Transesophageal echocardiographic correlates of thromboembolism in high-risk patients with nonvalvular atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators Committee on Echocardiography

Abstract

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 antithrombotic 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.