The Diagnostic Value Of Metabolomics In Patients With Acute Heart Failure

Objective:To investigate the difference of metabolomics between acute heart failure(AHF)patients and non-heart failure people,and study the correlation between metabolomics and left ventricular ejection fraction(LVEF)among patients with acute heart failure.Methods: This was a single-center case-control study.The cases were 41 acute heart failure patients who were admitted to the emergency department of Henan Provincial People's Hospital from January 2018 to December 2018.The controls were 30 people without heart failure and diastolic dysfunction,they were age-matched to the cases.The fasting blood samples were collected from femoral arterial.Qualitative and quantitative analyses of plasma metabolites were performed in 2 groups by high performance liquid chromatography tandem mass spectrometry(UHPLC-MS),and an orthogonal partial least squares-discriminant analysis(OPLS-DA)model was applied.The model tests were used substitution test,metabolites with significant differences between the two groups were screened and analyzed by ROC curve.The case group was further divided into two groups according to LVEF.Specifically,those with LVEF?45% were categoried into the group of retaining ejection fraction heart failure(HFp EF),and otherwise the other group of ejection fraction reducing heart failure(HFr EF).Qualitative and quantitative analysis of plasma metabolites was performed in HFp EF and HFr EF groups by UHPLC-MS,and an OPLS-DA model,and we also ploted the ROC curve.Results: Compared with the control group,we found that HF group had higher likelihood to have coronary heart disease(39% vs 7%,p=0.002),hypertension(61%vs 27%,p=0.017),hyperlipidemia(51% vs 17%,p=0.003),atrial fibrillation(27% vs3%,p=0.010),smoking history(41% vs 17%,p=0.037),and that HF group had higher creatinine level(11.2±6.9 vs 6.5±1.8,p=0.016),higher urea level(11.2±6.9vs 6.5±1.8,p=0.016),hypoproteinemia(32.2±5.8 vs 41.0±2.1,p<0.001),and significantly increased BNP level(3003.5±3656.6 vs 113.5±84.7,p<0.001).And compared with HFp EF group,HFr EF group had older age(69±14 vs 56±16,p=0.010),more coronary heart disease(65% vs 14%,p=0.001),more smoking history(65% vs19%,p=0.004),low serum sodium level(122.5±7.4 vs 133.2±9.1,p?0.001),and low albumin level(27.2±3.3 vs 32.2±5.8,p=0.007),high creatinine level(166.2±74.6 vs111.6±63.2,p=0.015),and high BNP level(4598.2±3631.7 vs 3003.5±3656.6,p=0.027).The metabolites of HF group vs control group and HFp EF vs HFr EF were analyzed that the metabolites of HF group were significantly different from those of the control group,the metabolites in the HFp EF and HFr EF groups were less differences.The metabolites involved amino acids,fatty acids,lipids,nucleosides and their derivatives.Adenine,pseudo uridine,N-acetyl-L-glutamic acid and L-alanine were of certain value in the diagnosis of HF when the metabolites in the HF group were compared to control group.The AUC were 0.988,0.944,0.929 and 0.905,respectively,and the AUC of four metabolites combined with BNP was 1.0.A comparison of metabolites between HFp EF group and HFr EF group showed that L-cystine could assist in the identification of HFp EF and HFr EF patients,and AUC was 0.693,the AUC of L-cystine combined with BNP was 0.719.Conclusions: There were significant differences in metabolism between HF group and control group.The metabolites involved multiple substances and pathways.The main metabolic pathways included amino acid metabolism,tricarboxylic acid cycle and lipid metabolism.The metabolites in the HFp EF and HFr EF groups were less differences.Adenine,pseudouridine,N-acetyl-L-glutamic acid and L-alanine were of similar value to BNP about the diagnosis of HF,and L-cystine could help to distinguish HFp EF and HFr EF patients.