Poor Outcome of Stroke Patients With Atrial Fibrillation in the Presence of Coexisting Spontaneous Echo Contrast
Background and Purpose—Spontaneous echo contrast (SEC) is frequently detected in patients with atrial fibrillation (AF). Coexisting SEC in patients with AF may be associated with heightened thrombogenicity, which affects stroke outcomes.
Methods—Consecutive stroke patients with nonvalvular AF who underwent transesophageal echocardiography were included in this study. We compared initial stroke severity and functional outcome at 3 months between the patients with and those without SEC.
Results—Of 440 patients with nonvalvular AF who underwent transesophageal echocardiography during a 7-year period, 193 (43.9%) patients had SEC. Stroke was more severe in the patients with SEC than in those without SEC (National Institute of Health Stroke Scale score: median [interquartile range], 5 [2–12] versus 3 [1–8]; P=0.004). The patients with SEC more frequently had poor functional outcomes (modified Rankin scale score of >2) at 3 months than those without SEC (32.3% versus 16.1%; P<0.001). On multivariate analysis, the presence of SEC was an independent factor of poor outcome (odds ratio, 2.09; 95% confidence interval, 1.24–3.53).
Conclusions—In the ischemic stroke patients with nonvalvular AF, coexisting SEC was associated with more severe stroke and was predictive of poor long-term functional outcome.
Spontaneous echo contrast (SEC) refers to smoke-like echoes that are visualized in echocardiography because of ultrasound backscattered from red blood cell aggregates.1 SEC is frequently detected in patients with atrial fibrillation (AF), which is the most common cardiac source of embolism.2,3 AF patients with coexisting SEC may have increased frequency of intracardiac thrombus and increased risk of stroke.4 Stroke patients with AF and concomitant cardiac sources of embolism had more severe stroke.5 In addition, coexisting SEC in patients with AF may also increase thrombotic burden, which can cause a more severe stroke. In this study, we investigated whether stroke severity and functional outcome differ according to the presence of coexisting SEC in stroke patients with nonvalvular AF (NVAF).
This is a retrospective observational study that used a prospective cohort of patients with acute ischemic stroke. We included consecutive stroke patients with NVAF who were admitted within 7 days after symptom onset between January 2008 and December 2014. Transesophageal echocardiography (TEE) was performed within 2 weeks after admission. TEE was considered in all the patients except in those with decreased consciousness, impending brain herniation, poor systemic conditions, inability to accept a transducer because of swallowing difficulty or tracheal intubation, or lacked informed consent. SEC was graded as mild, moderate, and severe. Stroke severity at admission was assessed by using the National Institute Health Stroke Scale (NIHSS). Poor functional outcome was defined as a modified Rankin scale (mRS) score of >2 at 3 months. Details of stroke evaluation, TEE procedure, the definition of risk factors, and statistical analyses seen in the online-only Data Supplement. This study was approved by the Institutional Review Board of the Yonsei University Health System.
During the 7-year period, 4252 consecutive stroke patients were registered to the cohort. Among them, 966 had AF (22.7%), of whom 517 (53.5%) underwent TEE. After excluding 77 patients who had valvular heart disease or were treated using a left atrial appendage (LAA) occluding device, 440 patients with NVAF were finally included in this study. Patients who did not undergo TEE were older than those underwent TEE, and were more likely women, more frequently had congestive heart failure, previous stroke history, higher CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes mellitus, stroke [doubled], vascular disease, age, and sex category [female]) scores, or higher NIHSS scores at admission (Table I in the online-only Data Supplement).
Of the 440 patients, 193 (43.9%) had SEC (mild in 88 [20.0%], moderate in 36 [8.2%], and severe in 69 [15.7%]). The patients with SEC were older, and more frequently had diabetes mellitus, a previous stroke history, lower platelet counts, and higher red blood cell distribution width, and they were on oral anticoagulation therapy at admission. The CHA2DS2-VASc scores were higher, and left atrial/LAA thrombus was more frequently found in the patients with SEC (18.7% versus 3.2%; P<0.001). The other baseline characteristics did not differ between the groups (Table II in the online-only Data Supplement).
Stroke was more severe in the patients with than in those without SEC (NIHSS score: median [IQR], 5 [2–12] versus 3 [1–8]; P=0.004; Table III in the online-only Data Supplement). After excluding 7 patients who had poor prestroke functional status, 431 patients (99.5%) had determinable functional outcomes at 3 months. The patients with SEC more frequently had poor functional outcomes (mRS score of >2) at 3 months than those without SEC (32.3% versus 16.1%; P<0.001; Figure). This result was not influenced by the status of anticoagulation at admission (Figure I in the online-only Data Supplement). Stroke severity and the proportion of patients with poor functional outcome increased as the grade of SEC increased (Figures II and III in the online-only Data Supplement). On multiple logistic regression, the presence of SEC was an independent factor of poor outcome (odds ratio, 2.09; 95% confidence interval, 1.24–3.53; Table).
In this study, 44% of the patients with NVAF had SEC, and patients with SEC more frequently had left atrial/LAA thrombus. These findings support the previous knowledge that SEC is frequent in patients with NVAF and associated with increased incidence of LAA thrombus. In addition, this study newly showed that the presence and degree of SEC were associated with an initially more severe stroke and worse functional outcome at 3 months after stroke onset.
Several explanations are possible for the severe stroke and poor outcomes in stroke patients with NVAF and coexisting SEC. Increased thrombogenecity in patients with SEC could be associated with increased risk of multiple or larger thrombus formation. This might cause larger infarctions, which result in more severe stroke. In this study, poor functional outcome at 3 months in the patients with SEC was independent of initial stroke severity and reperfusion therapy. This suggests that the presence of SEC or the condition that led to the development of SEC might also have a negative effect during the course of stroke.
SEC represents red blood cell aggregates. Experimental studies showed that red blood cell–rich thrombi are resistant to fibrinolytic agents.6 In fact, thrombi in patients with AF and concomitant SEC were suggested to be more resistant to fibrinolysis.7 Thus, endogenous fibrinolysis might less effectively occur in SEC-associated thrombus. In addition, patients with SEC more frequently had left atrial/LAA thrombus, which is a high-risk factor of recurrent stroke.4 In this study, the patients with SEC showed higher red blood cell distribution width. Red blood cell distribution width is a predictor of SEC.8 Increased red blood cell distribution width was associated with the future risk of stroke and poor functional outcomes in patients with acute stroke.9 These factors could affect negatively the progression and recurrence of stroke during follow-up, resulting in poor long-term functional outcome.
This study has limitations. First, 46.5% of the patients with NVAF did not undergo TEE. This resulted in selection bias and differences in demographic characteristics, including more severe stroke in the patients who did not undergo TEE than those underwent TEE. Second, in this study population, the frequency of anticoagulation before the stroke was low (16.1%). Oral anticoagulation may affect the presence of SEC. In addition, this study was conducted in a single center. Therefore, our results may not be applicable to a different NVAF cohort. Finally, the recurrence of stroke, which might affect long-term functional outcome, was not determined. Therefore, these limitations should be considered in the interpretation of our findings.
Although currently the presence of SEC is mostly considered in the context of stroke risk prediction, our data suggest that it also portends poor clinical outcome in patient with stroke.
Sources of Funding
This study was supported by a grant from the Korea Healthcare Technology Research and Development Project, Ministry of Health and Welfare, Republic of Korea (HI15C2814).
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.116.013351/-/DC1.
- Received March 29, 2016.
- Revision received April 22, 2016.
- Accepted April 26, 2016.
- © 2016 American Heart Association, Inc.