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Original article
Available online 18 June 2024
Proteomic biomarkers for noninvasive left atrial appendage thrombus prediction in patients with atrial fibrillation
Biomarcadores proteómicos para la predicción no invasiva de trombos en la orejuela izquierda de pacientes con fibrilación auricular
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ZhongHui Xiea,b,, Tao Chena,, Xu Lua,c,, MaoXiang Zhaoa,, Yating Chena, XinYan Wanga, Hang Zhoua, Juan Shena, Jun Guoa,
Corresponding author
guojun301@126.com

Corresponding authors.
, Yang Lia,
Corresponding author
liyangbss@163.com

Corresponding authors.
a Senior Department of Cardiology, The Sixth Medical Center of PLA General Hospital, Beijing, China
b Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, China
c Outpatient Department, The 44th Sanatorium of Retired Cadres in Haidian District, Beijing, China
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Received 03 October 2023. Accepted 23 April 2024
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Table 1. Integrated model for left atrial appendage thrombus prediction
Table 2. Comparison of the performance of left atrial appendage thrombus prediction models
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Abstract
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.

Keywords:
Atrial fibrillation
Thrombosis
Proteomics
Abbreviations:
AF
LAAT
MYL4
PCYOX1
SEC
Resumen
Introducción y objetivos

La escala CHA2DS2-VASc utilizada para evaluar el riesgo de formación de trombos en la orejuela izquierda (TOI) de pacientes con fibrilación auricular (FA) muestra poco valor predictivo. Además, el ecocardiograma transesofágico, utilizado para identificar los TOI, es semiinvasivo. Esto hace que el desarrollo de métodos alternativos para identificar TOI tenga un alto potencial clínico.

Métodos

Se realizó un análisis proteómico avanzado en muestras de plasma de 8 pacientes con FA no valvular, divididos en grupos con TOI y controles sin trombos (4 pacientes por grupo). Los biomarcadores asociados con TOI se validaron mediante inmunoenzimoanálisis en una cohorte de 179 pacientes con datos clínicos y de ecocardiografías transtorácica y transesofágica disponibles. Se desarrollaron modelos predictivos para evaluar la mejora en la predicción de TOI.

Resultados

El grupo de TOI mostró valores más altos de CHA2DS2-VASc y de diámetro de la aurícula izquierda y menores velocidades de flujo en la orejuela izquierda. El análisis proteómico identificó 30 proteínas de expresión diferenciada, entre ellas la miosina de cadena ligera (MYL4), la prenilcisteína oxidasa 1 (PCYOX1) y la decorina como potenciales biomarcadores de TOI. El desarrollo de modelos predictivos mostró que la PCYOX1 y la decorina proporcionaron un área bajo la curva (AUC) de 0,970 para la predicción de TOI comparado con 0,672 en el modelo que incluyó CHA2DS2-VASc y morfología en coliflor de la orejuela izquierda. El valor incremental de los biomarcadores proteómicos para la predicción de TOI en pacientes con FA no valvular se confirmó con análisis estadísticos adicionales mediante el índice de mejora de la discriminación y de la reclasificación.

Conclusiones

La concentración de las proteínas PCYOX1 y decorina mejoran la capacidad predictiva de TOI en pacientes con FA no valvular.

Palabras clave:
Fibrilación auricular
Trombosis
Proteómicas

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