NT-proBNP
NT-proBNP rises with strain on the heart. European guidelines treat below 125 pg/mL as making chronic heart failure unlikely and below 300 as ruling out acute heart failure, while UK guidance uses 400. Higher levels were linked to more heart failure and deaths. Obesity lowers the result, and age, kidney disease and atrial fibrillation raise it.
- Status
- A blood test ordered by a clinician. FDA classifies B-type natriuretic peptide test systems, used as an aid in the diagnosis of congestive heart failure, as class II devices with special controls [1].
- Measures
- The concentration of N-terminal pro-B-type natriuretic peptide in blood, a marker of the presence and severity of hemodynamic stress on the heart and of heart failure [2].
- Also called
- N-terminal pro-B-type natriuretic peptide, NT-proBNP, NT pro BNP, NTproBNP, proBNP, pro-BNP, N-terminal proBNP, amino-terminal pro-brain natriuretic peptide
- Tested for
- heart failure, shortness of breath, swollen legs, strain on the heart, heart risk screening, monitoring heart failure treatment
Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on
Linked in research3
- ModerateLinked to about twice the rate of heart disease, stroke or heart failure in the top third against the bottom third among 95,617 people without cardiovascular disease.
- ModerateLinked to about 2.4 times the deaths from any cause in the highest against the lowest category across 11 general population studies.
- LimitedOne trial of 300 people with diabetes and NT-proBNP above 125 pg/mL found intensified heart drug treatment cut cardiac hospital stays or deaths by 65%.
Reported risks0
No risks sourced yet.
Reference ranges
Each range is the one its source published, in pg/mL. Also reported in pmol/L. Where sources differ, each is shown.
European Society of Cardiology heart failure guidelines, 2021, rule-out outside an emergency
Adults with symptoms that suggest heart failure, seen in a non-acute setting · [3], [4]
| Range | What the source calls it |
|---|---|
| below 125 pg/mL | "HF unlikely" |
| 125 or above pg/mL | No name given |
A rule-out threshold. The guideline states that a concentration below 125 pg/mL makes a diagnosis of heart failure unlikely, and calls 125 pg/mL the upper limit of normal in the non-acute setting. In the studies it relied on, the negative predictive values of results below the threshold ranged from 0.94 to 0.98. A result at or above 125 does not establish heart failure: the guideline's pathway goes on to echocardiography, and it lists many cardiac and non-cardiac causes of a raised level, among them atrial fibrillation, increasing age and acute or chronic kidney disease. It adds that levels may be disproportionately low in people with obesity. For heart failure with preserved ejection fraction its table uses above 125 pg/mL in sinus rhythm and above 365 pg/mL in atrial fibrillation [3]. The factor to pmol/L on this page matches the paired values UK guidance prints, 400 ng/L for 47 pmol/L and 2,000 ng/L for 236 pmol/L, and ng/L is the same number as pg/mL [4].
European Society of Cardiology heart failure guidelines, 2021, acute setting, aged under 55
Adults younger than 55 being assessed for new onset acute heart failure · [3], [5]
| Range | What the source calls it |
|---|---|
| below 300 pg/mL | "acute heart failure ruled out" |
| 300 to 450 pg/mL | No name given |
| above 450 pg/mL | "rule-in value for acute HF" |
From the guideline's diagnostic workup of new onset acute heart failure. Below 300 pg/mL at any age the pathway reads acute heart failure ruled out. At 300 or above it moves toward confirmation, with a footnote giving rule-in values by age: above 450 pg/mL under 55, above 900 between 55 and 75, and above 1,800 over 75. A result between the rule-out and the rule-in value has no name in the guideline. The guideline notes that low values occur in some people with advanced heart failure, obesity, flash pulmonary edema or right-sided acute heart failure, and higher values with atrial fibrillation or reduced kidney function [3]. The pooled study behind these values drew its age bands at under 50, 50 to 75 and over 75, so the guideline's lowest band is drawn five years higher than the study's [5].
European Society of Cardiology heart failure guidelines, 2021, acute setting, aged 55 to 75
Adults aged 55 to 75 being assessed for new onset acute heart failure · [3], [5]
| Range | What the source calls it |
|---|---|
| below 300 pg/mL | "acute heart failure ruled out" |
| 300 to 900 pg/mL | No name given |
| above 900 pg/mL | "rule-in value for acute HF" |
From the same pathway and footnote. In the pooled study that proposed age-related cut points, 450, 900 and 1,800 pg/mL together gave 90% sensitivity and 84% specificity for acute heart failure among 1,256 patients with acute breathlessness, and 300 pg/mL had a 98% negative predictive value at any age [5][3].
European Society of Cardiology heart failure guidelines, 2021, acute setting, aged over 75
Adults older than 75 being assessed for new onset acute heart failure · [3], [5]
| Range | What the source calls it |
|---|---|
| below 300 pg/mL | "acute heart failure ruled out" |
| 300 to 1800 pg/mL | No name given |
| above 1800 pg/mL | "rule-in value for acute HF" |
From the same pathway and footnote. The rule-in value is highest in this age band, and the guideline lists advanced age among the non-cardiac causes of a raised level [3]. The age bands in the underlying study were under 50, 50 to 75 and over 75 [5].
National Institute for Health and Care Excellence guideline, 2018, updated 2025
Adults with suspected heart failure who have not yet been treated · [4]
| Range | What the source calls it |
|---|---|
| below 400 pg/mL | "heart failure less likely" |
| 400 to 2000 pg/mL | No name given |
| above 2000 pg/mL | "very high" A doctor, immediately |
Printed in ng/L, which is the same number as pg/mL. The guideline states that a level below 400 in an untreated person makes a diagnosis of heart failure less likely. It calls for specialist assessment and echocardiography within 6 weeks at 400 to 2,000, and urgently, within 2 weeks, above 2,000, because very high levels carry a poor prognosis. Its rule-out threshold is more than three times the 125 pg/mL of the European guideline for the same non-acute setting. It states that obesity, African or African-Caribbean family background, and treatment with diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitors, beta-blockers or mineralocorticoid receptor antagonists can reduce the level, and that high levels can have causes other than heart failure, including lung, kidney and liver disease, sepsis and diabetes [4].
How it compares with the reference method
Mixed results2
Ruling acute heart failure out and in
Shown to exclude acute heart failure with 99% sensitivity below 300 pg/mL, while about 4 in 10 people above the age-specific values did not have it.
The numbers and sources
- Compared with
- A final diagnosis of acute heart failure made by clinicians with access to imaging and the full record
- Effect
- In a diagnostic meta-analysis in acute care, NT-proBNP at a threshold of 300 pg/mL had a sensitivity of 0.99 (95% CI 0.97 to 1.00) and a negative predictive value of 0.98 (0.89 to 1.0) for acute heart failure. At higher thresholds sensitivity declined and specificity varied, and the authors conclude that imaging is required to confirm a diagnosis [11]. In a North American emergency department study, the age-specific values of 450, 900 and 1,800 pg/mL had sensitivities of 85.7%, 79.3% and 75.9%, specificities of 93.9%, 84.0% and 75.0%, and positive predictive values of 53.6%, 58.4% and 62.0%. The 300 pg/mL rule-out value had a sensitivity of 93.9% and a negative predictive value of 98.0% [12].
- Population
- 37 study cohorts with 15,263 test results [11]. 1,461 patients with breathlessness at 19 emergency departments, 277 of them with acute heart failure [12].
- Sources
- [11], [12]
- Caveats
- These figures describe people who came to hospital acutely breathless. They do not describe a result from a routine blood draw in someone without symptoms. A predictive value depends on how common heart failure is among those tested, which was 19% in the emergency department study [12].
Variation within one person
Shown to vary within one person by about 10% over days and about 34% over longer intervals in a meta-analysis of 21 studies.
The numbers and sources
- Compared with
- The same person's results on repeat blood draws
- Effect
- A meta-analysis of biological variation studies found within-person variation of NT-proBNP of 9.9% (95% CI 8.8 to 18.0) when samples were taken over less than 15 days and 34.3% (25.0 to 60.0) over more than 15 days [15]. In one of the studies, within-person variation was 21.8% and a change of 61.7% was needed between two results to exceed expected variation. The variation was comparable in patients with chronic heart failure and in healthy participants [16].
- Population
- 21 studies of biological variation, 3 of which met every item of the review's quality checklist [15]. 83 patients with chronic heart failure followed for 6 weeks and 28 people the study classed as healthy followed for 4 months [16].
- Sources
- [15], [16]
- Caveats
- The estimate depended on how often and for how long people were sampled. The studies state no threshold for agreement, so the result is given as numbers only [15].
Did not match the reference method3
Obesity
One study found NT-proBNP told acute heart failure apart less well in people with obesity, who run lower levels, and 300 pg/mL missed 9 of 271 cases.
The numbers and sources
- Compared with
- Diagnostic accuracy in patients without obesity in the same study
- Effect
- Among patients with acute breathlessness, the area under the curve for acute heart failure was 0.890 in those with obesity and 0.938 in those without. In patients with obesity the 300 pg/mL rule-out value had a sensitivity of 96.7% and missed 9 of 271 patients with acute heart failure. Lowering the cut-offs by 33% at a body mass index of 30 to 34.9 and by 50% at 35 or above raised sensitivity to 98.2%, missing 5 patients, and lowered specificity from 84.9% to 76.5% [13]. A cardiology society statement describes cut-off concentrations about 50% lower for people with obesity [2], and the European and UK guidelines both note lower levels with obesity [3][4].
- Population
- 2,038 patients presenting to emergency departments with acute breathlessness, 509 of them with obesity [13].
- Sources
- [13], [2], [3], [4]
- Caveats
- One diagnostic study in the acute setting. The adjusted cut-offs are a proposal from that study and are not part of the guideline ranges on this page [13].
Kidney function
Shown to run higher with reduced kidney function, where studies used a median cut point of 1,980 pg/mL against 450 with preserved function.
The numbers and sources
- Compared with
- Diagnostic accuracy in patients with an estimated GFR of 60 or above in the same studies
- Effect
- In a meta-analysis of studies that reported results by kidney function, most divided patients at an estimated GFR of 60 mL/min per 1.73 m². With reduced kidney function the area under the curve for acute decompensated heart failure ranged from 0.66 to 0.89 at a median cut point of 1,980 pg/mL. With preserved function it ranged from 0.72 to 0.95 at a cut point of 450 pg/mL. The authors conclude that NT-proBNP keeps its usefulness for diagnosis in reduced kidney function at higher cut points [8]. The European guideline lists renal dysfunction among the causes of a raised level [3].
- Population
- 4,287 patients in 9 diagnostic studies, with 1,325 cases of acute decompensated heart failure [8].
- Sources
- [8], [3]
- Caveats
- The cut points varied between the studies and were chosen within each one. None of the guideline ranges on this page is adjusted for kidney function.
Atrial fibrillation
One study found atrial fibrillation raised NT-proBNP in people without heart failure and cut its accuracy for acute heart failure from about 0.90 to between 0.70 and 0.76.
The numbers and sources
- Compared with
- Diagnostic accuracy in patients without atrial fibrillation in the same study
- Effect
- Among patients with acute breathlessness, atrial fibrillation without heart failure was associated with markedly higher natriuretic peptide levels than neither condition. The area under the curve for acute heart failure was 0.893 to 0.912 across three natriuretic peptides in patients without atrial fibrillation and 0.701 to 0.757 in patients with it [14]. The European guideline's table for heart failure with preserved ejection fraction uses an NT-proBNP above 365 pg/mL in atrial fibrillation in place of 125 pg/mL in sinus rhythm [3].
- Population
- 1,445 patients attending emergency departments with acute breathlessness, 242 of them with atrial fibrillation [14].
- Sources
- [14], [3]
- Caveats
- The abstract gives the accuracy as a range across three peptides and does not single out NT-proBNP. The authors call for adjusted thresholds in atrial fibrillation without proposing values [14].
What studies tie it to
Linked in research3
Heart failure, heart disease and stroke in people without cardiovascular disease
Linked to about twice the rate of heart disease, stroke or heart failure in the top third against the bottom third among 95,617 people without cardiovascular disease.
The numbers and sources
- Effect
- In an individual-participant meta-analysis, people in the top third of NT-proBNP had a risk ratio of 1.76 (95% CI 1.56 to 1.98) for coronary heart disease or stroke and 2.00 (1.77 to 2.26) for coronary heart disease, stroke or heart failure against the bottom third, after adjustment for conventional risk factors. Adding NT-proBNP to those risk factors raised the C-index by 0.019 for the combined outcome. The authors describe it as a strong predictor of first-onset heart failure [6].
- Population
- 95,617 participants without a history of cardiovascular disease in 40 prospective studies, with 5,500 coronary heart disease, 4,002 stroke and 2,212 heart failure outcomes [6].
- Sources
- [6]
- Caveats
- Observational. The comparison is between thirds of the distribution in people without cardiovascular disease, not between the bands of the guideline ranges on this page [6].
Death from any cause and from cardiovascular disease
Linked to about 2.4 times the deaths from any cause in the highest against the lowest category across 11 general population studies.
The numbers and sources
- Effect
- In a meta-analysis of prospective studies in the general population, the highest category of NT-proBNP against the lowest had a hazard ratio of 2.44 (95% CI 2.11 to 2.83) for death from any cause, 3.77 (2.85 to 5.00) for cardiovascular death and 2.35 (1.45 to 3.82) for death from coronary heart disease [7]. Among patients with acute heart failure in a pooled emergency department study, a level above 5,180 pg/mL at presentation went with death within 76 days (OR 5.2, 95% CI 2.2 to 8.1) [5]. In a meta-analysis by kidney function, the unadjusted risk ratio for death with a raised NT-proBNP was 3.01 (2.53 to 3.58) in patients with preserved kidney function and 3.25 (2.45 to 4.30) in patients with reduced function [8].
- Population
- 25,715 people in 11 studies [7]. 720 patients with acute heart failure among 1,256 with acute breathlessness [5]. 32,203 patients in 30 studies [8].
- Sources
- [7], [5], [8]
- Caveats
- Observational. The studies defined the highest and lowest categories by different cut points [7].
Treatment offered because the level was raised, in people with diabetes
One trial of 300 people with diabetes and NT-proBNP above 125 pg/mL found intensified heart drug treatment cut cardiac hospital stays or deaths by 65%.
The numbers and sources
- Effect
- People with type 2 diabetes, an NT-proBNP above 125 pg/mL and no cardiac disease were assigned to usual diabetes care or to additional treatment at a cardiac clinic, where renin-angiotensin system blockers and beta-blockers were raised to the highest tolerated doses. After 2 years, hospitalization or death due to cardiac disease was less frequent in the intensified group (HR 0.351, 95% CI 0.127 to 0.975) [10].
- Population
- 300 people with type 2 diabetes, mean age 67.5, with a median NT-proBNP of 265.5 pg/mL [10].
- Sources
- [10]
- Caveats
- One trial of 300 people with a wide confidence interval. It tested treating people selected by the marker. It did not compare them with people whose level was not raised, and it does not show what lowering the level itself does [10].
Checked, no link found1
Treatment steered by the level in heart failure
One trial found that adjusting heart failure drugs toward an NT-proBNP below 1,000 pg/mL did not reduce hospital stays or cardiovascular deaths against usual care.
The numbers and sources
- Effect
- Patients with heart failure and reduced ejection fraction were assigned to therapy titrated toward an NT-proBNP below 1,000 pg/mL or to usual care. Over a median 15 months, a first heart failure hospitalization or cardiovascular death occurred in 37% of each group (adjusted HR 0.98, 95% CI 0.79 to 1.22). Cardiovascular death occurred in 12% and 13%. The falls in NT-proBNP achieved did not differ significantly between the groups, and the trial was stopped early for futility [9].
- Population
- 894 patients at 45 sites in the United States and Canada, median age 63, with an ejection fraction of 40% or below and a recent heart failure event [9].
- Sources
- [9]
- Caveats
- The two groups reached similar NT-proBNP levels, so the trial compared two strategies of care more than two levels of the marker. Its abstract notes that earlier, smaller trials of guided therapy had inconsistent results [9].
Sources
- US Food and Drug Administration. 21 CFR 862.1117, B-type natriuretic peptide test system. Electronic Code of Federal Regulations. https://www.ecfr.gov/current/title-21/section-862.1117
- Mueller C, McDonald K, de Boer RA, et al. Heart Failure Association of the European Society of Cardiology practical guidance on the use of natriuretic peptide concentrations. European Journal of Heart Failure. 2019. https://doi.org/10.1002/ejhf.1494
- McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. European Heart Journal. 2021. https://doi.org/10.1093/eurheartj/ehab368
- National Institute for Health and Care Excellence. Chronic heart failure in adults: diagnosis and management. NICE guideline NG106. Published September 2018, last updated September 2025. https://www.nice.org.uk/guidance/ng106
- Januzzi JL, van Kimmenade R, Lainchbury J, 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. European Heart Journal. 2006. https://doi.org/10.1093/eurheartj/ehi631
- Natriuretic Peptides Studies Collaboration, Willeit P, Kaptoge S, et al. Natriuretic peptides and integrated risk assessment for cardiovascular disease: an individual-participant-data meta-analysis. The Lancet Diabetes and Endocrinology. 2016. https://doi.org/10.1016/S2213-8587(16)30196-6
- Geng Z, Huang L, Song M, Song Y. N-terminal pro-brain natriuretic peptide and cardiovascular or all-cause mortality in the general population: A meta-analysis. Scientific Reports. 2017. https://doi.org/10.1038/srep41504
- Schaub JA, Coca SG, Moledina DG, et al. Amino-Terminal Pro-B-Type Natriuretic Peptide for Diagnosis and Prognosis in Patients With Renal Dysfunction: A Systematic Review and Meta-Analysis. JACC: Heart Failure. 2015. https://doi.org/10.1016/j.jchf.2015.07.014
- Felker GM, Anstrom KJ, Adams KF, 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. JAMA. 2017. https://doi.org/10.1001/jama.2017.10565
- Huelsmann M, Neuhold S, Resl M, et al. PONTIAC (NT-proBNP Selected Prevention of Cardiac Events in a Population of Diabetic Patients Without a History of Cardiac Disease): A Prospective Randomized Controlled Trial. Journal of the American College of Cardiology. 2013. https://doi.org/10.1016/j.jacc.2013.05.069
- Roberts E, Ludman AJ, Dworzynski K, et al. The diagnostic accuracy of the natriuretic peptides in heart failure: systematic review and diagnostic meta-analysis in the acute care setting. BMJ. 2015. https://doi.org/10.1136/bmj.h910
- Januzzi JL, Chen-Tournoux AA, Christenson RH, et al. N-Terminal Pro-B-Type Natriuretic Peptide in the Emergency Department: The ICON-RELOADED Study. Journal of the American College of Cardiology. 2018. https://doi.org/10.1016/j.jacc.2018.01.021
- Kozhuharov N, Martin J, Wussler D, et al. Clinical effect of obesity on N-terminal pro-B-type natriuretic peptide cut-off concentrations for the diagnosis of acute heart failure. European Journal of Heart Failure. 2022. https://doi.org/10.1002/ejhf.2618
- Richards M, Di Somma S, Mueller C, et al. Atrial Fibrillation Impairs the Diagnostic Performance of Cardiac Natriuretic Peptides in Dyspneic Patients: Results From the BACH Study (Biomarkers in ACute Heart Failure). JACC: Heart Failure. 2013. https://doi.org/10.1016/j.jchf.2013.02.004
- Fernández-Calle P, Díaz-Garzón J, Bartlett B, et al. Biological Variation of Natriuretic Peptides and Other Cardiovascular Disease-Related Biomarkers: A Systematic Review and Meta-analysis. Clinical Chemistry. 2026. https://doi.org/10.1093/clinchem/hvag051
- Meijers WC, van der Velde AR, Muller Kobold AC, et al. Variability of biomarkers in patients with chronic heart failure and healthy controls. European Journal of Heart Failure. 2017. https://doi.org/10.1002/ejhf.669