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Heart Failure
Table 1: Causes of Increased and Relatively Decreased
NT-proBNP performed better than BNP in predicting death in the general
Natriuretic Peptides
population. Given these results, it is reasonable to assert that while both
BNP and NT-proBNP have a clear role for evaluation of dyspnea in
Increased Natriuretic Peptide Levels (Besides Heart Muscle Disease) primary care and both predict outcomes in apparently well patients, their
Cardiac Causes widespread routine use for identification of asymptomatic structural
Valvular heart disease heart disease is not yet defined. As these BNP and NT-proBNP appear to
Arrythmia
offer superior predictive ability for identifying structural heart disease in
Ischemic heart disease
those at a higher risk, such as those with diabetes or hypertension with
Non-cardiac Causes
LV hypertrophy on electrocardiography, such patients may represent the
Pulmonary hypertension
first area of application for natriuretic peptide testing for screening out
Renal insufficiency
asymptomatic structural heart disease.
Age
Relatively Decreased Natriuretic Peptide Levels
Management of Heart Failure
Obesity
An area of great interest in modern medicine is whether either BNP or
Cardiac medicines
NT-proBNP would be useful for the management of heart failure.
Figure 1: Suggested Application of Natriuretic
Conceptually, the use of a biomarker that independently associates
Peptides for Primary Care Diagnostic Evaluation
with cardiac structure and function as well as prognosis for guidance
of medical treatment of heart failure is attractive. Furthermore,
natriuretic peptides tend to ‘respond’ to therapeutic interventions for
Symptoms suggestive
of heart failure
heart failure (such as diuretics, angiotensin-converting enzyme or
angiotensin receptor inhibitors, β-blockers, aldosterone blockers, or
biventricular pacing), especially when prognosis is favorably affected
by such interventions. Accordingly, the use of either BNP or NT-proBNP
Physical examination, ECG, NP measurement
added to clinical assessment for management of heart failure appears
promising. A pre-requisite for the use of these markers for optimal
NP
NP below rule-out
management in heart failure is a clear understanding of the prognostic
elevated
cut point
value of either BNP and NT-proBNP, target/goal values for both markers
and their optimal modes of measurement (i.e. timing-wise).
Proceed with Search for other
cardiovascular work-up causes of symptoms
Acute Heart Failure
BNP and NT-proBNP levels at presentation predict both long- and
With the proper application of BNP or NT-proBNP in primary care short-term mortality in hospitalized patients with acutely destabilized heart
(see Figure 1), one can expect cost-effective exclusion of heart failure.
13
failure;
21
a follow-up post-treatment value may be more important. Logeart
Indeed, Heidenreich and colleagues suggested that use of natriuretic et al.
22
demonstrated that the strongest predictor of adverse outcome
peptides for excluding the need for echocardiography was associated following therapy for acute heart failure was the discharge BNP value; in a
with cost-effective care.
14
Furthermore, as echocardiography is costly similar fashion, Bayes-Genis et al.
23
established that trans-hospital (days
and not always immediately available, the use of a biomarker to act as one to seven) change in values of NT-proBNP among hospitalized patients
a gatekeeper for use of cardiac ultrasound is intuitively attractive. This with acute heart failure who suffered complications had a smaller drop
leads to another potential application: specifically, detecting in NT-proBNP values (15% or less) than those who survived (50% or
asymptomatic LV dysfunction. greater); NT-proBNP reduction percentage during admission for acute
heart failure was superior to the presenting NT-proBNP concentration for
It is important to emphasize that this application is somewhat less prognosis. Knebel et al.
24
showed similar findings despite poor correlation
supported by the data. Since the prevalence of asymptomatic LV between single hemodynamic parameters and NT-proBNP levels.
dysfunction is variable,
15
the widespread use of BNP or NT-proBNP (and
the use of a single cut-off value for ‘abnormal’) is somewhat challenging. In other studies,
22–23,25
it has been demonstrated that no change in
Nonetheless, some clarity may be gained when examining the results of BNP/NT-proBNP concentrations, irrespective of heart failure symptom
available studies. In one study,
16
the use of a BNP value of 75ng/l to detect improvement, is also associated with increased morbidity and mortality.
abnormal echocardiographic findings has a sensitivity and a specificity of In the most significant fashion study, Bettencourt and colleagues
85 and 97%, respectively. Vasan et al.
17
and Redfield et al.
18
found BNP demonstrated that an admission-to-discharge fall of >30% in NT-proBNP
levels were suboptimal to screen patients with asymptomatic systolic or values provided reassurance for a favorable short-term prognosis, while
diastolic dysfunction. In contrast, Galasko et al.
19
demonstrated that NT- those who had a less robust fall (or a rise) in NT-proBNP had worse
proBNP levels >80th percentile (greater than two times normal value) outcomes, with a readmission hazard ratio (HR) of 5.96 and a death HR
were associated with an approximate two-fold increase in the risk for of 3.67.
25
Hence, a suggested algorithm would be to obtain a BNP or
mortality and a 3.24-fold increase for the first major cardiovascular NT-proBNP value at baseline for a patient with acute heart failure, treat
events associated with LV dysfunction. In another study,
20
NT-proBNP and the patient using standard heart failure management guidelines, and
BNP were directly compared for detecting LV systolic dysfunction, and at the time of perceived ‘re-compensation’ re-measure BNP or
42 US CARDIOLOGY
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