European Journal of Heart Failure (2023) 25, 1891–1898 POSITION PAPER

doi:10.1002/ejhf.3036

Practical algorithms for early diagnosis of

heart failure and heart stress using
NT-proBNP: A clinical consensus statement
from the Heart Failure Association of the ESC
Antoni Bayes-Genis1* , Kieran F. Docherty2, Mark C. Petrie2, James L. Januzzi3,
Christian Mueller4, Lisa Anderson5, Biykem Bozkurt6, Javed Butler7,
Ovidiu Chioncel8, John G.F. Cleland9, Ruxandra Christodorescu10,
Stefano Del Prato11, Finn Gustafsson12, Carolyn S.P. Lam13, Brenda Moura14,15,
Rodica Pop-Busui16, Petar Seferovic17,18, Maurizio Volterrani19,20,
Muthiah Vaduganathan21, Marco Metra22, and Giuseppe Rosano23
1 Heart Institute, Hospital Unbiversitari Germasn Trias i Pujol, Universitat Autonoma de Barcelona, CIBERCV, Barcelona, Spain; 2 School of Cardiovascular and Metabolic Health,
University of Glasgow, Glasgow, UK; 3 Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 4 Department of Cardiology and
Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland; 5 Cardiovascular Clinical Academic Group, Molecular and Clinical
Sciences Research Institute, St. George’s, University of London and St George’s University Hospitals NHS Foundation Trust, London, UK; 6 Baylor College of Medicine Medicine,
DeBakey VA Medical Center, Houston, TX, USA; 7 Baylor Scott and White Research Institute, Dallas, Texas and University of Mississippi Medical Center, Jackson, MS, USA;
8 Emergency Institute for Cardiovascular Diseases ‘Prof. C.C. Iliescu’, and, University of Medicine Carol Davila, Bucharest, Romania; 9 British Heart Foundation Centre of Research

Excellence, School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK; 10 Department V Internal Medicine, University of Medicine and Pharmacy
V. Babes Timisoara, Institute of Cardiology Research Center, TimiS, oara, Romania; 11 Department of Clinical and Experimental Medicine, University of Pisa and Sant’Anna School
of Advanced Studies, Pisa, Italy; 12 Department of Cardiology, Rigshospitalet, Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; 13 National
Heart Centre Singapore, Duke-National University of Singapore, Singapore, Singapore; 14 CINTESIS – Centro de Investigação em Tecnologias e Serviços de Saúde, Porto,
Portugal; 15 Serviço de Cardiologia, Hospital das Forças Armadas, Pólo do Porto, Portugal; 16 Division of Metabolism, Endocrinology and Diabetes, Department of Internal
Medicine, University of Michigan, Ann Arbor, MI, USA; 17 Faculty of Medicine, University of Belgrade, Belgrade, Serbia; 18 Serbian Academy of Sciences and Arts, Belgrade, Serbia;
19 Cardio Pulmonary Department, IRCCS San Raffaele, Rome, Italy; 20 Exercise Science and Medicine, San Raffaele Open University, Rome, Italy; 21 Cardiovascular Division,

Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; 22 Cardiology and Cardiac Catheterization Laboratory, Cardio-Thoracic Department, Civil Hospitals;
Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy; and 23 IRCCS San Raffaele, Rome, Italy

Received 19 June 2023; revised 13 September 2023; accepted 13 September 2023 ; online publish-ahead-of-print 26 September 2023

Diagnosing heart failure is often difficult due to the non-specific nature of symptoms, which can be caused by a range of medical conditions.
Natriuretic peptides (NPs) have been recognized as important biomarkers for diagnosing heart failure. This document from the Heart
Failure Association examines the practical uses of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in various clinical scenarios.
The concentrations of NT-proBNP vary according to the patient profile and the clinical scenario, therefore values should be interpreted
with caution to ensure appropriate diagnosis. Validated cut-points are provided to rule in or rule out acute heart failure in the emergency
department and to diagnose de novo heart failure in the outpatient setting. We also coin the concept of ‘heart stress’ when NT-proBNP
levels are elevated in an asymptomatic patient with risk factors for heart failure (i.e. diabetes, hypertension, coronary artery disease),
underlying the development of cardiac dysfunction and further increased risk. We propose a simple acronym for healthcare professionals
and patients, FIND-HF, which serves as a prompt to consider heart failure: Fatigue, Increased water accumulation, Natriuretic peptide testing,

*Corresponding author. Department of Medicine, UAB, Head, Heart Institute. Hospital Universitari Germans Trias i Pujol, Carretera del Canyet s/n, 08916 Badalona, Spain.
Email: [email protected]

[Correction added on 16 October 2023, after first online publication: Lisa Anderson’s surname has been corrected in this version.]

© 2023 European Society of Cardiology.

 18790844, 2023, 11, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ejhf.3036 by Cochrane Colombia, Wiley Online Library on [06/06/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
1892 A. Bayes-Genis et al.

and Dyspnoea. Use of this acronym would enable the early diagnosis of heart failure. Overall, understanding and
utilizing NT-proBNP levels will lead to earlier and more accurate diagnoses of heart failure ultimately improving
patient outcomes and reducing healthcare costs.
..........................................................................................................
Keywords Heart failure • Natriuretic peptides • NT-proBNP

Introduction is an update to the 2019 HFA document of ‘Cardiology practical

..............................................................................................................................................
guidance on the use of natriuretic peptide concentrations’.15
Heart failure is common with major and adverse effects on quality
of life, survival, and healthcare costs.1 As heart failure treatments
reduce hospitalizations and death, early diagnosis is essential. The NT-proBNP for ruling out
most recent European Society of Cardiology (ESC) guidelines on
heart failure recommend measuring concentrations of N-terminal
and ruling in heart failure in the
pro-B-type natriuretic peptide (NT-proBNP), B-type natriuretic emergency department
peptide (BNP), or mid-regional pro-atrial natriuretic peptide Approximately 60–80% of heart failure diagnoses are made for
(MR-proANP) for the diagnostic evaluation of heart failure.1 The the first time in the emergency department (ED) as reported in a
very first ESC guideline on heart failure published in 1995 explicitly National Health Service audit.16 It is important to note that these
recommended the use of natriuretic peptides (NPs) to rule out statistics may not necessarily mirror the situation in different global
a diagnosis of heart failure.2 However, the most recent guidelines regions. When evaluating patients with possible heart failure, clini-
from the ESC, the American Heart Association/American College cian uncertainty is associated with increased morbidity and mortal-
of Cardiology and the American Diabetes Association now suggest ity and prolongs hospital length of stay.17 Studies have consistently
that NPs should also be considered to diagnosis (i.e. rule in) heart demonstrated that the use of NP testing in the ED results in more
failure.1,3–5 The universal definition of heart failure6 also under- accurate and timely diagnosis of heart failure, leading to faster initia-
scores the importance of measuring NPs for diagnosing heart tion of life-saving therapies and earlier discharge, with resulting clin-
failure. This paradigm shift recognizes NPs as a key component in ical and economic benefits.18–24 The use of NT-proBNP-supported
the early detection of heart failure, benefiting both specialists and strategies results in reductions in initial hospitalizations (14.5%),
non-specialists alike. admissions to cardiology (16.0%), admissions to intensive care
This clinical consensus statement will focus on NT-proBNP, as units (12.5%), ED readmissions (3.2%), and hospital readmissions
it is the most utilized peptide for diagnosing and managing heart (21.6%).25,26 As a result, the use of NP-based approaches leads to
failure in Europe.7 While there is a stoichiometric release of BNP lower inpatient management costs and total treatment costs.
and NT-proBNP, their half-lives differ. The estimated half-life for Despite compelling evidence supporting the use of NP testing for
BNP is ∼21 min, whereas for NT-proBNP, it is extended to around the early diagnosis of heart failure in ED, there is substantial varia-
70 min. Consequently, concentrations of NT-proBNP are higher tion in the availability of such testing across ESC member countries,
than those of BNP.8–10 Stability at room temperature facilitates as demonstrated by the HFA Atlas.14 The highest use of NPs in ED
the handling of specimens for NT-proBNP measurement in usually was found in Germany (with 19.8 hospitals per million people),
busy clinical laboratories; in this regard, NT-proBNP is a more whereas Kyrgyzstan and North Macedonia reported the lowest
convenient molecule to work with than BNP, whose stability is use (none), followed by the Russian Federation (0.02 hospitals per
dependent on the specific assay and is largely unstable at room million people). Certainly, differences in local healthcare system
temperature.11 Moreover, it is not affected by treatments that alter organization, delivery, local costs, and funding can contribute to
degradation of BNP (e.g. sacubitril/valsartan).12,13 Others may wish discrepancies in the use of NT-proBNP in ED. Practical algorithms
to develop dedicated algorithms for BNP and MR-proANP. for the use of NT-proBNP in ED are needed to ensure consistency
To address the variability in healthcare professionals’ diagnostic and standardization in the diagnosis of heart failure.
expertise, this clinical consensus statement utilizes cut-point In the ED, higher NP cut-points are utilized compared to the
recommendations for early diagnosis of heart failure and heart outpatient setting, reflecting the presence of ‘wet’ NPs charac-
stress, rather than relying on NT-proBNP as a continuous terized by acutely elevated BNP/NT-proBNP levels due to severe
variable. Furthermore, despite the prioritization of NP measure- congestion leading to greater myocardial stretching and increased
ment in clinical guidelines, the implementation and interpretation NP secretion. A single cut-point of 300 pg/ml NT-proBNP is
of NT-proBNP levels in real-world clinical practice remains considered to rule out the diagnosis of heart failure (Figure 1),
sub-optimal.14 To bridge this gap, the Heart Failure Association regardless of the patient’s age.27,28 When plasma NT-proBNP
(HFA) organized a workshop in London in February 2023. This is below this value, clinicians should evaluate the patient for
document serves as a summary of the workshop’s conclusions, non-cardiac causes of dyspnoea.
offering practical advice on the utilization of NT-proBNP for the For ruling in heart failure in the ED, age-adjusted cut-points
timely diagnosis of heart failure and heart stress. This document have been established: ≥450 pg/ml for patients under 50 years,

© 2023 European Society of Cardiology.

 18790844, 2023, 11, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ejhf.3036 by Cochrane Colombia, Wiley Online Library on [06/06/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
NT-proBNP for the diagnosis of heart failure and heart stress 1893

Patients presenting to the ED with very high NT-proBNP con-

........................................................................................................................................................................
centrations, particularly those above 5000 pg/ml, have a poor prog-
Suspicion of Heart Failure in the nosis.27,35 Patients with NT-proBNP concentrations above this
Emergency Department threshold require hospital admission, often in critical care, urgent
(History, physical exam, CXR, ECG) investigation and close monitoring. Treatment of congestion, usu-
ally administered intravenously, is necessary (Figure 1).
NT-proBNP is also a valuable diagnostic tool for identifying
“wet” NT-proBNP
worsening heart failure in other care settings. To identify patients
with known and treated heart failure, who are free from con-
Rule-out Grey zone Age-adjusted High-risk gestion, we utilize the term ‘dry’ NT-proBNP. Consequently, an
≤ 300pg/mL Rule-in Rule-in
<50y: ≥ 450pg/mL ≥ 5,000pg/mL NT-proBNP increase by more than 25% compared to the ‘dry’
50-74y: ≥ 900pg/mL
NT-proBNP value suggests worsening heart failure. A compre-
≥75y: ≥ 1800pg/mL
NO need to adjust
hensive clinical evaluation is essential to diagnose and manage
for sex, BMI, kidney suspected worsening heart failure, as elevated NT-proBNP
function, AF, LVEF
concentrations can be observed in other conditions.15,36,37
Heart Failure Heart Failure Heart Failure Heart Failure
Very Unlikely Not Likely Likely Very High-Risk
Evaluation for a
non-cardiac cause
Use clinical
judgement
Consider
admission
Admit, close
monitoring
NT-proBNP for ruling out
of dyspnoea is
advised
Consider
alternative diagnosis
Further tests
and treatment
Further tests
and treatment and ruling in de novo heart failure
Figure 1 NT-proBNP for diagnosis of heart failure in the emer- in the outpatient setting
gency department. AF, atrial fibrillation/flutter; BMI, body mass The diagnosis of heart failure in the outpatient setting can be
index; CXR, chest x-ray; ECG electrocardiogram; LVEF, left ven- challenging due to the wide range of non-specific symptoms which
tricular ejection fraction; NT-proBNP, N-terminal pro-B-type
patients can present to their general practitioner (GP). Many
natriuretic peptide.
patients who present to hospital and are diagnosed with heart
failure for the first time having previously presented to their GP
with symptoms suggestive of heart failure yet did not receive
≥900 pg/ml for patients aged 50–75 years, and ≥1800 pg/ml for investigations to diagnose heart failure (e.g. measurement of NP
patients over 75 years27,28 (online supplementary Table S1). If concentrations).16 Although measurement of NPs as a diagnostic
NT-proBNP concentrations exceed these cut-points, acute heart tool has been endorsed in guidelines for more than 20 years, their
failure is likely, and admission, further investigation, and treatment use has only increased slightly over time.38 A significant deficit per-
for heart failure should be advised. The age-adjusted rule-in values sists in the uptake of NP testing to diagnose or exclude heart failure
for NT-proBNP in the ED do not necessitate additional adjust- in the community39 ; this document should serve as a call to action.
ments for factors that can influence NP levels, such as renal dys- A single rule-out cut-point of 125 pg/ml for NT-proBNP has
function (low estimated glomerular filtration rate [eGFR]), obesity, been consistently recommended by guidelines in the outpatient
diabetes, or atrial fibrillation.29–32 setting to exclude a diagnosis of heart failure, regardless of the
The cut-points for the age-independent rule out and patient’s age (Figure 2).1,3
age-adjusted rule in of NT-proBNP levels were initially estab- In contrast, the outpatient setting lacks well-defined rule-in
lished by the International Collaborative of NT-proBNP (ICON) values for NT-proBNP. The guidelines from the United Kingdom
study in 2006.27 These cut-points were further validated in the National Institute for Health and Care Excellence (NICE) pro-
ICON-RELOADED study published in 2018, which included a pose a single rule-in threshold of 400 pg/ml for NT-proBNP.40
more contemporary population of older and more comorbid However, population studies have revealed significant age- and
patients.28 The consistency in the use of these cut-points across sex-based variations in NT-proBNP concentrations, suggesting
different studies highlights their utility in clinical practice.33 that a single rule-in threshold in the outpatient setting could
The ‘grey zone’ in NT-proBNP refers to a range of plasma result in unnecessary referrals for additional investigations such
concentrations that lie between the rule-out and rule-in values. as echocardiography.41–45 Additionally, comorbidities such as
In patients with acute dyspnoea in the ED, the grey zone for obesity and renal dysfunction may also affect NT-proBNP rule-in
NT-proBNP concentrations ranges between the age-independent concentrations.31 In order to ensure simplicity and ease of use,
rule-out value and the age-adjusted rule-in value. For example, this consensus document adopts a compromise approach by uti-
among individuals under 50 years, the grey zone is between 300 lizing age-specific rule-in cut-points exclusively. These cut-points
and 450 pg/ml, for those aged 50 and 75 years, it is between 300 are determined based on the 95th percentile of the Generation
and 900 pg/ml, and for those over 75 years, it is between 300 and Scotland cohort,41 following the same age strata as those employed
1800 pg/ml. Patients falling within the grey zone require further in the ED. The age-adjusted rule-in cut-points in the outpatient set-
diagnostic testing, such as echocardiography or cardiac imaging, ting have been established: ≥125 pg/ml for patients under 50 years,
and consideration of other clinical factors, to determine whether ≥250 pg/ml for patients aged 50-75 years, and ≥500 pg/ml for
they have heart failure or another underlying condition.34 patients over 75 years. If NT-proBNP concentrations surpass

© 2023 European Society of Cardiology.

 18790844, 2023, 11, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ejhf.3036 by Cochrane Colombia, Wiley Online Library on [06/06/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
1894 A. Bayes-Genis et al.

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Table 1 NT-proBNP cut-points for non-obese patients
without kidney failure and atrial fibrillation/flutter on
Suspected de novo Heart Failure as an baseline electrocardiogram
Outpatient
(History, physical exam, ECG) NT-proBNP (pg/ml)
......................................
Men Women
NT-proBNP ................................................................
<60 years >75 >125
60–69 years >125 >175
Rule-out Grey zone Age-adjusted High-risk
≤ 125pg/mL Rule-in Rule-in 70–79 years >175 >225
<50y: ≥ 125pg/mL ≥ 2,000pg/mL >80 years >250 >250
50-74y: ≥ 250pg/mL
≥75y: ≥ 500pg/mL
NT-proBNP, N-terminal pro-B-type natriuretic peptide.
Consider obesity,
race-based variations,
and treatment
(diuretics, RASi, MRA)
Implementing the proposed age-adjusted rule-in and
Heart Failure Heart Failure Heart Failure Heart Failure
Very Unlikely Not Likely Likely Very High-Risk age-independent rule-out criteria for patients with suspected
Evaluation for a Consider alternative Treat as appropriate Priority heart failure in the outpatient setting introduces a grey zone. For
non-cardiac cause diagnosis Arrange for Echocardiography
advised If clinical suspicion Echocardiography and evaluation by individuals under 50 years, there is no grey zone. For patients
remains, arrange (≤ 6 weeks) Heart Failure team
echocardiography (≤ 2 weeks) aged 50–75 years, the grey zone ranges from 125 to 250 pg/ml,
while for those over 75 years, it extends from 125 to 500 pg/ml.
Figure 2 NT-proBNP for diagnosis of de novo heart fail- It is crucial to conduct a thorough evaluation of patients within
ure in the outpatient setting. ECG electrocardiogram; MRA, the grey zone, considering factors such as obesity, race-based
mineralocorticoid receptor antagonist; NT-proBNP, N-terminal variations, and ongoing treatment (as many patients with a history
pro-B-type natriuretic peptide; RASi, renin–angiotensin system of hypertension may already be on diuretics, renin–angiotensin
inhibitor.
system inhibitors, or mineralocorticoid receptor antagonists).
In the outpatient setting, the extent of elevation in NP concen-
trations at the time of heart failure diagnosis is closely linked to the
these cut-points, it is indicative of likely heart failure, and arranging
risk of subsequent hospitalization and mortality.16 As a result, there
echocardiography within 6 weeks is advised (Figure 2).
has been a suggestion to utilize NT-proBNP concentrations at the
Complex cut-point schemes that incorporate multiple comor-
time of a community-based heart failure diagnosis as a triaging
bidities in addition to age can be taken into consideration, especially
tool to prioritize access to expedited diagnostic echocardiogra-
if they can be integrated into electronic health records that trig-
phy and to set up a follow-up plan for individuals with the highest
ger an alarm when NT-proBNP concentrations exceed specified
short-term risk of adverse events. The authors of this consensus
thresholds. These should include age- and sex-specific NT-proBNP
document align with the NICE guidelines on chronic heart failure,
cut-points for the diagnosis of HF with adjustments for renal
which recommend a cut-off value of NT-proBNP >2000 pg/ml.40 In
dysfunction, atrial fibrillation or flutter including ventricular rate
an analysis of primary care data from England, an NT-proBNP value
on the baseline resting electrocardiogram (ECG) and body mass
of >2000 pg/ml was associated with a more than two-fold higher
index (BMI). Table 1 shows suggested NT-proBNP cut-offs strat-
risk of heart failure hospitalization and 50% higher risk of mortality
ified by age and gender for non-obese patients without kidney
as compared with an NT-proBNP of 400–2000 pg/ml.47 We sug-
failure and atrial fibrillation/flutter on baseline ECG.46 The fol-
gest that, irrespective of age and sex, patients with an NT-proBNP
lowing suggested modifications for comorbid conditions are based
>2000 pg/ml should be prioritized for echocardiography and clini-
more on expert opinion rather than on strong evidence and should
cal evaluation within 2 weeks of diagnosis (Figure 2).
be refined as more information becomes available. When eGFR
is <30 ml/min/1.73 m2 , the cut-point for NT-proBNP should be
increased by 35%; for eGFR between 30 and 45 ml/min/1.73 m2
by 25% and for eGFR 45-60 ml/min/1.73 m2 by 15%. When BMI NT-proBNP in asymptomatic
is between 30 and 35 kg/m2 , the NT-proBNP cut-off should be patients with risk factors: heart
reduced by 25%; for BMI between 35 and 40 kg/m2 by 30% and over
40 kg/m2 by 40%. For atrial fibrillation or flutter, the NT-proBNP
stress
cut-point should be increased by 50% when the ventricular rate Various risk factors, such as hypertension, atherosclerotic cardio-
is ≤90 bpm at the time of the blood draw or by 100% when the vascular disease, diabetes, obesity, and others, contribute to an
ventricular rate is >90 bpm. increased susceptibility to the development of heart failure. In the
Further investigation is required to ascertain which of the two absence of symptoms of heart failure, patients with risk factors may
approaches, the simpler age-adjusted or the more sophisticated exhibit either heart health or heart stress. Heart health refers to
fully adjusted rule-in cut-points, offer a greater reduction in unnec- individuals who have a structurally normal heart and normal plasma
essary referrals and echocardiograms. concentrations of NPs and troponins.

© 2023 European Society of Cardiology.

 18790844, 2023, 11, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ejhf.3036 by Cochrane Colombia, Wiley Online Library on [06/06/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
NT-proBNP for the diagnosis of heart failure and heart stress 1895

In this consensus document, a new condition termed ‘heart (e.g. dietary salt intake, exercise, smoking, etc.) and the treatment

........................................................................................................................................................................
stress’ is introduced to identify asymptomatic individuals with risk of risk factors such as hypertension. NT-proBNP concentrations
factors and elevated plasma NPs, irrespective of the presence or may be re-evaluated within the following 6–12 months to deter-
absence of structural heart disease or cardiac dysfunction. NPs, mine the response to any intervention and the need for further
produced by cardiomyocytes under strain caused by either cardiac investigation (Figure 3). This advice, based on a consensus decision,
volume or pressure overload, serve as indicators of the molecular requires confirmation by prospective studies. It is important to val-
stress experienced by the heart.15 Patients with diabetes serve idate the heart stress algorithm using clinical trial data; conducting
as an example of this concept, as they often appear to have a post-hoc validation should be feasible from existing trial data or
structurally and functionally normal heart on imaging but increased registries (such as the UK Biobank).
concentrations of NT-proBNP that predict an increased risk of
developing heart failure and mortality.48,49
The proposed cut-points outlined in this consensus document FIND-HF – The HFA acronym
primarily focus on patients with diabetes, as this is the population for early diagnosis of heart failure
where most evidence exists. A recent consensus document by the
To promote early diagnosis of heart failure and assist healthcare
American Diabetes Association advises the use of a single cut-point
professionals and patients, we suggest the mnemonic acronym
of 125 pg/ml to determine heart failure risk.5
FIND-HF (Fatigue, Increased water accumulation, Natriuretic pep-
Following a similar structure to the previous sections, and given
tide testing, and Dyspnoea-Heart Failure), which serves as a
the additional evidence emerged since that consensus was pub-
reminder for healthcare providers to consider heart failure in
lished,50 here we propose rule-in and rule-out cut-points, including
patients with any of these features and the need to check
a grey zone in between. A rule-out cut-point of 50 pg/ml is sug-
NT-proBNP.
gested to provide reassurance to clinicians regarding the patient’s
The presence of clinical congestion with ankle swelling, or pul-
heart health and may prompt routine check-ups on an annual
monary crackles should not be a prerequisite for suspecting heart
basis.48,51 Age-specific rule-in cut-points, consistent with the age
failure. The diagnosis of heart failure should be made much ear-
strata used in the ED and outpatient setting, are proposed. For
lier, long before symptoms and signs are so severe that the patient
patients younger than 50 years, a rule-in level of 75 pg/ml is advised.
needs to be hospitalized.41 Many individuals initially exhibit symp-
For patients aged 50–74 years, a cut-point of 150 pg/ml, and for
toms such as ‘fatigue’ and ‘dyspnoea’ before signs of congestion
those over 75 years of age, a cut-point of 300 pg/ml is proposed
(peripheral oedema or increased jugular venous pressure). Rec-
(Figure 3). Increased concentrations indicate the likelihood of heart
ognizing this pattern is crucial, particularly for GPs, for the early
stress, prompting careful re-evaluation of the patient for problems
detection of heart failure. By adopting the FIND-HF mnemonic,
such as atrial fibrillation and chronic kidney disease, lifestyle advice
healthcare professionals should attain a higher level of suspi-
cion for heart failure and have a lower threshold for making NP
measurements.

Screening for
Heart Stress Fatigue
in Asymptomatic patients with T2D
(or other risk factors for CVD) Increased water accumulation
Natriuretic peptide testing
NT-proBNP Dyspnoea
HF – heart failure
Rule-out Grey zone Age-adjusted
≤ 50pg/mL Rule-in
<50y: ≥ 75pg/mL
50-74y: ≥ 150pg/mL In summary, the implementation of NP testing is necessary to
≥75y: ≥ 300pg/mL
improve the diagnosis of heart failure. In the ED it can quickly
rule a diagnosis of heart failure in or out. In the outpatient setting,
NT-proBNP assists the early detection of heart failure, prompting
further diagnostic tests, such as echocardiography, and the timely
Heart Stress Heart Stress Heart Stress
Very Unlikely Not Likely Likely initiation of appropriate treatments that will improve well-being
Repeat NT-proBNP Repeat NT-proBNP in 6 Arrange Echocardiography and reduce morbidity and mortality. We now introduce the con-
in one year months Assessment by Heart Failure
team if cardiac dysfunction cept of NT-proBNP as a measure of heart stress for asymptomatic
present
patients with risk factors (i.e. diabetes) that which may be used to
Figure 3 NT-proBNP for diagnosis of heart stress in asymp- identify patients at increased risk of developing heart failure. Rou-
tomatic patients with diabetes. CVD, cardiovascular disease; tine screening with NT-proBNP enables interventions to delay or
NT-proBNP, N-terminal pro-B-type natriuretic peptide; T2D, prevent disease progression and the development of heart failure.
type 2 diabetes. The mnemonic FIND-HF is introduced as a reminder for early diag-
nosis of heart failure for both healthcare professionals and patients.

© 2023 European Society of Cardiology.

 18790844, 2023, 11, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ejhf.3036 by Cochrane Colombia, Wiley Online Library on [06/06/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
1896 A. Bayes-Genis et al.

Inc, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceu-

Supplementary Information

........................................................................................................................................................................
tical, Janssen Research & Development LLC, Medscape/WebMD Global
Additional supporting information may be found online in the LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Quidel Corpora-
Supporting Information section at the end of the article. tion, Radcliffe Group Ltd., Recardio Inc, ReCor Medical, Roche Diagnostics,
Sanofi, Siemens Healthcare Diagnostics and Us2.ai; and is a co-founder and
Conflict of interest: A.B.G. has participated in advisory boards and/or non-executive director of Us2.ai. R.P.B. has received research support to
lectured for Abbott, AstraZeneca, Boehringer Ingelheim, Novartis, Roche the University of Michigan from Novo Nordisk and Medtronic, and consult-
Diagnostics, Vifor Pharma. M.C.P. has received research grants from ing fees from AstraZeneca, Bayer, Nevro, Roche, Procter & Gamble. M.M.
SQ Innovations, AstraZeneca, Roche, Boehringer Ingelheim, Pharmacos- has received honoraria from Cytokinetics and Vifor pharma for partici-
mos, Eli Lilly, Napp Pharmaceuticals, Novartis, and Novo Nordisk, and pation in committee for sponsored clinical trials and has received con-
has served on committees for AbbVie, Akero, Alnylam, AstraZeneca, sulting honoraria from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim,
Bayer, Boehringer Ingelheim, GlaxoSmithKline, Resverlogix, Teikoku, New Roche Diagnostics in the last 3 years. All other authors have nothing
Amsterdam and Novo Nordisk; he is a director of Global Clinical Trial to disclose.
Partners). J.L.J. is a Trustee of the American College of Cardiology; is
a board member of Imbria Pharmaceuticals and Director at Jana Care;
has received research support from Abbott, Applied Therapeutics, Heart- References
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