NPPB and heart failure: In heart failure, proBNP, the precursor of mature BNP, is the predominant circulating form and lacks significant GC-A activating properties compared to BNP.84 More recently, studies have revealed the presence of glycosylation of ANP, resulting in a molecular form with reduced GC-A activation.85 The presence of altered molecular forms of ANP and BNP with reduced cGMP production supports the use of native and designer synthetic NPs to rescue these NP structural abnormalities.