Effects Of Larger Dose Of Spironolactone On Ventricular Remodelling In Dilated Cardiomyopathy

Objective: Dilated cardiomyopathy (DCM) is a myocardial disease with high mortality. However, the etiology of dilated cardiomyopathy is not well recognized. Currently, there is specific therapy for DM, and conventional heart failure therapy remains the mainstay in the management of dilated cardiomyopathy. Over past decades we have achieved many advances in the treatment of congestive heart failure (CHF). There is a good body of evidence from randomized clinical trials (RCT) suggest that angiotensin~converting enztme inhibitor (ACEI), diuretics, cardiac glycoside, andβ~blocker combined with small dose of spironolactone (mean 26mg/d) could reverse ventricle remodelling in heart failure, and thus improve quility of life and reduce mortality. Even though, the mobidity and mortality of severe HF remains very high and one year~mortality is higher 50%. In our clinical practice, we found that higher dose of spironolactone is superior over low dose of spironolactone in management of heart failure. Thus, we designed this clincal study to determine the clincial efficacy and safety profile of large of spironolactone in reversing ventrilce remodelling in DCM. Methods: we enrolled 55 DCM patients between 2006 and 2007 hosptalized in our hospital. The diagnosis of DCM was made according to WHO/ISFC DCM diagnostic criteria with serum potassium <5.0mmol/L, and serum Creatine<2.0mg/dL. The patients'age ranged from 21 to 78 ( 36 males, aged 50.1±13.1, and 19 females, aged 43.1±17.4 years). The excluding criteria were: coronary artery disease , severe malignant arrhythmia, acuteinfection, cancer, apoplexy, renal failure, hyperthy roidism, severe hypertension, lung interstitial fibrosis, osteofibrosis, rheumatism and liver cirrhosis. The patients were randmized into two groups, one for smaller dose spironolactone (<40mg/d) and the other for larger dose spironolactone (> 60mg/d). The baseline therapy included hydrochlorothiazide, digitalis ACE inhibitor and Beta~blocker and they were all well matched between two groups at baseline. When hyperkalemia(serum potassium > 5.0 mmol/L) or renal impairment (serum creatine > 2.25 mg/dL) occurred during the study period, we then adjusted the dose of spironolactone to lower dose and added the dose of furosemide to increase renal potassium. If hyperkalemia or renal impairment persisted, the spironolactone was then discontinued.All the patients must fast over 12 hours before the blood samples were collected at 7:00~8:00 in the morning. Before blood sample collection, the patients should lie on bed for at least 15 minutes, and then the blood samples of 4~6mL were collected from median antebrachial vein. After blood samples in the plastic tubes coagulated under room temperature, they were centrifugated at 1500 rpm for 10 minutes. The obtained serum samples were stored at 70℃until assayed.The cardiac function parameter were measured by SONOLINE type ultrasonic diagnostic apparatus (Seimens company, Germany) using a 2.5MHZ frequency linear arrey transducer, which included: Left Ventricular end~systolic diameter (LVESD), Left Ventricular end~diastolic diameter (LVEDD), Left Ventricular fraction (LVEF). Body surface area (BSA) was calculated according to their length and weight,BSA(m2)=〔0.0061×length(cm)+0.0128×Weight(kg)〕~0.01529, at the same time, Left Ventricular end~shrinkable volume(LVEDV), Left Ventricular end~diastolic volume (LVESV) and BSA corrected index (Left Ventricular end ~shrinkable volume index LVESVI) and (Left Ventricular end ~diastolic volume index LVEDVI) were also caculated. SONOLINE technology parameter are all the same in all object.SPSS13.0 software pack were used to analyze all the data. Initially, the homogeneity of variance among all the groups was analyzed. All the measurement data was expressed by mean±standard deviation(SD) and students t test was performed to determine statistical significance. Chi~square test was used for analysis of categorical data. We took p<0.05 as statistical significance.Results:1 The average dose of spironolactone was 80.1±12.6mg/d in larger dose group and 25.5±2.8mg/d in smaller dose group respectively. The dose of spironolactone we used in the study is similar to the dose used in RALES , thus it can be used as a standard contrast in the latter.2 There was one patient died of acute pulmonary infection in larger dose group, whereas no one died in smaller dose group. One patient suffered hyperkaliemia in larger dose group. One patients in larger dose group and one in smaller dose group were lost to followup for the personal reasons.3 The clinial characteristics between two groups including age, CT ratio, NYHA class, LVEF,LVEDVI,LVESVI were well mathced (table 1).4 Serum Creatine,Serum Potasium and Serum Magnesium significantly increased compared with baseline (P<0.01). The patients in large dose of spironolactone had a slightly, but nevertheless statistically significant increase in Serum Creatine,Serum Potasium and Serum Magnesium than those in the smaller dose group at 6 months follow~up (P<0.05). However, they are all in normal limits. There was no significant difference between two groups in the occurrence of hyperkalemia and renal impairment during the study period.5 During 6 months follow~up, CT ratio,LVEF,LVEDVI,LVESVI were all improved in both groups compared with baseline (P<0.01), whereas, the patients in larger dose of spironolactone group had a greater improvement than did the patients in the smaller dose group (P<0.05, Table 3,4) .Conclusion: Severe complications such as severe hyperkaliemia, renal impairment did not increase in larger dose group after adjusting dose of spironolactone and/or adding other diuretics . Compared with the smaller dose of spironolactone, the adverse effects of large dose of spironolactone in Seram Creatine , Serum Potasium and Serum Magnesium were comparable between two groups, they have similar safety profile especially under closely monitoring. It was safe to use the larger dose spirolactone in dilated cardiomyopathy patients. The larger dose spironolactone was superior over lower dose of spironolactone in reversing the ventricular remodeling and improving cardiac systolic function.