Natriuretic peptides: role in the diagnosis and management of heart failure: a scientific statement from the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America and Japanese Heart Failure Society

Natriuretic peptides, brain (B‐type) natriuretic peptide (BNP) and N‐terminal prohormone of brain natriuretic peptide (NT‐proBNP) are globally and most often used for the diagnosis of heart failure (HF). In addition, they can have an important complementary role in the risk stratification of its prognosis. Since the development of angiotensin receptor–neprilysin inhibitors (ARNIs), the use of natriuretic peptides as therapeutic agents has grown in importance. The present document is the result of the Trilateral Cooperation Project among the Heart Failure Association of the European Society of Cardiology, the Heart Failure Society of America and the Japanese Heart Failure Society. It represents an expert consensus that aims to provide a comprehensive, up‐to‐date perspective on natriuretic peptides in the diagnosis and management of HF, with a focus on the following main issues: (1) history and basic research: discovery, production and cardiovascular protection; (2) diagnostic and prognostic biomarkers: acute HF, chronic HF, inclusion/endpoint in clinical trials, and natriuretic peptide‐guided therapy; (3) therapeutic use: nesiritide (BNP), carperitide (ANP) and ARNIs; and (4) gaps in knowledge and future directions.

[1]  R. Diaz,et al.  Efficacy of omecamtiv mecarbil in heart failure with reduced ejection fraction according to N‐terminal pro‐B‐type natriuretic peptide level: insights from the GALACTIC‐HF trial , 2023, European journal of heart failure.

[2]  A. Cohen-Solal,et al.  Cardiac remodelling – Part 1: From cells and tissues to circulating biomarkers. A review from the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology , 2022, European journal of heart failure.

[3]  Dave L Dixon,et al.  2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. , 2022, Journal of cardiac failure.

[4]  T. Kitai,et al.  Effect of carperitide on the 1 year prognosis of patients with acute decompensated heart failure , 2022, ESC heart failure.

[5]  aguda y crónica,et al.  Comments on the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. , 2022, Revista espanola de cardiologia.

[6]  Akshay S. Desai,et al.  Early B-Type Natriuretic Peptide Change in HFrEF Patients Treated With Sacubitril/Valsartan: A Pooled Analysis of EVALUATE-HF and PROVE-HF. , 2022, JACC. Heart failure.

[7]  G. Sinagra,et al.  [ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: what's new?] , 2022, Giornale italiano di cardiologia.

[8]  P. Ponikowski,et al.  Efficacy and Safety of Dapagliflozin in Heart Failure With Reduced Ejection Fraction According to N-Terminal Pro-B-Type Natriuretic Peptide: Insights From the DAPA-HF Trial , 2021, Circulation. Heart failure.

[9]  K. Anstrom,et al.  Effect of Treatment With Sacubitril/Valsartan in Patients With Advanced Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial. , 2021, JAMA cardiology.

[10]  W. Peacock,et al.  Multiple Cardiac Biomarker Testing Among Patients with Acute Dyspnea from the ICON-RELOADED Study. , 2021, Journal of cardiac failure.

[11]  G. Filippatos,et al.  Prognostic Importance of NT-proBNP and Effect of Empagliflozin in the EMPEROR-Reduced Trial. , 2021, Journal of the American College of Cardiology.

[12]  M. Yoshimura,et al.  Treatment with atrial natriuretic peptide induces adipose tissue browning and exerts thermogenic actions in vivo , 2021, Scientific Reports.

[13]  S. Solomon,et al.  Association Between Angiotensin Receptor–Neprilysin Inhibition, Cardiovascular Biomarkers, and Cardiac Remodeling in Heart Failure With Reduced Ejection Fraction , 2021, Circulation. Heart failure.

[14]  J. Bauersachs The struggle towards a Universal Definition of Heart Failure-how to proceed? , 2021, European heart journal.

[15]  B. Ploeger,et al.  NT‐proBNP Qualifies as a Surrogate for Clinical End Points in Heart Failure , 2021, Clinical pharmacology and therapeutics.

[16]  P. Ponikowski,et al.  Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure , 2021, European journal of heart failure.

[17]  Thomas J. Wang,et al.  Unexpectedly Low Natriuretic Peptide Levels in Patients With Heart Failure. , 2020, JACC. Heart failure.

[18]  D. Maeda,et al.  Disproportionately low BNP levels in patients of acute heart failure with preserved vs. reduced ejection fraction. , 2020, International journal of cardiology.

[19]  S. Solomon,et al.  Atrial Natriuretic Peptide and Treatment With Sacubitril/Valsartan in Heart Failure With Reduced Ejection Fraction. , 2020, JACC. Heart failure.

[20]  P. Ponikowski,et al.  N-Terminal Pro-B-Type Natriuretic Peptide and Clinical Outcomes: Vericiguat Heart Failure With Reduced Ejection Fraction Study. , 2020, JACC. Heart failure.

[21]  M. Kawai,et al.  Possible association between body temperature and B-type natriuretic peptide in patients with cardiovascular diseases. , 2020, Journal of cardiac failure.

[22]  S. Solomon,et al.  Reverse Cardiac Remodeling and Outcome After Initiation of Sacubitril/Valsartan. , 2020, Circulation. Heart failure.

[23]  Sanjiv J. Shah,et al.  Effects of Sacubitril/Valsartan on N-Terminal Pro-B-Type Natriuretic Peptide in Heart Failure With Preserved Ejection Fraction. , 2020, JACC. Heart failure.

[24]  A. Bayés‐Genís,et al.  CA125 outperforms NT-proBNP in acute heart failure with severe tricuspid regurgitation. , 2020, International journal of cardiology.

[25]  A. Bayés‐Genís,et al.  Factors associated with plasma antigen carbohydrate 125 and amino-terminal pro-B-type natriuretic peptide concentrations in acute heart failure , 2020, European heart journal. Acute cardiovascular care.

[26]  John G F Cleland,et al.  Natriuretic Peptide-Based Inclusion Criteria in a Heart Failure Clinical Trial: Insights From COMMANDER HF. , 2020, JACC. Heart failure.

[27]  S. Solomon,et al.  Natriuretic Peptides as Inclusion Criteria in Clinical Trials: A JACC Heart Failure Position Paper. , 2020, JACC. Heart failure.

[28]  A. Voors Should Enrichment With Natriuretic Peptide Levels Be Mandatory in Global Clinical Trials? , 2020, JACC. Heart failure.

[29]  W. Southern,et al.  BNP-Response to Acute Heart Failure Treatment Identifies High-Risk Population. , 2020, Heart, lung & circulation.

[30]  P. Ponikowski,et al.  Acute heart failure congestion and perfusion status – impact of the clinical classification on in‐hospital and long‐term outcomes; insights from the ESC‐EORP‐HFA Heart Failure Long‐Term Registry , 2019, European journal of heart failure.

[31]  W. Shimizu,et al.  JCS 2017/JHFS 2017 Guideline on Diagnosis and Treatment of Acute and Chronic Heart Failure - Digest Version. , 2019, Circulation journal : official journal of the Japanese Circulation Society.

[32]  S. Solomon,et al.  Association of Change in N-Terminal Pro-B-Type Natriuretic Peptide Following Initiation of Sacubitril-Valsartan Treatment With Cardiac Structure and Function in Patients With Heart Failure With Reduced Ejection Fraction. , 2019, JAMA.

[33]  K. Anstrom,et al.  Natriuretic Peptide Response and Outcomes in Chronic Heart Failure With Reduced Ejection Fraction. , 2019, Journal of the American College of Cardiology.

[34]  P. Ponikowski,et al.  Effects of Serelaxin in Patients with Acute Heart Failure. , 2019, The New England journal of medicine.

[35]  W. Shimizu,et al.  Predictors of responders for low-dose carperitide monotherapy in patients with acute heart failure , 2019, Heart and Vessels.

[36]  G. Filippatos,et al.  Heart Failure Association of the European Society of Cardiology practical guidance on the use of natriuretic peptide concentrations , 2019, European journal of heart failure.

[37]  T. Nagai,et al.  Effect of intravenous carperitide versus nitrates as first-line vasodilators on in-hospital outcomes in hospitalized patients with acute heart failure: Insight from a nationwide claim-based database. , 2019, International journal of cardiology.

[38]  B. Wessler,et al.  Relation between therapy‐induced changes in natriuretic peptide levels and long‐term therapeutic effects on mortality in patients with heart failure and reduced ejection fraction , 2019, European journal of heart failure.

[39]  Akshay S. Desai,et al.  B-Type Natriuretic Peptide During Treatment With Sacubitril/Valsartan: The PARADIGM-HF Trial. , 2019, Journal of the American College of Cardiology.

[40]  E. Braunwald,et al.  Angiotensin–Neprilysin Inhibition in Acute Decompensated Heart Failure , 2019, The New England journal of medicine.

[41]  K. Anstrom,et al.  NT-proBNP Goal Achievement Is Associated With Significant Reverse Remodeling and Improved Clinical Outcomes in HFrEF. , 2019, JACC. Heart failure.

[42]  R. Califf,et al.  Relationship Between Enrolling Country Income Level and Patient Profile, Protocol Completion, and Trial End Points: From the ASCEND-HF Trial , 2018, Circulation. Cardiovascular quality and outcomes.

[43]  Kazuhiro Yamamoto,et al.  Angiotensin Receptor Neprilysin Inhibitor in Japanese Patients With Heart Failure and Reduced Ejection Fraction - Baseline Characteristics and Treatment of PARALLEL-HF Trial. , 2018, Circulation journal : official journal of the Japanese Circulation Society.

[44]  R. Perera,et al.  Diagnostic accuracy of point-of-care natriuretic peptide testing for chronic heart failure in ambulatory care: systematic review and meta-analysis , 2018, British Medical Journal.

[45]  P. Ponikowski,et al.  Prevalence, predictors and clinical outcome of residual congestion in acute decompensated heart failure. , 2018, International journal of cardiology.

[46]  Y. Pinto,et al.  NT-proBNP (N-Terminal pro-B-Type Natriuretic Peptide)-Guided Therapy in Acute Decompensated Heart Failure: PRIMA II Randomized Controlled Trial (Can NT-ProBNP-Guided Therapy During Hospital Admission for Acute Decompensated Heart Failure Reduce Mortality and Readmissions?) , 2018, Circulation.

[47]  W. Peacock,et al.  N-Terminal Pro-B-Type Natriuretic Peptide in the Emergency Department: The ICON-RELOADED Study. , 2018, Journal of the American College of Cardiology.

[48]  S. Solomon,et al.  Natriuretic Peptides as Biomarkers of Treatment Response in Clinical Trials of Heart Failure. , 2018, JACC. Heart failure.

[49]  J. Januzzi,et al.  The Future of Biomarker-Guided Therapy for Heart Failure After the Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) Study , 2018, Current Heart Failure Reports.

[50]  A. Cohen-Solal,et al.  RELAX‐AHF, BLAST‐AHF, TRUE‐AHF, and other important truths in acute heart failure research , 2017, European journal of heart failure.

[51]  K. Anstrom,et al.  Effect of Natriuretic Peptide–Guided Therapy on Hospitalization or Cardiovascular Mortality in High-Risk Patients With Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial , 2017, JAMA.

[52]  P. Ponikowski,et al.  Effect of Ularitide on Cardiovascular Mortality in Acute Heart Failure , 2017, The New England journal of medicine.

[53]  Akshay S. Desai,et al.  Prognostic Implications of Changes in N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Heart Failure. , 2016, Journal of the American College of Cardiology.

[54]  M. Gheorghiade,et al.  The bumpy road to drug development for acute heart failure , 2016 .

[55]  A. Jaffe,et al.  Variability of biomarkers in patients with chronic heart failure and healthy controls , 2016, European journal of heart failure.

[56]  M. Guglin,et al.  Discharge BNP is a stronger predictor of 6-month mortality in acute heart failure compared with baseline BNP and admission-to-discharge percentage BNP reduction. , 2016, International journal of cardiology.

[57]  A. Bayés‐Genís,et al.  A Test in Context: Neprilysin: Function, Inhibition, and Biomarker. , 2016, Journal of the American College of Cardiology.

[58]  J. Lupón,et al.  Neprilysin and Natriuretic Peptide Regulation in Heart Failure , 2016, Current Heart Failure Reports.

[59]  C. Grady,et al.  Detection and Management of Geographic Disparities in the TOPCAT Trial , 2016, JACC. Basic to translational science.

[60]  Y. Pinto,et al.  Challenging the two concepts in determining the appropriate pre‐discharge N‐terminal pro‐brain natriuretic peptide treatment target in acute decompensated heart failure patients: absolute or relative discharge levels? , 2015, European journal of heart failure.

[61]  P. Lourenço,et al.  Predictors of Six-Month Mortality in BNP-Matched Acute Heart Failure Patients. , 2015, The American journal of cardiology.

[62]  M. Kuhn,et al.  Atrial Natriuretic Peptide Locally Counteracts the Deleterious Effects of Cardiomyocyte Mineralocorticoid Receptor Activation , 2014, Circulation. Heart failure.

[63]  Y. Pinto,et al.  A novel discharge risk model for patients hospitalised for acute decompensated heart failure incorporating N-terminal pro-B-type natriuretic peptide levels: a European coLlaboration on Acute decompeNsated Heart Failure: ÉLAN-HF Score , 2013, Heart.

[64]  S. Pocock,et al.  Learning from recent trials and shaping the future of acute heart failure trials. , 2013, American heart journal.

[65]  A. Hoes,et al.  B-type natriuretic peptide and prognosis in heart failure patients with preserved and reduced ejection fraction. , 2013, Journal of the American College of Cardiology.

[66]  J. Burnett,et al.  Neutral endopeptidase inhibition and the natriuretic peptide system: an evolving strategy in cardiovascular therapeutics. , 2013, European heart journal.

[67]  K. Swedberg,et al.  Clinical course and predictive value of congestion during hospitalization in patients admitted for worsening signs and symptoms of heart failure with reduced ejection fraction: findings from the EVEREST trial. , 2013, European heart journal.

[68]  A. Maisel,et al.  Post-acute care: the role of natriuretic peptides. , 2012, Congestive heart failure.

[69]  G. Ailhaud,et al.  Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes. , 2012, The Journal of clinical investigation.

[70]  Eric M. Reyes,et al.  Admission, Discharge, or Change in B-Type Natriuretic Peptide and Long-Term Outcomes: Data From Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure (OPTIMIZE-HF) Linked to Medicare Claims , 2011, Circulation. Heart failure.

[71]  L. Potter Natriuretic peptide metabolism, clearance and degradation , 2011, The FEBS journal.

[72]  R. Doughty,et al.  Age-dependent values of N-terminal pro-B-type natriuretic peptide are superior to a single cut-point for ruling out suspected systolic dysfunction in primary care. , 2010, European heart journal.

[73]  V. Hasselblad,et al.  Rationale and design of the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure Trial (ASCEND-HF). , 2009, American heart journal.

[74]  G. Filippatos,et al.  Determinants of plasma NT-pro-BNP levels in patients with atrial fibrillation and preserved left ventricular ejection fraction , 2009, Clinical Research in Cardiology.

[75]  Y. Okutani,et al.  Multicenter prospective investigation on efficacy and safety of carperitide as a first-line drug for acute heart failure syndrome with preserved blood pressure: COMPASS: Carperitide Effects Observed Through Monitoring Dyspnea in Acute Decompensated Heart Failure Study. , 2008, Circulation journal : official journal of the Japanese Circulation Society.

[76]  K. Nakao,et al.  Regulator of G-Protein Signaling Subtype 4 Mediates Antihypertrophic Effect of Locally Secreted Natriuretic Peptides in the Heart , 2008, Circulation.

[77]  V. Hasselblad,et al.  Rapid assay brain natriuretic peptide and troponin I in patients hospitalized with decompensated heart failure (from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness Trial). , 2007, The American journal of cardiology.

[78]  A. Ferreira,et al.  Intraindividual variation of amino-terminal pro-B-type natriuretic peptide levels in patients with stable heart failure. , 2006, The American journal of cardiology.

[79]  Y. Pinto,et al.  Usefulness of intermediate amino-terminal pro-brain natriuretic peptide concentrations for diagnosis and prognosis of acute heart failure. , 2006, The American journal of cardiology.

[80]  Antoni Bayes-Genis,et al.  NT-proBNP testing for diagnosis and short-term prognosis in acute destabilized heart failure: an international pooled analysis of 1256 patients: the International Collaborative of NT-proBNP Study. , 2006, European heart journal.

[81]  G. Baumann,et al.  NT-ProBNP in acute heart failure: correlation with invasively measured hemodynamic parameters during recompensation. , 2005, Journal of cardiac failure.

[82]  K. Aaronson,et al.  Short-term risk of death after treatment with nesiritide for decompensated heart failure: a pooled analysis of randomized controlled trials. , 2005, JAMA.

[83]  K. Aaronson,et al.  Risk of Worsening Renal Function With Nesiritide in Patients With Acutely Decompensated Heart Failure , 2005, Circulation.

[84]  A. Ferreira,et al.  N-Terminal–Pro-Brain Natriuretic Peptide Predicts Outcome After Hospital Discharge in Heart Failure Patients , 2004, Circulation.

[85]  M. Komajda,et al.  Comparison of echocardiography and plasma B-type natriuretic peptide for monitoring the response to treatment in acute heart failure. , 2004, European heart journal.

[86]  J. Hollander,et al.  Primary results of the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT). A multicenter study of B-type natriuretic peptide levels, emergency department decision making, and outcomes in patients presenting with shortness of breath. , 2004, Journal of the American College of Cardiology.

[87]  A. D. de Bold,et al.  Selective upregulation of cardiac brain natriuretic peptide at the transcriptional and translational levels by pro-inflammatory cytokines and by conditioned medium derived from mixed lymphocyte reactions via p38 MAP kinase. , 2004, Journal of molecular and cellular cardiology.

[88]  Daniel Levy,et al.  Plasma natriuretic peptide levels and the risk of cardiovascular events and death. , 2004, The New England journal of medicine.

[89]  L. Fisher,et al.  Changes in Brain Natriuretic Peptide and Norepinephrine Over Time and Mortality and Morbidity in the Valsartan Heart Failure Trial (Val-HeFT) , 2003, Circulation.

[90]  P. Krishnaswamy,et al.  A rapid test for B-type natriuretic peptide correlates with falling wedge pressures in patients treated for decompensated heart failure: a pilot study. , 2001, Journal of cardiac failure.

[91]  D. Goeddel,et al.  Selective activation of the B natriuretic peptide receptor by C-type natriuretic peptide (CNP). , 1991, Science.

[92]  D. Goeddel,et al.  A membrane form of guanylate cyclase is an atrial natriuretic peptide receptor , 1989, Nature.

[93]  Naoto Minamino,et al.  A new natriuretic peptide in porcine brain , 1988, Nature.

[94]  H. Imura,et al.  Clinical application of atrial natriuretic polypeptide in patients with congestive heart failure: beneficial effects on left ventricular function. , 1987, Circulation.

[95]  E. Espiner,et al.  HAEMODYNAMIC EFFECTS OF ATRIAL PEPTIDE INFUSION IN HEART FAILURE , 1986, The Lancet.

[96]  Andrew,et al.  Atrial natriuretic factor in normal subjects and heart failure patients. Plasma levels and renal, hormonal, and hemodynamic responses to peptide infusion. , 1986, The Journal of clinical investigation.

[97]  A. D. de Bold,et al.  A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. , 1981, Life sciences.

[98]  W. Kannel,et al.  The natural history of congestive heart failure: the Framingham study. , 1971, The New England journal of medicine.

[99]  G. Fonarow,et al.  2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. , 2017, Circulation.

[100]  M. Tosun,et al.  Effects of ivabradine therapy on heart failure biomarkers. , 2015, Cardiology journal.

[101]  S. Werns Effect of Nesiritide in Patients with Acute Decompensated Heart Failure , 2012 .

[102]  A. Clerico,et al.  [The cardiac natriuretic peptides]. , 2006, Minerva medica.

[103]  K. Kangawa,et al.  Purification and complete amino acid sequence of alpha-human atrial natriuretic polypeptide (alpha-hANP). , 1984, Biochemical and biophysical research communications.

[104]  B. Kisch Electron microscopy of the atrium of the heart. I. Guinea pig. , 1956, Experimental medicine and surgery.