Association Between Plasma 2-Oxoglutarate Levels And Short-Term Outcomes In Patients With Acute Heart Failure

Background:Acute heart failure(AHF)is a life-threatening condition with new or recurrent heart failure symptoms and signs that require urgent evaluation and management.It is the leading cause of hospitalization in people aged 65 and above.Increasing research has shown that heart failure is associated with metabolic dysfunction.During the occurrence and development of heart failure,all steps of substrate utilization,energy intake,transduction and utilization of myocardium are affected(also called metabolic remodeling).2-oxoglutarate(2OG),an intermediate metabolite in the tricarboxylic acid cycle,has been found to associate with chronic heart failure(HF),but its effect on short-term adverse outcomes in patients with acute HF(AHF)is uncertain.Methods:This prospective cohort study included 411 consecutive hospitalized patients with AHF.During hospitalization,fasting plasma samples were collected within the first 24 hours of admission.Plasma 20G levels were measured by hydrophilic interaction liquid chromatography-liquid chromatography tandem mass spectrometry(HILIC-LC/MS/MS).All participants were followed up for six months.Multiple logistic regression was used to determine the odds ratio(OR)and 95%confidence interval(Cl)for primary outcomes.Results:The AHF cohort consisted of HF with preserved ejection fraction(EF)(64.7%),mid-range EF(16.1%),and reduced EF(19.2%),the mean age was 65(±13)years,and 65.2%were male.Participants were divided into two groups based on median 20G levels(?g/ml):low group(<6.0,n?205)and high group(?6.0,n?206).There was a relatively modest correlation between 2OG and N-terminal pro B-type natriuretic peptide(NT-proBNP)levels(r?0.25;p<0.001).After adjusting for age,sex,and body mass index,we found that the progression of the NYHA classification was associated with a gradual increase in plasma 20G levels(p for trend<0.001).After six months of follow-up,76(18.5%)events were identified.A high baseline 2OG level was positively associated with a short-term rehospitalization and all-cause mortality(OR:2.2,95%Cl 1.3-3.7,P?0.003),even after adjusting for NT-proBNP and estimated glomerular filtration rate(eGFR)(OR:1.9,95%Cl 1.1-3.4,p=0.032).After a similar multivariable adjustment,the OR was 1.4(95%Cl 1.1-1.7,p?0.018)for a per-SD increase in 2OG level.ROC analysis showed that the AUC 0.63 95%CI(0.56-0.70)of 2OG in predicting poor prognosis of AHF was not significantly different from that of NT-proBNP model(p?0.33).Conclusions:(1)Plasma 2OG levels in patients with AHF was significantly higher than that in patients without HF;(2)Plasma 2OG was positively correlated with ALT,NT-proBNP and UA,and negatively correlated with LVEF.(3)High baseline 2OG levels are associated with adverse short-term outcomes in patients with AHF independent of NT-proBNP and eGFR.(4)The prediction value of plasma 2OG in the short-term prognosis of AHF was similar to that of NT-proBNP.Hence plasma 2OG measurements may be helpful for risk stratification and treatment monitoring in AHF.