May 19, 2020 — Structural changes of the atrium may occur long before the onset of atrial fibrillation (AF), and the late-breaking PREDICT-AF trial showed first time there is extensive extracellular matrix (ECM) remodeling, which can be used as a new predictor for AF. The study was presented at the Heart Rhythm Society (HRS) 2020 Science virtual meeting.
The Tissue, Blood and Biomarkers to Predict Future Atrial Fibrillation (PREDICT-AF) study showed that extensive ECM remodeling, reaching beyond the deposition of collagens, takes place in the atria of patients long before they develop AF, said Joris R. de Groot, M.D., Ph.D., Amsterdam UMC, Amsterdam, Netherlands, who presented the results. He said the high accuracy of a gene panel to predict future AF may inspire further research to provide targets for diagnosis and primary prevention of AF.
The study included 150 patients (age 68±7 years, 87% men, 115 CABG, 11 valve surgery, 24 combined surgeries). Patients without a history of AF undergoing cardiothoracic surgery with a CHA2DS2-VASc score ≥2 were included and the left atrial appendage was excised (PREDICT-AF NCT03130985). Rhythm monitoring with multiple Holters was performed for 2 years. The primary endpoint was late-onset AF: any atrial tachyarrhythmia >30 sec, occurring >50 days after surgery. The expression of 25 genes related to structural or electrical remodeling was quantified with qPCR in all patients and associated with late-onset AF using Cox-regression analyses. Genes were selected based on a discovery phase (transcriptome sequencing of 22 atrial tissues). Gene panels were used to determine C-statistics.
Median follow-up was two years [1.5-2]. Post-operative AF occurred in 63 (42%) patients ≤50 days post-surgery and late-onset AF in 18 (12%). Gene expression of all 25 genes was similar in patients with and without post-operative AF <50 days. Patients with late-onset AF exhibited numerical down regulation of KCNJ2 and up regulation of SCN2B. There was a marked increased expression of extracellular matrix (ECM) genes encoding collagens and matricellular proteins that act as structural proteins and fibrogenic mediators. We found a strong correlation between ECM genes and the fibroblast activator Endothelin-1.
The fraction of Vimentin positive cells (i.e. fibroblasts) was similar, suggesting fibroblast activation rather than proliferation. A gene panel including KCNJ2, COL8A2, and COL1A1 better discriminated late-onset AF (AUC=0.82) than a model with the most relevant clinical parameters (age≥75, LAVI and sex; AUC=0.69).
Find links to all the Heart Rhythm Society 2020 Late-Breaking Clinical Trials in Electrophysiology
1. PREventive Left Atrial appenDage Resection for the predICtion of fuTure Atrial Fibrillation: Design of the PREDICT AF Study. J Cardiovasc Med (Hagerstown). 2019 Nov;20(11):752-761. doi: 10.2459/JCM.0000000000000868.