Left Atrial Imaging Prior to Cardioversion: Leveraging Computed Tomography to Rule Out Thrombus
Phase: NA
Conditions: Atrial Fibrillation
Sponsor: Ottawa Heart Institute Research Corporation

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Left Atrial imaging prior to Cardioversion: Leveraging computed tomography to rule Out 
Thrombus. (LA CLOT) – A Pilot Study of Hospitalized and Emergency Department Patients 
 
Principal Investigator: Dr. Benjamin Chow 
Co-investigators: Dr. Emel Celiker guler, Dr. Andrew Crean, Dr. Carole Dennie, Dr. Gary 
Small, Dr. Guy Hebert, Dr. Mehrdad Golian, Dr. Ian Stiell 
 
Background 
Atrial fibrillation (AF) is the most common cardiac arrhythmia with an estimated 12 million 
individuals afflicted in European Union, 5.9 million in the USA and 350,000 in Canada are affected.1, 2  
The prevalence of AF is increasing and is projected to rise in the EU to 17.9 by 2050 and 10 million 
people in the USA by 2060.2-4 AF and its associated complications are a growing economical burden 
on the healthcare system and this burden on healthcare will continue to rise.5 
 
Atrial Fibrillation Guidelines 
Canadian AF guidelines updated recommendations in November 2018 regarding 
electrical/pharmcologic cardioversion.6 Prior to this update, previous guideline recommendations have 
been:7 
 
Non-anticoagulated AF/atrial flutter patients (without indication for emergent cardioversion) requiring 
rhythm control: 
1) May proceed to cardioversion if non-valvular AF onset was <48hours, 
2) If AF/atrial flutter onset is unknown or  >48 hours 
a. Anticoagulate and consider cardioversion after 3 weeks 
b. Admit to hospital for transesophageal echocardiography (TEE) prior to cardioversion 
c. Refer for outpatient TEE prior to cardioversion 
 
Transesophageal Echocardiography Prior to Cardioversion 
TEE is considered the reference standard to rule-out left atrial (LA) and left atrial appendage 
(LAA) thrombus prior to cardioversion. Several studies have examined the accuracy of TEE for 
detecting LAA thrombus. Compared to autopsy and intraoperative findings, TEE has a mean 
sensitivity of 100% and mean specificity of 99%.8 Klein et al. showed that TEE could be used prior to 
cardioversion to exclude LA thrombus with no significant increase in adverse embolic events.9 
The new Canadian guidelines have made new recommendations (Figure) that may have 
downstream ramifications on resources.6 They have suggested that “pharmacological or electrical 
cardioversion of symptomatic AF or atrial flutter without at least 3 weeks of previous therapeutic 
anticoagulation be reserved  
for patients with”: 
1) “non-valvular AF who  
present with a clear AF onset  
within 12 hours in the absence  
of recent stroke or transient 
ischemic attack (within 6 
months)”, and 
2) “non-valvular AF and a  
CHADS2 score < 2 who  
present after 12 hours but  
within 48 hours of AF onset”,  
and 
3) “as an alternative to at least 

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3 weeks of therapeutic anticoagulation before cardioversion, TEE may be used to exclude cardiac 
thrombus”. 
As such, these recommendations will likely reduce the frequency of immediate cardioversions 
(in the emergency department), increase referrals for inpatient and outpatient TEEs, and increase 
hospital admissions. We propose a randomized control trial that will assess the utility of cardiac CT to 
improve patient access and timely care. The results of this study could have worldwide impact by 
improving patient quality of life and timely access to cardioversion. 
 
Imaging to Rule Out LA Thrombus 
Currently, TEE is considered the reference standard technique for the detection of intracardiac 
thrombus. Although the gold standard, a TEE-guided therapy is still associated with an embolic rate of 
0.8%.9 TEE does have limitations which include: need for NPO x 6-8 hours, patient discomfort, 
potential complications asscoiated with the procedure (infection, aspiration, perforation, bleeding, etc) 
or with sedation.10 
Contrast enhanced ECG-gated cardiac CT (CCT) is  a sensitive, noninvasive alternative 
method used to  exclude of left atrial and LAA thrombus. CCT provides high spatial and good 
temporal resolution and its ability to detect thrombus has been evaluated.11-15 CCT, compared to TEE,  
for the exclusion of thrombus in the LAA had a sensitivity and specificity of 100% and 99.3%, 
respectively (Table 1).16 A high sensitivity is needed to minimize risk of embolus, and if a thrombus is 
detected on CT, a confirmatory TEE may be performed or patients may receive anticoagulation. Some 
argue that the potential benefits of CT and its lower associated procedural risk, the risk:benefit ratio 
would still favour CT. 
 
This research is novel because it will be the first to demonstrate in a RCT, that CT can be used 
as an alternative to TEE. More importantly, demonstrating that CT is cost-effective would be 
extremely attractive to all stakeholders given the growing financial burden of healthcare. 
 
Hypothesis 
• Primary Hypothesis: Compared to TEE, CCTA will: 
1. Reduce time to cardioversion for in-patients 
• Secondary Hypotheses: Compared to TEE, CCTA will: 
1. Reduce length of hospital or emergency room stay, 
2. Improve patient quality of life (QoL), 
3. Not increase adverse events (arterial embolism, procedural complications, bleeding), 
4. Have superior cost-effectiveness. 
 
Study Objective 
Overarching objective: To evaluate CCT as an alternative to TEE to expedite cardioversion, 
improve patient care and reduce hospital admissions for AF and atrial flutter. 
• Primary Objective: To determine if CCT can reduce time to cardioversion for in-patients 
• Secondary Objectives: 
o To determine if CCT can reduce length of stay (in-patient hospitalization and emergency 
department) 
o To determine if CCT improves patient QoL 
o To determine if CCT is associated with fewer or more adverse events 
o To determine the specificity of CCT (in patients with filling defects and subsequent TEE) 
 
Outcomes Measures  
1. Time to cardioversion (Time from referral for imaging) 
2. Hospital admission rate 
3. Length of hospital stay (in-patient and emergency department stay) 

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4. QoL before cardioversion, at hospital discharge and at 30 days 
5. Adverse events (embolic (arterial) event, procedural complication, major bleed (need 
definition)) 
a. Embolic arterial event 
b. Procedural complication 
c. All bleeding 
d. Major bleeding 
6. Operating characteristics (specificity, PPV) of CCT (subanalysis of patients receiving TEE 
after CCT) 
 
Study Design 
This randomized controlled trial will randomize patients undergoing cardioversion for AF or 
atrial flutter before 3 weeks of anticoagulation. This pilot (Vanguard) study will aim to demonstrate 
feasibility of enrolment and assist with final sample size calculation. 
 
Inclusion Criteria 
• Patients admitted to hospital or seen in the ED who require LA imaging prior to cardioversion 
• Age ≥18 years old 
• Able and willing to comply with the study procedures 
 
Exclusion Criteria 
• Indication for acute cardioversion (e.g. hemodynamic instability, acute coronary syndrome 
(ACS), or pulmonary edema) 
• Unwillingness or inability to provide informed consent 
• Contraindication to Cardiac CT 
o Severe renal insufficiency(GFR< 45ml/min) 
o Allergy to intravenous contrast agents 
o Contraindications to radiation exposure (for example, pregnancy) 
o Inability to perform 20-second breath-hold 
• Contraindication to TEE 
o Unrepaired tracheoesophageal fistula 
o Esophageal obstruction or stricture 
o Perforated hollow viscus 
o Poor airway control 
o Severe respiratory depression 
o Uncooperative, unsedated patient 
 
Methods 
Recruitment 
Patients who meet the inclusion/exclusion criteria will be randomized to either the 
interventional arm (CCT) or standard of care (SOC) arm (TEE). Prior to randomization, written 
informed consent will be obtained from each patient. Patients will undergo imaging as per clinical 
routine and reports will be issued immediately.  
 
TEE protocol 
TEE will be performed as per clinical routine using multiple standard tomographic planes to 
rule-out LA/LAA thrombus. Echocardiographic analysis will include: LAA-emptying velocity, and 
grading the severity of LAA spontaneous ECHO. The severity of the SEC will be graded on a 4 point 
scale with 1 = minor homogeneous contrast enhancement, 2 = significant homogeneous contrast 

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enhancement, 3 = significant, dense, and inhomogeneous, slow-moving contrast, and 4 = dense slow-
moving contrast. 
Cardiac CT protocol 
As per local protocol, a non-contrast enhanced prospective ECG-triggered image acquisition 
will be acquired. This will be followed by a contrast-enhanced prospective ECG-triggered will be 
acquired using a tri-phasic contrast protocols. Delayed CT images will be acquired 60 seconds after 
the initial contrast-enhanced CT scan.Cardiac CT image interpretation will be performed as per 
clinical routine. The LA and LAA will be assess for filling defects and characterized based upon 
attenuation values. If LA/LAA thrombus cannot be excluded, filling defects will be assessed on the 
delay images. Increases in attenuation would be consistent with pseudo-thrombus from  ‘slow flow’ 
and ‘incomplete opacification’. Areas where attenuation does not change significantly (persistent 
filling defect) will be diagnosed as thrombus. It will be recommended that patients with thrombus will 
undergo TEE. 
 
Prevention of Bias 
 
Enrolled patients will be processed through the usual clinical routine for patient booking and 
investigators will not influence timing of booking. 
 
Duration of Follow-up 
Patients will be followed for 30 days after cardioversion using electronic charts and telephone 
follow-up for QoL measures. 
 
Sample Size Calculation 
This pilot (Vanguard) study will aim to demonstrate feasibility of enrolment and assist with 
final sample size calculation. 
 
Statistic Methods 
Statistical analyses will be performed using SAS and/or SPSS. Statistical significance will be 
defined as p<0.05. Continuous variables will be presented as means and standard deviations, and 
categorical variables will be presented as frequencies with percentages. To compare variables, the 
Wilcoxon rank sum or T-test will be used to compare continuous variables and Fisher’s exact test for 
categorical variables. Costs will be calculated using Ontario Case Costing Initiative and the Ontario 
Schedule of Physician Fees and Benefits. 
 
Randomization 
Randomization will occur at time of referral for TEE and be performed using a random 
generator. Patients will be stratified according hospital location (CICU versus ward versus emergency 
department)  and according to mode of cardioversion (electrical versus pharmacologic) and patient 
sex. 
 
Ethical Considerations  
The investigator will ensure that this study is conducted in full conformance with the principles of the 
“Declaration of Helsinki” or with the laws and regulations of the country in which the research is 
conducted, whichever affords the greater protection to the individual. The study will fully adhere to the 
principles outlined in “Guideline for Good Clinical Practice” ICH Tripartite Guideline or with local law 
if it affords greater protection to the patient. It is the responsibility of the investigator, or a person 
designated by the investigator to obtain signed informed consent from each patient prior to participating 
in this study after adequate explanation of the aims, methods, anticipated benefits, and potential hazards 
of the study. The investigator or designee will also explain that the patients are completely free to refuse 
to enter the study or to withdraw from it at any time, for any reason. If new safety information results in 

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significant changes in the risk/benefit assessment, the consent form will be reviewed and updated if 
necessary.  
 
The protocol, informed consent and any accompanying material provided to the patient will be submitted 
by the investigator to the Ottawa Health Science Network Research Ethics Board (OHSN-REB) as 
appropriate. An approval letter or certificate (specifying the protocol number and title) from the OHSN-
REB must be obtained before study initiation by the investigator specifying the date on which the 
committee met and granted the approval. This applies whenever subsequent amendments/modifications 
are made to the protocol. Any modifications made to the protocol, informed consent or material provided 
to the patient after receipt of the REB approval must also be submitted by the investigator in accordance 
with local procedures and regulatory requirements. 
Conflict of Interest 
The investigators have no conflicts of interest to disclose. 
Direct Access to Source Data/Documents 
The Investigator and the study centre will accept responsibility of monitoring and auditing as well as 
inspections by the Ottawa Health Science Network Research Ethics Board and the University of Ottawa 
Heart Institute. They will also provide all study-related records, as well as source documents to these 
instances when they are requested to. The confidentiality of the participant’s identity shall be well 
protected and consistent with local and national regulations when the source documents are subject to 
direct access. 
 
Data Handling and Record Keeping 
The Investigator will maintain adequate and accurate records to enable the conduct of the study to be 
fully documented and the study data to be subsequently verified. These documents should be classified 
into two different separate categories: [1] Investigator's Study File and [2] patient clinical source 
documents. The Investigator's Study File will contain the protocol/amendments, CRF/DCS and schedule 
of assessments, Independent Ethics Committee/Institutional Review Board approval with 
correspondence, sample informed consent, staff curriculum vitae and authorization forms and other 
appropriate documents/correspondence, etc.  
 
Patient clinical source documents will include patient hospital/clinic records, physician's and nurse's 
notes, appointment book, original laboratory reports, special assessment reports, signed informed 
consent forms. All personal health information collected will be kept confidential unless release is 
required by law. For audit purposes only, the Ottawa Health Science Network Research Ethics Board 
and the University of Ottawa Heart Institute may review the patients’ medical records under the 
supervision of Dr. Benjamin Chow and his staff. The Master list containing the patients’ personal health 
information will be kept separate from the patient screening and enrollment logs. The Master List which 
links the patient with the independent study number will only be accessible by Dr. Benjamin Chow and 
his staff. The master link and study files will be stored separately and securely. 
 
All paper records will be stored in a locked filing cabinet and /or office. All electronic records, including 
the Master List, will be stored on a secure internal hospital server and password protected, again only 
accessible by Dr. Benjamin Chow and his staff. No identifiable information will be stored on any mobile 
devices (laptops, USB keys, CDS, DVDs, etc). The Investigator must keep source documents as 
described above on file for 10 years after completion or discontinuation of the study. After that period 
of time the documents may be destroyed, according to local regulations.   
 
 
 

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Publication Policy 
In accordance with standard editorial and ethical practice, the results of this study will be published or 
presented at congresses or scientific meetings. Patients will not be identifiable in any publications or 
presentations. 
 
 

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Table 1. Sensitivity and Specificity of CCTA with Delayed Imaging for the Detection of LA 
thrombus (compared to TEE). 
 
 
 
 
 
 
 
 
 
 
Table 2. Cost of CT and TEE in Canada and US. 
 
Canada 
USA (National Payment Amount) 
 
CT 
$ 
$581.76 
 
TEE 
$ 
$505.81 
 
 
 
 
 
 
 
Reference 
Delayed Images 
Sensitivity 
Specificity 
Kim (17)  
+ 
100% 
98% 
Jaber (18) 
+ 
100% 
100% 
Hur (19) 
+ 
100% 
98% 
Hur (12) 
+ 
100% 
100% 
Sawit (20) 
+ 
100% 
100% 
Lazoura (21) 
+ 
100% 
100% 
Mean 
 
100% 
99.3%