Extracellular matrix remodeling precedes atrial fibrillation: Results of the PREDICT-AF trial
Nicoline W E van den Berg, Jolien Neefs, Makiri Kawasaki, Fransisca A Nariswari, Robin Wesselink, Benedetta Fabrizi, Aldo Jongejan, Martijn N Klaver, Hanna Havenaar, Elise L Hulsman, Lisette I S Wintgens, Sarah W E Baalman, Eva R Meulendijks, Wim Jan van Boven, Jonas S S G de Jong, Bart P van Putte, Antoine H G Driessen, Lucas V A Boersma, Joris R de Groot, PREDICT-AF Investigators, Nicoline W E van den Berg, Jolien Neefs, Makiri Kawasaki, Fransisca A Nariswari, Robin Wesselink, Benedetta Fabrizi, Aldo Jongejan, Martijn N Klaver, Hanna Havenaar, Elise L Hulsman, Lisette I S Wintgens, Sarah W E Baalman, Eva R Meulendijks, Wim Jan van Boven, Jonas S S G de Jong, Bart P van Putte, Antoine H G Driessen, Lucas V A Boersma, Joris R de Groot, PREDICT-AF Investigators
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 CHA2DS2-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).
Keywords: Atrial fibrillation; Atrial remodeling; Biomarkers; Collagen VIII; Extracellular matrix; Tenascin.
Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
Source: PubMed