Association of atrial fibrillation burden and clinical profile with blood biomarkers: results from the ISOLATION ablation cohort

In atrial fibrillation (AF) patients scheduled for ablation, advances have been made in identifying biomarkers for outcome, however data on the association of clinical determinants, particularly AF burden, with blood biomarkers are scarce.

Our primary aim was to explore the relationships between clinical determinants, AF burden derived from single lead ECGs, and biomarker levels in AF patients scheduled for catheter ablation.

This cross-sectional analysis included AF patients undergoing catheter ablation in the ISOLATION study (July 2020 - May 2022, NCT04342312). Patient characteristics and blood samples were collected before ablation. AF burden was determined using hand-held electrocardiograms (ECG) during 4 weeks before ablation. Blood samples were analyzed for biomarkers, including BMP10, Ang-2, FGF23, DKK3, ESM-1, IGFBP-7, NT-proBNP, total NT-proBNP, hs-TNT, GDF-15, IL-6, FABP3, CA-125 (Table 1). For each biomarker we trained lasso regression models to identify the most important clinical determinants out of 64 available clinical features (including AF burden, anthropometrics, ECG, comorbidities).

Blood samples of 508 patients were analyzed. The mean age was 63 ±9 years, and 31.1% were female. 354 patients (70%) had paroxysmal, 154 (30%) persistent AF. Heart failure was reported in 77 patients (15%). In 140 patients (28%), AF was observed during blood drawing. In 389 patients, AF burden was available. After multivariable analysis the following clinical determinants were independently associated with biomarker levels: AF burden, AF during blood drawing, age, heart failure, decreased kidney function, and female sex (Figure 1). Most notably, rhythm at the time of sampling and AF burden were strongly associated with various biomarker levels. Female sex was positively associated with BMP10 and FGF23 (atrial fibrosis), but negatively associated with hs-TNT (cardiac injury).

Rhythm during blood drawing and AF burden are strong determinants of many biomarkers underpinning their relevance as co-variates in biomarker studies. Pro-fibrotic biomarkers are increased in female patients, while male patients more often show elevated biomarkers of myocardial injury.

Biomarkers and pre-procedural AF burden