Abstract
Metabolic disturbances represent functional perturbation in peripheral tissues and predict outcomes in patients with heart failure (HF). This study developed an amino acid-based metabolic panel and sought to see whether this panel could add diagnostic and prognostic value to currently used B-type natriuretic peptide (BNP) measurements. Mass spectrometry and ultra-performance liquid chromatography were performed on 1288 participants, including 129 normal controls and 712 patients at HF stages A to D in the initial cohort and 447 stage C patients in the validation cohort. Patients were followed up for composite events (death/HF-related rehospitalization). Histidine, ornithine, and phenylalanine were 3 metabolites found strongly significant to identify patients at stage C and were adopted to develop the HOP panel. Compared to BNP, HOP had better value in discriminating the patients at different stages, especially in elderly patients and those with atrial fibrillation, high body mass index, or kidney dysfunction. HOP was correlated with the distance of 6 min walking distance better than BNP. For prognosis, HOP predicted composite events in patients at stages C and D, independent of log (BNP), age, sex, left ventricular ejection fraction, New York Heart Association functional class, HF stage, diabetes mellitus, chronic kidney disease, hypertension, hemoglobin, and albumin. Higher BNP (≥750 pg/mL) along with higher HOP (≥14) robustly predicted lower event-free survival compared to all others [hazard ratio = 3.15 (2.23-4.46), p < 0.001]. The prognostic value of HOP was confirmed in the validation cohort. In conclusion, aiming for clinical applications, this study proved that the HOP panel provides diagnostic and prognostic value additive to BNP and traditional risk factors.