[Neuro-hormonal mechanisms in heart failure -- from physiopathology to treatment]

This review updates some recent advances of a new and exciting developments in basic and clinical cardiology: a) the role, in the congestive heart failure (CHF), of the neurohumoral systems (NHS) which act to maintain circulatory homeostatic equilibrium, and b) the therapeutic implications of such a role. Six NHS, acting in CHF, have presently been identified: three of them induce vasoconstriction and sodium retention (sympathetic nervous systems, renin-angiotensin-aldosterone system and arginine-vasopressine system); the remaining three offset or balance the former ones, acting, therefore as "counterregulators" (prostaglandins--PGE2 and PGI2--, dopaminergic system and atrial natriuretic factor). Each one of these NHS influences the "compensatory" mechanisms of heart failure, acting on the target-organs both by direct effects and by interaction with other NHS; consequently, in heart failure, all the NHS are stimulated with the respective increase in the plasma levels of their active agents. In asymptomatic stages of ventricular dysfunction the stimulation of the vasodilator-and-natriuretic systems appears to be predominant and able to maintain circulatory equilibrium. However, as the heart dysfunction increases and becomes symptomatic, the vasoconstrictor and sodium-retaining forces appear to predominate; this phenomenon becomes increasingly apparent as the functional class becomes more advanced. The hyperstimulation of these last systems has an extremely important role in the pathophysiology and clinical manifestations of congestive heart failure, as well as in its prognosis. Therefore, the attempts to correct these neurohormonal imbalance in patients with heart failure has a sound rational basis, not only to improve the symptoms and the exercise capacity but also to increase the survival of these patients. At the present time, amongst the potential pharmacological interventions acting on NHS in CHF, the blockade of the RAA system with ACE-inhibitors is generally accepted as the most feasible, the safest and the most effective therapeutic tool. In fact, its application has broadened from an earlier use in severe CHF to other symptomatic stages of cardiac failure, including the milder forms. In addition, preliminary data strongly suggest its unique usefulness in asymptomatic phase of ventricular dysfunction. Looking back at the medical therapy of heart failure, in can be concluded that we are starting a new era. Throughout 200 years (since the introduction of digitalis) the therapeutic goal in CHF has been the improvement of symptoms. With the developments of the present decade, a new and exciting goal is being offered to these patients, called by Packer "the second frontier", that is, the prolongation of their lives.