Application Of ~1H NMR-based Metabonomic Techniques And Echocardiography To Evaluate Myocardial Energy Metabonomics Of Chronic Heart Failure

BackgroudChronic heart failure (CHF) is a complex clinical syndrome characterized by cardiac dysfunction, neuroendocrine activation and abnormal distribution of peripheral flow, which is also a severe stage of several cardiovascular disease. The morbidity, mortality, and the 5-year survival rate of CHF are as high as malignant tumors. CHF can be disabling and severely reduce a patient’s quality of life.Lacking of objective diagnostic standard is one reason of the high mortality. There is no Gold Standard in diagnosis of CHF. The diagnosis mainly base on clinical symptoms and signs. Therefore searching for an objective index that can reflect physiological pathology of CHF is the main problem we currently facing. CHF is a chronic disease, and it can be caused by many factors, such as inflammatory cells and neural hormone. According to these factors, we found a series of new markers, such as BNP/NT-proBNP, inflammatory cytokine (c-reactive protein, tumor necrosis factor alpha and etc) and markers of myocardial injury (Troponin). These new markers developed the diagnosis and treatment of cardiovascular disease. Now, clinical evidence increasingly shows that nerve-hormone theory cannot explain fully development of heart failure. In recent years, people gradually realized that heart failure is a kind of metabolic disease, and myocardial energy metabolism disorders play an important role in the mechanism of CHF. Some drugs to reducing energy consumption and improving myocardial energy metabolism, such as ACEI, beta blockers, polarization fluid, trimetazidine, which were proven to have improved the prognosis of patients with CHF. Therefore, the energy metabolism may become new therapeutic targets of CHF. But so far, a simple and effective method to evaluate myocardial energy metabolism clinically is required. We are going to explore some new objective index using 1H NMR-based metabonomic techniques and echocardiography, which open a new way for evaluating the energy metabolic state of CHF and assessing the efficacy of treatment of energy metabolism accurately.Part one Application of 1H NMR-based metabonomic techniques to analyze serum of patients with Chronic heart failure Objective’H-NMR metabolomic analysis based on metabolic profiling was used to investigate the differences of serum metabolic patterns between patients with chronic heart failure and healthy controls to find tentative serum biomarkers. Based on the findings above, we will try to describe the metabolite changes related to the different phases of CHF. It will provide a novel technological platform for the early diagnosis and the mechanism study of CHF.Methods Pattern recognition methods were used to analyze serum 600 1D 1H-NMR spectra in the total of 37 CHF patient (LVEF≥40%, n=17 and LVEF<40%, n=20) and healthy controls (n=13).Results By using unsupervised PCA and supervised PLS constructed on OSC-filtered NMR data, we could distinguish 1H-NMR spectra of sera from CHF patients and healthy controls; the 1H-NMR spectra of sera from CHF patient(LVEF≥40%) and others(LVEF<40%) also could be discriminated. And the metabonomics difference between CHF and healthy controls at least lies in 15 serum metabolites.Conclusion 1.1H-NMR-based metabonomic approach can distinguish CHF patient(LVEF≥40% and LVEF<40%) from healthy controls; The application of OSC filtration can greatly improve the discrimination performance for the classification; therefore, we can preliminarily evaluate CHF making use of characteristic serum metabolic spectrum.2. We found 15 potential serum metabolites related to CHF. It is contributed to some areas such as screening serum biomarkers, early diagnosis, prognosis and targeted therapy for CHF.Part two Value of Doppler echocardiography derived myocardial energy expenditure measurements in chronic heart failure patientsObjective To evaluate the relationship between myocardial energy expenditure (MEE) level and cardiac function in chronic heart failure(CHF) patients.Methods The total of 99 CHF patients was divided into 3 groups according to the LVEF(LVEF≥50%, n=37; HFREF>35.1%-49.9%, n=30; HFREF≤35%, n=32) or the New York Heart Association (NYHA II, n=26; III, n=42; IV, n=31) criteria. Thirty patients with cardiovascular disease and without CHF served as control. Routine examinations including serum CRP (ELISA) and plasma NT-proBNP (chemiluminescence sandwich ELISA) were made on the next morning after admission, echocardiography were performed on the third day after admission. LVMW, LVMWI, RWT, LVIDd, LA, LV, LVEF, LVFS, E/A, EDT, IVRT, Tei index and MEE were measured or calculated. Results MEE were significantly higher in HFREF patients than in controls (P<0.01), and similar between HFNEF patients and controls (P>0.05). MEE increased in proportion to decrease of LVEF and increase of NYHA grades in CHF patients (all P<0.05). Bivariate analysis confirmed that MEE was significant correlated with LVMW, LVMWI, RWT, LVIDd, LA, LV, LVEF(r=-0.540, P<0.01), LVFS(r=-0.454, P<0.01), E/A, Tei index, NYHA grades, CRP and NT-proBNP.Conclusion MEE derived from standard echocardiographic measurements is an effective indicator for myocardial bioenergetics and significantsy correlated with cardiac function in CHF, especially in CHF patients with reduced LVEF.Part three Association of Myocardial Energy Expenditure Level Obtained from Doppler Echocardiography with Left Ventricular Systolic Function and Remodeling in Primary Hypertension PatientsObjective To investigate the value of myocardial energy expenditure (MEE) for assess left ventricular systolic function and remodeling in primary hypertension patients. Methods The total of 106 hypertensives and 24 normal subjects were recruited. The left ventricular structural and functional parameters were measured by Doppler Echocardiography. Hypertensives were divided into four groups according to left ventricular mass index(LVMI) and relative wall thickness (RWT):normal group (LVN,n=22), concentric remodeling group (LVCR,n=34),concentric hypertrophy group (LVCH,n=26) and eccentric hypertrophy group (LVEH,n=24).The correlation of MEE, circumferential end-systolic wall stress (cESS) and left ventricular structural and functional parameters were analysed.Results The hypertensive patients had significantly higher cESS than controls and they had significantly higher MEE than controls except LVCR.LVCH had the highest cESS and MEE in hypertensive patients. MEE showed significant correlations with indicators of left ventricular systolic function and remodeling in bivariate correlation analysis (all P<0.01).Conclusion MEE obtained noninvasively from echocardiographic measures could reflect different myocardial energy expenditure of different left ventricular patterns,both MEE and cESS may be effective indicators for assessing left ventricular systolic function in primary hypertension.