Tetranectin as a Potential Biomarker in Heart Failure with Ejection Fraction >45%: A Prospective Cohort Study

Heart failure (HF) with left ventricle ejection fraction (LVEF) >45% lacks reliable biomarkers for risk stratification complicating its management, as it encompasses both heart failure with preserved ejection fraction (HFpEF, LVEF ≥50%) and mildly reduced ejection fraction (HFmrEF, LVEF 45-49.9%). This study aimed to evaluate serum tetranectin (TETRA) as a novel biomarker for assessing disease severity and predicting mortality in patients with HF with EF >45%. In a prospective cohort study including 116 patients HF with EF>45% from a single center in Arad, Romania, stratified by NYHA class (G1: NYHA I, n=48; G2: NYHA II, n=37; G3: NYHA III-IV, n=31), serum TETRA levels were measured using ELISA. Echocardiographic parameters (E/e' ratio, LAVI, LAS, GLS, LVEF) and NT-proBNP were assessed at baseline, with all-cause mortality (9 deaths) tracked over a 12-month follow-up. Median TETRA levels decreased with worsening NYHA class (G1: 48.9 ng/mL, G2: 33.2 ng/mL, G3: 27.6 ng/mL; p < 0.001) and correlated negatively with NT-proBNP (rho = -0.66, p < 0.001), E/e' ratio (rho = -0.58, p = 0.003), and LAVI (rho = -0.52, p = 0.010), while positively correlating with LAS (rho = 0.55, p = 0.005). In univariable Cox analysis, lower TETRA levels were associated with higher all-cause mortality (HR = 1.38 per 10 ng/mL decrease, 95% CI: 1.06-1.81, p = 0.045), but this association was not significant after adjustment for age and NT-proBNP (HR = 1.22, 95% CI: 0.94-1.86, p = 0.112). TETRA levels are inversely associated with severity in heart failure with EF>45% and may reflect disease progression.