Heart failure with preserved ejection fraction (HF-PEF) accounts for more than 50% of heart failure cases. To date, medical therapy has failed to show improvements in diastolic dysfunction, cardiac remodelling, or cardiovascular outcomes. As mineralocorticoid receptor activation by aldosterone contributes to the pathophysiology of HF through several different mechanisms, the Aldosterone Receptor Blockade in Diastolic Heart Failure (Aldo-DHF) trial was designed to assess the effects of spironolactone on diastolic dysfunction and exercise capacity in patients with HF-PEF.
Aldo-DHF was a multicenter, prospective, randomised, double-blind, placebo-controlled trial conducted between March 2007 and April 2012. 422 ambulatory patients (mean age 67 years; 52% female) with chronic NYHA class II or III HF, a preserved ejection fraction of 50% or greater, and evidence of diastolic dysfunction, were random assigned to 25mg of spironolactone once daily or matching placebo. The co-primary endpoints were changes in diastolic function (E/e’) on echocardiography and maximal exercise capacity (peak VO2) on cardiopulmonary exercise testing, both measured at 12 months.
While diastolic dysfunction was found to improve in patients taking spironolactone, it worsened in the placebo group (P<.001). In addition, spironolactone induced reverse remodeling (decrease in left ventricular mass) and improved neuroendocrine activation, but did not improve VO2, heart failure symptoms or quality of life.
Long-term aldosterone receptor blockade with spironolactone improved diastolic function but did not affect clinical symptoms or exercise capacity. Therefore, further investigation into the clinical significance of these echocardiographic findings will be required in larger studies.
- Edelmann F, Wachter R, Schmidt AG et al. Effect of Spironolactone on Diastolic Function and Exercise Capacity in Patients With Heart Failure With Preserved Ejection Fraction. The Aldo-DHF Randomized Controlled Trial. JAMA 2013;309:781-91. doi: 10.1001/jama.2013.905.