Decompensated Heart Failure Is Associated With Reduced Corin Levels and Decreased Cleavage of Pro–Atrial Natriuretic Peptide

BACKGROUND: By promoting salt and water excretion, the corin and the atrial natriuretic peptide (ANP) system should help to maintain fluid balance in heart failure. Yet, the development of fluid retention despite high levels of ANP-related peptides suggests that this compensatory system is limited. METHODS AND RESULTS: Levels of circulating corin (the pro-ANP-converting enzyme) and pro-ANP were measured in hospitalized patients with heart failure, using novel immunoassays. Patients (n=14) had severe heart failure (New York Heart Association class III-IV) with a median ejection fraction of 18% and median brain natriuretic peptide levels of 1940 pg/mL. In heart failure, median plasma corin levels were 7.6-fold lower than measured in plasma from 16 normal control subjects (180 versus 1368 pg/mL, P<0.01). In contrast, in patients with heart failure, levels of plasma N-terminal ANP peptides (N-ANP and pro-ANP) levels were markedly elevated (42.0 versus 7.5 ng/mL, P<0.01). Levels of uncleaved pro-ANP, measured by novel immunoassays, were significantly higher in patients with heart failure (P<0.01), suggesting that corin cleavage of pro-ANP was impaired. Median plasma levels of cyclic guanosine monophosphate were elevated in patients with heart failure (150.0 versus 7.6 pmol/mL, P<0.01), and plasma cyclic guanosine monophosphate levels positively correlated with the fractional amount of cleaved pro-ANP (r(s)=0.59, P<0.03) but not with levels of uncleaved pro-ANP, implying that the cellular response to ANP remained intact. CONCLUSIONS: Taken together, these data suggest that there may be patients for whom low corin levels and impaired pro-ANP cleavage contribute to acute decompensation.