Heart failure, ventricular remodelling and the renin-angiotensin system: insights from recently completed clinical trials.

Abstract

Increased insight has been gained into the pathophysiology of heart failure, which is now recognized as a milieu created by specific diseases that cause myocardial dysfunction resulting in haemodynamic abnormalities. Subsequent compensatory circulatory and hormonal changes cause substantive metabolic derangement, and it is the haemodynamic and metabolic abnormalities that produce the congestive and low cardiac output symptoms and physical findings associated with heart failure. One of the earliest abnormalities noted in the failing heart is activation of the renin-angiotensin-neurohormonal axis. This is associated with both dilation and hypertrophy of the left ventricle. This remodelling may be regulated, at least in part, by myocardial tissue angiotensin-converting enzyme systems. Clinical drug trials in patients with heart failure have demonstrated that certain agents reduce mortality and interdict detrimental hormonal activity and remodelling. The Veterans Administration's (VHEFT-I and II) and Scandinavian (CONSENSUS-I) heart failure trials, as well as Studies of Left Ventricular Dysfunction (SOLVD) and the post myocardial infarction captopril trial (SAVE--Survival and Ventricular Enlargement) indicate that vasodilators and, in particular, angiotensin-converting enzyme inhibitors, decrease heart failure mortality. Furthermore, diminution in morbidity measured as a reduction in hospitalization for congestive heart failure or myocardial infarction was a dramatic beneficial effect noted even in relatively asymptomatic patients with left ventricular dysfunction. Importantly, in the SOLVD and SAVE trials, the diminution in major ischaemic events observed in the treatment groups were noted whether drug was started one week (SAVE) or one year (SOLVD) post infarct.(ABSTRACT TRUNCATED AT 250 WORDS)