Abstract 15838: Atrial Natriuretic Peptide Compensatory Response is Impaired in Human Acute Decompensated Heart Failure

Abstract

Atrial and B-type natriuretic peptides (ANP and BNP) are cardiac hormones secreted as compensatory measures to preserve cardiorenal homeostasis. Treating heart failure (HF) with sacubitril/valsartan increased ANP and not BNP, suggesting the ANP system may confer therapeutic benefit. Thus, the presence of an ANP deficient subgroup of HF patients possibly posing higher risk for HF severity, underscores a need to characterize both, the biologically active and inactive (NT-proANP and NT-proBNP) natriuretic peptides (NPs)(latter resistant to degradation), to highlight the extent of NP production in HF. Characterizing neprilysin (NEP) activity may also provide insights into the degree of NP degradation in HF. This study aims to both highlight the cardiac NP response in acute decompensated HF(ADHF) by measuring molecular forms of ANP and BNP together with defining circulating soluble NEP activity as to assess mechanisms impairing the NP response in HF. We recruited 47 healthy individuals with neither cardiovascular nor metabolic disease and compared ANP, BNP, NT-proANP, NT-proBNP, and NEP activity levels with 107 recruited ADHF patients. In ADHF, compared to a healthy setting, median ANP, BNP, NT-proANP, and NT-proBNP were all elevated (15.7 vs. 118.1 pg/mL , p<0.0001; 23 vs. 515 pg/ml, p<0.0001; 60.1 vs. 651.6 pg/mL, p<0.0001; 46 vs. 3330 pg/mL, p<0.0001, respectively). However, circulating NEP activity was significantly lower in ADHF than in healthy circulation (32 vs. 12.3 nM/mL/min, p<0.0001). NPs did not correlate with NEP activity in healthy circulation. However, only ANP (r = 0.4788, p<0.0001) and NT-proANP (r = 0.6819, p<0.0001) correlated with NEP activity in ADHF. The presence of an impaired ANP response in ADHF, underscored by insufficient increases in NT-proANP than NT-proBNP, suggests decreased ANP production may induce not only an ANP deficient ADHF state, but be characteristic of ADHF. The presence of NEP activity in ADHF circulation, despite lower NEP activity compared to healthy individuals, suggests ANP degradation may second impaired production, further lowering ADHF ANP levels. Our studies support augmenting the ANP system in ADHF through either endogenous stimulation or exogenous supplementation as optimal therapeutic strategies.