Diagnostic accuracy of D-dimer to detect left atrial thrombus in patients with atrial fibrillation: A systematic review and meta-analysis

Background

There is conflicting evidence about the use of biomarkers to diagnose left atrial thrombus in patients with atrial fibrillation.

Objective

The purpose of this study was to assess the diagnostic accuracy of D-dimer to detect left atrial thrombus in patients with atrial fibrillation.

Methods

We searched 4 electronic databases from inception to December 16, 2020. The reference standard was left atrial thrombus detected by transesophageal echocardiography. Study quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 tool. We used a bivariate model to calculate the pooled sensitivity and specificity with their 95% confidence intervals (CIs). The optimal cutoff and predictive values were also estimated.

Results

Eleven cross-sectional studies involving 4380 patients were included. The median prevalence of left atrial thrombus was 12%. In 7 studies, the pooled sensitivity of D-dimer at 500 ng/mL was 50% (95% CI 26%–74%) and the pooled specificity was 88% (95% CI 76%–95%). The pooled sensitivity of age-adjusted D-dimer was 36% (95% CI 14%–66%) and the pooled specificity was 99% (95% CI 96%–99%) in 2 studies. The optimal cutoff of D-dimer was 390 ng/mL in 10 studies with a pooled sensitivity of 68% (95% CI 44%–85%) and a pooled specificity of 73% (95% CI 54%–86%). The positive and negative predictive values were 21.8% and 95.4%, respectively. The risk of bias was low or unclear for all domains. Concerns about applicability were low for almost all studies.

Conclusion

Our meta-analysis suggests that D-dimer has the potential to be useful to rule out left atrial thrombus in patients with atrial fibrillation.

Introduction

Atrial fibrillation (AF) is the most common sustained cardiac rhythm disturbance worldwide. AF is associated with increased morbidity and mortality mostly related to thromboembolic events.¹ Compared with patients with sinus rhythm, those with AF have a 5-fold increased risk of ischemic stroke.¹ Cardioembolic stroke is one of the most feared complications of AF because it is related to significant disability.

AF is characterized by a disorganized atrial electrical activity, resulting in an ineffective contraction and blood stasis, especially in the left atrial appendage.² The left atrial appendage is the main source of thrombus in patients with valvular and nonvalvular AF. The other 2 components of Virchow’s triad for thrombogenesis (endocardial injury and hypercoagulability) also play a key role in the thrombus formation in these patients.³ In summary, these mechanisms lead to a prothrombotic state in AF.

In patients with AF, the thrombus usually originates in the left atrial appendage and is accurately detected by transesophageal echocardiography (TEE). Currently, the CHA₂DS₂-VASc score is widely used to predict the thromboembolic risk associated with AF.² However, there is no laboratory test to aid the diagnosis of left atrial thrombus (LAT). Plasma fibrin D-dimers are degradation products of cross-linked fibrin by the endogenous fibrinolytic system, which appear to be a useful parameter for assessing the degrees of hypercoagulability.⁴ Plasma levels of D-dimer are routinely measured to rule out the diagnosis of deep venous thrombosis or acute pulmonary embolism.⁴ A correlation between D-dimer levels and the presence of LAT in patients with AF has been described in previous studies with conflicting results.5, 6, 7 Therefore, we performed a systematic review and meta-analysis to assess the diagnostic accuracy of D-dimer levels to detect the presence of LAT in patients with AF.