Abstract 5930: The Effect of Spironolactone on Myocardial Structure and Function Measured by Echocardiography in Patients with Early Stage Chronic Kidney Disease

Abstract

Introduction Early stage chronic kidney disease (CKD) is associated both with a high rate of adverse cardiovascular events and abnormal myocardial structure and function. Activation of the renin-angiotensin-aldosterone system is common in CKD and may result in adverse inflammatory, fibrotic and hypertrophic effects upon the heart and vasculature. Treatment with ACE inhibitors and ARBs frequently fails to suppress aldosterone production. We hypothesized that addition of the aldosterone antagonist spironolactone to ACE Inhibitors and ARB’s might reduce left ventricular (LV) mass and improve systolic and diastolic function measured by echocardiography. Methods One hundred and seventeen patients with stage 2 and 3 CKD, controlled hypertension (<130/85mmHg) and no history of cardiovascular disease or diabetes were recruited in to a double blind placebo controlled trial. After an active 4 week run in of spironolactone 25mg daily, patients were randomized to continue this treatment or receive placebo for a further 36 weeks. Echocardiographic assessment of LV mass, systolic and diastolic LV function was performed before run in and after 40 weeks of treatment. Results Compared to placebo, spironolactone reduced LV mass (mean (SD) −10g ± 10 vs.+3g ± 13, p<0.01). There was an improvement in LV Tei Index (−0.08 ± 0.1 vs. −0.001 ± 0.1, p<0.01) and mean basal long axis annular systolic velocities (Sm +1.4cm/s ± 1.9 vs. +0.1cm/s ± 1.1, p<0.01) but no difference in ejection fraction (+3% ± 5 vs.+2% ± 7). Transmitral E/A filing ratio (E/A +0.3 ± 0.3 vs −0.02 ± 0.2, p<0.05), basal annular early myocardial diastolic velocities (Ea +0.5cm/s ± 2.1 vs. −0.3cm/s ± 2.1, p<0.05), E/Ea ratio (−0.7 ± 1.9 vs. 0.1 ± 2.0, p<0.05), and colour flow propogation velocities (+8.7 ± 16.3 vs. −0.1 ± 16.6, p<0.05) were all improved. Systolic blood pressure was reduced with spironolactone but was not an independent predictor of change in any echocardiographic parameters. Conclusion Treatment with spironolactone reduced LV mass and improved both systolic and diastolic LV function. These data suggest that aldosterone plays an important role in cardiovascular disease in CKD and provides support for a clinical outcome trial investigating the use of aldosterone inhibitors to reduce cardiovascular risk.