Accumulating studies have documented the vital role of LASEC in predicting cardiovascular events[13, 14]. In the present study, approximately 34.26% (37/108) of the NVAF patients had LASEC, which is in line with previous data[15].
To gain better understanding of discriminating predictive indicators in LASEC, changes of local vascular biomarkers in the left atrium and peripheral femoral blood were investigated. Our data showed elevated local and peripheral blood levels of sP-selectin and vWF in NVAF patients with LASEC, suggesting the endothelial dysfunction and abnormal platelet activation in patients had LASEC. Increased sP-selectin and vWF are linked with high risk of stroke and adverse outcomes. Also, this study found the levels of sP-selectin and vWF concerning the LASEC group in peripheral blood were higher than those in left atrial blood, which controverts with previous studies[16, 17]. A possible explanation is that vascular dysfunction and platelet activation also occurred in other sites, and the mean CHA2DS2-VASc scores were 2.5 ± 1.6 in this study, which means most patients had higher thromboembolism risk than previous studies. In a pile of papers, it was demonstrated that thrombi were not rare in the right atrium[18, 19, 20] .Hence sP-selectin and vWF levels in peripheral vessels maybe more accurate and comprehensive, instead of those in left atrium blood.
Platelet- and endothelial-derived microparticles are closely related to hemostasis and thrombosis[21, 22]. Endothelial injury activates platelets and releases MPs which are abundant of micro-RNA and cytokines, resulting in activating relevant signaling and thrombosis formation. Sample collection, processing, MPs isolation and related technology was challenging as MPs are easily to degrade or elevate[23, 24]. In this study, fresh whole blood samples were used and freezing was avoided to obtained precise quantification. Similarly, we found significantly enhanced peripheral PMPs and EMPs but not local PMPs and EMPs in LASEC group comparing non LASEC group.
To examine the predictive role of peripheral serological indicator, we conducted the ROC analyses of sP-selectin, vWF, PMPs and EMPs. Despite the sP-selectin exclusively derives from platelets, it could be partially released on endothelial cells[25, 26]. VWF is a multimeric glycoprotein synthesized and secreted by injured vascular endothelium[27]. At a cutoff value of 42.23 ng/mL, sP-selectin presented sensitivity of 59.46% and specificity of 74.65%. The cutoff of vWF was 11.64 µg/mL, with a sensitivity of 86.49% and specificity of 40.85%. There are limited studies on MPs numbers of NVAF patients during anticoagulation. Here we identified at a cutoff of 5.59×103/µL, PMPs had sensitivity of 48.65% and specificity of 71.83%. And at a cutoff of 2.52×103/µL, EMPs had sensitivity of 64.86% and specificity of 66.20%. We found the combination of four markers were prior to PMPs, sP-selectin, EMPs and vWF alone.
Of course there are some limitations in our study. Firstly, the study was based on a single-center. More cases need to be enrolled to verify whether the severity of LASEC would influence the expressions of sP-selectin, vWF and microparticles. Secondly, atrial inflammation and irregular blood flow induced by AF may cause endothelial dysfunction, but the impaired endothelial function of AF patients would improve after catheter ablation regardless of the type of AF[28]. Further studies concerning the variations of biomarkers over time are still in need.
To summarize, spontaneous echo contrast was commonly seen in left atrium of patients with non-valvular atrial fibrillation. Our data demonstrated the elevated expressions of sP-selectin, vWF, PMPs and EMPs in NVAF patients with LASEC. We provided useful indicators and related thresholds regarding the existence of LASEC in atrial fibrillation.