Left Atrial Appendage Thrombus Detected During Hyperacute Stroke Imaging Is Associated With Atrial Fibrillation
Background and Purpose:
Left atrial appendage (LAA) is the likely embolic source in atrial fibrillation (AF)–related cardioembolic strokes. We sought to determine the prevalence of LAA thrombus on hyperacute stroke imaging and its association with AF.
We retrospectively examined the clinical and radiological features of patients assessed through the hyperacute stroke imaging pathway over a 12-month period at Christchurch Hospital. The LAA was included in the computed tomography angiogram scan-range as part of the multimodal imaging protocol. Two radiological readers blinded to clinical information independently assessed for the presence of LAA thrombus. The association between AF and LAA thrombus was determined by multivariable logistic regression analysis.
Of 303 patients included in the analysis, the overall prevalence of LAA thrombus was 6.6% and 14.9% in patients with known AF. Patients with LAA thrombus were older (85 versus 75 years, P<0.01), more commonly had known or newly diagnosed AF (75% versus 30%, P<0.01) and heart failure (30% versus 8%, P=0.01), and was associated with intracranial large vessel occlusion (65% versus 39%, P=0.02). In the multivariable model, AF (odds ratio, 3.71 [95% CI, 1.25–11.01] P=0.02) was independently associated with LAA thrombus after adjusting for age and congestive heart failure. Interrater reliability was moderate (kappa=0.56).
LAA thrombus is a potential radiological marker of AF and can be assessed as a part of hyperacute stroke imaging.
The main barrier to anticoagulant treatment in ischemic stroke due to atrial fibrillation (AF)/flutter is the low diagnostic yield for AF detection using short-term cardiac rhythm monitoring.1 Prolonged rhythm monitoring improves AF detection and, although has been shown to be cost-effective, still carries a significant cost.2 In New Zealand, and likely other jurisdictions, implantable prolonged rhythm monitor is not routinely available for stroke workup in the public sector. The US and European guidelines consider these monitors are reasonable investigations but state the evidence behind the recommendations is not robust.3,4 Thrombus in the left atrial appendage (LAA) can be detected noninvasively on computed tomography (CT) angiography (CTA) and maybe a radiological marker of AF or atrial cardiopathy—2 potential causes of cardioembolic stroke.5,6 The prevalence of LAA thrombus on CTA in the context of AF is between 2% to 25% and is highly sensitive and specific when compared with transesophageal echocardiogram.6,7 Inclusion of the LAA in a multimodal hyperacute stroke imaging protocol may aid etiological workup and potentially allow targeted early anticoagulation for at-risk patients.
In this study, we examined the prevalence of CTA detected LAA thrombus during hyperacute stroke imaging and assessed the association between LAA thrombus and AF.
The data that support the findings of this study are available from the corresponding author upon reasonable request. We retrospectively reviewed the clinical and radiological features of consecutive patients with ischemic stroke or transient ischemic attack with completed multimodal CT imaging at Christchurch Hospital, a large endovascular thrombectomy capable tertiary hospital, over a 12-month period between September 2018 and August 2019. The local protocol has been described in detail elsewhere8 and provides immediate multimodal CT imaging to previously functionally independent patients with clinical deficit within 24-hours of onset. The imaging protocol consists of noncontrast CT, followed by CT perfusion and CTA from aortic arch to vertex (detailed description in the Data Supplement). We modified the angiography protocol at the start of September 2018 by extending the scan-range 3 cm below the carina to include the LAA. All patients were examined using either a 128-slice (SOMATOM Definition Flash, Siemens Healthcare, Forchheim, Germany) or 64-slice (GE VCT Lightspeed, GE Healthcare, Waukesha WI) CT scanner.
LAA Thrombus Assessment
We predefined the radiological CTA LAA interpretation into 3 categories:
Positive: A well-defined ovoid/round LAA filling defect not caused by motion artifact or atrial trabeculae, with a Hounsfield unit <100 (Figure [A]).
Indeterminate: Not fulfilling criteria for positive or negative (Figure [B]).
Negative: LAA completely opacifies with contrast, with the exception of changes that can be explained by motion artifact or atrial trabeculae (Figure [C]).
The CTA images were reviewed independently by 2 radiology readers (A. Lim, 7 years of neuroradiology experience; R. Keenan, >20 years of cardiac radiology experience) blinded to clinical and other radiology results including presence of intracranial large vessel occlusion (LVO). All readers had >10 practice cases derived from historical patients before study commencement. Where there was disagreement between the readers, the interpretation was resolved by agreement.
Additional radiation exposure for extending the CTA to LAA in millisievert was estimated by comparing the radiation exposure of patients in this study with no LAA coverage, to the same number of consecutive patients with adequate LAA coverage.
Patient variables collected included basic demographics (age, sex), vascular risk factors, and LVO on intracranial CTA. AF was considered present if it was diagnosed before presentation or captured on ECG during the admission. LVO was defined as an occlusion involving internal carotid artery, basilar artery, and the first segments of anterior cerebral, middle cerebral, or posterior cerebral arteries. These sites are considered targets for endovascular thrombectomy at our center.
Standard descriptive statistics were used. χ2 and Fisher exact test were used for categorical variables and Mann-Whitney U test for continuous variables. We performed univariate comparisons of clinical variables between patients with and without LAA thrombus. Clinical variables significantly associated with LAA thrombus (P<0.05) were entered into a multivariable logistic regression model. The multivariable model examined the association between clinical factors and LAA thrombus. We amalgamated the indeterminate and negative subgroups into a single negative thrombus variable for our analyses except for reliability assessment. Kappa statistic was used to examine interrater reliability for CTA LAA thrombus determination. All statistical analyses were defined a priori and were performed on SPSS 23 (IBM, Armonk, NY). A P value of <0.05 was considered significant.
This observation study has approval from local research office and patient consent was not required as per local legislation.
There were 468 patients imaged via our hyperacute stroke protocol, 165 were excluded owing to stroke mimic diagnoses (143) or inadequate CTA coverage (22), leaving 303 patients for analysis (Figure I in the Data Supplement). The median age was 74 years (interquartile range, 66–84), and 147 patients (49%) were women. The main vascular risk factors are summarized in Table 1, AF was present in 101 patients (33%), whereas 123 patients (41%) had LVO. All but 3 scans in the analysis were performed on the 128-slice Siemens scanner.
|Variable||All; n=303||Left atrial appendage thrombus; n=20||No left atrial appendage thrombus; n=283||P value|
|Age, y (interquartile range)||74 (66–84)||85 (80–88)||75 (65–83)||<0.01|
|Female sex, %||147 (49)||13 (65)||134 (47)||0.13|
|Hypertension, %||162 (53)||9 (45)||153 (54)||0.49*|
|Diabetes, %||61 (20)||3 (15)||58 (21)||0.77*|
|Atrial fibrillation, %||101 (33)||15 (75)||86 (30)||<0.01|
|Hyperlipidemia, %||47 (16)||1 (5)||46 (16)||0.33*|
|Ischemic heart disease, %||86 (28)||7 (35)||79 (29)||0.61*|
|Congestive heart failure, %||28 (9)||6 (30)||22 (8)||0.01*|
|Previous stroke/transient ischemic attack, %||81 (27)||8 (40)||73 (26)||0.19*|
|Current smoker, %||19 (6)||0 (0)||19 (7)||0.62*|
|Peripheral vascular disease, %||7 (2)||0 (0)||7 (2)||1.00*|
|Large vessel occlusion, %||123 (41)||13 (65)||110 (39)||0.02|
The overall prevalence of LAA thrombus was 6.6% (20 patients) and was 6× higher (14.9%) in patients with AF. Of the 283 patients without definite LAA thrombus, 96 (34%) were considered indeterminate, and 86 (30%) patients had AF. Patients with LAA thrombus were older (85 versus 75 years, P<0.01), more commonly had AF (75% versus 30%, P<0.01), congestive heart failure (30% versus 8%, P<0.01), and LVO (65% versus 39%, P=0.02). One patient (5%) with CTA LAA thrombus had an early recurrent contralateral LVO within 30 days of index stroke, whereas early recurrent LVO did not occur in the negative LAA thrombus group. In multivariable logistic regression, AF was independently associated with presence of CTA LAA thrombus (odds ratio, 3.71 [95% CI, 1.25–11.01], P=0.02) after adjusting for age (odds ratio, 1.05 [95% CI, 1.02–1.07], P<0.01) and congestive heart failure (odds ratio, 5.85 [95% CI, 2.31–14.80], P<0.01; Table 2).
|Variable||Odds ratio (95% CI)||P value|
|Atrial fibrillation||3.71 (1.25–11.01)||0.02|
|Age, per year||1.05 (1.02–1.07)||<0.01|
|Congestive heart failure||5.85 (2.31–14.80)||<0.01|
The kappa statistics for interrater reliability on the 3-point rating system was 0.56 indicating moderate agreement. The sensitivity and specificity for AF in the presence of CTA LAA thrombus was 15% and 98%, respectively.
Of the 22 patients with inadequate coverage, 18 had arch-to-vertex CTA performed without any coverage of the LAA. The median radiation exposure was 5.94 mSv for patients without LAA coverage compared to 7.11 mSv in 18 consecutive patients with adequate CTA LAA coverage.
Our results suggest CTA detected LAA thrombus could be a potential radiological marker of AF in patients with acute stroke being considered for reperfusion therapy. LAA assessment could be routinely performed as part of a hyperacute multimodal imaging protocol without additional time delay and minimal increased radiation exposure.
A previous study selectively performed extended CTA to the thoracic diaphragm in 44 patients suspected of cerebral ischemia, including 17 patients with known AF and 4 patients with embolic stroke of undetermined source.9 LAA thrombus was detected in 2 patients (11%) with AF and in no patients with embolic stroke of undetermined source.9 However, this study was limited by small sample size and selection of patients suspected of LVO.
Our overall prevalence of 6.6% is lower than a recent meta-analysis of 19 studies (n=2955), where CTA LAA thrombus was detected in 8.9%. Although the studies included in the meta-analysis consisted of a heterogeneous group of patients biased towards patients with known AF.7 Furthermore, the detection rate of 15% in patients with AF in the present study is also comparable to ≈20% detection rate using transesophageal echocardiogram in patients with AF with recent cerebral or systemic embolism.10
Identifying LAA thrombus may have important implications for patients with ischemic stroke, especially in light of negative embolic stroke of undetermined source trials.11 LAA thrombus may be a risk indicator for early recurrent stroke and may influence decisions regarding timing of anticoagulation.5 The risk of early recurrent stroke in AF may be as high as 1.3% per day within the first 10 days,12 this could be plausibly higher in those with clot in their LAA. Recent studies suggest early anticoagulation in AF-related stroke is safe,13,14 and it would be reasonable to consider early anticoagulation in patients with AF with LAA thrombus. Although only representing 2.5% of patients in our cohort, in patients not known to have AF, LAA thrombus may indicate undetected paroxysmal AF or atrial cardiopathy5 and can allow targeted prolonged rhythm monitoring. The extra radiation exposure (≈1 mSv) carries a ≈0.005% lifetime risk of fatal cancer15 may be offset by identifying patients for early anticoagulation and preventing recurrent stroke, in addition to targeted rhythm monitoring.
Our report has strengths: it is the largest contemporary series to date, with a well characterized clinical cohort, and our patients were assessed with modern advanced multimodality imaging techniques. We also acknowledge the limitations. We were unable to validate the LAA thrombus visualized on CTA with subsequent echocardiography. It is likely we may have understated the true prevalence of LAA thrombus, which could be present in a proportion of patients from the indeterminate group; our protocol is essentially a nongated single-phase CTA, which has a lower diagnostic yield compared with dual-phase CTAs6 and likely accounts for the moderate interrater agreement observed. Although the detection rate (15%) of LAA thrombus rate in AF is similar to that reported in transesophageal echocardiogram in patients with recent embolism,10 we may have underestimated the prevalence using single-phase CT. We have subsequently modified our local protocol to include a delayed phase CTA of the LAA. Further studies with concurrent transesophageal echocardiogram or dual-phase CTA are required to validate our findings including the yield of LAA thrombus in the nonknown-AF population. As a consequence, our results should be considered preliminary and do not currently obviate the need for cardiac rhythm monitoring in clinical practice.
LAA thrombus is a potential radiological marker for underlying AF in patients with stroke. Routine LAA imaging as part of the acute stroke imaging protocol is feasible and may provide valuable information to guide subsequent management. Further prospective data from centers that nonselectively perform multimodal imaging in acute ischemic stroke would be necessary to establish the role of routine LAA imaging.
computed tomography angiography
left atrial appendage
Sources of Funding
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