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, M N Klaver, H Havenaar, Elise L. Hulsman, Lisette 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
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: -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).