NEUROHORMONES IN PATIENTS WITH ISCHEMIC LEFT-VENTRICULAR DYSFUNCTION

Measurements of plasma neurohormones in patients with left ventricular dysfunction are generally performed for research purpose rather than for diagnostic purpose or to guide therapy. These studies have shown t hat in patients with left ventricular dysfunction, several neurohormon al systems were activated, even in the absence of symptoms of congesti ve heart failure. This suggested that the cardiovascular system was no t in a steady state and pointed out potential culprits for the progres sion of the disease. It has also been shown that the levels of several of these markers, particularly plasma norepinephrine, had an importan t prognostic value. Another value of neurohormonal studies obviously i s the design of new therapeutic approaches aimed at improving symptoms and prognosis. In this respect, important therapeutic successes have been obtained with agents that interfere with the actions of some of t hese neurohormonal systems, such as with the use of the angiotensin-co nverting enzyme (ACE) inhibitors, particularly captopril and enalapril , and to a lesser extent, with beta-blockers. It can therefore be expe cted that, in the future, most patients with severe ischemic dysfuncti on will be treated with an ACE inhibitor. Nonetheless, neurohormonal c ontrol is not complete with these drugs; powerful vasoconstrictor forc es, such as endothelin-1, remain activated, and an escape of angiotens in II from the control of ACE inhibition may exist. Thus, morbidity (e .g., progression towards congestive heart failure and angina pectoris) and mortality remain high despite treatment with ACE inhibitors. In t he search for further improvements, the new generation of long-acting dihydropyridines is worth considering. Their afterload reducing action , coupled with powerful coronary vasodilation, might hypothetically de lay the progression of ischemic LV dysfunction. In addition, the impro ved pharmacokinetic profile of these drugs avoiding wide peak and trou gh variations in plasma levels may avoid triggering some neurohormonal reflexes.