Exclusion of Intra-Atrial Thrombus Diagnosis Using D-Dimer Assay Before Catheter Ablation of Atrial Fibrillation

JACC: CLINICAL ELECTROPHYSIOLOGY

VOL.

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ª 2018 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER

Exclusion of Intra-Atrial Thrombus Diagnosis Using D-Dimer Assay Before Catheter Ablation of Atrial Fibrillation Antoine Milhem, MD,a Pierre Ingrand, MD, PHD,b Frédéric Tréguer, MD,c Olivier Cesari, MD,d Antoine Da Costa, MD,e Dominique Pavin, MD,f Philippe Rivat, MD,g Nicolas Badenco, MD,h Sélim Abbey, MD,i Noura Zannad, MD,j Pierre François Winum, MD,k Jacques Mansourati, MD,l Philippe Maury, MD,m Hugues Bader, MD,n Arnaud Savouré, MD,o Frédéric Sacher, MD,p Marius Andronache, MD,q Caroline Allix-Béguec, PHD,a Christian De Chillou, MD, PHD,q,r Frédéric Anselme, MD, PHD,o the ATE Study Group

ABSTRACT OBJECTIVES This study hypothesized that the association of D-dimer blood level and several clinical items in a new risk score could predict the absence of atrial thrombus. BACKGROUND Symptomatic and drug resistant atrial fibrillation (AF) can be treated by catheter ablation. The procedure-related risk of thromboembolism is limited by the pre-operative use of transesophageal echocardiography (TEE) to detect atrial thrombi. METHODS Patients admitted for catheter ablation of AF (n ¼ 2,494) were prospectively included in a multicenter study. TEE was systematically performed before the procedure to search for atrial thrombus (primary endpoint). D-dimer level, CHADS2 score, left ventricular ejection fraction, pre-operative anticoagulation regimen, and medical history were collected. A logistic regression model was used to identify factors associated with the presence of atrial thrombus (hypertension, history of stroke, heart failure, D-dimer level >270 ng/ml). These factors were aggregated in a new score called atrial thrombus exclusion (ATE). RESULTS The incidence of atrial thrombus was 1.92%. CHADS2 score and D-dimer level were significantly associated with atrial thrombus (p < 0.0001 and p < 0.0001, respectively). A zero CHADS2 score failed to exclude all atrial thrombi (5 false negatives; sensitivity: 89.58%, specificity: 52.2%). No false negative was found with a zero ATE score, which had a specificity of 37% and a higher sensitivity (100%) than the CHADS2 score (p < 0.031) to predict the absence of intraatrial thrombi on TEE. Conversely, the positive predictive value was poor, and the ATE score should not be used to conclude a positive diagnosis of thrombus. CONCLUSIONS An ATE score of zero was strongly associated with the absence of atrial thrombus. This new score could be useful to rule out a diagnosis of atrial thrombus before catheter ablation of AF. (J Am Coll Cardiol EP 2018;-:-–-) © 2018 by the American College of Cardiology Foundation.

From the aGroupe Hospitalier de la Rochelle Ré Aunis, La Rochelle, France; bEpidemiology and Biostatistics, INSERM CIC 1402 Université de Poitiers, CHU Poitiers, Poitiers, France; cClinique St-Joseph, Trélazé, France; dClinique Saint Gatien, Tours, France; e

CHU Saint-Etienne, Saint-Etienne, France; fCHU Rennes, Rennes, France; gPolyclinique Vauban, Valenciennes, France; hAPHP,

Hôpital Pitié Salpêtrière, Paris, France; iNouvelles Cliniques Nantaises, Groupe Confluent, Nantes, France; jCHR Metz-Thionville, Metz, France; kCHU Nîmes, Nîmes, France; lCHU Brest, Brest, France;

m

CHU Toulouse, Toulouse, France; nCH Pau, Pau, France;

o

CHU Rouen, Rouen, France; pCHU Bordeaux, Bordeaux, France; qCHU Nancy, Vandœuvre lès-Nancy, France; and rINSERM-IADI

U1254, Vandœuvre lès-Nancy, France. This study was supported by a grant from Medtronic. Dr. de Chillou has been a consultant for Biosense Webster, Abbott, Boston Scientific, and Stereotaxis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. All 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 17, 2018; revised manuscript received August 20, 2018, accepted September 11, 2018.

ISSN 2405-500X/$36.00

https://doi.org/10.1016/j.jacep.2018.09.009

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ABBREVIATIONS AND ACRONYMS AF = atrial fibrillation

trial fibrillation (AF) is the most com-

For the sake of data homogenization, results ranging

mon form of cardiac arrhythmia and

from 45 to 270 ng/ml with the VIDAS test were all

is

considered as being <270 ng/ml.

associated

with

increased

morbidity and mortality mostly related to

ATE = atrial thrombus

thromboembolic events. Catheter ablation is

exclusion

recommended as a curative treatment of

INR = international normalized

drug-resistant and symptomatic AF. The

ratio

presence of atrial thrombus, usually located

LVEF = left ventricular ejection

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Atrial Thrombus Exclusion Score

fraction

in the left atrial appendage, is a contraindica-

OR = odds ratio

tion to catheter ablation of AF. Transesopha-

TEE = transesophageal

geal echocardiography (TEE) remains the

echocardiography

gold standard for the diagnosis of left atrial thrombi (1). CHADS2 and CHA 2DS2-VASc scores are widely used to predict the thromboembolic risk associated with AF (2,3).

TEE. TEE was performed according to the guidelines

of the European Association of Cardiovascular Imaging within 48 h before the ablation procedure (4). The detection of a hyperechoic mass revealed an intraatrial thrombus. Its presence contraindicated the ablation procedure. Because the aim of the study was to propose an alternative method to TEE to eliminate an atrial thrombus, the findings that resulted from the TEE were not collected (sludge, left appendage velocity). Operators were blinded to the results of the D-dimer levels.

D-dimers (plasma fibrin D-dimers) are degradation

VARIABLES. Clinical data including age, sex, hyper-

products of cross-linked fibrin by the endogenous

tension, diabetes mellitus, heart failure, history of

fibrinolytic system, and their plasma levels are

stroke, medical and surgical history, AF history,

routinely measured to rule out diagnosis of deep

anticoagulation protocol, left ventricular ejection

venous thrombosis or pulmonary embolism. Like-

fraction (LVEF), plasma D-dimer level, and presence

wise, we hypothesized that a low level of plasma

of atrial thrombus were collected. Effective anti-

D-dimers could contribute to ruling out a diagnosis of

coagulation was arbitrarily defined as the prescription

atrial thrombus.

of a direct oral anticoagulant agent or vitamin K

This prospective multicenter study was designed

antagonist therapy with a weekly international

to assess the ability of a new composite score, which

normalized ratio (INR) >2 during the 3 weeks pre-

combined plasma D-dimer levels and clinical data, to

ceding TEE. Paroxysmal AF was defined as recurrent

rule out a diagnosis of atrial thrombus before catheter

AF that spontaneously terminated within 7 days.

ablation of AF.

Persistent AF was defined as AF that lasted for at least 7 days or required cardioversion, and also included

METHODS

long-lasting AF (>1 year of AF).

PARTICIPANTS. This

The presence of left atrial thrombus was a contraconsecutive

indication to catheter ablation. The ablation proced-

patients hospitalized for catheter ablation of AF

ure and patient monitoring were performed according

(paroxysmal or persistent) or left atrial tachycardia.

to local practices.

It

was

conducted

study

enrolled

between

August

2015

and

December 2016 in 29 French electrophysiology facilities

where

TEE

was

regularly

performed

for

thrombus formation screening before catheter ablation in the left atrium. The study complied with the Declaration

of

Helsinki.

The

patients

received

appropriate information by the physicians before inclusion in the trial. The study was approved by the institutional review board and was registered in the clinicaltrials.gov database (NCT02199080).

STATISTICAL ANALYSIS. The primary endpoint was

the presence of atrial thrombus diagnosed by TEE. Statistical significance was established with a p value <0.05. Continuous variables were presented as mean  SD, and categorical variables were presented as counts and percentage. Relationships between the primary endpoint and continuous variables or categorical variables were explored using the MannWhitney test, chi-square analysis, and Fisher exact test, respectively. Continuous variables were con-

PLASMA D-DIMER LEVEL MEASUREMENT. Plasma D-

verted into

dimer level was systematically measured within 48 h

threshold value. Binary variables significantly asso-

binary variables by determining

before catheter ablation. Two different tests were

ciated with the primary endpoint were included in a

used: LIATEST (Stago, Asnières sur Seine, France) and

multivariate

VIDAS (BioMerieux, Marcy l’Etoile, France). Both

stepwise selection method that used Wald’s test sig-

tests have the same cutoff value (500 ng/ml) to rule

nificance criterion with entry and exit levels set both

logistic

regression

model

using

a

a

out a diagnosis of venous thromboembolism. The

at p < 0.05. Independent factors associated with atrial

lowest measurable values were 270 and 45 ng/ml

thrombus were aggregated in a new score. The

using the LIATEST and VIDAS tests, respectively.

sensitivity, specificity, and negative predictive value

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of this new score were calculated. Sensitivities of the new score and CHADS2 score were compared using the likelihood ratio test. Calibration plots and the Hosmer-Lemeshow test were used to assess goodness of fit and model calibration. Statistical analysis was performed using SAS V9.4 statistical

software

(SAS

Institute,

Cary,

North

Carolina).

T A B L E 1 Baseline Characteristics (N ¼ 2,494)

60.7  10.7

Age, yrs Female

676 (27.1)

Paroxysmal fibrillation

1,335 (53.5)

Persistent fibrillation

996 (39.9)

Left atrial tachycardia

163 (6.5)

LVEF, %

57.4  10.0

Medical history

RESULTS

Previous left atrial ablation

593 (23.8)

Hypertension

916 (36.7)

Diabetes mellitus

227 (9.1)

Heart failure

304 (12.2)

CHARACTERISTICS OF PARTICIPANTS. Among the

Stroke

115 (4.6)

2,506 patients included over the 18-month study

Venous thromboembolism

45 (1.8)

Inflammatory disease

34 (1.4)

Neoplasia

25 (1.0)

Infectious disease

6 (0.2)

Recent surgery

4 (0.2)

BASELINE

DEMOGRAPHIC

AND

CLINICAL

period, 12 were excluded from the analysis because of missing key data (D-dimer value). Of the remaining 2,494 patients, 166 were missing LVEF measurements. The study population consisted of 1,818 men

Anticoagulation

(72.9%) and 676 women (27.1%), with a median age of

No anticoagulant therapy

235 (9.4)

62 years. The patients experienced paroxysmal AF

Dabigatran

269 (10.8)

(53.5%), persistent AF (39.9%), and left atrial tachy-

Rivaroxaban

596 (23.9)

cardia (6.5%). Catheter ablation was a first attempt in

Apixaban

321 (12.9)

Effective vitamin K antagonists

814 (32.6)

1,901 cases (76.2%). The median LVEF was 60%. Hypertension, diabetes mellitus, heart failure, and

Noneffective vitamin K antagonists

245 (9.8)

Other

14 (0.6)

history of stroke were reported in 36.7%, 9.1%, 12.2%, Values are mean  SD or n (%).

and 4.6% of the cases, respectively (Table 1). PRIMARY

ENDPOINT. Forty-eight

thrombi

were

documented by TEE (incidence of 1.92%; 95% confidence interval: 1.42% to 2.54%) before or at the beginning of the ablation procedure.

LVEF ¼ left ventricular ejection fraction.

associated with the presence of atrial thrombus (p < 0.0001). The results are summarized in Table 2. The center effect was tested and was not statisti-

CHADS 2 SCORE. In our study, 1,282 patients had a

cally significant (p ¼ 0.98).

CHADS 2 score of zero, and of these, 5 had atrial thrombus (0.4%) (Table 2) (CHADS 2 score: Online

T A B L E 2 Univariate Analysis of Variables Related to the Presence of Atrial

Figure 1).

Thrombus

PLASMA

D-DIMER

THRESHOLD. Plasma

D-dimer

levels were measured with LIATEST and VIDAS in 1,173 and 1,321 patients, respectively. The receiver-operating characteristic curve of plasma D-dimer level was built (area under the receiver-operating characteristic curve: 0.658) (ATE Score: Online Figure 2). RISK FACTORS. Among the tested continuous vari-

Age, yrs

Atrial Thrombus (n ¼ 48)

No Atrial Thrombus (n ¼ 2,446)

p Value*

66.4  8.1

60.6  10.7

<0.0001 0.0086

Age ($75 yrs)

8 (16.7)

148 (6.1)

Female

15 (31.3)

661 (27.0)

0.51

Persistent fibrillation

28 (58.3)

968 (39.6)

0.011

Hypertension

0.0004

30 (62.5)

886 (36.2)

Diabetes mellitus

9 (18.8)

218 (8.9)

0.036

Heart failure

19 (39.6)

285 (11.7)

<0.0001

ables, age (p < 0.0001), CHADS 2 score (p < 0.0001),

LVEF, %

46.7  15.1

57.6  9.7

<0.0001

LVEF (p < 0.0001), and D-dimer assay (p < 0.0001)

History of stroke

6 (12.5)

109 (4.5)

0.021

were significantly associated with the presence of

Previous left atrial ablation

9 (18.8)

584 (23.9)

0.50

atrial thrombus.

Anticoagulation before ablation

47 (97.9)

2,212 (90.4)

0.082

0

5 (10.4)

1,277 (52.2)

1

20 (41.7)

744 (30.4)

2

13 (27.1)

299 (12.2)

$3

10 (20.8)

126 (5.2)

30 (62.5)

930 (38.0)

The following categorical variables were significantly associated with the presence of atrial thrombus using univariate analysis: age older than 75 years (odds ratio [OR]: 3.1; p ¼ 0.0086), hypertension (OR: 2.93; p ¼ 0.0004), diabetes (OR: 2.35; p ¼ 0.036), heart

<0.0001

CHADS2 score

D-dimers (> 270 ng/ml)

0.0008

failure (OR: 4.97; p < 0.0001), history of stroke (OR: 3.06; p ¼ 0.021), and D-dimer level >270 ng/ml (OR: 2.717; p ¼ 0.0008). Persistent arrhythmia was also

Values are mean  SD or n (%). *p Value based on Mann-Whitney or Fisher exact test. Abbreviation as in Table 1.

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T A B L E 3 Multivariate Logistic Regression Analysis of Variables

T A B L E 4 Distribution of the ATE Score in the Study Population

Related to the Presence of Atrial Thrombus ATE Score

No. of Patients (%)

OR*

95% CI

p Value

0

911 (36.5)

Hypertension

2.37

1.30–4.32

0.0048

1

988 (39.6)

Heart failure

3.93

2.15–7.18

<0.0001

2

481 (19.3)

History of stroke

2.55

1.04–6.26

0.041

3

111 (4.5)

D-dimers (> 270 ng/m)

2.29

1.25–4.16

0.0070

4

3 (0.1)

*c-index for model fit ¼ 0.774. CI ¼ confidence interval; OR ¼ odds ratio.

Using multivariate logistic regression analysis, hypertension (p ¼ 0.0048), heart failure (p < 0.0001), history of stroke (p ¼ 0.041), and a D-dimer plasma level >270 ng/ml (p ¼ 0.007) were found to be independently associated with the existence of atrial thrombus (Table 3).

Values are n (%). ATE ¼ atrial thrombus exclusion.

previous anticoagulation in patients with AF who have episodes lasting >48 h, TEE is mandatory (1). INCIDENCE OF THROMBUS. The incidence of intra-

atrial thrombus of 1.92% (95% confidence interval: 1.42% to 2.54%) found in our study is in line with incidences reported in the published data (range

BIOCLINICAL SCORE. A new score was constructed

0.6%

by combining a history of stroke, congestive heart

thrombus before a left atrial ablation is likely

failure, high plasma D-dimer level, and hypertension.

dependent on the characteristics of the study popu-

The distribution of the atrial thrombus exclusion

lation, the quality of anticoagulation, and the diag-

(ATE) score in the study population is shown in

nostic methods (Table 5).

Table 4. The distribution of thrombus number as a function of the ATE score is depicted in Figure 1. This score was significantly associated with the presence of endocardial thrombus (p < 0.0001). The receiver-operating characteristic curve was constructed (area under the receiver-operating characteristic curve: 0.77). An ATE score of zero stood for the absence of thrombus, with a sensitivity of 100%, a specificity of 37%, and a negative predictive value of 100% (no false negative). The sensitivity of the CHADS 2 score was 89.9% (95% confidence interval: 77.34% to 99.65%) (5 false negatives). The sensitivities of the ATE score and the CHADS 2 score were significantly different (p ¼ 0.031). The Hosmer-Lemeshow test was significant (p ¼ 0.0022) in relation with departures to loglinearity. This limit led to building the ATE score as an ordinal scale.

DISCUSSION CURRENT RECOMMENDATIONS. As stated in the 2017

HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter ablation of AF, there is a wide disparity in the practice of experienced teams

to

3.6%)

(5–11).

The

incidence

of

atrial

PREVIOUS ANTICOAGULATION. Apparent effective

anticoagulation before ablation does not definitively eliminate the risk of atrial thrombus formation. As reported in Table 5, almost all atrial thrombi were identified while patients were on effective anticoagulation treatment, as assessed by recurrent INRs within the therapeutic range weeks before AF ablation. To our knowledge, there are no data on thrombi incidence in patients on direct oral anticoagulant treatment in this setting. In a retrospective study of 672 patients with AF, Zylla et al. (12) reported an incidence of atrial thrombi that was significantly higher in patients treated with phenprocoumon (17.8%) than in those treated with dabigatran or rivaroxaban (3.9%). In our study, 47 of 48 patients with atrial thrombus had previous anticoagulation before TEE. Among the 1,059 patients treated with warfarin, an atrial thrombus was found in 27 (2.5%), including 18 patients with a weekly INR >2 for >3 weeks. Among the 1,186 patients treated with direct oral anticoagulant agents, an atrial thrombus was found in 19 (1.6%) of them (dabigatran: 6 of 269; rivaroxaban: 10 of 596; apixaban: 3 of 321).

regarding indications for TEE. Although most teams

PLASMA

systematically perform TEE before or at the beginning

Several studies have investigated the association be-

D-DIMER

LEVEL

AND ATRIAL

THROMBUS.

of ablation, some experts personalize their practice

tween endocardial thrombus and plasma D-dimer

according to each patient’s AF type (paroxysmal or

level. Yasaka et al. (13) reported a significantly higher

persistent), thromboembolic risk score, or previous

plasma D-dimer level in 18 of 63 mitral stenosis

effective anticoagulation. However, in the absence of

patients with an atrial thrombus visualized on

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F I G U R E 1 ATE Score

The atrial thrombus exclusion (ATE) score is based on bioclinical parameters. A zero score matched up with the absence of intra-atrial thrombus.

transthoracic echocardiography compared with pa-

thrombus using this single parameter. Because of the

tients without atrial thrombus. Likewise, a higher D-

measurement methods used (no value <270 ng/ml

dimer level was found in 19 of 109 patients with

using LIATEST), the cutoff value of 270 ng/ml was

nonvalvular AF (14). In 73 AF patients who underwent

chosen to favor the negative predictive value of the

systematic TEE before electrical cardioversion, a

test.

plasma D-dimer level <600 mg/ml had a negative predictive value of 98% to rule out the presence of

SCORES PREDICTING THE ABSENCE OF THROMBUS.

thrombus (15). The authors pointed out that the only

Several multicenter studies investigated the CHADS2

false negative was a patient with an intra-atrial ul-

score or its constitutive variables as predictor of

trasound image that did not disappear when the pa-

absence of atrial thrombus before isolation of the

tient

which

pulmonary veins (Table 5). Puwanant et al. (6), Scherr

suggested a possible false positive of echo. Recently,

et al. (5), and Yamashita et al. (10) reported an

in a much larger study (925 patients with nonvalvular

increased incidence of intra-atrial thrombus as the

received

anticoagulant

treatment,

AF), in which TEE and plasma D-dimer measurement

CHADS2 score rose. However, among these 3 studies,

were systematically performed, a cutoff value of 1,115

only Scherr et al. found that a CHADS 2 score $2 was

ng/ml (determined by receiver-operating character-

an independent factor associated with the presence of

istic curve) had a negative predictive value of 97% to

thrombus. In all of these studies, the incidence of

rule out a diagnosis of intra-atrial thrombus (16).

thrombi was low when the CHADS 2 score was equal to

It is noteworthy, in these 2 studies, that the cutoff

zero (0% to 1%). Based on this result, some authors

value was determined to obtain the best sensitivity/

suggested that TEE could be skipped in patients

specificity ratio, but not to maximize the negative

without clinical risk factors for thromboembolism.

predictive value.

However, they warned that prospective multicenter

We reported here the results of the first multi-

studies were needed to confirm this hypothesis.

center study that evaluated plasma D-dimer level as a

In our study, 1,282 patients had a CHADS2 score of

potential predictive factor to rule out the presence of

zero, and atrial thrombus was found in 5 patients

intra-atrial thrombus in the setting of AF ablation. We

(0.4%). The plasma D-dimer levels of these 5 patients

found that a low plasma D-dimer value was signifi-

were all above the cutoff value of 270 ng/ml (411, 490,

cantly associated with absence of thrombus. Howev-

640, 730, and 1,080 ng/ml). The new thromboembolic

er, it was not possible to determine a cutoff value to

risk score, ATE, which combined clinical items and

definitively exclude the presence of an intracardiac

plasma D-dimer level, provided a negative predictive

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T A B L E 5 Comparison of Trials Investigating Predictors of Atrial Thrombi Before Catheter Ablation of AF

Author

Date Type of trial Systematic TEE

Puwanant

Scherr

Yamashita

McCready

Wallace

2009

2009

2010

2010

2010

Calvo

2011

Monocentric

Monocentric

Monocentric

Monocentric

Monocentric

Monocentric

Yes

Yes

Yes

Yes

Yes

Yes

1,058

732

446

635

172

408

Incidence of atrial thrombus

6 (0.6%)

12 (1.6%)

13 (2.9%)

12 (1.9%)

7 (3.6%)

6 (1.47%)

Incidence of sludge

16 (1.5%)

—

—

—

—

Patients

Warfarin >3 months and bridge with LMWH or VKA maintained

Anticoagulation treatment

Thrombus on effective anticoagulation No. of patients with paroxysmal AF Thrombus in patients with paroxysmal AF Risk score used Score ¼ 0 Thrombus with score ¼ 0 Sludge with score ¼ 0 Independent factors associated with thrombus in multivariate analysis

Warfarin >4 weeks Warfarin if and bridge CHADS2 >1 with LMWH

Warfarin >4 weeks and bridge with LMWH

Warfarin > 4 weeks and bridge with LMWH if persistent AF or CHADS2 >1

— Warfarin >4 weeks and bridge with LMWH if CHADS2 >1

6

12

11

12

7

5

881

379

310

305

103

237

3

3

1

1

3

0

CHADS2

CHADS2

CHADS2

Clinical risk score*

—

—

498 (47%)

370 (50.5%)

199 (44.6%)

248 (39%)

—

—

0 (0%)

1 (0.3%)

2 (1%)

0 (0%)

1

—

0

—

—

—

—

—

ND

ND

Heart failure, LVEF <35%

CHADS2, left atrial Age >75 yrs, heart Age >75 yrs, diameter disease, hypertension, persistent AF heart disease

*Age >75 years, hypertension, diabetes, stroke, cardiomyopathy, valvular disease. AF ¼ atrial fibrillation; LMWH ¼ low molecular weight heparin; LVEF ¼ left ventricular ejection fraction; ND ¼ not defined; TEE ¼ transesophageal echography; VKA ¼ vitamin K antagonist.

value of 100%. The diagnostic performance of this

predictive of intra-atrial thrombus. In clinical prac-

score was significantly better than that of the CHADS2

tice, the D-dimer assay should be of interest only in

score. Among the patients with a zero CHADS 2 score,

the absence of the other risk factors (hypertension,

422 (including the 5 patients with intra-cardiac

stroke, heart failure).

thrombus) had an ATE score of 1. Conversely, 51 patients with a CHADS2 score of 1 were considered at no risk of thrombus according to a zero ATE score.

STUDY LIMITATIONS. We did not collect the history

of vascular disease (peripheral artery disease, coronary artery disease). The CHA 2DS2VASc score was

PRACTICAL VALUE OF USING THE ATE SCORE. This

therefore not considered. The CHA 2DS 2VASc score (3)

new score appears to be simple, combining common

is the standard score for thromboembolic risk

clinical data and a frequently used and inexpensive

assessment in nonvalvular AF (17). Nevertheless, it is

biological marker (plasma D-dimer level).

known that arterial disease and female sex are mod-

In our study, an ATE score of zero ruled out the

erate risk factors for thromboembolic events (18). The

presence of atrial thrombus with a sensitivity of

use of CHA2DS 2VASc score would likely not have

100%. Based on this result, 911 TEE examinations

provided better results than the CHADS2 score to rule

(36.5%) could have been avoided. Beyond the cost

out intra-atrial thrombus.

factor, scheduling TEE can sometimes be difficult in busy

electrophysiology

laboratories

and

may

Two methods were used for plasma D-dimer level measurement, but studies showed their equivalent

lengthen hospitalization time if performed the day

effectiveness (19). The absence of the numerical value

before ablation. In that perspective, not having to

of <270 ng/ml might have limited the possibility of

schedule TEE could simplify the ablation procedure.

establishing a more precise threshold to eliminate the

Nevertheless, some physicians might perform TEE

presence of endocardial thrombus. However, all pa-

anyway, to guide transseptal punctures.

tients with intra-atrial thrombus were found to have a

In the diagnosis of venous thromboembolic dis-

plasma D-dimer level >411 ng/ml.

ease, the positive predictive value of D-dimer remains

Echocardiography data were not exhaustive. Data

low. In this study, 930 patients without intra-atrial

for LVEF were missing in some cases. It was a likely

thrombi had D-dimer levels >270 ng/ml. A D-dimer

relevant variable to assess the risk of endocardial

level above this threshold cannot be considered as

thrombus (6). We decided not to include this

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parameter in the multivariate analysis in order to

Collaborators and members of the ATE study

favor more accessible clinical data in the final model.

group: Alain Al Arnaout, Walid Amara, Mathieu

Measurements of the left atrium were not collected

Amelot, Clément Bars, Lucile Becoulet, Paul Bru,

although some studies showed a relationship be-

Philippe Chevalier, Jean-Philippe Darmon, Jean-

tween the size of the left atrium and the presence of

Claude

atrial thrombus (5,20).

Duplantier-Duchene, Fabrice Extramiana, Jean-Paul

Effective

anticoagulation

was

systematically

Faugier,

Deharo, Charles

Antoine Guenancia,

Dompnier, Jérôme

Cécile

Horvilleur,

considered for patients treated with direct oral

François Jourda, Gabriel Laurent, Nicolas Lellouche,

anticoagulant agents without a specific questionnaire

Isabelle Magnin Poull, Olivier Piot, Antoine Roux,

on treatment adherence.

Yannick Saludas, Julien Seitz, and Jérôme Taieb.

Because positive and negative predictive values varied according to the prevalence of the outcome,

ADDRESS

these values might change if the score is applied in a

Milhem, Service de Cardiologie, Groupe Hospitalier

different cohort.

de la Rochelle Ré Aunis, rue du Dr. Schweitzer, 17019 La

CONCLUSIONS

FOR

Rochelle,

CORRESPONDENCE:

France.

E-mail:

Dr. Antoine

antoine.milhem@

ch-larochelle.fr.

Regardless of previous anticoagulation and duration of AF episodes, the proposed ATE score, which com-

PERSPECTIVES

bined clinical items and plasma D-dimer level, could have ruled out the presence of atrial thrombus in our

COMPETENCY IN MEDICAL KNOWLEDGE: Pending confir-

prospective multicenter study. This result needs to be

mation by a large multicenter study, the use of this new score

confirmed in other independent sets of patients

could prevent use of imaging examinations, including TEE,

before conclusions can be drawn.

before left atrial ablation procedures. This concept could also be

ACKNOWLEDGMENTS The authors are grateful to

Nikki Sabourin-Gibbs for her help in editing the manuscript. The authors are particularly grateful to Virginie Laurençon for her involvement in carrying out this

extended to other clinical situations when a thrombus is suspected. TRANSLATIONAL OUTLOOK: These results could encourage the research and development of new biomarkers of thrombosis.

research.

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KEY WORDS clinical biological score, diagnostic performance, preoperative transesophageal echocardiography

A PPE NDI X For supplemental figures, please see the online version of this paper.