| Background:The "2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure" issued by European Society of Cardiology(ESC)in May 2016.ESC for the first time divided the patients with chronic heart failure(CHF)into HF with preserved ejection fraction(HFp EF)group,HF with mid-range ejection fraction(HFmr EF)group and HF with reduced ejection fraction(HFr EF)group.ESC for the first time suggested that identifying HFmr EF as a separate group will stimulate research into the underlying characteristics,pathophysiology and treatment of this group of patients.“2012 ESC HF guidelines” emphasized diagnosis of HF by biomarkers and echocardiography;while the “2016 ESC HF guidelines” focused on the role of clinical manifestations,NT-proBNP,and echocardiography,the latter is more comprehensive,rational,and accurate than the previous guidelines.Previous studies of biomarkers in HF was based on patients with HFp EF and HFr EF,our study will be the first to incorporate HFmr EF patients according to the “2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure”,and assessed the differences of clinical features and biomarkers of HF among patients with HFmr EF,HFp EF and HFr EF.We also assessed the relationship between biomarkers and diastolic function of each group for the first time in China.Objectives:1.Assessing the diagnostic utility of serum growth differentiation factor-15(GDF-15)and N-terminal pro brain natriuretic peptide(NT-proBNP),galectin-3(Gal-3),C ystatin C level in patients with HFp EF,HFmr EF and HFr EF;and further exploring the clinical significance of combining serum GDF-15,NT-proBNP,Gal-3,and C ystatin C assay in patients with CHF,HFpEF,HFmr EF and HFr EF F.2.Exploring the difference between serum biomarkers and indicator of different diastolic function—mitral E/e’.Methods:We selected in the department of cardiology hospitalization which conform to the "2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure" diagnostic criteria of the patients with CHF,according to "the guidelines" we will be divided patients with CHF into HF with reduced ejection fraction(HFr EF,n = 29)group,HF with mid-range ejection fraction(HFmr EF,n = 30)group and HF with preserved ejection fraction(HFp EF,n = 68)group.In the same period,we selected patients with hospital-based and normal cardiac function served as the control group(n = 33).We detected groups serum GDF-15,NT-proBNP,Gal-3 and C ystatin C level.Then all the subjects were grouped according to different state of diastolic function,divided into E/e’ < 8 group(n = 32),E/e’ = 8 ~ 15 group(n = 104)and the E/e’ > 15 group(n = 24),and we further exploring the differences of biomarkers in each groups.Results:1.The serum GDF-15,NT-proBNP,Gal-3 in CHF group was significantly higher than that in control group(both P < 0.01),while the serum C ystatin C in CHF group had no statistical significance compared with control group(both P > 0.05).Serum NT-proBNP in HFr EF group were higher than those in HFmr EF and HFpEF(both P < 0.01),and both HFmr EF group were significantly higher than those in HFpEF group(P < 0.01).Serum GDF-15 in HFrEF group was higher than those in HFmrEF and HFp EF group(both P < 0.01),while HFmr EF group had no statistical significance compared with HFpEF group(P > 0.05);Serum Gal-3 in each subgroup of CHF group had no statistical significance(both P > 0.05).2.The lg(GDF-15)and Gal-3 were positively correlated with lg(NT-proBNP)(r = 0.474,0.211 respectively,both P < 0.01),and negatively related to left ventricular ejection fraction(r =-0.4,-0.202 respectively,both P < 0.01).3.Serum levels of NT-proBNP,GDF-15 in diastolic dysfunction groups(E/e’ = 8~15,E/e’ > 15)were higher than those in normal diastolic function(E/e’ < 8)group(both P < 0.01).4.To distinguish CHF from controls,the area under of Receiver Operating Characteristic curve(AUC)of NT-proBNP,GDF-15,Gal-3 was 0.91,0.851,0.732,respectively.The cut-off of these 3 biomarkers was 1319.89pg/ml,468.3pg/ml,11.57ng/ml,respectively.The sensibility was 0.906,0.858,0.606,respectively;the specificity was 0.879,0.727,0.818 respectively;the sensibility of combined detection of NT-proBNP + GDF-15 was highest(sensibility = 0.929,specificity = 0.879,AUC = 0.95).To distinguish HFp EF from controls,the specificity of combined detection of NT-proBNP + GDF-15 was highest(sensibility = 0.868,specificity = 0.879,AUC = 0.916).To distinguish HFmrEF and HFr EF from controls,the sensibility of NT-proBNP was 0.9 and 0.931,respectively;the specificity was equal to 1.5.The values of troponin,LVEDd and LAD in patients with HFmr EF were significantly higher than that in control group(both P < 0.01);the values of LVEDd and E/e’ were significantly elevated in patients with HFmrEF as compared with HFpEF;while the values of troponin,LVEDd,LAD and E/e’in patients with HFmr EF had no statistical significance compared with HFr EF(both P > 0.05).Conclusions:1.The serum levels of GDF-15,NT-proBNP and Gal-3 can be well reflects severity of CHF,and also be used for clinical assessment of condition of patients with C HF;while the serum level of C ystatin C in CHF group had no statistical significance compared with control group.2.The serum levels of NT-proBNP and GDF-15 can be well reflects severity of diastolic function,and can be used as a good biomarker of diastolic dysfunction.3.Comprehensive assessment of sensitivity,specificity,economic benefits and clinic maneuverability in three biomarkers of HF and combined detection those biomarkers,our study found the best combination of clinical diagnosis for HFpEF and CHF were the NT-proBNP + GDF-15;the best indicator of clinical diagnosis for HF mr EF and HFr EF was NT-proBNP.4.Patients of HFmr EF have a worse systolic and diastolic dysfunction than patients of HFpEF;although the patients of HFmr EF and HFr EF have similar diastolic dysfunction,there are different LVEF. |
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