1. Extracellular matrix remodeling precedes atrial fibrillation: Results of the PREDICT-AF trial.
- Author
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van den Berg NWE, Neefs J, Kawasaki M, Nariswari FA, Wesselink R, Fabrizi B, Jongejan A, Klaver MN, Havenaar H, Hulsman EL, Wintgens LIS, Baalman SWE, Meulendijks ER, van Boven WJ, de Jong JSSG, van Putte BP, Driessen AHG, Boersma LVA, and de Groot JR
- Subjects
- Aged, Biglycan metabolism, Biomarkers analysis, Biomarkers blood, Cardiac Surgical Procedures methods, Collagen metabolism, Electrocardiography, Ambulatory methods, Electrocardiography, Ambulatory statistics & numerical data, Female, Humans, Male, Predictive Value of Tests, Prognosis, Prophylactic Surgical Procedures methods, Tenascin metabolism, Thrombospondins metabolism, Atrial Appendage pathology, Atrial Appendage surgery, Atrial Fibrillation blood, Atrial Fibrillation diagnosis, Atrial Fibrillation prevention & control, Atrial Remodeling physiology, Extracellular Matrix metabolism, Extracellular Matrix pathology, Heart Atria pathology, Heart Atria physiopathology
- Abstract
Background: To which extent atrial remodeling occurs before atrial fibrillation (AF) is unknown., Objective: The PREventive left atrial appenDage resection for the predICtion of fuTure Atrial Fibrillation (PREDICT-AF) study investigated such subclinical remodeling, which may be used for risk stratification and AF prevention., Methods: Patients (N = 150) without a history of AF with a CHA
2 DS2 -VASc score of ≥2 at an increased risk of developing AF were included. The left atrial appendage was excised and blood samples were collected during elective cardiothoracic surgery for biomarker discovery. Participants were followed for 2 years with Holter monitoring to determine any atrial tachyarrhythmia after a 50-day blanking period., Results: Eighteen patients (12%) developed incident AF, which was associated with increased tissue gene expression of collagen I (COL1A1), collagen III (COL3A1), and collagen VIII (COL8A2), tenascin-C (TNC), thrombospondin-2 (THBS2), and biglycan (BGN). Furthermore, the fibroblast activating endothelin-1 (EDN1) and sodium voltage-gated channel β subunit 2 (SCN2B) were associated with incident AF whereas the Kir2.1 channel (KCNJ2) tended to downregulate. The plasma levels of COL8A2 and TNC correlated with tissue expression and predicted incident AF. A gene panel including tissue KCNJ2, COL1A1, COL8A2, and EDN1 outperformed clinical prediction models in discriminating incident AF., Conclusion: The PREDICT-AF study demonstrates that atrial remodeling occurs long before incident AF and implies future potential for early patient identification and therapies to prevent AF (ClinicalTrials.gov identifier NCT03130985)., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)- Published
- 2021
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