Dataset Information

Efficacy of exogenous atrial natriuretic peptide in patients with heart failure with preserved ejection fraction: deficiency of atrial natriuretic peptide and replacement therapy.

ABSTRACT:

Aims

Exogenous atrial natriuretic peptide (ANP) may be a logical treatment for heart failure (HF) patients with ANP deficiency. Lower ANP concentrations may result from HF with preserved ejection fraction (HFpEF), which also results in lower brain natriuretic peptide levels in HFpEF relative to HF with reduced ejection fraction (HFrEF), although clinical features regarding circulating ANP in HFpEF and HFrEF have not been fully investigated during acute HF. Here, we characterized the differential regulation of circulating ANP and the efficacy of exogenous ANP (carperitide) in patients with acute HF, especially HFpEF.

Methods and results

Serum ANP levels before treatment and the diuretic effect of 0.0125 ?g/kg/min of carperitide alone for the first 6 h were prospectively evaluated in 113 patients with acute HF who were divided into two groups: HFpEF vs. HFrEF. We mainly analysed the impact of baseline ANP levels and the presence of HFpEF on the diuretic effect of exogenous ANP. There was an inverse relationship between ANP levels and the diuretic effect of exogenous ANP (r² = 0.19, P < 0.001). Patients with HFpEF had lower ANP levels (P < 0.001) and a greater diuretic effect of exogenous ANP than patients HFrEF (P < 0.001). HFpEF was an independent predictor of greater diuretic effect of exogenous ANP (P = 0.003), as with a lower baseline ANP level (P = 0.004).

Conclusions

Patients with HFpEF might have an aspect of ANP deficiency and represent a promising therapeutic target for modulating circulating ANP.

SUBMITTER: Matsumoto S

PROVIDER: S-EPMC7754892 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

Efficacy of exogenous atrial natriuretic peptide in patients with heart failure with preserved ejection fraction: deficiency of atrial natriuretic peptide and replacement therapy.

Matsumoto Shingo S Nakazawa Gaku G Ohno Yohei Y Ishihara Mai M Sakai Katsuaki K Nakamura Norihito N Murakami Tsutomu T Natsumeda Makoto M Kabuki Takayuki T Shibata Atsushi A Kida Keisuke K Konishi Masaaki M Ishii Shunsuke S Ikeda Takanori T Ikari Yuji Y

ESC heart failure 20201010 6

<h4>Aims</h4>Exogenous atrial natriuretic peptide (ANP) may be a logical treatment for heart failure (HF) patients with ANP deficiency. Lower ANP concentrations may result from HF with preserved ejection fraction (HFpEF), which also results in lower brain natriuretic peptide levels in HFpEF relative to HF with reduced ejection fraction (HFrEF), although clinical features regarding circulating ANP in HFpEF and HFrEF have not been fully investigated during acute HF. Here, we characterized the diff ...[more]

PMID: 33037750

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Project description:BackgroundNT-proBNP (N-terminal pro-B-type natriuretic peptide) levels are variably elevated in heart failure with preserved ejection fraction (HFpEF), even in the presence of increased left ventricular filling pressures. NT-proBNP levels are prognostic in HFpEF and have been used as an inclusion criterion for several recent randomized clinical trials. However, the underlying biologic differences between HFpEF participants with high and low NT-proBNP levels remain to be fully understood.MethodsWe measured 4928 proteins using an aptamer-based proteomic assay (SOMAScan) in available plasma samples from 2 cohorts: (1) Participants with HFpEF enrolled in the PHFS (Penn Heart Failure Study; n=253); (2) TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial) participants in the Americas (n=218). We assessed the relationship between SOMAScan-derived plasma NT-proBNP and levels of other proteins available in the SOMAScan assay version 4 using robust linear regression, with correction for multiple comparisons, followed by pathway analysis.ResultsNT-proBNP levels exhibited prominent proteome-wide associations in PHFS and TOPCAT cohorts. Proteins most strongly associated with NT-proBNP in both cohorts included SVEP1 (sushi, von Willebrand factor type-A, epidermal growth factor, and pentraxin domain containing 1; βTOPCAT=0.539; P<0.0001; βPHFS=0.516; P<0.0001) and ANGPT2 (angiopoietin 2; βTOPCAT=0.571; P<0.0001; βPHFS=0.459; P<0.0001). Canonical pathway analysis demonstrated consistent associations with multiple pathways related to fibrosis and inflammation. These included hepatic fibrosis and inhibition of matrix metalloproteases. Analyses using cut points corresponding to estimated quantitative concentrations of 360 pg/mL (and 480 pg/mL in atrial fibrillation) revealed similar proteomic associations.ConclusionsCirculating NT-proBNP levels exhibit prominent proteomic associations in HFpEF. Our findings suggest that higher NT-proBNP levels in HFpEF are a marker of fibrosis and inflammation. These findings will aid the interpretation of NT-proBNP levels in HFpEF and may guide the selection of participants in future HFpEF clinical trials.

Dataset Information

Efficacy of exogenous atrial natriuretic peptide in patients with heart failure with preserved ejection fraction: deficiency of atrial natriuretic peptide and replacement therapy.

Aims

Methods and results

Conclusions

Publications

Efficacy of exogenous atrial natriuretic peptide in patients with heart failure with preserved ejection fraction: deficiency of atrial natriuretic peptide and replacement therapy.

Similar Datasets

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