Heart failure and angiotensin converting enzyme inhibition: Problems and perspectives

Heart failure has become the most widely studied syndrome in cardiology ove r the recent years. Despite the encouraging achievements by angiotensin con verting enzyme (ACE) inhibitors, the mortality of patients with chronic hea rt failure remains high. There are several factors which can potentially be responsible for the fact that about 80% of patients with a failing heart d efy protection by ACE inhibitors: different activation of tissue and system ic renin-angiotensin system (RAS) in a particular heart disease and the dis tinct ability of various ACE inhibitors to block cardiac ACE, alternative p athways for angiotensin II formation (chymase), genetic polymorphism of the RAS system and the complexity of neuroendocrine activation. Moreover, chro nic heart failure can provoke disturbances in the reactivity of peripheral vessels and metabolism of striated muscles. These factors may then potentia te the vicious circle of heart failure. New therapeutic approaches, which c ould further reduce the mortality in patients with heart failure involve an giotensin II type I receptor antagonists, beta-blockers, aldosterone antago nists and blockers of the endothelin receptor. A number of questions associ ated with functions of the RAS still remain open and their solution could b e of substantial benefit for patients with a failing heart.