Key result
Low circulating TTR tetramer levels in heart failure linked to ~2.2-fold higher all-cause mortality.
Why the study?
Reduced circulating transthyretin (TTR) levels are linked to transthyretin amyloidosis, but their potential as a biomarker for heart failure (HF) outcomes was unclear.
Does measurement of circulating transthyretin tetramer levels predict all-cause and cardiovascular deaths or rehospitalizations in patients with heart failure?
Observational (n=2,178)
Does measurement of circulating transthyretin tetramer levels predict all-cause and cardiovascular deaths or rehospitalizations in patients with heart failure?
Circulating transthyretin tetramer levels are significantly reduced in heart failure patients and independently predict all-cause mortality and rehospitalization, offering additive prognostic value when combined with NT-proBNP.
Low TTR tetramer levels were associated with higher HF mortality and rehospitalization risk; hypothesis-generating for prognostication and requires prospective validation before clinical adoption.
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.
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Zhang et al. (2026) conducted an observational in Heart failure (n=2,178). Low circulating transthyretin (TTR) tetramer levels vs. Higher TTR levels / healthy controls was evaluated on All-cause and cardiovascular deaths or rehospitalizations (2.189-fold (all-cause death); 1.563-fold (rehospitalization), p=0.036 (all-cause death); 0.008 (rehospitalization)). Low circulating TTR tetramer levels in heart failure were linked to a higher risk of all-cause death (2.189-fold, P=0.036) and rehospitalization (1.563-fold, P=0.008).
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