Low factor XI activity in heart failure: A potential marker of disease severity?

Advanced heart failure (HF) is characterized by progressive cardiac remodeling and recurrent episodes of decompensation, highlighting the need for biomarkers reflecting disease severity. Coagulation factor XI (FXI), beyond its established role in hemostasis, may influence inflammatory and remodeling pathways in the heart, but its relevance in advanced HF remains unclear.

This study evaluated the association between FXI activity and clinical, laboratory, and echocardiographic parameters in patients with advanced HF.

We prospectively enrolled 91 patients with advanced HF (New York Heart Association class III-IV) from a tertiary HF day-care service between November 2024 and February 2025. FXI activity was measured using a PTT-based assay, and patients were stratified by the median FXI level (<89% vs. ≥89%).

Patients with lower FXI activity required higher intravenous diuretic doses (120 vs. 60 mg/week; P = 0.02), had more frequent HF clinic visits (2 vs. 1 per week; P = 0.01), and exhibited higher N-terminal pro-B-type natriuretic peptide levels (3350 vs. 2000 pg/ml; P = 0.01). Prolonged PT-international normalized ratio (>1.5) was more prevalent in the low-FXI group (24% vs. 2%; P = 0.006). Echocardiographic findings included larger LV end-diastolic diameter (mean 5.5 vs. 5.03 cm; P = 0.01), greater left atrial area (median 29 vs. 25 cm2; P = 0.007), higher prevalence of pulmonary hypertension (41% vs. 20%; P = 0.04), and more frequent moderate-to-severe mitral regurgitation (34% vs. 13%; P = 0.02).

Reduced FXI activity is associated with adverse clinical and echocardiographic profiles in advanced HF. These findings support a potential biomarker or cardioprotective role for FXI and call for caution in applying FXI-targeted therapies in this population.