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 pathophysioloical status present at the onset of treatment. We compared in a rat model the effects of ACE inh ibition (lisinopril, 10 mg . kg(-1). d(-1)) initiated early (1 week) o r late (3 months) after myocardial infarction (ie, at time points corr esponding to moderate or severe CHF without or with established cardia c remodeling). Methods and Results Survival was improved by early trea tment at 3 months (from 76% to 95%) and by both early and delayed trea tment at 9 months (placebo, 28%; early, 90%; delayed, 61%). Delayed tr eatment was initiated in a more severe pathophysiological context of C HF than early treatment, illustrated in untreated rats by higher left ventricular (LV) end-diastolic and central venous pressures and by inc reased LV weight and LV cavity circumference. After 9 months, early an d delayed treatments reduced systolic, LV end-diastolic, and central v enous pressures. Both treatments also similarly decreased LV weight, L V cavity circumference, and LV collagen density. Conclusions In this r at model of CHF, early and delayed ACE inhibitor treatments both incre ase survival and exert similar beneficial effects on cardiac hemodynam ics and remodeling. Although early treatment prevents the development of ventricular dysfunction and remodeling, delayed treatment is capabl e of reversing cardiac hypertrophy and remodeling, as well as ventricu lar dysfunction. Thus, ACE inhibitors exert marked beneficial effects even when treatment is initiated late into the evolution of heart fail ure (ie, at a time of established ventricular dysfunction and remodeli ng).