Monitoring B-type natriuretic peptide in patients undergoing therapy with neprilysin inhibitors. An emerging challenge?
B-type natriuretic peptide (BNP) is primarily synthesized by the ventricles of the heart as a 108-amino acid polypeptide precursor (i.e., proBNP), which is then cleaved into a 76-amino acid biologically inert N-terminal fragment (NT-proBNP) and a biologically active 32-amino acid peptide (BNP). The generation of BNP is considerably enhanced in response to high ventricular filling pressures, so that the measurement of either the active hormone or NT-proBNP has become a mainstay in patients with congestive heart failure. Recent evidence was brought that the enzyme neprilysin efficiently degrades circulating BNP in vivo, whereas proBNP and NT-proBNP are virtually resistant to enzymatic cleavage. Increasing emphasis is currently placed on the fact that that measuring BNP in patients taking the novel and promising neprilysin inhibitors such as LCZ696 may not reliably reflect cardiac dysfunction. Since laboratory monitoring in patients with heart failure should be aimed to define the role of BNP in modulating fluid hemostasis and cardiac remodeling, but natriuretic peptides should also serve as reliable biomarkers of cardiac function and treatment response in these patients, the assessment of neither BNP nor NT-proBNP alone provides a comprehensive biological and clinical picture. Therefore, it seems reasonable to suggest both BNP and the neprilysin-resistant peptide NT-proBNP should be concomitantly assessed in patients with heart failure who take neprilysin inhibitors, so allowing to concomitantly monitor the progression of heart failure and to assess the actual cardiorenal potency of circulating BNP.
Section of Clinical Biochemistry, University of Verona, Verona, Italy. Electronic address: giuseppe.lippi@univr.it.
Giuseppe
G
Lippi
Research Institute Hospital 12 de Octubre ('i+12'), Madrid, Spain.
Fabian
F
Sanchis-Gomar
D000613:Aminobutyrates / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001713:Biphenyl Compounds; D004338:Drug Combinations; D016903:Drug Monitoring / Q000639:trends*; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy; D006801:Humans; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D015260:Neprilysin / Q000037:antagonists & inhibitors* / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D000068756:Valsartan
D000613:Aminobutyrates; D001713:Biphenyl Compounds; D004338:Drug Combinations; D010446:Peptide Fragments; D013777:Tetrazoles; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D000068756:Valsartan; D015260:Neprilysin; C549068:sacubitril and valsartan sodium hydrate drug combination
B-type natriuretic peptide; BNP; Heart failure; Neprilysin