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Updated: Jun 26, 2025
Estimating Bilateral Atrial Function by Cardiovascular Magnetic Resonance Feature Tracking in Patients with Paroxysmal Atrial Fibrillation
Published on: July 20, 2022
Proteomic biomarkers for noninvasive left atrial appendage thrombus prediction in patients with atrial fibrillation
ZhongHui Xie1, Tao Chen2, Xu Lu3
1Senior Department of Cardiology, The Sixth Medical Center of PLA General Hospital, Beijing, China; Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China.
Insights
New protein biomarkers, prenylcysteine oxidase 1 (PCYOX1) and decorin, significantly improve the prediction of left atrial appendage thrombus (LAAT) in atrial fibrillation (AF) patients. This offers a more accurate, noninvasive risk assessment than current methods.
Area of Science:
- Cardiology
- Proteomics
- Biomarker Discovery
Background:
- Current methods for assessing left atrial appendage thrombus (LAAT) risk in atrial fibrillation (AF) patients, such as the CHA2DS2-VASc score and transesophageal echocardiography, have limitations in predictive value and invasiveness.
- There is a critical need for noninvasive and more accurate diagnostic tools for identifying LAAT risk.
Purpose of the Study:
- To identify novel protein biomarkers for the noninvasive prediction of LAAT in patients with nonvalvular AF.
- To develop and validate predictive models incorporating these biomarkers to improve LAAT risk assessment.
Main Methods:
- Deep proteomic analysis of plasma samples from nonvalvular AF patients with and without LAAT.
- Validation of identified protein biomarkers using enzyme-linked immunosorbent assay (ELISA) in a larger cohort.
- Development of predictive models to evaluate the diagnostic performance of novel biomarkers.
Main Results:
- Deep proteomic analysis identified 30 differentially expressed proteins, highlighting myosin light chain 4, prenylcysteine oxidase 1 (PCYOX1), and decorin as potential LAAT biomarkers.
- A predictive model incorporating PCYOX1 and decorin achieved an AUC of 0.970 for LAAT prediction, significantly outperforming a model based on CHA2DS2-VASc score and LAA morphology (AUC 0.672).
- The incremental value of these proteomic biomarkers was confirmed through net reclassification and integrated discrimination improvement indices.
Conclusions:
- Protein levels of PCYOX1 and decorin significantly enhance the predictive accuracy for LAAT in patients with nonvalvular AF.
- These novel biomarkers offer a promising noninvasive approach for improved LAAT risk stratification in AF patients.
Introduction And Objectives:
The CHA2DS2-VASc score, used to assess the risk of left atrial appendage thrombus (LAAT) formation in patients with atrial fibrillation (AF), has limited predictive value. Moreover, transesophageal echocardiography imaging, the gold standard diagnostic method to identify thrombi, is semi-invasive. Consequently, there is a need for alternative and noninvasive diagnostic methods for LAAT risk assessment.
Methods:
Deep proteomic analysis was conducted in plasma samples from 8 patients with nonvalvular AF, divided into thrombus and control groups (4 patients in each group) based on the presence or absence of LAAT. Biomarkers associated with LAAT were validated using an enzyme-linked immunosorbent assay in a cohort of 179 patients with available clinical, transthoracic, and transesophageal echocardiography data. Predictive models were developed to assess the improvement in LAAT identification.
Results:
The LAAT group had higher CHA2DS2-VASc scores, larger LA diameter, and lower LAA flow velocities. Deep proteomic analysis identified 30 differentially expressed proteins, including myosin light chain 4, prenylcysteine oxidase 1 (PCYOX1), and decorin as potential diagnostic biomarkers of LAAT. The model showed that PCYOX1 and decorin provided an area under the curve (AUC) of 0.970 for LAAT prediction compared with 0.672 in a model including the CHA2DS2-VASc score and LAA cauliflower morphology. The incremental value of proteomic biomarkers for LAAT in patients with nonvalvular AF was further confirmed with the net reclassification improvement and integrated discrimination improvement indices.
Conclusions:
Protein levels of PCYOX1 and decorin improve the predictive performance for LAAT in patients with nonvalvular AF.
