BNP in the management of heart failure

• the NICE clinical guideline on CHF the use of BNP as a diagnostic tool for heart failure (1,2)
  • refer patients with suspected heart failure and previous myocardial infarction (MI) urgently, to have transthoracic Doppler 2D echocardiography and specialist assessment within 2 weeks (1)
  • refer people with suspected heart failure and an NT-proBNP level above 2,000 ng/litre (236 pmol/litre) urgently, to have specialist assessment and transthoracic echocardiography within 2 weeks - because very high levels of NT-proBNP carry a poor prognosis
    
    
  • refer people with suspected heart failure and an NT-proBNP level between 400 and 2,000 ng/litre (47 to 236 pmol/litre) to have specialist assessment and transthoracic echocardiography within 6 weeks
    
    
  • review alternative causes for symptoms of heart failure in people with NTproBNP levels below 400 ng/litre. If there is still concern that the symptoms might be related to heart failure, discuss with a physician with subspeciality training in heart failure
    
    
  • perform transthoracic echocardiography to exclude important valve disease, assess the systolic (and diastolic) function of the (left) ventricle, and detect intracardiac shunts
    • if a poor image is produced by transthoracic echocardiography
      • consider alternative methods of imaging the heart (for example, radionuclide angiography [multigated acquisition scanning], cardiac MRI or transoesophageal echocardiography)
        
        
  • note that:
    • obesity, African or African-Caribbean family origin, or treatment with diuretics, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, angiotensin II receptor blockers (ARBs) or mineralocorticoid receptor antagonists (MRAs) can reduce levels of serum natriuretic peptides
      
      
    • high levels of serum natriuretic peptides can have causes other than heart failure (for example, age over 70 years, left ventricular hypertrophy, ischaemia, tachycardia, right ventricular overload, hypoxaemia [including pulmonary embolism], renal dysfunction [eGFR less than 60 ml/minute/1.73m2], sepsis, chronic obstructive pulmonary disease, diabetes, or cirrhosis of the liver)
      
      
    • the level of serum natriuretic peptide does not differentiate between heart failure due to left ventricular systolic dysfunction and heart failure with preserved left ventricular ejection fraction

Notes:

• in the emergency department patients with dyspnoea, BNP and amino terminal proBNP concentrations had similar diagnostic accuracy for detecting patients with congestive heart failure (3,4)
  
  
• BNP and proBNP and cardiovascular risk
  • higher concentrations of BNP or proBNP, are consistently associated with increased risk of death and cardiovascular events (5)
    • proBNP concentrations of >= 100 ng/l increased risk of all-cause mortality in patients with or without stable coronary artery disease (6)
  • there is also evidence that pro-BNP is a marker of long-term mortality in patients with stable coronary disease and provides prognostic information above and beyond that provided by conventional cardiovascular risk factors and the degree of left ventricular systolic dysfunction (7)
  • BNP and cardiac toponin in healthy older adults (13)
    • a study investigated the prognostic value of detectable cardiac troponin T (TnT) and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in a population of community-dwelling older adults
      • revealed that apparently healthy adults with detectable TnT or elevated NT-proBNP levels are at increased risk of death
      • those with both TnT and NT-proBNP elevations are at even higher risk, and the increased risk persists for years
  • proBNP and cardiovascular risk in type 2 Diabetes (14)
    • NT-proBNP was a biomarker with a discriminatory ability to predict both death and CV events as accurately as a multivariable risk model in T2DM patients with CVD and/or CKD comorbidity. NT-proBNP significantly improved the risk stratification of high-risk T2DM patients when added to the multivariable risk prediction model
      
      
• BNP measurement was superior to two-dimensional echocardiographic determination of EF in identifying CHF, regardless of the threshold value, in patients with acute dyspnoea (8)
• in patients with atrial fibrillation (AF)
  • the presence of AF is associated with higher circulating BNP levels, suggesting that a higher diagnostic threshold should be used in patients with AF 9)
• patients with both a completely normal ECG and normal BNP are unlikely to have heart failure (10)
• BNP and management of heart failure (11):
  • low concentrations of BNP make heart failure unlikely
    • a low concentration (< 100pg/ml) makes heart failure unlikely
  • high levels of BNP in heart failure predict a poor prognosis
    • plasma BNP appears to be the most useful single predictor of prognosis. A very high level on optimal drug treatment (above 500 pg/ml) suggests a poor prognosis, and a low level (below 100pg/ml) suggests the patient will do well
  • driving down BNP levels by aggressive treatment improves the clinical outcome
    • treatment with a diuretic, ACE inhibitor or angiotensin receptor blocker (ARB) reduces the concentration, and beta-blockers may initially increase but then decrease the blood concentration. Reduced excretion of BNP in serious kidney dysfunction (creatinine above 200 ìmol/l) can contribute to increased plasma BNP levels
    • patients with heart failure do better if the doctor is aware of the plasma BNP concentration and tries to drive it down to a low level (<100 pg/ml) by more aggressive use of beta-blockers and ACE inhibitors or ARBs
  • BNP is not recommended for screening for cardiac dysfunction in the general population
  • NICE state that (1):
    • consider measuring NT-proBNP (N-terminal pro-B-type natriuretic peptide) as part of a treatment optimisation protocol only in a specialist care setting for people aged under 75 who have heart failure with reduced ejection fraction and an eGFR above 60 ml/min/1.73m2
• obesity and natiuretic peptides
  • main confounder in the interpretation of natriuretic peptides is the concurrent presence of obesity, which is associated with lower BNP/NT-proBNP levels than expected from heart failure severity (14)

Reference:

• (1) NICE (August 2010). chronic heart failure
• (2) NICE (September 2018).Chronic heart failure in adults: diagnosis and management
• (3) Mueller T et al. Diagnostic accuracy of B type natiuretic peptide and amino terminal proBNP in the emergency diagnosis of heart failure. Heart 2005; 91: 606-12
• (4) Moe GW et al. N-terminal pro-B-type natriuretic peptide testing improves the management of patients with suspected acute heart failure: primary results of the Canadian prospective randomized multicenter IMPROVE-CHF study.Circulation. 2007 Jun 19;115(24):3103-10.
• (5) Marz W et al. N-terminal pro-B-type natriuretic peptide predicts total and cardiovascular mortality in individuals with or without stable coronary artery disease: the Ludwigshafen Risk and Cardiovascular Health Study.Clin Chem. 2007 Jun;53(6):1075-83.
• (6) Doust JA et al. How well des B-type natriuretic peptide predict death and cardiac events in patients with heart failure: systematic review. BMJ 2005;330:625
• (7) Kragelund C et al. N-terminalpro-B-type natriuretic peptide and long-term mortality in stable coronary heart disease. N Eng J Med 2005;352:666-75
• (8) Steg PG et al. B-type natriuretic peptide and echocardiographic determination of ejection fraction in the diagnosis of congestive heart failure in patients with acute dyspnea. Chest 2005;128:21-9.
• (9) Knudsen CW et al. Impact of atrial fibrillation on the diagnostic performance of B-type natriuretic peptide concentration in dyspneic patients: an analysis from the Breathing Not Properly Multinational Study. J Am Coll Cardiol 2005;46:838-44
• (10) Commentary. Evidence Based Medicine 2006; 11:117.
• (11) British Heart Foundation (November 2008). The roel of B-type natriuretic peptide (BNP) in the management of heart failure.
• (12) Daniels LB et al. Minimally elevated cardiac troponin T and elevated N-terminal pro-B-type natriuretic peptide predict mortality in older adults: results from the Rancho Bernardo StudyJ Am Coll Cardiol. 2008 Aug 5;52(6):450-9.
• (13) Malachias MVB, Jhund PS, Claggett BL, et al.NT-proBNP by Itself Predicts Death and Cardiovascular Events in High-Risk Patients With Type 2 Diabetes Mellitus. J Am Heart Assoc. 2020;9:e017462. DOI: 10.1161/JAHA.120.017462
• (14) Daniels L et al. How obesity affects the cut-points for B-type natriuretic peptide in the diagnosis of acute heart failure. Results from the Breathing Not Properly Multinational Study. Am Heart J. 2006 May;151(5):999-1005.