Effect of canrenone on left ventricular mechanics in patients with mild systolic heart failure and metabolic syndrome: The AREA-in-CHF study

Abstract

Background and aim We analyzed the effect of the mineralocorticoid receptor antagonist canrenone on LV mechanics in patients with or without metabolic syndrome (MetS) and compensated (Class II NYHA) heart failure (HF) with reduced ejection fraction (EF ≤ 45%) on optimal therapy (including ACE-i or ARB, and β-blockers). Methods and results From a randomized, double-blind placebo-controlled trial (AREA-in-CHF), patients with (73 on canrenone [Can] and 77 on placebo [Pla]), based on modified ATPIII definition (BMI ≥ 30 kg/m 2 instead of waist girth) or without MetS (146 by arm). In addition to traditional echocardiographic parameters, we also evaluated myocardial mechano-energetic efficiency (MME) based on a previously reported method. At baseline, Can and Pla did not differ in age, BMI, blood pressure (BP), metabolic profile, BNP, and PIIINP. Compared with MetS-Pla, and controlling for age, sex and diabetes, at the final control MetS-Can exhibited increased MME, preserved E/A ratio, and decreased atrial dimensions (0.04 < p < 0.0001). At baseline, degree of diastolic dysfunction was similar in MetS-Can and MetS-Pla but after 12 months, diastolic function improved in MetS-Can, compared to MetS-Pla ( p < 0.002): moderate-to-severe diastolic dysfunction decreased from 26% to 12% with canrenone whereas it was unchanged with placebo (both 26%). Can, but not Pla, reduced BNP in both patients with or without MetS ( p < 0.0001). Conclusions Treatment with canrenone given on the top of optimal therapy in patients with MetS and chronic, stabilized HF with reduced EF, protects deterioration of MME, improves diastolic dysfunction and maximizes the decrease in BNP.