Biomarkers For Characterization Of Heart Failure-distinction Of Heart Failure With Preserved And Reduced Ejection Fraction

AIM: Midregion pro-atrial natriuretic peptide(MR-pro ANP)is a stable precursor of ANP and is increased in response to increased atrial wall stretch in heart failure.We aimed to study the clinical correlates and prognostic significance of plasma MR-pro ANP in heart failure with preserved ejection fraction(HFp EF)vs.reduced ejection fraction(HFr EF),compared with N-terminal pro-brain natriuretic peptide(NT-pro BNP).METHODS: MR-pro ANP and NT-pro BNP were prospectively measured in 168 consecutive patients with HFr EF(EF<50%;n=68)and HFp EF(EF?50%;n=100).Patients were followed up for a composite outcome of death or first HF rehospitalization for 12 months.RESULTS: Median MR-pro ANP baseline values were similarly elevated in HFp EF [IQR,53.0(48.1,62.6)pg/ml] and HFr EF [59.0(49.6,64.6)pg/ml](P = 0.184),whereas NT-pro BNP was significantly lower in HFp EF than HFr EF [869.6(354,1871.5)vs.5638.0(2621.2,10272.0)pg/ml,p<0.001].NT-pro BNP levels were negatively correlated with LVEF and positively correlated with LVDD,and LVMI in patients with HFr EF;while MR-pro ANP levels were positively correlated with LAD and LAVI.In patients with HFp EF,NT-pro BNP levels just had close associations with LAVI,and MR-pro ANP levels had close associations with LAD,LAVI and E/Ea.Baseline MR-pro ANP levels were associated with higher levels of AUC in patients with HFp EF compared with plasma NT-pro BNP levels(AUC: 0.902 vs.0.873),while NT-pro BNP levels were associated with higher levels of AUC in patients with HFr EF(0.924 vs.0.971).The ratio of NT-pro BNP to MR-pro ANP provided the best discriminatory ability between the two HF types(AUC=0.825).During a median follow-up of 12 months,there were 57 events(20 HFr EF,37 HFp EF).MR-pro ANP remained a significant independent predictor for composite outcome even after adjusting for important clinical predictors in patients with HFp EF,but not for patients with HFr EF,whereas NT-pro BNP had a similar prognostic value for both entities.CONCLUSIONS: MR-pro ANP seems to be a biomarker for atrial volume overload and pressure,can provide additional diagnostic information for the diagnosis of HFp EF in addition to NT-pro BNP levels,and have particularly strong predictive value in HFp EF patients.