Of Left Atrial Appendage Thrombus In Patients Presenting For Left Atrial Ablation Of Atrial Fibrillation Despite Pre-Operative Anticoagulation.
Credits:Joseph P. de Bono*, Sacha Bull, John Paisey, David Tomlinson, Kim Rajappan, Yaver Bashir, Harald Becher and Timothy R Betts.
Department of Cardiology John Radcliffe Hospital, Oxford
Running Head: Left atrial thrombus complicating ablation of atrial fibrillation
*Corresponding Author: Timothy Betts, Department of Cardiology, John Radcliffe H ospital, Oxford, OX3 9DU.
One of the recognised complications of
left atrial ablation for atrial fibrillation (AF) is stroke. Left atrial (LA) thrombus,
which may be dislodged by catheter manipulation, is an absolute
contraindication to ablation. It is unclear whether imaging of the left atrial
appendage (LAA) by transesophageal echo (TEE) is mandatory to exclude LA clot
prior to ablation, particularly in “low-risk” patients with paroxysmal AF and
normal left ventricular (LV) function.
Methods and results:
We carried out a retrospective analysis
of pre-ablation TEE in patients presenting for ablation of AF. All patients
received a minimum of 4 weeks therapeutic anticoagulation before stopping oral
anticoagulants 3 days before their procedure. Images from 244 ablation
procedures carried out in 148 patients were examined, including 106 patients
with paroxysmal AF and normal LV function.
Despite at least 4 weeks of pre-operative
therapeutic anticoagulation with Coumadin (INR>2.0), LAA thrombus was
identified in 4 patients (2.7%). These included 2 patients with paroxysmal AF
and normal LV function, although both had a high arrhythmia burden. The thrombi
regressed with intensification of anticoagulation.
In conclusion, pre-operative imaging of
the LAA remains advisable to exclude thrombus prior to ablation for AF even in
patients with paroxysmal AF and normal LV function.
Keywords: Left atrial thrombus, Catheter ablation, Atrial fibrillation,
Left atrial (LA) ablation is increasingly becoming a key therapeutic option for the
treatment of symptomatic, drug-refractory paroxysmal and persistent atrial
fibrillation (AF). The majority of patients are in low risk categories for
thromboembolic stroke and would not normally be formally anticoagulated. Although
a variety of techniques are used, all ablation procedures involve extensive
manipulation of catheters within the LA and widespread ablation using either
radiofrequency energy or cryoablation  . Periprocedural cerebrovascular accidents
(CVAs) are a recognised complication. Clinically significant neurological
events occur in around 0.5-1% of patients, but the incidence of silent embolic
events is likely to be much higher [2-4] .
The presence of LA thrombus is an absolute contraindication to manipulation of
catheters within the LA  . AF is associated with the development
of LA thrombus, particularly in the left atrial appendage (LAA), which can be visualized
by transesophageal echocardiography (TEE)  .
A number of strategies have been developed to reduce the incidence of
peri-procedural stroke in patients undergoing ablation for AF [1,
These include routine anticoagulation of patients for at least one month prior
to ablation and routine TEE immediately prior to the procedure to rule out the
presence of LAA clot. It is not known whether TEE should be mandatory in all
patients, particularly if they have been therapeutically anticoagulated prior
to admission, or whether it can be restricted purely to ‘high risk’ patient  . We carried out a retrospective study
to identify the incidence and predictors of LAA thrombus in patients presenting
for LA ablation of AF despite four weeks of therapeutic anticoagulation to
determine whether pre-operative TEE should be recommended in all patients or
only those deemed to be at high risk.
A retrospective review of the medical
records and TEE findings in consecutive patients presenting for LA ablation of AF
in our institution between December 2003 and November 2007 were noted. All received at
least 6 weeks of anticoagulation with Coumadin prior to ablation aiming for a
target international normalised ratio (INR) of 2.5. Following the loading
period, INR was measured weekly. Patients were required to have an INR greater
than 2 for at least 4 weeks prior to ablation. Any patient with a sub-therapeutic
INR during this period was excluded from the study. Coumadin was stopped 3 days
prior to admission. Heparin was not administered prior to the ablation
procedure. All patients underwent a TEE on the morning of their ablation. Procedures
were regarded as separate when there was at least a three month gap between
The TEE images were reviewed independently by two experienced blinded echocardiographers
for the presence or absence of LAA thrombus.In cases of disagreement, the
images were reviewed by a third independant echocardiographer, however in all
cases where a definite thrombus was identified there was no disagreement
between the original reviewers.
A thrombus was considered to be present if a mass detected in the
appendage appeared to be distinctfrom the underlying endocardium,
was not caused by pectinate muscles, and was detected in more than
one imaging plane  .
The patients’ records were examined to identify risk factors for embolic events using
the CHADS2 scoring system  Atrial fibrillation was classified
according to the ACC/AHA/ESC 2006 guidelines and HRS/EHRA/ECAS consensus
10] . Where appropriate measurements are given as the mean +/- standard deviation.
One hundred forty eight consecutive patients were studied who
had undergone a total of 244 LA ablation procedures for AF (median 1 per
patient, range 1-5). The clinical details of the patients are shown in table 1. Thrombus was identified in the LAA prior
to 4 procedures (1.6%).
Table 1:Clinical characteristics of patients undergoing left atrial ablation for atrial fibrillation
TEE - Transesophageal echo, TIA – Transient ischaemic attack
The first patient was a 61 year old male with
a history of non-insulin dependent diabetes mellitus, impaired left
ventricular (LV) function and a history of prior transient ischaemic attacks
(CHADS2 score 4, high risk). 6 months earlier he had undergone LA ablation for
persistent AF. Following this he had suffered from recurrent episodes of
paroxysmal AF and two episodes of persistent atypical flutter requiring
cardioversion. At the time of his second procedure he was in sinus rhythm, but
the ablation was abandoned following the detection of LAA thrombus by TEE. His target INR was increased to 3. Three months later he was readmitted and TEE no longer showed LAA thrombus.
Patient 2 was a 61 year old male with severely
impaired LV function and a very dilated LA on transthoracic echocardiogram (7.0
cm, CHADS2 score 1 but high risk due to extreme LA dilatation). He had
undergone two previous cardioversions for recurrent persistent AF. He was in
sinus rhythm at the time of his ablation procedure, but TEE showed LAA thrombus
and the procedure was abandoned. Intensification of his anticoagulation regime
(target INR 3.0) led to a significant reduction in size of the thrombus, but
even with further increases in anticoagulation (target INR 3.5), a filling
defect persisted in the LAA and we were unable to exclude persistent LAA
thrombus. He was referred for a surgical maze procedure.
Patient 3 was a 63 year old male with
normal left ventricular function whose only risk factor for thromboembolism was
hypertension (CHADS2 score 1, low risk). He suffered from recurrent paroxysmal
AF with frequent paroxysms lasting 2-3 days in duration. He was in AF at the
time of his TEE which showed LAA thrombus. The thrombus markedly reduced in
size with more intensive anticoagulation (INR 3.0), but again did not disappear
completely despite increasing his target INR to 3.5 for 6 months. He was also
referred for a surgical maze procedure.
Patient 4 was a 42 year old female with
no risk factors for thromboembolic events (CHADS2 score 0, low risk) and normal
left ventricular function. She had paroxysmal AF and spent a number of hours
each day in AF. She was in AF at the time of her TEE which showed LAA thrombus.
The thrombus resolved completely with increased anticoagulation and she
underwent a successful ablation 3 months later.
Those patients where TEE did not show any LAA thrombus proceeded to LA ablation (240 procedures). Following ablation
two patients suffered clinical cerebrovascular events. However, both patients
recovered rapidly and were discharged with only minor deficits within a few
days of their ablations.
In this study we have investigated the role of TEE to detect LAA thrombus prior to
ablation for AF. Despite at least four weeks of therapeutic anticoagulation
prior to ablation, thrombus is present in the LAA in 1.6% of procedures (2.7%
of patients). Although two patients might be expected to be at high risk of
thrombus with impaired LV function and either a massively dilated LA or the presence
of multiple risk factors for embolic events, thrombus was also identified in
two low risk patients with paroxysmal AF with a normal left ventricular
ejection fraction. Thus the presence of thrombus could not be excluded by the absence
of conventional risk factors for embolic events.
Previous studies have suggested that the risk of thrombus in such patients with structurally normal
hearts and paroxysmal AF is so low as to make TEE redundant  . In our study 106 patients had paroxysmal AF
and structurally-normal hearts yet there was still a 1.1% (0-3.1%) incidence of thrombus. Redfearn’s survey of Canadian centres
showed a similar overall 1.1% incidence of LAA thrombus in all patients presenting for ablation of atrial fibrillation in
centres where TEE is routinely performed  . However this survey showed no apparent difference in the
incidence of embolic events with a strategy of universal pre-procedure TEE compared to one of performing TEE on selected
high-risk patients. Khan et al used CT to detect LAA thrombus in a large group of patients referred for pulmonary vein
isolation with additional TEE in approximately half their patients, including all those where LAA thrombus was suspected
from the CT scan. They identified an incidence of LAA thrombus of 0.4% in persistent AF and 0.14% in paroxysmal AF  .
However, TEE was not performed in all their patients and only patients undergoing solely pulmonary vein isolation were included; patients
where more extensive ablation was planned were excluded, which may explain the lower incidence of thrombi. Both the patients in our study
who had paroxysmal AF and normal LV function had high AF burdens with many hours of AF each day which may have prevented any
restoration of mechanical function in the LAA during periods of sinus rhythm, allowing thrombus to develop; however studies of
thromboembolic risk in medically-treated patients have not shown differences between patients with persistent and paroxysmal AF  .
Pre-existing LAA thrombus is not the only cause of thromboembolic events resulting from LA ablation
[13, 14] . Ablation of the LA itself creates a thrombogenic environment, excessive temperatures
can lead to coagulum formation, whilst soft thrombus may also form within the LA during ablation  .
Despite universal screening for LAA thrombus two patients in this study had neurological events. Both these patients made a rapid
and almost complete recovery. It is possible that the nature of the neurological events may differ considerably depending on
etiology. In addition, although the presence of known LAA thrombus is a contraindication to LA ablation, the risk of embolic events
as a result of LA ablation in the presence of an undetected LAA thrombus is unknown and is likely to be significantly less than 100%.
Thus failure to identify all LAA thrombi prior to ablation is only likely to lead to a small increase in overall event rates. As the
incidence of embolic events in patients undergoing left atrial ablation is already low, it is likely that any attempt to use randomised
controlled trials to address the role of pre-ablation imaging of the LAA would be limited by the extremely large numbers of patients required to
adequately power such a study.
Although all the thrombi identified in
this study reduced significantly in size with intensification of
anticoagulation, in two of our patients a small residual thrombus remained in
the LAA and TEE was unable to show conclusively complete disappearance of clot.
These results are very similar to those observed by Benrhardt et al. who showed
that in patients with long standing persistent AF, one year of anticoagulation
reduced the size of all LAA thrombi but only led to complete resolution in 56%
of patients  . In patients with pre-existing
thrombus therefore, even 6 weeks of continuous anticoagulant therapy could not
completely exclude persistent LAA thrombus.
In the present study all patients received the same anticoagulation regime with Warfarin being continued until three days prior to
the procedure. Some centres continue Warfarin or use bridging heparin until the day of the procedure itself to reduce the risk of
thrombus formation and it is possible that our patients’ thrombi may have developed in the short period prior to the procedure as
the INR fell  . Continuing anticoagulation right up the day of ablation using either Warfarin or heparin may
reduce the risk of thrombus obviating the need for TEE on the day of the procedure. The incidence of persistent thrombus using this
approach has not been formally assessed.
Even with prolonged therapeutic
anticoagulation prior to ablation, LAA thrombus can still be identified using TEE in patients presenting for ablation of AF who are apparently at low risk. The presence of
paroxysmal AF, a normal ejection fraction and the absence of other risk factors
for thromboembolism does not exclude the presence of LAA thrombus. Thus imaging
of the LAA prior to ablation is recommended in all patients undergoing LA
ablation for AF, particularly where anticoagulation is discontinued prior to
the procedure even for a short period of time. TEE is currently the gold
standard for imaging thrombus in the LAA, but increasingly other imaging
modalities are being used for this purpose including CT and MRI. Further
studies are required to identify the optimal strategy to maximize both
operative success and efficiency whilst minimizing the risk of complications. 
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