| Background and ObjectiveCerebrovascular diseases are important causes of mortality and disability. It has been the first cause of death in China. Among them, the cardiac stroke accounted for a quarter of all stroke patients. The patients of stroke which is caused by atrial fibrillation accounts for more than50%of all cardiac stroke patients, plays an important role in the pathogenesis and prevention of stroke. Atrial fibrillation (AF) has been known as one of the most important and common risk factors for ischemic stroke.AF is a common arrhythmia in the clinical setting. Left atrial thrombus, which is closely related to blood stasis and hypercoagulable states in the left atrium, is usually thought to be the embolic source in patients with both valvular and nonvalvular AF. Approximately80%of the embolus which caused symptoms embolism in cerebral vascular, and finally, cause brain disorders even the neurologic disability.TEE is an important tool in the detection of cardiac sources of embolism. The use of Transesophageal echocardiography (TEE) in the assessment of the heart as an embolic source has been widely accepted because of its greater aspect angle and capacity for spatial resolution of basal cardiovascular structures. TEE has enabled the diagnosis of other risk factors associated with an increased risk of stroke. However, the left atrial thrombus is not the only embolic source in ischemic stroke patients with AF. Other possible sources of embolism should be investigated, such as Left atrial spontaneous echo contrast (LASEC).LASEC is a dynamic smoke-like signal that is detected by TEE in patients with stasis of blood in the left atrium. Thrombi and spontaneous echo contrast (SEC) in the left atrium are associated with elevated thromboembolic risk. The most common conditions predisposing to LASEC are AF. Some findings studied the association of LASEC and previous stroke or peripheral embolism, suggests that LASEC maybe a precursor of thrombus.LASEC, which is an important part of the cardiac stroke incidence and predictors, is still a major concern for us to determine how to prevent and manage patients with stroke. But there is a lot of controversy and issues with the predictive value of LASEC to ischemic stroke. However, there is no clear consensus about the need for antithrombotic treatment in AF patients with LASEC. Most of the research is graded by binary classification. Binary outcome is unlikely to be more informative than a qualitative estimate. Qualitative grading may be adequate for the majority of clinical studies.A few studies suggest that grading of SEC might be useful. The degree of SEC has been graded qualitatively as mild or severe based on the detection of dynamic intracavitary echoes at high or low gains, respectively. But its classification is still affected by the subjective understanding of the observer, and failed to further explore the predictive value of LASEC in different classification to stroke.In our study, color coding technique was being used to improve image quality and to quantified LASEC. The ultrasound signal (video intensity, VI) from different levels of SEC in left atrium was measured respectively and analyzed to provide quantitative classification for the grading of LASEC. The usefulness of classification and quantitative of LASEC was been discussed to predict stroke. The use of LASEC as a continuous variable in place of the VI may provide greater discriminative power in clinical studies than the more limited analysis of SEC as a binary variable. Methods1. Patient Selection1.1Inclusion criteria:This prospective single-centre observational study was designed on an intention-to-stroke basis. We conducted a prospective study in202patients who underwent TEE examination between2007and2011. AF was defined as rapid oscillations or fibrillatory waves varying in size, shape, and timing, and associated with an irregular, frequently rapidly ventricular response. Persistent, chronic AF was confirmed by12-lead electrocardiography at least two separate occasions. All the patients were evaluated by history, physical examination, laboratory tests, TTE, and TEE.1.2Exclusion criteria:Exclusion criteria for the study were:age<18years old or>80years old, patients who could not tolerate TEE and who refused to participate were excluded; a documented carotid plaques; in cases of segmental systolic dysfunction, history of Moyamoya disease, TIA or stroke, or, ejection fraction<30%; received pulmonary vein isolation or valve replacement treatment in hosptial. definite disagreement on the diagnosis of the LASEC between2echocardiographers; not signing written informed consent. Informed consent was obtained from all the patients and the study protocol was approved by our hospital’s ethics committee.1.3Group Standard:The patients were divided into2groups according to a stroke onset or not during follow-up. The severity of LASEC was graded from0to4by two independent observers. Interobserver differences in the grading of SEC were resolved by consensus. The observation of SEC was standardized by varying both the gain and compress settings throughout their full range during each study.2. Echocardiographic and colour coding:TTE was performed with a Contrast Pulse Sequencing TM, Sequoia512, Siemens, Germany and a2.5-MHz transducer. Left atrial diameter and left ventricular ejection fraction were obtained from M-mode tracings. Left atrial area was measured by planimetry in the parasternal short-axis view. Left atrial diameter was obtained by measuring the largest diameter of the left atrium in the four-chamber view. The cardiac chambers and valves were visualized in the four-chamber view. The structure and function of all valves were visualized through the Color Doppler ultrasonography. TEE was performed with a biplane5-MHz transducer. Patients were studied after topical anesthesia of the hypopharynx with10%lidocaine spray. The left atrium and the left atrial appendage were inspected closely for the presence of thrombus and SEC. The image of LASEC was been color coded. Background-subtracted signal was measured from a region of interest placed over the aortic root. The average Ⅵ of LASEC was measured in the maximum region of left atrium.3. Clinical Features and CHADS2score:The medical record so far patients were reviewed to determine the following clinical features:age; serum cholesterol; history of hypertension, diabetes, smoking, prior myocardial infarction, cardiomyopathy, or congestive heart failure; previous anticoagulant or antiplatelet therapy; and a history of ischemic stroke or peripheral embolism. The CHADS2score was calculated for each patient by assigning1point each for age75years, hypertension, diabetes mellitus, and heart failure and2points for previous stroke or transient ischemic attack.4. Follow-up and outcome assessment:All patients completed the2years follow-up. This was obtained by reviewing hospital records, direct contact with the patients’ primary physician, or contact with the patient by means of a questionnaire. Cerebral infarction was defined clinically as a new neurologic deficit which associated with a cerebral infarction on brain imaging lasting24h and not attributable to dysfunction of a single cranial nerve, spinal cord, or the peripheral nervous system. The diagnosis of cerebral infarction was confirmed by corresponding positive evidence on computed tomography or magnetic resonance imaging.5. Statistical Analysis:Data were processed and analyzed with the SPSS software program (Statistical Package for the Social Sciences) version13.0and the MedCale software program for Windows. Independent-Sample T tests, one-way ANOVA, x2or Fisher’s exact tests, Bivariate Correlation, Logistic regression, ROC curve were used in the study. All tests were two tailed, and significant levels were defined as P<0.05in all statistical analyses. Results1. Clinical outcome:Of the202patients,139were males and63were females. The mean age of our patients was54.83±12.16years, range18-80years. History of smoke was presented in39patients; Mean heart rate of our patients was82.80±17.99beats per minute, range52-130beats per minute. The Mean blood pressure of our patients was128.56±18.92/79.28±12.95mmHg. Hypertension was presented in59patients, Diabetes Mellitus (DM) was presented in30patients. Coronary heart disease was presented in45patients. Hyperuricemia was presented in22patients. Hyperlipidemia was presented in46patients. Coronary heart disease was presented in18patients. Left atrial thrombus was present in16patients (Left atrial appendage in13patients, atrial cavity only in1patient, main cavity and appendage in2patients). LASEC was present in83patients-1in38patients,2in22patients,3in11patients,4in11patients.2. LASEC and colour coding:A significant difference of the average of VI between each grade of LASEC (F=119.002, P<0.001). The average of VI in patients with LASEC (gradel:VI=10.05±3.88, grade2:VI=20.18±4.79, grade3: VI=29.45±6.70, grade4:VI=46.91±12.49) was significantly higher than the average VI in patients without LASEC (VI=3.36±2.09). There was a correlation of the VI and the grade of LASEC (r=0.855, P<0001).3. Risk factors of stroke:The relevant laboratory parameters and medication profiles were similar between groups. A significant difference between the patient of stroke group and the control group at the CHADS2score (1.53±1.17vs0.87±0.85, P=0.028), the ratio of left atrial thrombus (1.53±1.17vs0.87±0.85, P=0.028), the ratio of LASEC (78.9%vs36.6%, P<0.001) and the VI of LASEC (28.42±18.13vs8.45±10.17, P<0.001). There was a correlation of the incidence rate of stroke and the VI of LASEC (r=0.363, P<0001).4. LASEC of different levels:The prevalence of established risk-factors for stroke including Hypertension、Diabetes Mellitus、Coronary heart disease was similar in different grades of LASEC. There was no significant difference of different grade of LASEC in the echocardiographic parameters except left atrial diameter. There was no significant difference of the other indexes except the ratio of RVHD and type of AF.5. Incidence of stroke in different grades of LASEC:There was a correlation of the incidence rate of stroke and the grade of LASEC(r=0.313, P<0001), as the same the incidence rate of left atrial thrombus and the grade of LASEC(r=0.316, P<0001). There was no significant difference of the incidence rate of stroke between the patients of gradel and gradeO of LASEC. While the incidence rate of stroke in the group of grade2-4of LASEC was significantly higher than the group of grade0.6. Multivariate analysis of stroke:Multivariate logistic regression analysis showed an increased likelihood of a thromboembolic event in patients who had left atrial thrombus (P=0.021) or LASEC (P=0.031). There was no significant difference of the incidence rate of stroke between the patients of gradel and gradeO of LASEC(P=0.288, OR=2.329). In other words, LASEC of grade1did not increase the risk of stroke.7. ROC curve of LASEC to predict stroke:LASEC and left atrial thrombus both increase the risk of stroke in the ROC curve analysis (P<0.05). The area under the ROC curve of VI of LASEC was significantly higher than the binary classify of LASEC (Area Difference=0.144±0.072, Z=1.988, P=0.047); The predictive value of stroke can be enhanced by quantified LASEC with VI. The optimal threshold value of the VI of LASEC to predict stroke is8.5(sensitivity=89.5%and specificity=69.6%), which are both significantly higher than the binary classify of LASEC (sensitivity=78.9%and specificity=63.0%).Conclusions1. Color coding technique can be used to quantify and to grade LASEC.2. The predictive value of stroke can be enhanced by quantified LASEC with VI. |
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