To date,
thrombus formation in the LAA (22,23), we addition-
only 1 prospective study investigated a DOAC in non-
ally determined their prevalence on TEE before PVI.
anticoagulated
and
SEC was defined as a dynamic swirling echodensity
showed a low thrombus resolution rate of 60% (20).
within the LAA. LAA sludge was defined as a sta-
Therefore, important clinical uncertainties, regarding
tionary echodensity within the LAA that did not fulfill
the indication for pre-procedural TEE and the
criteria for a thrombus (absence of a globular,
patients
with
LA
thrombus
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F I G U R E 1 Different Forms of Thrombi in the LAA
(A) Round thrombus not attached to the left atrial appendage (LAA) wall, with low echodensity. (B) Small thrombus attached to the LAA wall with high echodensity. (C) Intermediate echodense thrombus filling out the tip of the LAA. (D) Small round thrombus in a chicken wing–like LAA.
organized structure) (22,23). In ambiguous cases, a
Wilcoxon rank-sum tests, as appropriate. Separate
second cardiologist was consulted and the follow-up
univariate logistic regression models were built to
TEE was analyzed. Pulsed-wave Doppler was used
investigate clinical risk factors for the presence of a
to measure the LAA emptying velocity and a peak
composite endpoint including presence of LAA
velocity #20 cm/s was considered abnormal (24). LAA
thrombus, LAA sludge, and SEC. Significantly associ-
morphology of patients with thrombi was judged by 2
ated variables in univariate models were then
physicians and classified as “cauliflower,” “wind-
computed in a combined multivariate model. All an-
sock,” “cactus,” or “chicken wing” (25). PVI proced-
alyses were performed on the level of TEE and not on
ures were cancelled if a LAA thrombus was identified.
a patient level, unless otherwise specified. A p value
If only LAA sludge or SEC were identified, PVI was
of #0.05 was considered statistically significant. All
performed as scheduled.
statistical
STATISTICAL
(version 9.4, SAS Institute Inc., Cary, North Carolina).
ANALYSIS. Baseline
characteristics
analyses
were
performed
using
SAS
were stratified by presence or absence of LAA thrombus. Categorical variables were presented as
RESULTS
numbers (proportions) and compared using Fisher exact test. The distribution of continuous variables
PATIENT
was checked using kurtosis, skewness, and visual
procedural TEE examinations from 1,358 patients
CHARACTERISTICS. Overall,
inspection of the histogram. Continuous variables
scheduled for PVI were included. Baseline charac-
were presented as mean SD or median (interquartile
teristics are shown in Table 1. Mean age at the time of
range [IQR]) and compared using Student’s t-tests or
TEE was 61.1 9.9 years and 72% were male. Mean
1,753
pre-
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the LAA, translating into a number needed to screen
T A B L E 1 Baseline Characteristics
Age, yrs Male BMI, kg/m2 Paroxysmal AF AF at TEE
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Thrombus on TEE Before PVI
of 159 TEE to detect 1 thrombus. A comparison of the
All Patients
N
No LAAT (n ¼ 1,742)
LAAT (n ¼ 11)
p Value
61.1 9.9
1,753
61.0 9.9
66.0 10.1
0.10
1,268 (72.3)
1,753
1,262 (72.0)
6 (54.6)
0.20
27.3 4.7
1,753
27.3 4.6
27.0 5.4
0.80
1,050 (59.9)
1,753
1,045 (60.0)
5 (45.5)
0.40
congestive heart failure (p ¼ 0.007), and a lower
510 (29.1)
1,753
505 (29.0)
5 (45.5)
0.20
glomerular filtration rate (p ¼ 0.03), but no differences were observed for OAC or anti-arrhythmic drug
History of CHF
215 (12.3)
1,753
210 (12.1)
5 (45.5)
0.007
Arterial hypertension
997 (56.9)
1,753
988 (56.4)
9 (81.8)
0.10
Diabetes
147 (8.4)
1,753
144 (8.3)
3 (27.3)
0.06
History of stroke/TIA
151 (8.6)
1,753
149 (8.6)
1 (9.1)
0.90
Vascular disease
165 (9.4)
1,753
163 (9.4)
2 (18.2)
0.30
CHA2DS2-VASc score
1.8 1.4
1,753
1.8 1.4
3.1 1.6
0.002
clinical characteristics between patients with and without LAA thrombus is shown in Table 1. Patients with a thrombus had a higher CHA 2DS2 -VASc score (p ¼ 0.002) (Figure 2), more often a history of
therapy. More details on patients with LAA thrombi are presented in Table 2. Of the 11 patients with a detected LAA thrombus, 4 (36%) were in sinus rhythm and
0
339 (19.3)
339 (19.5)
0 (0)
5 (46%) had paroxysmal AF. Five patients (46%) were
1
495 (28.2)
493 (28.3)
2 (18.2)
anticoagulated with DOAC and 3 (27%) with VKA. Two
2
428 (24.4)
426 (24.5)
2 (18.2)
patients were on reduced dosages of DOAC, 1 with an
3
279 (15.9)
275 (15.8)
4 (36.4)
appropriate dose reduction to 15 mg rivaroxaban and
$4
212 (12.1)
209 (12.0)
3 (27.3)
the other with an inappropriate dose reduction to
High-sensitivity troponin T, ng/l
8.0 20.7
1,270
8.0 20.7
15.5 14.5
0.10
Elevated BNP/ NT-proBNP
593 (62.4)
951
591 (62.3)
2 (100)
0.50
148 (139–156)
1,655
148 (139–156)
146 (135–153)
0.40
INR
1.7 (1.2–2.4)
1,748
1.7 (1.2–2.4)
1.7 (1.3–3.0)
0.40
C-reactive protein, mg/l
1.4 (0.7–2.8)
1,747
1.4 (0.7–2.8)
2.6 (1.9–5.9)
0.03
83 (73–95)
1,749
83 (73–95)
86 (78–103)
0.40
30 mg edoxaban. In all patients on VKA, the INR was within therapeutic range with 2.0, 2.6, and 3.0, respectively. Two patients had a history of cardiac
Hemoglobin, g/l
Creatinine, mmol/l GFR, ml/min/1.73 m2
92.4 (72.5–114.4) 1,749 92.4 (72.7–114.4) 72.1 (56.9–102.2)
Medication
0.03
surgery. In 1 patient with mitral valve reconstruction and documented incomplete surgical closure of the LAA 3 years before, a thrombus was detected in the residual LAA. This patient had a CHA2 DS2-VASc score of 1 and had no anticoagulation. The other patient
1,753 1,498 (86)
1489 (86)
8 (73)
0.20
had undergone biological replacement of the aortic
Vitamin K antagonist
605 (40)
603 (41)
3 (27)
0.80
valve and coronary bypass surgery 5 years before
DOAC
893 (60)
887 (60)
5 (45)
0.90
thrombus detection. LAA morphology was judged as a
151 (9)
149 (9)
2 (18)
0.40
Clopidogrel
9 (0.01)
9 (0.01)
0 (0)
0.90
windsock in 6 patients and as a chicken wing in 4
Amiodarone
294 (17)
291 (17)
3 (27)
0.30
OAC
Aspirin
Values are mean SD, n (%), or median (interquartile range). Data are compared using Student’s t-test, Wilcoxon test, or Fisher exact test, as appropriate. AF ¼ atrial fibrillation; BMI ¼ body mass index; BNP ¼ B-type natriuretic peptide; CHA2DS2-VASc ¼ Congestive Heart Failure, Hypertension, Age $75 Years, Diabetes Mellitus, Prior Stroke or Transient Ischemic Attack or Thromboembolism, Vascular Disease, Age 65 to 74 Years, Sex; CHF ¼ congestive heart failure; DOAC ¼ direct oral anticoagulants; GFR ¼ glomerular filtration rate; INR ¼ international normalized ratio; LAAT ¼ left atrial appendage thrombus; NT-proBNP ¼ N-terminal pro–B-type natriuretic peptide; OAC ¼ oral anticoagulants; TEE ¼ transesophageal echocardiography; TIA ¼ transient ischemic attack.
patients, and 1 LAA was not evaluated because of incomplete surgical closure. ECHOCARDIOGRAPHIC DATA. Overall, median LA
diameter was 41 (IQR: 37 to 46) mm, median indexed LA volume was 37.4 (IQR: 30.1 to 46.1) ml/m 2, and mean LVEF was 57.0 10.1% (Table 3). In the 11 patients with a thrombus, mean thrombus size was 90 mm2 . Patients with a detected thrombus had a
CHA2DS 2-VASc score was 1.8 1.4 and 60% of the TEE were performed in patients with paroxysmal AF. OAC therapy was prescribed during 86% (51% with DOACs, 35% with VKA) of the TEE (Online Table 1). During 30 TEE (3.4%), DOACs were used in reduced dosages. Based on current approved recommendations at the time of the TEE (26), the reduced dose was appropriate in 4 of them (13.3%). Overall, rivaroxaban was the most frequently used DOAC (663 TEE). Baseline characteristics stratified by the presence or absence of the combined endpoint are shown in Online Table 2. PREVALENCE OF THROMBUS AND CHARACTERIS-
lower LAA-emptying velocity (p ¼ 0.0009), lower LVEF (p ¼ 0.0049), and more frequently SEC (p ¼ 0.0001) and LAA sludge (p < 0.0001), but no difference in LA size was found. In addition, SEC and LAA sludge were found in 47 TEE (2.7%) and 5 (0.003%), respectively. Besides detection of LAA thrombi in 11 patients, TEE revealed another relevant diagnostic finding that led to cancellation of PVI in 7 additional patients. Those included severe valvular disease in 2, fibroelastoma in 1, LA myxoma in 1, atresia of the vena cava inferior in 1, and extracardiac findings in another 2 patients (newly diagnosed Morbus Hodgkin and an esophageal stricture). Echo-
TICS OF PATIENTS WITH THROMBUS. A left atrial
cardiographic data stratified by the presence or
thrombus was found in 11 of 1,753 TEE (0.6%), all in
absence of the combined endpoint are shown in
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F I G U R E 2 Patients With and Without LAAT Across the CHA 2 DS 2 -VASc Score
Relative frequency of patients with and without left atrial appendage thrombi (LAAT) across the CHA2DS2-VASc (Congestive Heart Failure, Hypertension, Age $75 Years, Diabetes Mellitus, Prior Stroke or Transient Ischemic Attack or Thromboembolism, Vascular Disease, Age 65 to 74 Years, Sex) score.
Online Table 3. No major TEE-related complications
and 153 days, respectively. The third patient with a
were recorded.
CHA2DS2-VASc score of 6 was initially prescribed
RISK FACTORS ASSOCIATED WITH LAA THROMBUS, LAA SLUDGE, AND SEC. The combined endpoint of
LAA thrombus, LAA sludge, and SEC occurred in 54 TEE (Table 4). In univariate models, factors significantly associated with an increased risk for the combined
endpoint
were
higher
age
(odds
ratio
[OR]:1.035; 95% CI: 1.005 to 1.067; p ¼ 0.02), higher body mass index (OR: 1.063; 95% CI: 1.010 to 1.118; p ¼ 0.02), nonparoxysmal AF (OR: 5.496; 95% CI: 2.872 to 10.517; p < 0.0001), documented AF on the surface electrocardiogram (ECG) before PVI (OR: 3.174; 95% CI: 1.837 to 5.486; p < 0.0001), and a higher CHA2DS2-VASc score (OR: 1.495; 95% CI: 1.262 to 1.772; p < 0.0001). After computation of these individual risk factors in a combined, multivariate model, nonparoxysmal AF (OR: 3.694; 95% CI: 1.860 to 7.336; p ¼ 0.0002), documented AF on the surface ECG before PVI (OR: 1.986; 95% CI: 1.114 to 3.542; p ¼ 0.02), and a higher CHA 2DS2-VASc score (OR: 1.410; 95% CI: 1.135 to 1.752; p ¼ 0.002) remained significantly associated with the combined endpoint. MANAGEMENT
OF
PATIENTS
WITH
LAA
THROMBI.
rivaroxaban
without
thrombus
resolution
after
4 weeks and subsequently was changed to VKA with detection of thrombus resolution after 109 days. In the 8 patients taking OAC, 3 were on VKA and 5 on a DOAC. In 2 of the patients on VKA, the target INR was increased to 2.5 to 3.0, and the third patient was switched to dabigatran. Of the 5 patients on DOAC, 4 were switched to another DOAC and 1 to VKA. Of the patients already on OAC, thrombus resolution was successful in 6 of 8 patients (75%). Both patients with thrombus persistence despite a change in treatment— increase in target INR and subsequent change to rivaroxaban and addition of aspirin in the first and change from rivaroxaban to apixaban in the second— were treated with cardiac resynchronization therapy and atrioventricular node ablation. With the reported management, over a mean follow-up of 38 months, of the 11 patients with a LAA thrombus, no stroke, but 1 transient ischemic attack was observed 28.5 months after initial thrombus detection in a patient with successful thrombus resolution in the follow-up TEE.
DISCUSSION
An overview of the treatment algorithms is shown in the Central Illustration. In 2 of the 3 patients who were
To the best of our knowledge, the present analysis
not on OAC therapy and had a CHA2DS 2-VASc score of
represents the largest study investigating the preva-
1 at the time of LAA thrombus detection, VKA was
lence and management of LA thrombi detected on
initiated with successful thrombus resolution after 65
TEE in patients undergoing PVI. We report several
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T A B L E 2 Individual Characteristics of Patients With Detected LAA Thrombi
Age (yrs)
Sex
BMI (kg/m2)
Paroxysmal AF
CHA2 DS 2-VASc score
AF at TEE
LAVI (ml/m2)
1
81
F
24
No
5
Yes
35.0
73
2
75
F
22
No
6
No
46.0
38
Patient #
LVEF (%)
3
73
F
22
No
2
Yes
—
60
4
64
M
31
Yes
3
No
—
48
5
72
F
24
Yes
5
No
53.4
42
6
43
M
20
Yes
1
No
—
70
7
69
M
28
No
3
Yes
43.5
40
8
59
M
28
Yes
1
No
—
65
9
69
M
25
Yes
3
No
40.4
58
10
59
M
35
No
3
Yes
45.9
25
11
62
F
37
No
2
Yes
40.8
61
TABLE 2 Continued
Patient #
LAA Peak Velocity (cm/s)
LAA Morphology
Thrombus Size (mm)
OAC at TEE
Therapy Change
Success
Days Until Resolution
1
17
Wind sock
10 8
Rivaroxaban 1 15 mg
Apixaban 2 5 mg
No
—
2
14
Chicken wing
15 10
No OAC
1. Rivaroxaban 20 mg 2. VKA
Yes
109
3
25
Chicken wing
—
VKA
VKA with INR 2.5–3.0
Yes
57
4
—
Chicken wing
86
VKA
Dabigatran 2 150 mg
Yes
131
5
25
Wind sock
13 13
Rivaroxaban 1 20 mg
Dabigatran 2 150 mg
Yes
18
6
40
Post-surgical
5 10
No OAC
VKA
Yes
65
7
10
Wind sock
13 8
VKA
1. VKA with INR 2.5–3.0. 2. Rivaroxaban 20 mg þ ASS
No
—
8
90
Wind sock
89
No OAC, ASS
VKA
Yes
153
9
11
Wind sock
13 7
Rivaroxaban 1 20 mg
Apixaban 2 5 mg
Yes
51
10
—
Wind sock
44
Edoxaban 1 30 mg
Apixaban 2 5 mg
Yes
37
11
13
Chicken wing
19 11
Rivaroxaban 1 20 mg
VKA
Yes
56
ASS ¼ acetylsalicylic acid; LAA ¼ left atrial appendage; LAVI ¼ left atrial volume indexed; LVEF ¼ left ventricular ejection fraction; VKA ¼ vitamin K antagonist; other abbreviations as in Table 1.
new and clinically important findings in a contemT A B L E 3 Echocardiographic Data
porary, well-defined population mainly treated with DOAC.
All Patients
N
No LAAT (n ¼ 1,742)
LAAT (n ¼ 11)
p Value
Overall, the prevalence of LAA thrombi was very
LVEF, %
57.0 10.2
1,517
57.1 10.1
50.0 13.8
0.0049
low with 0.6%. Besides detection of LAA thrombi,
$55
1,059 (69.8)
1,054 (70.0)
5 (45.5)
45–54
289 (19.1)
288 (19.1)
1 (9.1)
30–44
133 (8.8)
129 (8.6)
4 (36.4)
<30
36 (2.4)
35 (2.3)
1 (9.1)
TEE revealed other relevant diagnostic findings that led to cancellation of PVI in another 0.4%. In contrast to previous studies, LAA thrombi were
LA diameter, mm
41.0 (37.0–46.0)
1,232
41.0 (37.0–46.0)
41.0 (38.0–42.0)
0.40
detected in patients with paroxysmal and non-
LAV, ml
75.0 (59.0–93.0)
1,121
75.0 (59.0–93.0) 78.0 (70.0–87.0)
0.60
paroxysmal AF, independent of the type of OAC
LAVI, ml/m2
37.4 (30.1–46.1)
1,121
37.4 (30.1–46.1)
40.8 (36.8–45.9)
0.10
therapy, with a CHA2 DS2-VASc score $1, in patients
LAA peak velocity, cm/s
53.1 23.6
1,298
53.3 23.5
27.2 25.4
0.0009
with preserved and impaired LVEF, and in sinus
LAA peak velocity impaired
158 (10.4)
1,515
152 (10.1)
6 (66.7)
<0.0001
PFO
299 (21.2)
1,408
298 (21.3)
1 (9.1)
0.5
SEC
47 (2.7)
1,750
43 (2.5)
4 (36.4)
0.0001
LAA sludge
5 (0.3)
1,750
1 (0.1)
4 (36.4)
<0.0001
Values are mean SD, n (%), or median (interquartile range). Data are compared using Student’s t-test, Wilcoxon test, or Fisher exact test, as appropriate. LA ¼ left atrium; LAV ¼ left atrial volume; PFO ¼ persisting foramen ovale; SEC ¼ spontaneous echo contrast; other abbreviations as in Tables 1 and 2.
rhythm and AF documented on the ECG before PVI (9,11,12,16). Therefore, no patient group without a risk for LAA thrombus could be determined in our study.
These
differences
with
previous
in-
vestigations could be due to varying local echocardiographic criteria for LAA thrombus as well as different distributions of risk factors (9,11,12,16). However, as we report the results of an unselected patient
population
with
guideline-recommended
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Thrombus on TEE Before PVI
indications for PVI, we believe that the present analysis represents a typical patient population
T A B L E 4 Relationships of Clinical Risk Factors With LAAT, LAA Sludge and SEC
Univariate Models
encountered in daily clinical practice.
Combined Model
OR (95% CI)
p Value
OR (95% CI)
p Value
PVI declined to 42% to 73%, mainly due to incre-
Age
1.035 (1.005–1.067)
0.02
0.999 (0.962–1.037)
0.94
mental use of uninterrupted or “nearly uninter-
BMI
1.063 (1.010–1.118)
0.02
1.031 (0.978–1.087)
0.26
5.496 (2.872–10.517)
<0.0001
3.694 (1.860–7.336)
0.0002
AF on ECG before PVI
3.174 (1.837–5.486)
<0.0001
1.986 (1.114–3.542)
0.02
CHA2DS2-VASc score
1.495 (1.262–1.772)
<0.0001
1.410 (1.135–1.752)
0.002
In recent years, rates of pre-procedural TEE before
rupted” anticoagulation strategies, reallocation of resources, and alternative imaging modalities such as cardiac computed tomography (16,27,28). Although
Non-paroxysmal AF
one might expect missed LAA thrombi with increased
N ¼ 1,753 in separate and combined models.
risk for thromboembolic stroke due to this decline in
CI ¼ confidence interval; ECG ¼ electrocardiogram; OR ¼ odds ratio; PVI ¼ pulmonary vein isolation; other abbreviations as in Tables 1 and 3.
TEE, the risk of peri-interventional stroke remained low and even decreased over time in some studies (8,27,29). This might be explained by the patient
anticoagulation regimens (27,30). Besides TEE, alter-
population undergoing PVI, an operator learning
native
curve with routine use of interventional techniques
computed tomography, show high sensitivity and
to decrease the risk of thromboembolic stroke (e.g.,
specificity rates for LAA thrombi in comparison to
constant sheath flushing, minimizing catheter ex-
TEE and might have also picked up most abnormal-
changes)
ities found in our study (28). But, both modalities are
and
contemporary
peri-interventional
imaging
modalities,
especially
cardiac
C ENTR AL I LL U STRA T I O N Management of LA Thrombi
11 Thrombi
Initial therapy
DOAC (5)
VKA (3)
Therapy change
↑ INR (2)
+ (1)
DOAC (1)
+ (1)
Other DOAC (4)
– (1)
+ (3)
No OAC (2)
VKA (1)
DOAC (1)
VKA (1)
+ (1)
– (1)
+ (1)
Success
– (1)
Therapy change
DOAC + ASS (1)
VKA (1)
Success
– (1)
+ (1)
Göldi, T. et al. J Am Coll Cardiol EP. 2019;-(-):-–-. Success was defined as resolution of thrombus on the subsequent transesophageal echocardiogram. ASS ¼ acetylsalicylic acid; DOAC ¼ direct oral anticoagulants; INR ¼ international normalized ratio; OAC ¼ oral anticoagulants; VKA ¼ vitamin K antagonist.
8
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limited by local expertise and availability compared
DOAC was uncertain as no routine plasma level
with TEE. Furthermore, the benefit of LAA thrombus
measurements were performed. Third, the observa-
detection can be questioned because the true impact
tional nature does not allow drawing causal in-
of the presence of LAA thrombus during a PVI pro-
ferences. Fourth, the small number of detected LAA
cedure on the peri-interventional stroke risk is not
thrombi limits the investigation of associated risk
known due to a lack of prospective outcome data.
factors. The use of a composite endpoint increased
However, considering the elective nature of PVI, we
statistical power; however, a possibility of type II
believe that the potential risk of dislodging LAA
error remains. Fifth, the combined endpoint does not
thrombus during PVI is real and should be minimized
allow drawing conclusions on specific risk factors for
as much as possible.
LAA thrombi. As SEC is not considered a contraindi-
Considering the decreasing rates of pre-procedural
cation for ablation or cardioversion, the clinical
TEE, it is important to allocate pre-interventional
applicability of the combined endpoint regarding the
imaging to those patients at highest risk for LAA
safety of these interventions is limited. Sixth, our
thrombi by using clinical risk factors. However, the
study did not evaluate a strategy of no TEE with
limitation for identifying these risk factors in any
careful OAC monitoring in comparison to TEE in all
study is that an unfeasibly high number of study
patients. Therefore, a definite conclusion about the
participants are needed, because of the low occur-
true benefit of pre-procedural TEE in addition to
rence rate of LAA thrombi. We therefore used a
optimal OAC therapy cannot be made. Strengths of
combined endpoint of LAA thrombi, LAA sludge, and
our study are the large sample size, the well-
SEC to make such a risk factor analysis feasible. Both
characterized study participants, and the unselected
LAA sludge and SEC are well-known high-risk
patient cohort.
markers for LAA thrombi (22,23), so it can be expected that risk factors for all 3 overlap. In the current study,
CONCLUSIONS
patients with nonparoxysmal AF, a higher CHA 2DS2VASc score, and AF documented on the surface ECG
In patients with AF scheduled for PVI, LA thrombi are
before PVI had a higher risk for the combined
rare and present in <1%. Thrombi were found in pa-
endpoint.
pre-
tients on VKA and DOAC, in low-risk patients, and
interventional TEE is not routinely performed in all
despite sinus rhythm. Thrombus resolution was seen
patients due to limited TEE capacities, resources for
in the majority of patients over a mean period of
pre-procedural imaging should be allocated to these
11 weeks.
patient groups.
ACKNOWLEDGMENTS The authors thank the staff
Therefore,
in
centers
where
In patients with detected LAA thrombus, different
and participants of the BEAT AF PVI (Basel Atrial
changes in treatment led to thrombus resolution in
Fibrillation Pulmonary Vein Isolation) study for their
>80% of patients. Both a switch from one DOAC to
important contributions.
another or from VKA to DOAC or vice versa and an increase in the dosage were found to be useful
ADDRESS
treatment strategies. However, as there was no pre-
Kühne, Department of Cardiology, Universitätsspital
defined management strategy for LAA thrombi in our
Basel, Petersgraben 4, 4031 Basel, Switzerland.
study, our data do not allow for the recommendation
E-mail: [email protected].
FOR
CORRESPONDENCE:
Dr. Michael
of one treatment strategy over the other or the determination of whether leaving patients on an unchanged
strategy
but
ensuring
adequate
anti-
PERSPECTIVES
coagulation dosing and compliance might have yielded different results. Independent of the chosen
COMPETENCY IN MEDICAL KNOWLEDGE: Our
change in treatment, a follow-up TEE for confirma-
data may help clinicians to identify patient groups
tion of thrombus resolution should be performed, as
that should undergo a TEE before PVI in centers
the thrombus persisted in 18% of the patients.
where pre-interventional TEE is not routinely per-
STUDY
LIMITATIONS. Some
potential
limitations
have to be considered in the interpretation of our study. First, the retrospective study design and single-center data may limit the generalizability of our findings. Second, as we report data from clinical practice, the compliance of patients treated with
formed due to limited capacities. TRANSLATIONAL OUTLOOK: Further, larger registry studies are needed to improve identification of patient groups with AF at highest risk for LA thrombi.
JACC: CLINICAL ELECTROPHYSIOLOGY VOL.
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12. Khan MN, Usmani A, Noor S, et al. Low incidence of left atrial or left atrial appendage thrombus in patients with paroxysmal atrial fibrillation and normal EF who present for pulmonary vein antrum isolation procedure. J Cardiovasc Electrophysiol 2008;19:356–8. 13. Scherr D, Dalal D, Chilukuri K, et al. Incidence and predictors of left atrial thrombus prior to catheter ablation of atrial fibrillation. J Cardiovasc Electrophysiol 2009;20:379–84. 14. Frenkel D, D’Amato SA, Al-Kazaz M, et al. Prevalence of left atrial thrombus detection by transesophageal echocardiography: a comparison of continuous non-vitamin K antagonist oral anticoagulant versus warfarin therapy in patients undergoing catheter ablation for atrial fibrillation. J Am Coll Cardiol EP 2016;2:295–303. 15. Wallace TW, Atwater BD, Daubert JP, et al. Prevalence and clinical characteristics associated with left atrial appendage thrombus in fully anticoagulated patients undergoing catheter-directed atrial fibrillation ablation. J Cardiovasc Electrophysiol 2010;21:849–52. 16. Balouch M, Gucuk Ipek E, Chrispin J, et al. Trends in transesophageal echocardiography use, findings, and clinical outcomes in the era of minimally interrupted anticoagulation for atrial fibrillation ablation. J Am Coll Cardiol EP 2017;3: 329–36. 17. Gunawardene MA, Dickow J, Schaeffer BN, et al. Risk stratification of patients with left atrial appendage thrombus prior to catheter ablation of atrial fibrillation: an approach towards an individualized use of transesophageal echocardiography. J Cardiovasc Electrophysiol 2017;28:1127–36. 18. Seidl K, Rameken M, Drögemüller A, et al. Embolic events in patients with atrial fibrillation and effective anticoagulation: value of transesophageal echocardiography to guide direct-
fibrillation developed in collaboration with EACTS. Eur Heart J 2016;37:2893–962. 22. Lowe BS, Kusunose K, Motoki H, et al. Prognostic significance of left atrial appendage “sludge” in patients with atrial fibrillation: a new transesophageal echocardiographic thromboembolic risk factor. J Am Soc Echocardiogr 2014;27: 1176–83. 23. Beppu S, Nimura Y, Sakakibara H, Nagata S, Park Y-D, Izumi S. Smoke-like echo in the left atrial cavity in mitral valve disease: its features and significance. J Am Coll Cardiol 1985;6:744–9. 24. Kamp O, Verhorst PM, Welling RC, Visser CA. Importance of left atrial appendage flow as a predictor of thromboembolic events in patients with atrial fibrillation. Eur Heart J 1999;20: 979–85. 25. Beigel R, Wunderlich NC, Ho SY, Arsanjani R, Siegel RJ. The left atrial appendage: anatomy, function, and noninvasive evaluation. J Am Coll Cardiol Img 2014;7:1251–65. 26. Steffel J, Verhamme P, Potpara TS, et al., for the ESC Scientific Document Group. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J 2018;39:1330–93. 27. Cappato R, Calkins H, Chen SA, et al. Updated worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circ Arrhythm Electrophysiol 2010;3:32–8. 28. Vira T, Pechlivanoglou P, Connelly K, Wijeysundera HC, Roifman I. Cardiac computed tomography and magnetic resonance imaging vs. transoesophageal echocardiography for diagnosing left atrial appendage thrombi. Europace 2019;21:e1–10. 29. Kuck KH, Brugada J, Fürnkranz A, et al., for the
current cardioversion. Final results of the Ludwigshafen Observational Cardioversion Study. J Am Coll Cardiol 2002;39:1436–42.
FIRE AND ICE Investigators. Cryoballoon or radiofrequency ablation for paroxysmal atrial fibrillation. N Engl J Med 2016;374:2235–45.
19. Zhan Y, Joza J, Al Rawahi M, et al. Assessment
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and management of the left atrial appendage thrombus in patients with nonvalvular atrial fibrillation. Can J Cardiol 2018;34:252–61.
embolic risk in patients with atrial fibrillation undergoing transesophageal echocardiography before pulmonary vein isolation. J Am Coll Cardiol 2009;54:2032–9.
20. Lip GY, Hammerstingl C, Marin F, et al., for the X-TRA Study and CLOT-AF Registry Investigators. Left atrial thrombus resolution in atrial fibrillation or flutter: results of a prospective study with rivaroxaban (X-TRA) and a retrospective observa-
11. McCready JW, Nunn L, Lambiase PD, et al. Incidence of left atrial thrombus prior to atrial fibrillation ablation: is pre-procedural transoesophageal echocardiography mandatory? Euro-
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21. Kirchhof P, Benussi S, Kotecha D, et al. 2016
KEY WORDS left atrial appendage thrombus, pulmonary vein isolation, transesophageal echocardiography
A PP END IX For supplemental tables, please see the online version of this paper.
9
VOL.
-, NO. -, 2019
ª 2019 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER
Prevalence and Management of Atrial Thrombi in Patients With Atrial Fibrillation Before Pulmonary Vein Isolation Tobias Göldi, MD,a,b,* Philipp Krisai, MD,a,b,* Sven Knecht, PHD,a,b Stefanie Aeschbacher, PHD,a,b Florian Spies, MSC,a,b Ivan Zeljkovic, MD,c Beat A. Kaufmann, MD,a,b Beat Schaer, MD,a,b David Conen, MD, MPH,b,d Tobias Reichlin, MD,e Stefan Osswald, MD,a,b Christian Sticherling, MD,a,b Michael Kühne, MDa,b
ABSTRACT OBJECTIVES This study aimed to investigate the prevalence and management of left atrial (LA) thrombi detected by transesophageal echocardiography (TEE) in patients with atrial fibrillation undergoing pulmonary vein isolation (PVI). BACKGROUND Little data are available on LA thrombi before PVI. METHODS All patients scheduled for PVI between April 2010 and April 2018 undergoing pre-procedural TEE were analyzed. Management of LA thrombus was at the discretion of the treating physician. RESULTS In this study, 1,753 pre-procedural TEE from 1,358 patients (mean age 61 10 years, 28% female) were included. Anticoagulation was used in 86% of all TEE (51% with direct oral anticoagulants [DOAC], 35% with vitamin K antagonists [VKA]). Thrombi were found in 11 TEE (0.6%), all in the LA appendage. Of the 11 patients with a thrombus, 5 (46%) had paroxysmal atrial fibrillation, 2 (18%) had a CHA2DS2-VASc (Congestive Heart Failure, Hypertension, Age $75 Years, Diabetes Mellitus, Prior Stroke or Transient Ischemic Attack or Thromboembolism, Vascular Disease, Age 65 to 74 Years, Sex) score of 1, and 5 (46%) were in sinus rhythm at the time of TEE. Of the 8 patients (72%) on anticoagulation therapy, 5 were treated with DOAC and 3 with VKA. Starting anticoagulation (n ¼ 3), switching to VKA with a target international normalized ratio of 2.5 to 3 (n ¼ 3), or switching to a DOAC (n ¼ 1) or a different DOAC (n ¼ 4) resulted in thrombus resolution in 9 of 11 patients (82%). CONCLUSIONS In patients with atrial fibrillation scheduled for PVI, LA thrombi are rare and present in <1%. Thrombi were found in patients on VKA and DOAC, in low-risk patients, and despite sinus rhythm. Thrombus resolution was achieved in the majority of patients by changing the anticoagulation regimen. (J Am Coll Cardiol EP 2019;-:-–-) © 2019 by the American College of Cardiology Foundation.
From the aDepartment of Cardiology, University Hospital of Basel, Basel, Switzerland; bCardiovascular Research Institute Basel, University Hospital Basel, Basel, Switzerland; cSestre Milosrdnice University Hospital, Zagreb, Croatia;
d
Population Health
Research Institute, McMaster University and Department of Cardiology, Hamilton Health Sciences, Hamilton, Ontario, Canada; and the eDepartment of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. Dr. Schaer serves on the Speakers Bureau of Medtronic. Dr. Conen has received speaker honoraria from Servier, Canada. Dr. Kühne has received grants from Bayer, Pfizer-BMS, the Swiss National Science Foundation, and the Swiss Heart Foundation; and lecture or consulting fees from Daiichi-Sankyo, Boehringer Ingelheim, Bayer, Pfizer-BMS, AstraZeneca, Sanofi, Novartis, Merck Sharp & Dohme, Medtronic, Boston Scientific, St. Jude Medical, Biotronik, Sorin, Zoll, Biosense Webster, and Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. *Drs. Göldi and Krisai contributed equally to this work and are joint first authors. The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page. Manuscript received May 30, 2019; revised manuscript received September 5, 2019, accepted September 6, 2019.
ISSN 2405-500X/$36.00
https://doi.org/10.1016/j.jacep.2019.09.003
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A
ABBREVIATIONS AND ACRONYMS AF = atrial fibrillation
trial fibrillation (AF) is the most com-
management of LA thrombi before PVI, remain due to
mon arrhythmia and its incidence is
the
increasing (1,2). Patients with AF
associated thromboembolic stroke.
are at increased risk of death and cardiovas-
CI = confidence interval
cular
DOAC = direct oral anticoagulants
ECG = electrocardiogram INR = international normalized ratio
events,
especially
LVEF = left ventricular ejection fraction
SEC = spontaneous echo
clinical risk factors associated with a high risk for LA thrombi.
minimize the risk of thromboembolic stroke
3 weeks or a pre-procedural transesophageal echocardiography (TEE) in sinus rhythm
anticoagulation (7). Adhering to these recomrary studies investigating catheter ablation
TEE = transesophageal
for AF was shown to be as low as 0.3% (8).
echocardiography
VKA = vitamin K antagonists
Previous
studies
investigating
pre-
procedural TEE in patients with sufficient
anticoagulation have shown conflicting results with LAA thrombus prevalence ranging from 0.2% to 3.6% (9–16).
The aim of this study was to analyze the prevalence
and subsequent stroke occurrence (5,6). To
mendations, the risk of stroke in contempo-
contrast
PVI-
cohort of patients undergoing PVI and to investigate
TEE is recommended even with sufficient
PVI = pulmonary vein isolation
of
stroke (3,4). The left atrial appendage (LAA)
(6,7). For patients in AF, a pre-procedural
OR = odds ratio
consequences
plays a crucial role in LA thrombus formation
a sufficient anticoagulation for at least
LAA = left atrial appendage
detrimental
and management of LA thrombi in an unselected
(PVI), current guidelines recommend either
LA = left atrium
possible
thromboembolic
associated with pulmonary vein isolation
IQR = interquartile range
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Thrombus on TEE Before PVI
Some
studies
suggested
omitting
pre-
procedural TEE in patients without risk factors including a normal left ventricular ejection fraction (LVEF) (12,16), normally sized LA (11,16), a CHADS2 (Congestive Heart Failure, Hypertension History, Age $75 Years, Diabetes Mellitus History, Stroke or Transient Ischemic Attack Symptoms Previously) score of 0 points (10), or a CHA 2DS2-VASc (Congestive Heart Failure, Hypertension, Age $75 Years, Diabetes Mellitus, Prior Stroke or Transient Ischemic Attack or Thromboembolism, Vascular Disease, Age 65 to 74 Years, Sex) score #1 (17) in patients taking direct oral
METHODS STUDY POPULATION. All 7,541 TEE performed be-
tween April 2010 and April 2018 at the University Hospital Basel, a tertiary health care institution, were screened for eligibility. Only fully completed TEE prior to scheduled first and redo PVI were included. Follow-up TEE for verification of thrombus resolution and TEE for other indications were excluded. Two TEE were not successful due to esophageal resistance and were also excluded. During this time period, no PVI was performed without a prior TEE. Anticoagulation prior to scheduled PVI was performed according
to
current
guidelines
based
on
the
CHA 2DS2-VASc score (21). In all patients with an indication for anticoagulation, OAC therapy was prescribed for at least 3 weeks prior to PVI. The type of anticoagulation was left to the discretion of the treating physician. For anticoagulation with a VKA, the target INR was 2.0 to 3.0. In patients on VKA, PVI was performed without interrupting anticoagulation. In patients on DOACs, the morning dose before the PVI procedure was withheld. In patients on a singledose regimen (rivaroxaban, edoxaban) and a medication intake in the evening, anticoagulation was not interrupted for PVI.
anticoagulants (DOAC) with paroxysmal AF (9).
TRANSESOPHAGEAL
However, other studies showed presence of LAA
was performed using an iE33 or EPIQ 7 (Philips Med-
ECHOCARDIOGRAPHY. TEE
thrombi
(14,15).
ical Systems, Andover, Massachusetts) ultrasound
Furthermore, a study investigating sufficiently anti-
system with X7-2t and X8-2t transducers by experi-
coagulated patients before electrical cardioversion for
enced echocardiographers not involved in the abla-
also
in
these
patient
groups
AF found LAA thrombi in up to 7.7% of all performed
tion procedure. Specifically, the LA and LAA were
TEE (18). Treatment options for an LAA thrombus
scanned in multiple mid-esophageal imaging planes
including initiation of vitamin K antagonists (VKA) in
from 0 to 180 . LAA thrombus was defined as a
non-anticoagulated patients and increasing interna-
localized echo mass distinct to the LAA pectinate
tional normalized ratio (INR) targets to 2.5 to 3.5 in
muscles (Figure 1). As both LAA sludge and sponta-
previously anticoagulated patients are based on
neous echo contrast (SEC) have been shown to be
expert opinion and retrospective studies only and
high-risk markers for thromboembolic events and
lead to resolution rates close to 90% (19). To date,
thrombus formation in the LAA (22,23), we addition-
only 1 prospective study investigated a DOAC in non-
ally determined their prevalence on TEE before PVI.
anticoagulated
and
SEC was defined as a dynamic swirling echodensity
showed a low thrombus resolution rate of 60% (20).
within the LAA. LAA sludge was defined as a sta-
Therefore, important clinical uncertainties, regarding
tionary echodensity within the LAA that did not fulfill
the indication for pre-procedural TEE and the
criteria for a thrombus (absence of a globular,
patients
with
LA
thrombus
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F I G U R E 1 Different Forms of Thrombi in the LAA
(A) Round thrombus not attached to the left atrial appendage (LAA) wall, with low echodensity. (B) Small thrombus attached to the LAA wall with high echodensity. (C) Intermediate echodense thrombus filling out the tip of the LAA. (D) Small round thrombus in a chicken wing–like LAA.
organized structure) (22,23). In ambiguous cases, a
Wilcoxon rank-sum tests, as appropriate. Separate
second cardiologist was consulted and the follow-up
univariate logistic regression models were built to
TEE was analyzed. Pulsed-wave Doppler was used
investigate clinical risk factors for the presence of a
to measure the LAA emptying velocity and a peak
composite endpoint including presence of LAA
velocity #20 cm/s was considered abnormal (24). LAA
thrombus, LAA sludge, and SEC. Significantly associ-
morphology of patients with thrombi was judged by 2
ated variables in univariate models were then
physicians and classified as “cauliflower,” “wind-
computed in a combined multivariate model. All an-
sock,” “cactus,” or “chicken wing” (25). PVI proced-
alyses were performed on the level of TEE and not on
ures were cancelled if a LAA thrombus was identified.
a patient level, unless otherwise specified. A p value
If only LAA sludge or SEC were identified, PVI was
of #0.05 was considered statistically significant. All
performed as scheduled.
statistical
STATISTICAL
(version 9.4, SAS Institute Inc., Cary, North Carolina).
ANALYSIS. Baseline
characteristics
analyses
were
performed
using
SAS
were stratified by presence or absence of LAA thrombus. Categorical variables were presented as
RESULTS
numbers (proportions) and compared using Fisher exact test. The distribution of continuous variables
PATIENT
was checked using kurtosis, skewness, and visual
procedural TEE examinations from 1,358 patients
CHARACTERISTICS. Overall,
inspection of the histogram. Continuous variables
scheduled for PVI were included. Baseline charac-
were presented as mean SD or median (interquartile
teristics are shown in Table 1. Mean age at the time of
range [IQR]) and compared using Student’s t-tests or
TEE was 61.1 9.9 years and 72% were male. Mean
1,753
pre-
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the LAA, translating into a number needed to screen
T A B L E 1 Baseline Characteristics
Age, yrs Male BMI, kg/m2 Paroxysmal AF AF at TEE
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Thrombus on TEE Before PVI
of 159 TEE to detect 1 thrombus. A comparison of the
All Patients
N
No LAAT (n ¼ 1,742)
LAAT (n ¼ 11)
p Value
61.1 9.9
1,753
61.0 9.9
66.0 10.1
0.10
1,268 (72.3)
1,753
1,262 (72.0)
6 (54.6)
0.20
27.3 4.7
1,753
27.3 4.6
27.0 5.4
0.80
1,050 (59.9)
1,753
1,045 (60.0)
5 (45.5)
0.40
congestive heart failure (p ¼ 0.007), and a lower
510 (29.1)
1,753
505 (29.0)
5 (45.5)
0.20
glomerular filtration rate (p ¼ 0.03), but no differences were observed for OAC or anti-arrhythmic drug
History of CHF
215 (12.3)
1,753
210 (12.1)
5 (45.5)
0.007
Arterial hypertension
997 (56.9)
1,753
988 (56.4)
9 (81.8)
0.10
Diabetes
147 (8.4)
1,753
144 (8.3)
3 (27.3)
0.06
History of stroke/TIA
151 (8.6)
1,753
149 (8.6)
1 (9.1)
0.90
Vascular disease
165 (9.4)
1,753
163 (9.4)
2 (18.2)
0.30
CHA2DS2-VASc score
1.8 1.4
1,753
1.8 1.4
3.1 1.6
0.002
clinical characteristics between patients with and without LAA thrombus is shown in Table 1. Patients with a thrombus had a higher CHA 2DS2 -VASc score (p ¼ 0.002) (Figure 2), more often a history of
therapy. More details on patients with LAA thrombi are presented in Table 2. Of the 11 patients with a detected LAA thrombus, 4 (36%) were in sinus rhythm and
0
339 (19.3)
339 (19.5)
0 (0)
5 (46%) had paroxysmal AF. Five patients (46%) were
1
495 (28.2)
493 (28.3)
2 (18.2)
anticoagulated with DOAC and 3 (27%) with VKA. Two
2
428 (24.4)
426 (24.5)
2 (18.2)
patients were on reduced dosages of DOAC, 1 with an
3
279 (15.9)
275 (15.8)
4 (36.4)
appropriate dose reduction to 15 mg rivaroxaban and
$4
212 (12.1)
209 (12.0)
3 (27.3)
the other with an inappropriate dose reduction to
High-sensitivity troponin T, ng/l
8.0 20.7
1,270
8.0 20.7
15.5 14.5
0.10
Elevated BNP/ NT-proBNP
593 (62.4)
951
591 (62.3)
2 (100)
0.50
148 (139–156)
1,655
148 (139–156)
146 (135–153)
0.40
INR
1.7 (1.2–2.4)
1,748
1.7 (1.2–2.4)
1.7 (1.3–3.0)
0.40
C-reactive protein, mg/l
1.4 (0.7–2.8)
1,747
1.4 (0.7–2.8)
2.6 (1.9–5.9)
0.03
83 (73–95)
1,749
83 (73–95)
86 (78–103)
0.40
30 mg edoxaban. In all patients on VKA, the INR was within therapeutic range with 2.0, 2.6, and 3.0, respectively. Two patients had a history of cardiac
Hemoglobin, g/l
Creatinine, mmol/l GFR, ml/min/1.73 m2
92.4 (72.5–114.4) 1,749 92.4 (72.7–114.4) 72.1 (56.9–102.2)
Medication
0.03
surgery. In 1 patient with mitral valve reconstruction and documented incomplete surgical closure of the LAA 3 years before, a thrombus was detected in the residual LAA. This patient had a CHA2 DS2-VASc score of 1 and had no anticoagulation. The other patient
1,753 1,498 (86)
1489 (86)
8 (73)
0.20
had undergone biological replacement of the aortic
Vitamin K antagonist
605 (40)
603 (41)
3 (27)
0.80
valve and coronary bypass surgery 5 years before
DOAC
893 (60)
887 (60)
5 (45)
0.90
thrombus detection. LAA morphology was judged as a
151 (9)
149 (9)
2 (18)
0.40
Clopidogrel
9 (0.01)
9 (0.01)
0 (0)
0.90
windsock in 6 patients and as a chicken wing in 4
Amiodarone
294 (17)
291 (17)
3 (27)
0.30
OAC
Aspirin
Values are mean SD, n (%), or median (interquartile range). Data are compared using Student’s t-test, Wilcoxon test, or Fisher exact test, as appropriate. AF ¼ atrial fibrillation; BMI ¼ body mass index; BNP ¼ B-type natriuretic peptide; CHA2DS2-VASc ¼ Congestive Heart Failure, Hypertension, Age $75 Years, Diabetes Mellitus, Prior Stroke or Transient Ischemic Attack or Thromboembolism, Vascular Disease, Age 65 to 74 Years, Sex; CHF ¼ congestive heart failure; DOAC ¼ direct oral anticoagulants; GFR ¼ glomerular filtration rate; INR ¼ international normalized ratio; LAAT ¼ left atrial appendage thrombus; NT-proBNP ¼ N-terminal pro–B-type natriuretic peptide; OAC ¼ oral anticoagulants; TEE ¼ transesophageal echocardiography; TIA ¼ transient ischemic attack.
patients, and 1 LAA was not evaluated because of incomplete surgical closure. ECHOCARDIOGRAPHIC DATA. Overall, median LA
diameter was 41 (IQR: 37 to 46) mm, median indexed LA volume was 37.4 (IQR: 30.1 to 46.1) ml/m 2, and mean LVEF was 57.0 10.1% (Table 3). In the 11 patients with a thrombus, mean thrombus size was 90 mm2 . Patients with a detected thrombus had a
CHA2DS 2-VASc score was 1.8 1.4 and 60% of the TEE were performed in patients with paroxysmal AF. OAC therapy was prescribed during 86% (51% with DOACs, 35% with VKA) of the TEE (Online Table 1). During 30 TEE (3.4%), DOACs were used in reduced dosages. Based on current approved recommendations at the time of the TEE (26), the reduced dose was appropriate in 4 of them (13.3%). Overall, rivaroxaban was the most frequently used DOAC (663 TEE). Baseline characteristics stratified by the presence or absence of the combined endpoint are shown in Online Table 2. PREVALENCE OF THROMBUS AND CHARACTERIS-
lower LAA-emptying velocity (p ¼ 0.0009), lower LVEF (p ¼ 0.0049), and more frequently SEC (p ¼ 0.0001) and LAA sludge (p < 0.0001), but no difference in LA size was found. In addition, SEC and LAA sludge were found in 47 TEE (2.7%) and 5 (0.003%), respectively. Besides detection of LAA thrombi in 11 patients, TEE revealed another relevant diagnostic finding that led to cancellation of PVI in 7 additional patients. Those included severe valvular disease in 2, fibroelastoma in 1, LA myxoma in 1, atresia of the vena cava inferior in 1, and extracardiac findings in another 2 patients (newly diagnosed Morbus Hodgkin and an esophageal stricture). Echo-
TICS OF PATIENTS WITH THROMBUS. A left atrial
cardiographic data stratified by the presence or
thrombus was found in 11 of 1,753 TEE (0.6%), all in
absence of the combined endpoint are shown in
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F I G U R E 2 Patients With and Without LAAT Across the CHA 2 DS 2 -VASc Score
Relative frequency of patients with and without left atrial appendage thrombi (LAAT) across the CHA2DS2-VASc (Congestive Heart Failure, Hypertension, Age $75 Years, Diabetes Mellitus, Prior Stroke or Transient Ischemic Attack or Thromboembolism, Vascular Disease, Age 65 to 74 Years, Sex) score.
Online Table 3. No major TEE-related complications
and 153 days, respectively. The third patient with a
were recorded.
CHA2DS2-VASc score of 6 was initially prescribed
RISK FACTORS ASSOCIATED WITH LAA THROMBUS, LAA SLUDGE, AND SEC. The combined endpoint of
LAA thrombus, LAA sludge, and SEC occurred in 54 TEE (Table 4). In univariate models, factors significantly associated with an increased risk for the combined
endpoint
were
higher
age
(odds
ratio
[OR]:1.035; 95% CI: 1.005 to 1.067; p ¼ 0.02), higher body mass index (OR: 1.063; 95% CI: 1.010 to 1.118; p ¼ 0.02), nonparoxysmal AF (OR: 5.496; 95% CI: 2.872 to 10.517; p < 0.0001), documented AF on the surface electrocardiogram (ECG) before PVI (OR: 3.174; 95% CI: 1.837 to 5.486; p < 0.0001), and a higher CHA2DS2-VASc score (OR: 1.495; 95% CI: 1.262 to 1.772; p < 0.0001). After computation of these individual risk factors in a combined, multivariate model, nonparoxysmal AF (OR: 3.694; 95% CI: 1.860 to 7.336; p ¼ 0.0002), documented AF on the surface ECG before PVI (OR: 1.986; 95% CI: 1.114 to 3.542; p ¼ 0.02), and a higher CHA 2DS2-VASc score (OR: 1.410; 95% CI: 1.135 to 1.752; p ¼ 0.002) remained significantly associated with the combined endpoint. MANAGEMENT
OF
PATIENTS
WITH
LAA
THROMBI.
rivaroxaban
without
thrombus
resolution
after
4 weeks and subsequently was changed to VKA with detection of thrombus resolution after 109 days. In the 8 patients taking OAC, 3 were on VKA and 5 on a DOAC. In 2 of the patients on VKA, the target INR was increased to 2.5 to 3.0, and the third patient was switched to dabigatran. Of the 5 patients on DOAC, 4 were switched to another DOAC and 1 to VKA. Of the patients already on OAC, thrombus resolution was successful in 6 of 8 patients (75%). Both patients with thrombus persistence despite a change in treatment— increase in target INR and subsequent change to rivaroxaban and addition of aspirin in the first and change from rivaroxaban to apixaban in the second— were treated with cardiac resynchronization therapy and atrioventricular node ablation. With the reported management, over a mean follow-up of 38 months, of the 11 patients with a LAA thrombus, no stroke, but 1 transient ischemic attack was observed 28.5 months after initial thrombus detection in a patient with successful thrombus resolution in the follow-up TEE.
DISCUSSION
An overview of the treatment algorithms is shown in the Central Illustration. In 2 of the 3 patients who were
To the best of our knowledge, the present analysis
not on OAC therapy and had a CHA2DS 2-VASc score of
represents the largest study investigating the preva-
1 at the time of LAA thrombus detection, VKA was
lence and management of LA thrombi detected on
initiated with successful thrombus resolution after 65
TEE in patients undergoing PVI. We report several
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T A B L E 2 Individual Characteristics of Patients With Detected LAA Thrombi
Age (yrs)
Sex
BMI (kg/m2)
Paroxysmal AF
CHA2 DS 2-VASc score
AF at TEE
LAVI (ml/m2)
1
81
F
24
No
5
Yes
35.0
73
2
75
F
22
No
6
No
46.0
38
Patient #
LVEF (%)
3
73
F
22
No
2
Yes
—
60
4
64
M
31
Yes
3
No
—
48
5
72
F
24
Yes
5
No
53.4
42
6
43
M
20
Yes
1
No
—
70
7
69
M
28
No
3
Yes
43.5
40
8
59
M
28
Yes
1
No
—
65
9
69
M
25
Yes
3
No
40.4
58
10
59
M
35
No
3
Yes
45.9
25
11
62
F
37
No
2
Yes
40.8
61
TABLE 2 Continued
Patient #
LAA Peak Velocity (cm/s)
LAA Morphology
Thrombus Size (mm)
OAC at TEE
Therapy Change
Success
Days Until Resolution
1
17
Wind sock
10 8
Rivaroxaban 1 15 mg
Apixaban 2 5 mg
No
—
2
14
Chicken wing
15 10
No OAC
1. Rivaroxaban 20 mg 2. VKA
Yes
109
3
25
Chicken wing
—
VKA
VKA with INR 2.5–3.0
Yes
57
4
—
Chicken wing
86
VKA
Dabigatran 2 150 mg
Yes
131
5
25
Wind sock
13 13
Rivaroxaban 1 20 mg
Dabigatran 2 150 mg
Yes
18
6
40
Post-surgical
5 10
No OAC
VKA
Yes
65
7
10
Wind sock
13 8
VKA
1. VKA with INR 2.5–3.0. 2. Rivaroxaban 20 mg þ ASS
No
—
8
90
Wind sock
89
No OAC, ASS
VKA
Yes
153
9
11
Wind sock
13 7
Rivaroxaban 1 20 mg
Apixaban 2 5 mg
Yes
51
10
—
Wind sock
44
Edoxaban 1 30 mg
Apixaban 2 5 mg
Yes
37
11
13
Chicken wing
19 11
Rivaroxaban 1 20 mg
VKA
Yes
56
ASS ¼ acetylsalicylic acid; LAA ¼ left atrial appendage; LAVI ¼ left atrial volume indexed; LVEF ¼ left ventricular ejection fraction; VKA ¼ vitamin K antagonist; other abbreviations as in Table 1.
new and clinically important findings in a contemT A B L E 3 Echocardiographic Data
porary, well-defined population mainly treated with DOAC.
All Patients
N
No LAAT (n ¼ 1,742)
LAAT (n ¼ 11)
p Value
Overall, the prevalence of LAA thrombi was very
LVEF, %
57.0 10.2
1,517
57.1 10.1
50.0 13.8
0.0049
low with 0.6%. Besides detection of LAA thrombi,
$55
1,059 (69.8)
1,054 (70.0)
5 (45.5)
45–54
289 (19.1)
288 (19.1)
1 (9.1)
30–44
133 (8.8)
129 (8.6)
4 (36.4)
<30
36 (2.4)
35 (2.3)
1 (9.1)
TEE revealed other relevant diagnostic findings that led to cancellation of PVI in another 0.4%. In contrast to previous studies, LAA thrombi were
LA diameter, mm
41.0 (37.0–46.0)
1,232
41.0 (37.0–46.0)
41.0 (38.0–42.0)
0.40
detected in patients with paroxysmal and non-
LAV, ml
75.0 (59.0–93.0)
1,121
75.0 (59.0–93.0) 78.0 (70.0–87.0)
0.60
paroxysmal AF, independent of the type of OAC
LAVI, ml/m2
37.4 (30.1–46.1)
1,121
37.4 (30.1–46.1)
40.8 (36.8–45.9)
0.10
therapy, with a CHA2 DS2-VASc score $1, in patients
LAA peak velocity, cm/s
53.1 23.6
1,298
53.3 23.5
27.2 25.4
0.0009
with preserved and impaired LVEF, and in sinus
LAA peak velocity impaired
158 (10.4)
1,515
152 (10.1)
6 (66.7)
<0.0001
PFO
299 (21.2)
1,408
298 (21.3)
1 (9.1)
0.5
SEC
47 (2.7)
1,750
43 (2.5)
4 (36.4)
0.0001
LAA sludge
5 (0.3)
1,750
1 (0.1)
4 (36.4)
<0.0001
Values are mean SD, n (%), or median (interquartile range). Data are compared using Student’s t-test, Wilcoxon test, or Fisher exact test, as appropriate. LA ¼ left atrium; LAV ¼ left atrial volume; PFO ¼ persisting foramen ovale; SEC ¼ spontaneous echo contrast; other abbreviations as in Tables 1 and 2.
rhythm and AF documented on the ECG before PVI (9,11,12,16). Therefore, no patient group without a risk for LAA thrombus could be determined in our study.
These
differences
with
previous
in-
vestigations could be due to varying local echocardiographic criteria for LAA thrombus as well as different distributions of risk factors (9,11,12,16). However, as we report the results of an unselected patient
population
with
guideline-recommended
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Thrombus on TEE Before PVI
indications for PVI, we believe that the present analysis represents a typical patient population
T A B L E 4 Relationships of Clinical Risk Factors With LAAT, LAA Sludge and SEC
Univariate Models
encountered in daily clinical practice.
Combined Model
OR (95% CI)
p Value
OR (95% CI)
p Value
PVI declined to 42% to 73%, mainly due to incre-
Age
1.035 (1.005–1.067)
0.02
0.999 (0.962–1.037)
0.94
mental use of uninterrupted or “nearly uninter-
BMI
1.063 (1.010–1.118)
0.02
1.031 (0.978–1.087)
0.26
5.496 (2.872–10.517)
<0.0001
3.694 (1.860–7.336)
0.0002
AF on ECG before PVI
3.174 (1.837–5.486)
<0.0001
1.986 (1.114–3.542)
0.02
CHA2DS2-VASc score
1.495 (1.262–1.772)
<0.0001
1.410 (1.135–1.752)
0.002
In recent years, rates of pre-procedural TEE before
rupted” anticoagulation strategies, reallocation of resources, and alternative imaging modalities such as cardiac computed tomography (16,27,28). Although
Non-paroxysmal AF
one might expect missed LAA thrombi with increased
N ¼ 1,753 in separate and combined models.
risk for thromboembolic stroke due to this decline in
CI ¼ confidence interval; ECG ¼ electrocardiogram; OR ¼ odds ratio; PVI ¼ pulmonary vein isolation; other abbreviations as in Tables 1 and 3.
TEE, the risk of peri-interventional stroke remained low and even decreased over time in some studies (8,27,29). This might be explained by the patient
anticoagulation regimens (27,30). Besides TEE, alter-
population undergoing PVI, an operator learning
native
curve with routine use of interventional techniques
computed tomography, show high sensitivity and
to decrease the risk of thromboembolic stroke (e.g.,
specificity rates for LAA thrombi in comparison to
constant sheath flushing, minimizing catheter ex-
TEE and might have also picked up most abnormal-
changes)
ities found in our study (28). But, both modalities are
and
contemporary
peri-interventional
imaging
modalities,
especially
cardiac
C ENTR AL I LL U STRA T I O N Management of LA Thrombi
11 Thrombi
Initial therapy
DOAC (5)
VKA (3)
Therapy change
↑ INR (2)
+ (1)
DOAC (1)
+ (1)
Other DOAC (4)
– (1)
+ (3)
No OAC (2)
VKA (1)
DOAC (1)
VKA (1)
+ (1)
– (1)
+ (1)
Success
– (1)
Therapy change
DOAC + ASS (1)
VKA (1)
Success
– (1)
+ (1)
Göldi, T. et al. J Am Coll Cardiol EP. 2019;-(-):-–-. Success was defined as resolution of thrombus on the subsequent transesophageal echocardiogram. ASS ¼ acetylsalicylic acid; DOAC ¼ direct oral anticoagulants; INR ¼ international normalized ratio; OAC ¼ oral anticoagulants; VKA ¼ vitamin K antagonist.
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limited by local expertise and availability compared
DOAC was uncertain as no routine plasma level
with TEE. Furthermore, the benefit of LAA thrombus
measurements were performed. Third, the observa-
detection can be questioned because the true impact
tional nature does not allow drawing causal in-
of the presence of LAA thrombus during a PVI pro-
ferences. Fourth, the small number of detected LAA
cedure on the peri-interventional stroke risk is not
thrombi limits the investigation of associated risk
known due to a lack of prospective outcome data.
factors. The use of a composite endpoint increased
However, considering the elective nature of PVI, we
statistical power; however, a possibility of type II
believe that the potential risk of dislodging LAA
error remains. Fifth, the combined endpoint does not
thrombus during PVI is real and should be minimized
allow drawing conclusions on specific risk factors for
as much as possible.
LAA thrombi. As SEC is not considered a contraindi-
Considering the decreasing rates of pre-procedural
cation for ablation or cardioversion, the clinical
TEE, it is important to allocate pre-interventional
applicability of the combined endpoint regarding the
imaging to those patients at highest risk for LAA
safety of these interventions is limited. Sixth, our
thrombi by using clinical risk factors. However, the
study did not evaluate a strategy of no TEE with
limitation for identifying these risk factors in any
careful OAC monitoring in comparison to TEE in all
study is that an unfeasibly high number of study
patients. Therefore, a definite conclusion about the
participants are needed, because of the low occur-
true benefit of pre-procedural TEE in addition to
rence rate of LAA thrombi. We therefore used a
optimal OAC therapy cannot be made. Strengths of
combined endpoint of LAA thrombi, LAA sludge, and
our study are the large sample size, the well-
SEC to make such a risk factor analysis feasible. Both
characterized study participants, and the unselected
LAA sludge and SEC are well-known high-risk
patient cohort.
markers for LAA thrombi (22,23), so it can be expected that risk factors for all 3 overlap. In the current study,
CONCLUSIONS
patients with nonparoxysmal AF, a higher CHA 2DS2VASc score, and AF documented on the surface ECG
In patients with AF scheduled for PVI, LA thrombi are
before PVI had a higher risk for the combined
rare and present in <1%. Thrombi were found in pa-
endpoint.
pre-
tients on VKA and DOAC, in low-risk patients, and
interventional TEE is not routinely performed in all
despite sinus rhythm. Thrombus resolution was seen
patients due to limited TEE capacities, resources for
in the majority of patients over a mean period of
pre-procedural imaging should be allocated to these
11 weeks.
patient groups.
ACKNOWLEDGMENTS The authors thank the staff
Therefore,
in
centers
where
In patients with detected LAA thrombus, different
and participants of the BEAT AF PVI (Basel Atrial
changes in treatment led to thrombus resolution in
Fibrillation Pulmonary Vein Isolation) study for their
>80% of patients. Both a switch from one DOAC to
important contributions.
another or from VKA to DOAC or vice versa and an increase in the dosage were found to be useful
ADDRESS
treatment strategies. However, as there was no pre-
Kühne, Department of Cardiology, Universitätsspital
defined management strategy for LAA thrombi in our
Basel, Petersgraben 4, 4031 Basel, Switzerland.
study, our data do not allow for the recommendation
E-mail: [email protected].
FOR
CORRESPONDENCE:
Dr. Michael
of one treatment strategy over the other or the determination of whether leaving patients on an unchanged
strategy
but
ensuring
adequate
anti-
PERSPECTIVES
coagulation dosing and compliance might have yielded different results. Independent of the chosen
COMPETENCY IN MEDICAL KNOWLEDGE: Our
change in treatment, a follow-up TEE for confirma-
data may help clinicians to identify patient groups
tion of thrombus resolution should be performed, as
that should undergo a TEE before PVI in centers
the thrombus persisted in 18% of the patients.
where pre-interventional TEE is not routinely per-
STUDY
LIMITATIONS. Some
potential
limitations
have to be considered in the interpretation of our study. First, the retrospective study design and single-center data may limit the generalizability of our findings. Second, as we report data from clinical practice, the compliance of patients treated with
formed due to limited capacities. TRANSLATIONAL OUTLOOK: Further, larger registry studies are needed to improve identification of patient groups with AF at highest risk for LA thrombi.
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Thrombus on TEE Before PVI
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KEY WORDS left atrial appendage thrombus, pulmonary vein isolation, transesophageal echocardiography
A PP END IX For supplemental tables, please see the online version of this paper.
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