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Transesophageal Echocardiographic Correlates of Thromboembolism in High-Risk Patients with Nonvalvular Atrial Fibrillation

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The Stroke Prevention in Atrial Fibrillation Investigators Committee on Echocardiography For members of The Stroke Prevention in Atrial Fibrillation Investigators Committee on Echocardiography, see Appendix. Acknowledgments: The authors thank the patients enrolled in the Stroke Prevention in Atrial Fibrillation study who willingly underwent transesophageal echocardiography to advance the effort to prevent stroke in persons with atrial fibrillation. Grant Support: By grants R01-NS-33351 and R01-NS-24224 from the U.S. Public Health Service, National Institute of Neurological Disorders and Stroke, National Institutes of Health. Requests for Reprints: SPAF Statistical Coordinating Center, Statistics and Epidemiology Research Corp., 1107 NE 45th Street, Suite 520, Seattle, WA 98105.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1998;128(8):639-647. doi:10.7326/0003-4819-128-8-199804150-00005
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Background: Transesophageal echocardiography (TEE) visualizes potential sources of embolism in patients with atrial fibrillation, but the clinical significance of TEE findings has not been prospectively established.

Objective: To define TEE predictors of stroke in patients with atrial fibrillation and to examine response to anti-thrombotic therapy.

Design: Prospective correlation of TEE findings at study entry with subsequent ischemic stroke during 1.1-year mean follow-up of participants in a randomized trial.

Setting: 18 echocardiography laboratories.

Patients: 382 patients with atrial fibrillation at high risk for thromboembolism.

Intervention: Adjusted-dose warfarin (international normalized ratio, 2 to 3) or low-intensity warfarin (international normalized ratio, 1.2 to 1.5) plus aspirin (325 mg/d).

Measurements: Size of left atrium and left atrial appendage, flow velocity, spontaneous echocardiographic contrast, thrombus, and plaque on the aortic arch.

Results: 23 ischemic strokes occurred. In patients with dense spontaneous echocardiographic contrast (20%), the rate of stroke was 18.2% per year with combination therapy (2.9 times the rate in patients without this finding; P = 0.06) and 4.5% per year with adjusted-dose warfarin (P = 0.09 for rate reduction). Appendage thrombus, detected in 10% of patients, was associated with dense spontaneous echocardiographic contrast (P < 0.001), was seen more frequently after 2 weeks of combination therapy (15%) than after 2 weeks of adjusted-dose warfarin (4%) (P = 0.004), and tripled the overall rate of stroke (P = 0.04). Patients with complex aortic plaque (35%) had a fourfold increased rate of stroke compared with plaque-free patients (P = 0.005); adjusted-dose warfarin decreased risk by 75% (P = 0.02). Dense spontaneous echocardiographic contrast and complex aortic plaque were independent of each other as predictors of thromboembolism.

Conclusions: In high-risk patients with atrial fibrillation, subsequent rates of thromboembolism are correlated with dense spontaneous echocardiographic contrast, thrombus of the atrial appendage, and aortic plaque. Adjusted-dose warfarin reduces the rate of stroke among patients with dense contrast and complex plaque. In patients with atrial fibrillation, the pathogenesis of stroke is multifactorial, and warfarin seems effective for the diverse mechanisms.


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Figure 1.
Prevalence of thrombus of the left atrial appendage (LAA) in high-risk patients with atrial fibrillation according to study group assignment.

Striped bars represent combination therapy with low-intensity warfarin and aspirin, 325 mg/d; white bars represent adjusted-dose warfarin. Error bars represent 95% CIs.

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Figure 2.
Event rates during combination therapy in subsets defined according to findings on transesophageal echocardiography.

Ratios in parentheses relate events to patients with the specified criteria. * = Left atrial abnormality refers to thrombus of the left atrial appendage (14% of patients), dense spontaneous echocardiographic contrast (18% of patients), or peak antegrade (emptying) velocity of blood flow from the left atrial appendage less than 20 cm/s (35% of patients). The 95% CIs for the events are as follows: left atrial abnormality, 2.9% to 21.0% per year; complex aortic plaque, 4.5% to 32.0% per year; both, 9.8% to 43% per year; and neither, 0.2% to 9.5% per year.

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