Objective: Congestive heart failure is a complex clinical syndrome. It is the severe stage of all kinds of heart diseases. The morbidity rate is high and survival rate is similar with cancers in 5 years. A large number of researches have shown that during heart failure, the long and excessive activation of neuro-endocrine system is an important cause for the further deterioration of chronic heart failure. Aldosterone plays an important role in the pathophysiology of heart failure. Aldosterone promotes the retention of sodium and water, the loss of potassium, myocardial fibrosis, ventricular remodeling, baroreceptor dysfunction and sympathetic activation. Aldosterone-receptor blocker can inhibit the harmful roles of aldosterone. In the Randomized Aldosterone Evaluation Study (RALES), spironolactone (26mg/d) was shown to reduce the mortality and improve cardiac function of CHF patients who had already received routine therapy including diuretics, digoxin , ACEI andβ-blocker. We have tried to use larger dosage of spironolactone(≥60mg/d) to treat the severe CHF patients and received well curative effect. The aim of this study is to observe the changes of heart rate variability(HRV), ventricular remodeling and biochemical parameters after intervention with larger and smaller dosage of spironolactone respectively, and to explore the effects of larger dosage of spironolactone on autonomic nervous system, and to analyze the condition of safety using sprinolactone in larger dosage.Methods: Sixty patients with CHF (27 men and 33 women, age from 56 to 75, mean age 64.38±4.98 years) were recruited, including ischemic heart disease, idiopathic dilated cardiomyopathy and hypertensive heart disease. All patients had New York Heart Association(NYHA)Ⅲ～Ⅳclass, Left Ventricular Ejection Fraction(LVEF)≤35% and Left Ventricular End-Diastolic Diameter(LVEDD) >55mm. and excluding following patients: acute coronary syndrome, non-sinus cardiac rhythm, sinoatrial block,second-degree or third-degree atrioventricular block, bundle branch block or WPW syndrome , severe malignant arrhythmia, severe hypertension, primary operable valvular heart disease, congenital heart disease, diabetes mellitus, hyperthyroidism, severe liver or renal dysfunction, serum potassium >5.0mmol/L, creatine >2.5mg/dl, cancer, apoplexy or any life-threatening disease. All patients received routine therapy, including furosemide or hydrochlorothiazide, digoxin, ACEI or angiotensinⅡrecepter blocker (ARB) and/orβ-blocker, the patients stable for at least two weeks. Spironolactone was not permitted before the study.The patients were randomly assigned to smaller dosage spironolactone group (≤40mg/d) and larger dosage spironolactone group (≥60mg/d). There were 30 patients in each group. Diuretics or potassium supplements were recommended according to the level of serum potassium and water retention, all cardioactive drugs were unchanged during the study. No patients withdrawn from the study unless they had severe adverse events. The dosage of spironolactone has been reduced or diuretics adjusted if serum potassium is more than 5.0 mmol/L. Patients were withdrawn from the study if serum potassium is more than 6.0 mmol/L or creatine is more than 4 mg/dL during the intervention. HRV and cardiac function parameters were measured at baseline、3 and 6 months after intervention, respectively. Serum electrolytes and creatinine were measured at baseline and 1、2、3 weeks and 1、3、6 months, respectively.Time domain analysis was performed using twenty-four hour continuous ECG recordings. The main time domain analysis parameters included:①standard deviation of all normal sinus R-R intervals over 24 hours (SDNN);②standard deviation of the averaged normal sinus R-R intervals for all 5-minute segment (SDNN);③the root mean square of differences of successive R-R intervals (rMSSD);④percentage of successive nomal sinus R-R interval longer than 50ms (PNN50).Frequency domain analysis was performed using ECGlab 2.0. The main parameters included low-frequency(LF)、 high-frequency(HF) and LF/HF.The cardiac function parameters were measured by SONOLINE type ultrasonic diagnostic apparatus (Seimens Company, Germany) using a 2.5MHZ frequency linear arrey transducer, including Left Ventricular End-Systolic Diameter (LVESD)、Left Ventricular End-Diastolic Diameter (LVEDD)、Left Ventricular Ejection Fraction (LVEF)、Left Ventricular Posterior Wall Thickness (LVPWT) and Intraventricular Septation Thickness (IVST). Body surface area (BSA) was calculated according to their height and weight, and Left Ventricular Mass Index (LVMI) was calculated according to Devereux Formula, at the same time, to caculate Left Ventricular End-Systolic Volume Index (LVESVI) and Left Ventricular End-Diastolic Volume Index (LVEDVI).SAS V8 software pack was used to performed all the data statistical-analysis.Chi-square test was used to analyze categorical data. Measurement data was normal distribution and homoscedasticity was denoted by mean±standard deviation (SD), student t-test was used to analyze the comparison between two groups and paired t-test was used to analyze the comparison within the group. We take p0.05), and comparable with each other(Table1).4 Time domain analysis parameters after 3 months and 6 months of therapy: SDNN、SDANN、rMSSD、PNN50、and frequency domain analysis parameter HF were significantly improved compared with baseline in both groups (P0.05).5 After 3 months and 6 months of therapy, LVEF, LVMI, LVEDVI and LVESVI were all improved compared with baseline in both groups (P0.05). After 6 months of therapy, though serum potassium and creatine increased more in larger dosage group than in smaller dosage group (P0.05) (Table4). Two patients developed gynecomastia in larger dosage group while none in smaller dosage group, but there was not statistical difference in two groups.(P>0.05).Conclusion: Compared with the smaller dosage, the larger dosage spironolactones was better in increasing HRV of the CHF patient, and improving autonomic nervous system function and ventricular remodeling. Although larger dosage spironolactone can increase serum potassium, magnesium and creatine, renal dysfunction and severe high potassium were not found. The adverse events of gynecomastia did not increase markedly in larger dosage group compared with the smaller dosage group. So it was safe to use the larger dosage spirolactone in the patients with medium or severe heart failure if only observing the patients carefully , monitoring frequently and using the smaller dosage ACEI and adjusting the duretics dosage correctly.