Impact of Spironolactone on Endothelial Function in Patients with Single Ventricle Heart

Abstract

Mid-term survivors of the Fontan procedure are at risk for progressive heart failure, and endothelial dysfunction is thought to contribute to this process. Aldosterone antagonism has been shown to improve survival in adults with heart failure and the effects are mediated in part by changes in endothelial function. In the present study, we sought to determine if a short course of spironolactone improves endothelial function and alters serum cytokine profiles in adolescents and adults with single ventricle heart. Subjects had baseline assessment of flow-mediated dilation and cytokine profiles (C-reactive protein, interleukin-6, interleukin-1b, interleukin-10, tumor necrosis factor-alpha). They were started on spironolactone 25 mg once a day and uptitrated to 50 mg once daily. After 4 weeks, flow-mediated dilation and cytokine profiles were re-evaluated. Ten subjects (median age 28 years) were enrolled and completed the protocol. The median flow-mediated dilation at baseline was 9.1% and did not change significantly after 4 weeks of spironolactone 7.6%, P = .46. There was mild elevation in serum cytokine profiles and only interleukin-1b decreased significantly with therapy, 0.39 to 0.23 pg/mL, P = .04. In this small study, a short course of spironolactone did not improve endothelial function or alter the majority of serum cytokine levels. Whether single ventricle patients might realize other potential benefits of aldosterone antagonism such as reduced cardiac fibrosis remains to be determined.