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Heart Failure
Table 1: Some Causes of Elevation of NT-proBNP Levels in
Patients with acute HF had NT-proBNP levels that were extremely elevated
Cardiac and Non-cardiac Clinical Conditions
compared with patients who had dyspnea without acute HF. In the PRIDE
study,
53
an NT-proBNP cut-off of 300ng/l had a high negative predictive value
Cardiac causes:
to rule out HF compared with a value of 900ng/l, which had a comparable
1. Cardiomyopathies
positive predictive value to a BNP value of 100ng/l to ‘rule in’ HF. Further
a. Hyperthrophic
analyses suggested that an NT-proBNP level of 450ng/l was superior to
b. Restrictive
diagnose younger patients with HF. This concept of age-adjusted HF
c. Dilated
2. Myocarditis
cut-points for NT-proBNP were further evaluated in the ICON study,
54
where
3. Valvular heart disease:
age-adjusted cut-off values for NT-proBNP were found to yield higher positive
a. Aortic stenosis and aortic regurgitation
predictive value for HF than a single cut-off. NT-proBNP levels of 450ng/l (for
b. Mitral stenosis and mitral regurgitation those aged <50 years), 900ng/l (for those aged 50–75 years), and 1,800ng/l
4. Atrial arrhythmias (for those aged >75 years) were suggested to ‘rule in’ heart failure, while an
Non-cardiac causes:
age-independent cut-off of 300ng/l excluded HF.
1. Septic shock
2. Stroke
While age stratification necessarily injects more complexity than using a
3. Pulmonary hypertension
single cut-point, it has already been shown that a single BNP cut-point of
4. Pulmonary embolism
100ng/l (equal to an NT-proBNP of 900ng/l, analytically speaking) is mainly
5. Adult respiratory distress syndrome
useful for the diagnosis of HF in middle-aged patients;
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however, this cut-
6. Anemia
off yields an 89% negative predictive value for excluding the diagnosis of
HF at best, and is certainly less useful for evaluating the elderly or those with
Table 2: Studies to Determine NT-proBNP ‘Rule-in’ and ‘Rule-out’ renal dysfunction. Given the advantages of age adjustment with respect to
Values for Acute Heart Failure Patients
sharpening sensitivity for the diagnostic evaluation of the young while
improving the specificity of HF diagnosis in the elderly, the International
Study # Patients NT-proBNP Cut-point (ng/l)
NT-proBNP consensus panel
5,6
endorsed the triple cut-point for the
Rule Out Rule In
diagnostic evaluation of heart failure in patients presenting with acute
Bayes-Genis et al.
56
100 253 973
dyspnea (see Table 2). While a BNP of 200ng/l has been suggested for those
Mueller et al.
57
251 295 825
PRIDE
53
study 599 300 900
with impaired renal function, no guidance regarding optimal cut-points for
ICON
54
study 1,256 300 Age-stratified*
BNP in the elderly exist.
31
NT-proBNP = amino-terminal pro-B-type natriuretic peptide; PRIDE = ProBNP Investigation of
More insights regarding the value of NT-proBNP testing have been gained
Dyspnea in the Emergency Department study; ICON = International Collaborative of NT-proBNP
from the PRIDE study.
42,45,58–62
NT-proBNP testing was superior to clinical
study. * = 450/900/1,800 ng/l for ages <50, 50–75, and >75 years.
judgment for correctly identifying HF in dyspneic patients, and was useful for
this indication in the presence or absence of clinician indecision for the
context, NT-proBNP has very good negative predictive value, which makes it diagnosis.
58
NT-proBNP testing was accurate across the range of renal function
a good screening test in the primary care setting to rule out HF rather than in PRIDE,
42
and was unaffected by the presence of lung disease
59
or obesity.
45
diagnose it.
48
For this indication, an NT-proBNP value of 125ng/l for ruling Neither sex nor race affected cut-points for NT-proBNP,
60
and NT-proBNP was
out HF among patients <75 years of age is useful
47–52
(see Figure 1). As noted equally useful for diagnosis and prognosis in patients with diabetes mellitus.
61
above, age has a significant effect on NT-proBNP levels, and values of Concentrations of NT-proBNP strongly correlated with various cardiac
300–450ng/l have been proposed for those aged >75 years.
52
structure and functional abnormalities in PRIDE,
62
yet remained strongly
prognostic even in the presence of echo data; indeed, an NT-proBNP
Utility of NT-proBNP for Diagnosing Acute Heart Failure in concentration <300ng/l effectively excluded a broad range of abnormalities
Those with Dyspnea in the Emergency Department on echo, suggesting this cut-point to be useful to reduce the need for
NT-proBNP levels are typically increased in those with acutely unnecessary echocardiography in the evaluation of dyspnea.
decompensated HF, with concentrations that are usually much higher than
in those with early or asymptomatic HF. Thus, the cut-off values for It is important to recognize patients with ‘intermediate’ or ‘gray’ zone
NT-proBNP-based diagnostic evaluation are considerably higher. NT-proBNP values (levels between cut-point of 300ng/l and the consensus
Nonetheless, NT-proBNP retains its excellent diagnostic value for acute recommended age-adjusted cut point for ‘rule in’ heart failure) and their
symptom evaluation and management. clinical correlation. The most important differential diagnoses are in mild HF,
such as New York Heart Association class II symptoms,
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non-systolic HF,
63,64
Several clinical trials have lent clarity as to the appropriate application of HF with increased BMI,
45,65
and other diagnosis
66
(see Table 3). Importantly,
NT-proBNP for acute symptom evaluation. Among these are the landmark intermediate or gray zone NT-proBNP values are not associated with benign
ProBNP Investigation of Dyspnea in the Emergency Departments (PRIDE)
53
prognosis regardless of the cause, hence they should be taken seriously.
and the International Collaborative of NT-proBNP (ICON)
54
studies. In the
PRIDE study,
53
patients who presented to the emergency department with A challenging situation is the evaluation of patients with prior HF, since
acute dyspnea were analyzed using NT-proBNP levels, clinical examination, NT-proBNP values will typically be elevated. A useful tip when evaluating
and other diagnostic modalities to determine the diagnosis of HF. these patients is to ascertain their ‘dry’ NT-proBNP level (the concentration
62 US CARDIOLOGY
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