PATHOPHYSIOLOGY AND THERAPY OF HEART-FAILURE, NEW INSIGHTS AND DEVELOPMENTS .1.

During the last decades heart failure has become a syndrome of major concern. Despite a decline in the occurrence of coronary artery disease and improved treatment of systemic hypertension, its primary aetiologic factors, the incidence of heart failure has been ever increasing. It is estimated that in the U.S.A. and most of western Europe approximately 1% of the population suffers from congestive heart failure. Its importance is directly related to its very adverse prognosis with an annual mortality rate as high as 50-60% in the advanced stages of failure. Although treatment with certain vasodilators or converting enzyme inhibitors may improve survival to some extent, the remaining mortality rate still remains high. As it is also extremely difficult to improve the clinical well-being of heart failure patients, emphasis is now on the early phase of failure and in particular on the preceding stage of asymptomatic ventricular dysfunction. Recent animal and human data indicate the significance of myocardial hypertrophy as a first step towards progressive myocardial muscle dysfunction superimposed on the initial cardiac event which leads to asymptomatic ventricular dysfunction. Moreover, there is evidence that neurohumoral activation occurs before heart failure has developed. Although available data only relate to circulating neurohormones, early alterations in local paracrine or autocrine acting systems may well be at issue. Also, whereas heart failure is generally considered a cardiac disorder, there is accumulating evidence that peripheral systems such as the skeletal musculature and the kidney are markedly involved. Changes in peripheral tissue function are not necessarily related to a reduction in cardiac pump function and tissue perfusion, but may be intrinsic of nature. Thus, significant abnormalities in skeletal muscle oxidative metabolism occur which are not secondary to regional flow disturbances. The recognition of cardiac and peripheral changes before or during the early phases of heart failure are likely to alter the current strategies in the treatment of this syndrome.