Determinants of the beneficial effect of mineralocorticoid receptor antagonism on exercise capacity in heart failure with reduced ejection fraction

Abstract

Background: The determinants of the impact of mineralocorticoid receptor antagonism (MRA) on exercise tolerance in heart failure with reduced ejection fraction (HFrEF) have not been sufficiently characterised.
Aim: We sought to investigate the factors associated with improvement in exercise capacity following the introduction of spironolactone to therapy in HFrEF patients, as well as to assess the association between improvement in exercise capacity and changes in cardiac functional characteristics with treatment.
Methods: In 120 patients (age 62 ± 11 years) with stable chronic HFrEF, remaining on optimal pharmacotherapy, spironolactone 25 mg/d was added to treatment. Echocardiographic assessment, including myocardial deformation, and treadmill exercise tests were performed at baseline and at six-month follow-up.
Results: According to the functional improvement at follow-up, patients were stratified into two groups: with increase in exercise capacity > 20% (IMPRpos, n = 68) and < 20% (IMPRneg, n = 52) of the baseline value. The IMPRpos subset demonstrated significantly larger improvement in left ventricular systolic and diastolic functions at follow-up, as assessed by global longitudinal deformation (GLS), ejection fraction, and tissue e’ velocity. Functional improvement > 20% was independently predicted by diabetes (odds ratio [OR] 5.62, p = 0.011), estimated glomerular filtration rate (OR 0.95, p = 0.008), and B-type natriuretic peptide (BNP) at baseline (OR 0.54, p = 0.027), and associated with increase in GLS at follow-up (OR 1.40, p = 0.019).
Conclusions: In patients with HFrEF, improvement in exercise capacity in response to the addition of spironolactone to treatment is more evident in the presence of diabetes, decreased renal function and lower BNP, and improvement in GLS is a contributor to this beneficial effect of MRA.