Myocardial infarction (MI) induces severe structural and functionnal changes of the left ventricle (LV) leading to heart failure (HF). The gold-standard treatment in HF patients with reduced ejection fraction (HFrEF) combines aldosterone antagonists such as spironolactone (SPI), ACE-inhibitors such as lisinopril (LIS) and β-blockers such as atenolol (ATE), to improve cardiac function and reduce morbi-mortality. Despite its beneficial effects, the initiation period of such treatment seems to play a major role on the kinetics of heart failure following MI.

We evaluated the cardiac outcomes of a combination therapy introduced at 2 time points on rats presenting MI.

After MI, treated rats [SPI (10mg.kg-1.d-1), LIS (1mg.kg-1.d-1) and ATE (1mg.kg-1.d-1)] were divided into 2 groups: treatment started either 1 day (early) or 1 month (late) after MI. Longitudinal follow-up of LV remodeling and function was assessed by Echocardiography-Doppler every month during 4 months. LV fibrosis was quantified with picrosirius red staining.

Early treatment did not induce beneficial cardiac effects, whereas late treatment significantly improved cardiac function from 2 months, as shown by the increased EF (+19%), and persists over time. It was associated after 3 months with a significant beneficial decrease in the E/A ratio (−44%), a marker of diastolic function. Compared with MI, late combination therapy also prevented LV remodeling, as shown by a significant decreased LV dilation (−7%) and cardiac fibrosis (−30%).

Only late management of MI by combination therapy had a cardioprotective effect on cardiac function and remodeling. These findings raise the pivotal role of early adaptive cardiac remodeling following MI.