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Differential Regulation of ANP and BNP in Acute Decompensated Heart Failure: Deficiency of ANP.

ABSTRACT: OBJECTIVES:This study investigated the differential regulation of circulating atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in patients with acute decompensated heart failure (ADHF) and tested the hypothesis that a relative deficiency of ANP exists in a subgroup of patients with ADHF. BACKGROUND:The endocrine heart releases the cardiac hormones ANP and BNP, which play a key role in cardiovascular (CV), renal, and metabolic homeostasis. In heart failure (HF), both plasma ANP and BNP are increased as a compensatory homeostatic response to myocardial overload. METHODS:ANP and BNP concentrations were measured in a small group of patients with ADHF (n = 112). To support this study's goal, a total of 129 healthy subjects were prospectively recruited to establish contemporary normal values for ANP and BNP. Plasma 3',5'cyclic guanosine monophosphate (cGMP), ejection fraction (EF), and body mass index (BMI) were measured in these subjects. RESULTS:In cases of ADHF, 74% of patients showed elevated ANP and BNP. Importantly, 26% of patients were characterized as having normal ANP (21% of this subgroup had normal ANP and elevated BNP). Cyclic GMP was lowest in the ADHF group with normal levels of ANP (p < 0.001), whereas BMI and EF were inversely related to ANP levels (p = 0.003). CONCLUSIONS:Among a subgroup of patients hospitalized with ADHF, the presence of an ANP deficiency is consistent with a differential regulation of ANP and BNP and suggests the existence of a potentially compromised compensatory cardiac endocrine response. These findings have implications for the pathophysiology, diagnostics, and therapeutics of human HF.

SUBMITTER: Reginauld SH

PROVIDER: S-EPMC6778016 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Differential Regulation of ANP and BNP in Acute Decompensated Heart Failure: Deficiency of ANP.

Reginauld Shawn H SH Cannone Valentina V Iyer Seethalakshmi S Scott Christopher C Bailey Kent K Schaefer Jacob J Chen Yang Y Sangaralingham S Jeson SJ Burnett John C JC

JACC. Heart failure 20190911 10

<h4>Objectives</h4>This study investigated the differential regulation of circulating atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in patients with acute decompensated heart failure (ADHF) and tested the hypothesis that a relative deficiency of ANP exists in a subgroup of patients with ADHF.<h4>Background</h4>The endocrine heart releases the cardiac hormones ANP and BNP, which play a key role in cardiovascular (CV), renal, and metabolic homeostasis. In heart failure (HF) ...[more]

PMID: 31521687

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Project description:BackgroundLoop diuretics are an essential component of therapy for patients with acute decompensated heart failure, but there are few prospective data to guide their use.MethodsIn a prospective, double-blind, randomized trial, we assigned 308 patients with acute decompensated heart failure to receive furosemide administered intravenously by means of either a bolus every 12 hours or continuous infusion and at either a low dose (equivalent to the patient's previous oral dose) or a high dose (2.5 times the previous oral dose). The protocol allowed specified dose adjustments after 48 hours. The coprimary end points were patients' global assessment of symptoms, quantified as the area under the curve (AUC) of the score on a visual-analogue scale over the course of 72 hours, and the change in the serum creatinine level from baseline to 72 hours.ResultsIn the comparison of bolus with continuous infusion, there was no significant difference in patients' global assessment of symptoms (mean AUC, 4236±1440 and 4373±1404, respectively; P=0.47) or in the mean change in the creatinine level (0.05±0.3 mg per deciliter [4.4±26.5 μmol per liter] and 0.07±0.3 mg per deciliter [6.2±26.5 μmol per liter], respectively; P=0.45). In the comparison of the high-dose strategy with the low-dose strategy, there was a nonsignificant trend toward greater improvement in patients' global assessment of symptoms in the high-dose group (mean AUC, 4430±1401 vs. 4171±1436; P=0.06). There was no significant difference between these groups in the mean change in the creatinine level (0.08±0.3 mg per deciliter [7.1±26.5 μmol per liter] with the high-dose strategy and 0.04±0.3 mg per deciliter [3.5±26.5 μmol per liter] with the low-dose strategy, P=0.21). The high-dose strategy was associated with greater diuresis and more favorable outcomes in some secondary measures but also with transient worsening of renal function.ConclusionsAmong patients with acute decompensated heart failure, there were no significant differences in patients' global assessment of symptoms or in the change in renal function when diuretic therapy was administered by bolus as compared with continuous infusion or at a high dose as compared with a low dose. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00577135.).

Project description:BACKGROUND:Acute decompensated heart failure (ADHF) is the most common presenting phenotype of acute heart failure (AHF). The main goal of this article was to review the contemporary management strategies in these patients and to describe how future clinical trials may address unmet clinical needs. AREAS OF UNCERTAINTY:The current pathophysiologic understanding of AHF is incomplete. The guideline recommendations for the management of ADHF are based only on algorithms provided by expert consensus guided by blood pressure and/or clinical signs of congestion or hypoperfusion. The lack of adequately conducted trials to address the unmet need for evidence therapy in AHF has not yet been surpassed, and at this time, there is no evidence-based strategy for targeted decongestive therapy to improve outcomes. The precise time point for initiation of guideline-directed medical therapies (GDMTs), as respect to moment of decompensation, is also unknown. DATA SOURCES:The available data informing current management of patients with ADHF are based on randomized controlled trials, observational studies, and administrative databases. THERAPEUTIC ADVANCES:A major step-forward in the management of ADHF patients is recognizing congestion, either clinical or hemodynamic, as a major trigger for heart failure (HF) hospitalization and most important target for therapy. However, a strategy based exclusively on congestion is not sufficient, and at present, comprehensive assessment during hospitalization of cardiac and noncardiovascular substrate with identification of potential therapeutic targets represents "the corner-stone" of ADHF management. In the last years, substantial data have emerged to support the continuation of GDMTs during hospitalization for HF decompensation. Recently, several clinical trials raised hypothesis of "moving to the left" concept that argues for very early implementation of GDMTs as potential strategy to improve outcomes. CONCLUSIONS:The management of ADHF is still based on expert consensus documents. Further research is required to identify novel therapeutic targets, to establish the precise time point to initiate GDMTs, and to identify patients at risk of recurrent hospitalization.

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Differential Regulation of ANP and BNP in Acute Decompensated Heart Failure: Deficiency of ANP.

Publications

Differential Regulation of ANP and BNP in Acute Decompensated Heart Failure: Deficiency of ANP.

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