The effect of spironolactone on diastolic function in haemodialysis patients

Abstract

Heart failure with preserved ejection fraction (HFpEF) is highly prevalent in patients on maintenance haemodialysis (HD) and lacks effective treatment. We investigated the effect of spironolactone on cardiac structure and function with a specific focus on diastolic function parameters. The MiREnDa trial examined the effect of 50 mg spironolactone once daily versus placebo on left ventricular mass index (LVMi) among 97 HD patients during 40 weeks of treatment. In this echocardiographic substudy, diastolic function was assessed using predefined structural and functional parameters including E/e'. Changes in the frequency of HFpEF were analysed using the comprehensive 'HFA-PEFF score'. Complete echocardiographic assessment was available in 65 individuals (59.5 ± 13.0 years, 21.5% female) with preserved left ventricular ejection fraction (LVEF > 50%). At baseline, mean E/e' was 15.2 ± 7.8 and 37 (56.9%) patients fulfilled the criteria of HFpEF according to the HFA-PEFF score. There was no significant difference in mean change of E/e' between the spironolactone group and the placebo group (+ 0.93 ± 5.39 vs. + 1.52 ± 5.94, p = 0.68) or in mean change of left atrial volume index (LAVi) (1.9 ± 12.3 ml/m2 vs. 1.7 ± 14.1 ml/m2, p = 0.89). Furthermore, spironolactone had no significant effect on mean change in LVMi (+ 0.8 ± 14.2 g/m2 vs. + 2.7 ± 15.9 g/m2; p = 0.72) or NT-proBNP (p = 0.96). Treatment with spironolactone did not alter HFA-PEFF score class compared with placebo (p = 0.63). Treatment with 50 mg of spironolactone for 40 weeks had no significant effect on diastolic function parameters in HD patients.The trial has been registered at clinicaltrials.gov (NCT01691053; first posted Sep. 24, 2012).

Keywords: Diastolic function; E/e’; Echocardiography; HFpEF; Haemodialysis; Spironolactone.

Conflict of interest statement

Tobias Hauser, Vivien Dornberger, Uwe Malzahn, Sören Grebe, Dan Liu, Matthias Nauck, Nele Friedrich, Marcus Dörr, Vera Krane and Fabian Hammer declared no conflicts of interest. Stefan Störk reported grants from the German Ministry for Education and Research, research grants from Bayer and Boehringer and speaker honoraria/consultation fees from Astra Zeneca, Bayer, Boehringer, Novartis, Pfizer, Sanofi, Servier, all outside the submitted work. Christoph Wanner received grant support and honoraria outside of the present trial from Boehringer-Ingelheim, Idorsia and Sanofi-Genzyme and honoraria from AstraZeneca, Bayer, Chiesi, FMC, GILEAD, GSK, Lilly, MSD and Vifor.

Figures

Fig. 1

Echocardiographic assessment of cardiac remodelling and diastolic dysfunction in three exemplary female ESKD patients with preserved ejection fraction. Upper, middle, and lower panels respectively show apical 4-chamber view (upper panel), pulsed-wave Doppler evaluated diastolic filling pattern (middle panel), and tissue Doppler early diastolic mitral annular velocity (e´, lower panel). a Apparently healthy heart, LVMi = 59 g/m2, LVEF = 72%, LAVi = 33 ml/m2, E/e’ = 8.9 b Beginning LV hypertrophy and mild diastolic dysfunction, LVMi = 103 g/m2, LVEF = 61%, LAVi = 53 ml/m2, E/e’ = 12.6 c Severely enlarged LV and severely impaired diastolic function, LVMi = 147 g/m2, LVEF = 67%, LAVi = 56 ml/m2, E/e’ = 33.0

Fig. 2

a Change in E/e’ after 40 weeks of treatment with spironolactone or placebo (p = 0.68) b Change in left atrial volume index (LAVi) after 40 weeks of treatment with spironolactone or placebo (p = 0.89) Whiskers represent 95% CI

Fig. 3

Mean change in LVMi by LVMi at baseline after 40 weeks of treatment with spironolactone compared to placebo (p = 0.72)

Fig. 4

Changes in the HFA-PEFF score class after 40 weeks of treatment with spironolactone or placebo (p = 0.63)