Transcript Whistle Stop Talk No. 5

Whistle Stop Talk
No. 5
BNP + NTproBNP INFORMATION AND
GUIDELINES
Susie Bowell BA Hons, RGN
Heart Failure Specialist Nurse
B-TYPE NATRIURETIC PEPTIDES
Natriuretic peptides are vasodilatory
neurohormones released from the
ventricles in response to wall stress/strain
BNP is synthesized in myocytes as larger
molecules (e.g., proBNP) that are
subsequently cleaved to yield the active
peptide hormone (e.g., BNP) and the
biologically inactive N-terminal peptide
fragment (e.g., NT-proBNP)
Myocardial stretch consequent to volume
status is an important trigger for the
release of natriuretic peptides 9
When interpreting results for either BNP
or NT-proBNP, clinicians should remember
that a significant percentage of their
release is triggered by filling pressures,
particularly when there are very high
concentrations of either peptide (e.g. BNP
> 500 pg/mL or NT-proBNP > 5000
pg/mL)10
BNP counteracts the vasoconstriction
that occurs as a compensatory
mechanism in heart failure by
relaxing vascular smooth muscle cells
It promotes natriuresis and diuresis
Suppresses the RAAS
Improves diastolic relaxation
NTproBNP is more stable than BNP.
Raised in both HFrEF and HFpEF in
presence of increased wall stress
Role of bnp/nt-probnp
blood test
Screening
Diagnosis of HF
– In patients with non-specific symptoms
Prognostic indicator
– Heart failure, acute coronary syndromes
Monitoring / guiding therapy in HF
Valve disease assessment / prognosis
Rodeheffer R. JACC 2004;44:740-9
Screening for asymptomatic left
ventricular dysfunction with bnp
• In one study of 75 MI survivors without HF, plasma BNP levels had an 84%
sensitivity in identifying the presence of asymptomatic LVSD.6
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Another study in 1252 randomly selected individuals, aged 25 to 74 years, found that
plasma BNP levels had a 77% sensitivity and 87% specificity in identifying 19
asymptomatic and 18 symptomatic individuals with LVEF 30%.
When the population was limited to patients older than 55 years with a history of
Coronary Artery Disease, BNP sensitivity rose to 92%, and specificity was reduced to
72%.7.
The prevalence of ALVD in patients at risk for HF is 5.1%. Because of its
excellent net present value, NT-pro-BNP assessment can be used by general
practitioners to rule out ALVD in hypertensive or diabetic patients [PROBE-HF]
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Mixed TRIAL EVIDENCE FOR DIAGNOSING HF USING
NTproBNP +/- ecg
• A recent systematic review and meta-analysis concluded
that the accuracy of both tests is comparable and that
either can be used; there is no evidence to justify the use of
both together. 3
• Galasko et al4 argued in their study, that performing both
ECG and NTproBNP produced no additional cost savings.
• Goode et al5 found the converse to be true. In their
primary care screening study in high risk patients, the cost
benefit of using NTproBNP alone occurred at the expense
of test sensitivity (76%).
• Ng et al found in their community screening program that
the ECG alone was neither sensitive nor specific for
identification of definite or borderline LVSD 6.
Guiding/monitoring hf
treatment
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Recent guidelines stress the importance of serial measurement of BNP or NT-proBNP
for this indication 13
Neurohormonal agents, such as ACE inhibitors and ARBs, cause peptide concentrations
to fall due to their favourable effects on filling pressures and cardiac haemo-dynamics
as well as their effects on ventricular remodelling10
Beta-blockers may initially increase natriuretic peptide concentrations, however in
chronic optimal beta-blocker therapy, the concentrations of natriuretic peptides fall,
reflecting the remodelling of the left ventricle10
Unless in cases of significant congestion or marked elevation of BNP or NT-proBNP,
strategies for lowering natriuretic peptide concentrations should focus on therapies
with mortality benefit in chronic HF care, such as ACE inhibitors, ARBs, beta-blockers,
aldosterone antagonists, exercise therapy or optimization (or placement) of cardiac
resynchronization therapy10
Not all patients show ‘‘response’’ to BNP- or NT-proBNP-guided care; in this setting,
continued optimization of medication is advised, with review of salt/water restriction,
diet, lifestyle and medication adherence10
When a patient is truly optimized but is a BNP or NT-proBNP ‘‘non-responder’’ with an
elevated ‘‘dry’’ natriuretic peptide value, their prognosis is poor and alternative modes
of therapy should be considered10
Mortality prediction
• Studies in a variety of populations have shown that the plasma level of NTproBNP predicts mortality, for example, in -:
– in post-myocardial infarction patients4
– in emergency department patients with dyspnoea (the ProBNP
Investigation of Dyspnoea in the Emergency Department [PRIDE]
study)2
– in patients with a diagnosis of severe CHF (the Carvedilol Prospective
Randomized Cumulative Survival [COPERNICUS] trial)3
– NT-proBNP level and NYHA classification bear the best prognostic
information in elderly patients with CHF, but this is limited to the first
year after measurement5
Valve disease
assessment/prognosis
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Overall there was a steady increase in natriuretic peptide levels with decreasing
valve area and a large increase when ejection fraction fell below 50%.
Synthesis and release of brain natriuretic peptide (BNP) are increased in heart
failure and plasma levels provide important therapeutic and prognostic
information 13
In general peptide levels are greater with increasingly severe valvular abnormality,
the presence of symptoms and with pronounced ventricular remodelling. Both in
aortic stenosis and degenerative mitral regurgitation there is evidence that BNP
might identify those asymptomatic patients on the verge of developing symptoms
or haemodynamic compromise13
Plasma natriuretic peptide levels are elevated in symptomatic patients with aortic
stenosis. Measurement of natriuretic peptides may complement clinical and
echocardiographic evaluation of patients with aortic stenosis14
NTproBNP
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There are several conditions which may affect the serum NP levels beyond heart
failure – for example
Left Ventricular Hypertrophy,
Ischaemia,
Tachycardia,
Right Ventricular overload,
Hypoxaemia (including pulmonary embolism),
Renal dysfunction,
Sepsis,
Advanced age and
Cirrhosis of the liver.
Levels may be lower in obesity and in females
Results should be interpreted in the context of current pharmacological treatment
and taking into consideration all of the above.
How therapies affect
levels
10
Therapies for heart failure that may lower B-type natriuretic peptide (BNP) or NTproBNP
concentrations
Therapy
Effect on BNP/NT-proBNP
Diuresis (loop or thiazide)
ACE-1
ARB
Beta blockers
Aldosterone Antagonists
CRT
Exercise
Rate control of AF
BNP infusions
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Some transiently ↑, most ↓
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N-BNP ↓, BNP ↑, then ↓
ACE-I: angiotensin converting enzyme inhibitor; AF: atrial fibrillation; ARB: angiotensin receptor
blocker; BNP: B-type natriuretic peptide; CRT: cardiac resynchronisation therapy; NT-pro BNP:
amino terminal pro B type natriuretic peptide
Bnp/NT-proBNP
Cut off levels in European Society of Cardiology guidelines
are lower than NICE guidelines.
Be aware that affected by ACE, BB’s and diuretics especially.
In patients who are treatment naive, if BNP or NTproBNP is
entirely normal, HF, as a diagnosis at the time, can be ruled
out. Intermediate results mean that HF is still possible.
NTproBNP test from CMFT is currently funded by CCG for
central patients. BNP testing from UHSM is currently going
through the commissioning process and should be available
shortly
Esc BNP/NT-pro Guidelines
The exclusion threshold differs for patients presenting with acute onset or
worsening of symptoms (e.g. to a hospital emergency department) and those
presenting with a more gradual onset of symptoms.
For patients presenting with acute onset or worsening of symptoms, the optimal
exclusion cut-off point is 300 pg/mL for NT-proBNP and 100 pg/mL for BNP.
For patients presenting in a non-acute way, the optimum exclusion cut-off point is
125 pg/mL for NT-proBNP and 35 pg/mL for BNP. The sensitivity and specificity of
BNP and NT-proBNP for diagnosis are lower in non-acute patients.
Esc Guidelines
Suspected heart failure
Non acute onset
Acute onset
ECG
Chest X-ray
ECG
Possibly chest X-ray
Echocardiography
BNP/NTproBNP
BNP/NTproBNP
ECG normal and
NTproBNP<300pg/mL or
BNP<100pg/mL
ECG abnormal and
NTproBNP≥300pg/mL or
BNP≥100pg/mL
ECG abnormal or
NTproBNP≥125pg/mL or
BNP≥35pg/mL
Heart Failure unlikely
Echocardiography
ECG normal and
NTproBNP<125pg/mL or
BNP<35pg/mL
Heart Failure unlikely
Echocardiography
If heart failure confirmed
determine aetiology and
start appropriate treatment
NICE GUIDELINES
A high natriuretic peptide level is not only of diagnostic significance, but also of
prognostic significance11
Thresholds:
BNP >400 pg/ml or NT-proBNP>2000 pg/ml - need an echocardiogram and specialist clinical
assessment no longer than 2 weeks from the time of presentation.
BNP 100-400 pg/ml or NT-proBNP 400-2000 pg/ml - need an echocardiogram and clinical
assessment by the Specialist within 6 weeks from the time of presentation
BNP <100 pg/ml or NT-proBNP <400 pg/ml in the absence of heart failure therapy: Heart
Failure is an unlikely cause for the presentation
NB units of pg/mL and ng/L are different ways of expressing the same result
NICE Guidelines for
Diagnosis of heart failure
1. Refer patients with suspected heart failure and previous myocardial infarction (MI) urgently,
to have echocardiography and specialist assessment within 2 weeks.
2. Measure serum natriuretic peptides BNP or NTproBNP in patients with suspected heart
failure without previous MI.
3. Because very high levels of serum natriuretic peptides carry a poor prognosis, refer patients
with suspected heart failure and a BNP level above 400 pg/ml or an NTproBNP level above
2000 pg/ml (236 pmol/litre) urgently, to have transthoracic Doppler 2D echocardiography
and specialist assessment within 2 weeks.
NICE HF GUIDELINES 2010
Nice algorithm
Recommendations from (hf
expert) consensus group
Martin R Cowie, Paul O Collinson, Henry Dargie, FD Richard Hobbs, Theresa A McDonagh, Kenneth McDonald, Nigel Rowell March 2010, Volume 17, Issue 2 Br J Cardiol 2010;17:76–80
‘The decision cut-points recommended by the consensus group for use in acute
and chronic healthcare settings are shown in table 1. While the manufacturers cite
a single cut-point for both settings, the group felt that having a lower value for
primary care would increase GPs’ confidence in the test as there will be minimal
risk of false-negative results’
LAB INFORMATION
cmft – nt-pro-bnp
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Central Manchester Foundation Trust – Biochemistry:
The core opening hours of the laboratory are 8.00am to 5.00pm Monday-Friday. The out of
hours service is manned by a limited number of staff from 5.00pm to 8.30am and only one
Biomedical Scientist is available between 8.30pm and 8.30am.
Results Line
If you need to telephone for results call the ‘Results-Line’ 0161 276 8766 Monday–Friday
8.00 am–8.00 pm
Duty Biochemist
The Duty Biochemist can be “bleeped” on 4375 during normal hours. Out of normal hours,
one of the Consultant staff is available via the Trust switchboard.
Mobile number: 07771 703383
NTproBNP is more stable than BNP and does not need to be analysed within a four hour period and ca
Analyte
Reference Range
Turnaround Time
Specimen Notes
NTproBNP
Up to 400pg/ml
Only available
routinely for GP
samples
Yellow top tube
(serum)
Lab information uhsm - bnp
Results/general enquiries - ext 2125
Opening Times
Staff are present 24 hours/day
Routine work - Monday - Friday, 09.00 - 17.30hrs
All other times, staff are present for essential and emergency work.
BNP is not as stable as NTproBNP. Samples of BNP need to be
assayed within 4 hours
UHSM LAB INFORMATION
EDTA plasma sample
Results in ng/L
Samples need to be received same day
Interpretative comments on all results
BNP < 100 ng/L
A diagnosis of heart failure is unlikely
in an untreated patient
BNP 100 - 400 ng/L :
Suggest refer for Echo and post Echo a specialist assessment if appropriate in < 6 weeks
BNP > 400 ng/L
Suggest refer for Echo and
post Echo a specialist assessment if appropriate in < 2 weeks
.
Uhsm contacts information
Dr Graham Horsman
Consultant Chemical Pathologist
Biochemistry Department
Wythenshawe Hospital
0161 291 4791 (Direct)
0161 291 2122 (Secretary)
Dr Anne-Marie Kelly
Consultant Chemical Pathologist
Biochemistry Department
Wythenshawe Hospital
0161 291 2132 (Direct)
0161 291 2122 (Secretary)
Duty Biochemist
Biochemistry Department
Wythenshawe Hospital
0161 291 2136
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