Circulating transthyretin tetramer as potential prognostic biomarker for outcome prediction in patients with heart failure

Abstract

Reduced circulating transthyretin (TTR) levels are linked to transthyretin amyloidosis (ATTR), but their potential as a biomarker for heart failure (HF) outcomes is unclear. We conducted a study with 462 HF patients and 1716 controls, measuring TTR tetramer levels using ultra-performance liquid chromatography. Over a median follow-up of 34 months, we assessed all-cause and cardiovascular deaths or rehospitalizations. HF patients had significantly lower TTR levels than controls (3.346±1.190 vs. 4.591±1.049 μmol/L, P<0.001), correlating with New York Heart Association classification. Patients with reduced ejection fraction had lower TTR levels (3.030±1.157 vs. 3.614±1.160 μmol/L, P<0.001) than those with preserved function. Low TTR levels were linked to a higher risk of all-cause death (2.189-fold, P=0.036) and rehospitalization (1.563-fold, P=0.008), but not with specific cardiovascular outcomes. Combining TTR with NT-proBNP improved mortality risk prediction (AUC of 0.774), enhancing prognostic value. These results suggest the TTR tetramer is a promising biomarker for HF diagnosis and prognosis, aiding in patient management and supporting regular assessments.Central Illustration