Early Versus Delayed Angiotensin-Converting Enzyme Inhibition in Experimental Chronic Heart Failure Effects on Survival, Hemodynamics, and Cardiovascular Remodeling

Background The efficacy of ACE inhibitors in congestive heart failure (CHF) might be affected by the pathophysiological status present at the onset of treatment. We compared in a rat model the effects of ACE inhibition (lisinopril, 10 mg·kg−1·d−1) initiated early (1 week) or late (3 months) after myocardial infarction (ie, at time points corresponding to moderate or severe CHF without or with established cardiac remodeling). Methods and Results Survival was improved by early treatment at 3 months (from 76% to 95%) and by both early and delayed treatment at 9 months (placebo, 28%; early, 90%; delayed, 61%). Delayed treatment was initiated in a more severe pathophysiological context of CHF than early treatment, illustrated in untreated rats by higher left ventricular (LV) end-diastolic and central venous pressures and by increased LV weight and LV cavity circumference. After 9 months, early and delayed treatments reduced systolic, LV end-diastolic, and central venous pressures. Both treatments also similarl...