Impact of left atrial appendage flow velocity on thrombus resolution and clinical outcomes in patients with atrial fibrillation and silent left atrial thrombi: insights from the LAT study

Abstract

Aims: Blood stasis is crucial in developing left atrial (LA) thrombi. LA appendage peak flow velocity (LAAFV) is a quantitative parameter for estimating thromboembolic risk. However, its impact on LA thrombus resolution and clinical outcomes remains unclear.

Methods and results: The LAT study was a multicentre observational study investigating patients with atrial fibrillation (AF) and silent LA thrombi detected by transoesophageal echocardiography (TEE). Among 17 436 TEE procedures for patients with AF, 297 patients (1.7%) had silent LA thrombi. Excluding patients without follow-up examinations, we enrolled 169 whose baseline LAAFV was available. Oral anticoagulation use increased from 85.7% at baseline to 97.0% at the final follow-up (P < 0.001). During 1 year, LA thrombus resolution was confirmed in 130 (76.9%) patients within 76 (34-138) days. Conversely, 26 had residual LA thrombi, 8 had thromboembolisms, and 5 required surgical removal. These patients with failed thrombus resolution had lower baseline LAAFV than those with successful resolution (18.0 [15.8-22.0] vs. 22.2 [17.0-35.0], P = 0.003). Despite limited predictive power (area under the curve, 0.659; P = 0.001), LAAFV ≤ 20.0 cm/s (best cut-off) significantly predicted failed LA thrombus resolution, even after adjusting for potential confounders (odds ratio, 2.72; 95% confidence interval, 1.22-6.09; P = 0.015). The incidence of adverse outcomes including ischaemic stroke/systemic embolism, major bleeding, or all-cause death was significantly higher in patients with reduced LAAFV than in those with preserved LAAFV (28.4% vs. 11.6%, log-rank P = 0.005).

Conclusion: Failed LA thrombus resolution was not rare in patients with AF and silent LA thrombi. Reduced LAAFV was associated with failed LA thrombus resolution and adverse clinical outcomes.

Keywords: Atrial fibrillation; Left atrial appendage flow velocity; Left atrial thrombus; Oral anticoagulant; Transesophageal echocardiography.

Graphical abstract

Figure 1

Study flow chart. LA, left atrial; LAAFV, left atrial appendage peak flow velocity; TEE, transoesophageal echocardiography; MDCT, multidetector computed tomography.

Figure 2

Oral anticoagulants at baseline and final follow-up. (A) Detailed percentages of oral anticoagulants at baseline and the final follow-up. (B) The table displays how to change the oral anticoagulants from baseline to the final follow-up. The number of patients prescribed each oral anticoagulant is described in each column. The vertical and horizontal columns represent the prescribed oral anticoagulants at baseline and the final follow-up, respectively. The shaded column indicates the prescription of the same oral anticoagulants at baseline and at the final follow-up. The percentages indicate the percentage of drugs used at baseline that were prescribed at the final follow-up. (C) Successful resolution rate stratified by (a) the prescribed oral anticoagulant at baseline and at the end of follow-up and (b) the time in therapeutic range in patients who took vitamin K antagonist during the study period. *Of the five patients without oral anticoagulant at the final follow-up, three patients died, and two patients survived. One patient died of heart failure, one died of cardioembolic stroke, and another died of acute limb ischaemia. They were in critical condition and may not have been able to undergo oral anticoagulant. Conversely, all two survivors underwent surgical LA appendage removal. Thus, oral anticoagulants therapy was no longer considered necessary. DOAC, direct oral anticoagulant; DTI, direct thrombin inhibitor; PT-INR, prothrombin time-international normalization ratio.

Figure 3

Distribution of left atrial appendage peak flow velocity. (A) The histograms of the left atrial appendage peak flow velocity at baseline. (B) Box-and-whisker and scatter plots of left atrial appendage peak flow velocity. Left atrial appendage peak flow velocity was larger in patients with successful thrombus resolution than in those with failed resolution (P = 0.003 by Mann–Whitney U test). LAAFV, left atrial appendage peak flow velocity.

Figure 4

The scatter plot shows an association between the log-transformed left atrial appendage peak flow velocity and left atrial diameter (A), left ventricular diastolic diameter (B), left ventricular systolic diameter (C), left ventricular ejection fraction (D), tricuspid regurgitation pressure gradient (E), and log-transformed brain natriuretic peptide levels (F). BNP, brain natriuretic peptide; LA, left atrial; LAAFV, left atrial appendage peak flow velocity; LV, left ventricular; TRPG, tricuspid regurgitation pressure gradient.

Figure 5

Analysis of left atrial appendage peak flow velocity and left atrial thrombus resolution. (A) receiver operating characteristic curve analysis revealed significant value of left atrial appendage peak flow velocity for predicting thrombus resolution. (B) Percentage of patients confirming left atrial thrombus resolution was compared between patients with left atrial appendage peak flow velocity ≥ 20.0 cm/s and those with left atrial appendage peak flow velocity < 20.0 cm/s. (C) Predicted probability curve for left atrial thrombus resolution across varying left atrial appendage peak flow velocities. Actual data points were plotted to provide a visual comparison between the predicted and observed outcomes. The incremental value of left atrial appendage peak flow velocity for predicting left atrial thrombus resolution is suggested. LA, left atrial; LAAFV, left atrial appendage peak flow velocity; ROC, receiver operating characteristic curve.

Figure 6

Clinical outcomes. Kaplan–Meier survival curves at the endpoint of (A) ischaemic stroke and systemic embolism, (B) major bleeding, (C) all-cause deaths, and (D) composite of the three events. The event rate was compared using the log-rank test between patients with left atrial appendage peak flow velocity ≥ 20.0 cm/s and those with left atrial appendage peak flow velocity < 20.0 cm/s. LAAFV, left atrial appendage peak flow velocity.