Role of Cardiac Natriuretic Peptide Testing in Heart Failure

The long-predicted natriuretic and endocrine function of the heart was demonstrated more than 20 years ago (1) by the discovery of atrial natriuretic peptide [atrial natriuretic factor, A-type natriuretic peptide (ANP)]. This led to the description of a family of structurally similar but genetically distinct peptides, constituting the natriuretic peptide (NP) family, which contribute to the maintenance of cardiovascular homeostasis. These looped peptides are the naturally occurring antagonists of the renin-angiotensin-aldosterone system and of the sympathetic nervous system. They promote natriuresis and diuresis, act as vasodilators, and exert antimitogenic effects on cardiovascular tissues.Two members of the NP family, ANP and brain natriuretic peptide [B-type natriuretic peptide (BNP)] are secreted by the hemodynamically stressed heart mainly in response to myocardial stretch induced by volume load. ANP and BNP appear to form a dual, integrated NP system with ANP acting as a rapid-response hormone and BNP as a backup hormone activated only after prolonged ventricular overload. The NP system is activated to its highest degree in ventricular dysfunction and has an important role in maintaining the compensated state of asymptomatic heart failure (HF) and delaying disease progression. The increased plasma ANP and BNP seen in HF patients is not unique: NPs are increased in all patients with edematous disorders, such as renal failure or ascitic liver cirrhosis, that lead to increased atrial tension or central blood volume (2).The NPs are synthesized as preprohormones. The endocrinologically active C-terminal peptides (ANP and BNP) and their N-terminal prohormone fragments are found in plasma. It is uncertain at present whether the proteolytic cleavage of proBNP to N-terminal proBNP (NT-proBNP) 1–76 and BNP (C-terminal 32 amino acids) occurs at the time of secretion or later in the circulation (3). ProBNP is, however, a substrate of the transmembrane serine protease corin, suggesting that proBNP is …