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Over the past 100 years, cardiovascular disease has become a leading cause of morbidity and mortality worldwide. A tremendous increase in incidence and prevalence of heart failure has been observed in the United States. The cost of managing heart failure itself is $56 billion a year, 70% of which is due to hospitalization. Although we have made tremendous advances in our understanding of the pathophysiology and treatment of congestive heart failure, the diagnosis of the disease still remains difficult. Unfortunately, the signs and symptoms of congestive heart failure are nonspecific. The recognition of the role of B-type natriuretic peptide as an objective marker for the diagnosis, severity, and prognosis of acute coronary syndromes and congestive heart failure was truly a breakthrough for clinicians and patients faced with cardiovascular disease. Also, the high levels of endogenous B-type natriuretic peptide may be released as a“distress hormone” that is, these levels are no longer effective in maintaining the balance of vasoconstriction and vasodilation. Hence it makes intuitive and practical sense that giving back B-type natriuretic peptide in the form of exogenous nesiritide might restore neurohormonal homeostasis. Therefore, lately there has been a lot of interest shown in the use of recombinant B-type natriuretic peptide as a drug. This article reviews the literature concerning the use of these peptides in a variety of clinical scenarios and the use of recombinant B-type natriuretic peptide in decompensated heart failure.