NCT01176968.

Aims: Spironolactone improves prognosis in severe heart failure (HF). We investigated its effects in patients with mild-moderate HF treated with an ACE inhibitor and beta-blocker. Methods and results: Randomised, double-blind, parallel-group, 3-month comparison of placebo and spironolactone (25 mg daily) in 40 patients in New York Heart Association (NYHA) class I (20%), II (70%) or III (10%), with a left ventricular ejection fraction of b 40%.The mean (standard error) changes from baseline in the spironolactone and placebo groups were, respectively: i) B-type natriuretic peptide (BNP) − 53.4(22.2) pg/mL and + 3.3(12.1) pg/mL, P = 0.04, ii) pro-collagen type III N-terminal amino peptide (PIIINP) −0.6(0.2) μmol/L and + 0.02(0.2) μmol/L, P = 0.02 and iii) creatinine + 10.7(3.2) μmol/L and −0.3(2.6) μmol/L, P = 0.01.Compared with placebo, spironolactone therapy was associated with a reduction in self-reported health-related quality of life: change in visual analog score: −6 (3) vs. + 6 (4); P = 0.01.No differences were observed on other biochemical, neurohumoral, exercise and autonomic function assessments. Conclusion: In patients with mild-moderate HF, spironolactone reduced neurohumoral activation (BNP) and a marker of collagen turnover (PIIINP) but impaired renal function and quality of life. The benefit-risk ratio of aldosterone blockade in mild HF is uncertain and requires clarification in a large randomised trial.

Objective-To examine long term morbidity and mortality following atrial inflow corrective procedures for transposition of the great arteries (TGA) and to investigate factors that influence morbidity and mortality.

1 Calcium antagonists reduce myocardial contractility in vitro. Nicardipine is a dihydropyridine derivative with enhanced selectivity for vascular smooth muscle. 2 We have studied the pharmacokinetics and the haemodynamic effects that occur in man following bolus intravenous administration of nicardipine. 3 Ten normotensive male subjects received either nicardipine or placebo i.v., allocated in a randomised double-blind manner, over 60 s 4 Plasma nicardipine concentration, blood pressure, heart rate, and systolic time intervals were measured before dosing and at frequent intervals between I and 360 min post dosing. 5 At 160 jug kg-', adequate plasma levels of nicardipine were obtained to permit analysis of individual pharmacokinetic variables, and significant and consistent haemodynamic effects were seen. 6 After injection ofnicardipine, systolic BP and the QS2 (measure of total electromechanical systole) and QT intervals were not altered. 7 The changes in BP and heart rate were consistent with arteriolar vasodilatation. 8 The changes in PEP and LVET suggest an increase in cardiac contractility, which is unlikely to be a direct effect of nicardipine on the myocardium but rather a result of afterload reduction. 9 The close correlation of nicardipine plasma level with haemodynamic effect should permit accurate dose titration. 10 The net increase in contractility should allow nicardipine to be administered safely with fi-adrenoceptor blocking drugs.Keywords blood pressure calcium antagonist heart rate nicardipine systolic time intervals concentration effect modelling