Therapeutic targets and expectations for the treatment of heart failure

Drug therapy for heart failure holds considerable promise. Direct support of cardiac pumping activity with positive inotropic drugs provides a specific correction for the failing myocardium. Vasodilatation of the systemic arteriolar resistance and venous capacitance systems affords a different but equally rational remedy. Volume and pressure load on the heart is reduced and this augments the pharmacodynamic effects of drugs with positive inotropic activity. For this reason, drugs possessing both pharmacodynamic attributes are an important development in heart failure. The precise clinical targets at which heart failure therapy must be aimed are: (i) relief of symptoms and improvement in quality of life; (ii) reduced risk of morbid events, particularly ventricular arrhythmias; and (iii) extension of survival. Whilst the pathophysiological targets for drug intervention are the same at all stages of the syndrome, expectations of benefit are likely to depend on the stage at which therapy is instituted. In early or mild heart failure, when the patient is not markedly impaired by symptoms, the most that can be expected from treatment is a marginal improvement in quality of life but a major improvement in survival expectancy. In contrast, treatment of severe heart failure may be expected to improve the quality of life substantially by relieving the oppressive symptoms of the advanced syndrome, but only a relatively small increase, if any, in survival. Nevertheless, when the syndrome is terminal, improvement in quality of life carries a clinical priority far in excess of prolonged survival.