1. Extracellular matrix remodeling precedes atrial fibrillation: Results of the PREDICT-AF trial
- Author
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Jonas S.S.G. de Jong, Nicoline W.E. van den Berg, Elise L. Hulsman, J. Neefs, Robin Wesselink, Joris R. de Groot, Wim-Jan van Boven, Bart P. van Putte, Antoine H.G. Driessen, Aldo Jongejan, Sarah W.E. Baalman, Fransisca A. Nariswari, Predict-Af Investigators, Makiri Kawasaki, Hanna Havenaar, E R Meulendijks, Lisette I S Wintgens, Lucas V.A. Boersma, Benedetta Fabrizi, M. N. Klaver, Cardiology, Graduate School, ACS - Heart failure & arrhythmias, Epidemiology and Data Science, APH - Methodology, ACS - Atherosclerosis & ischemic syndromes, ACS - Microcirculation, Cardiothoracic Surgery, ACS - Pulmonary hypertension & thrombosis, and APH - Personalized Medicine
- Subjects
Male ,medicine.medical_specialty ,Tenascin ,Collagen VIII ,Extracellular matrix ,Predictive Value of Tests ,Physiology (medical) ,Internal medicine ,Biglycan ,medicine ,Humans ,Atrial Appendage ,Heart Atria ,Cardiac Surgical Procedures ,Fibroblast ,Aged ,Subclinical infection ,biology ,business.industry ,Atrial fibrillation ,Prophylactic Surgical Procedures ,Prognosis ,medicine.disease ,medicine.anatomical_structure ,Cardiothoracic surgery ,Electrocardiography, Ambulatory ,Cardiology ,biology.protein ,Female ,Collagen ,Thrombospondins ,Atrial remodeling ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers ,Atrial Remodeling - 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 ).
- Published
- 2021