TY - JOUR
T1 - Extracellular matrix remodeling precedes atrial fibrillation: Results of the PREDICT-AF trial
AU - van den Berg, Nicoline W. E.
AU - Neefs, Jolien
AU - Kawasaki, Makiri
AU - Nariswari, Fransisca A.
AU - Wesselink, Robin
AU - Fabrizi, Benedetta
AU - Jongejan, Aldo
AU - Klaver, Martijn N.
AU - Havenaar, Hanna
AU - Hulsman, Elise L.
AU - Wintgens, Lisette I. S.
AU - Baalman, Sarah W. E.
AU - Meulendijks, Eva R.
AU - van Boven, Wim Jan
AU - PREDICT-AF Investigators
AU - de Jong, Jonas S. S. G.
AU - van Putte, Bart P.
AU - Driessen, Antoine H. G.
AU - Boersma, Lucas V. A.
AU - de Groot, Joris R.
N1 - Funding Information: We thank M.H. van der Ree, MD, G.B. Kamermans, S.N.J. Pultoo, BSc, and M.M. Terpstra, BSc; F.J.F. Broeyer, MD, PhD (Ziekenhuis Amstelland); M. van Deudekom, RN (Rijnstate); and A. van Rijn, RN (Dijklander Ziekenhuis) for their support in clinical data collection. We thank O.J. de Boer, PhD, A.C. van der Wal, MD, PhD, and M.F.M. Oosterhout, MD, PhD for histological analyses; S. LaBoissiere, PhD (Genome Quebec) and A. Pacis, PhD (McGill University) for the RNA sequencing analysis; and A.H. Zwinderman, PhD for statistical advice. Funding Information: Funding sources: This work was supported by a grant from ZonMW/NWO (ZorgOnderzoek NederlandMedische Wetenschappen, Nederlandse Organisatie voor, Wetenschappelijk Onderzoek), 106.146.310 (to Dr de Groot). Funding Information: Disclosures: Dr de Groot has been supported by research grants from Abbott, AtriCure, Boston Scientific, Bayer, Daiichi Sankyo, Johnson & Johnson, and Medtronic Servier and has received consultancy fees from AtriCure, Bayer, Daiichi Sankyo, Johnson & Johnson, and Medtronic (outside the submitted work). Dr Driessen is a consultant to AtriCure. The rest of the authors report no conflicts of interest. Publisher Copyright: © 2021 Heart Rhythm Society
PY - 2021/12
Y1 - 2021/12
N2 - 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).
AB - 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).
KW - Atrial fibrillation
KW - Atrial remodeling
KW - Biomarkers
KW - Collagen VIII
KW - Extracellular matrix
KW - Tenascin
UR - http://www.scopus.com/inward/record.url?scp=85112512437&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.hrthm.2021.07.059
DO - https://doi.org/10.1016/j.hrthm.2021.07.059
M3 - Article
C2 - 34332113
SN - 1547-5271
VL - 18
SP - 2115
EP - 2125
JO - Heart Rhythm
JF - Heart Rhythm
IS - 12
ER -