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Heart Failure
Table 3: Diagnoses Associated with an NT-proBNP Concentration
Other Applications of NT-proBNP
in Patients without Acute Heart Failure as a Cause of Dyspnoea
Acute myocardial ischaemia stimulates release of NT-proBNP by a variety
in the ICON Study
66
of mechanisms, including myocardial stretch and ventricular
dysfunction, and NT-proBNP has prognostic value across the spectrum of
Diagnosis Patients (n=99) (%)
Chronic obstructive pulmonary disease/asthma 12 (12)
acute coronary syndrome (ACS). Several studies
88–91
demonstrate that
Pneumonia/bronchitis 12 (12)
NT-proBNP levels obtained during the acute or subacute phase of ACS
Acute coronary syndromes/chest pain 12 (12) are predictors, independent of other cardiac risk factors, including
Arrhythmia/bradycardia 8 (8)
troponins, for mortality: higher levels are associated with increased
Lung cancer (including metastases) 5 (5)
mortality. In the Platelet Receptor Inhibition in Ischemic Syndrome
Anxiety disorder 5 (5)
Management (PRISM) study,
92
measurement of NT-proBNP levels at
Pulmonary emboli 3 (3)
baseline, 48 hours and 72 hours (serial measurements) found that
Pulmonary hypertension 1 (1)
Pericarditis 1 (1)
baseline NT-proBNP levels >250ng/l were associated with higher event
Other* 21 (21)
rates (adjusted odds ratio [OR] 3.7, 95% confidence interval [CI]
Unknown 19 (19) 2.3–5.7; p<0.001). In patients with low NT-proBNP baseline levels, a rise
in NT-proBNP levels over 72 hours to >250ng/l was also linked to an
* Includes anemia, cancer, gastrointestinal pathologies, sleep apnea, and septic shock.
adverse 30-day prognosis (OR 24.0, 95% CI 8.4–68.5; p≤0.001). The
potential role of NT-proBNP to guide therapeutic interventions for
et al.,
68
who demonstrated that an NT-proBNP increase of ≥30% patients with acute coronary syndrome is of interest. As demonstrated
during hospitalisation was associated with a re-admission hazard ratio in the Fast Revascularization during Instability in Coronary Artery Disease
(HR) of 5.96 and a death HR of 3.67. Those with a <30% decrease in (FRISC) II
93
and Global Use of Strategies To Open Occluded Coronary
NT-proBNP levels had intermediate outcomes, while those with a Arteries (GUSTO) IV
94
trials, one-year mortality was significantly lower
>30% drop from baseline to discharge in their NT-proBNP with revascularisation in patients with NT-proBNP above the 25th
concentrations had the best outcomes. Thus, recommendations are to percentile of 237ng/l (relative risk [RR] 0.63, 95% CI 0.5–0.8). In
aim for an NT-proBNP fall of >30% from presentation; when a contrast, a Conservative Treatment in Unstable Coronary Syndromes
baseline NT-proBNP is not available, a ‘discharge’ NT-proBNP level of (ICTUS) substudy
95
showed that an early invasive strategy for patients
4,137ng/l is a reasonable target, as an 8% increase in the likelihood of with high NT-proBNP levels was not associated with mortality reduction.
death or re-admission over six months per 1,000ng/l of NT-proBNP Thus, the use of natriuretic peptides to guide therapeutic intervention
levels over this threshold have been described (p<0.0001). Lending for ACS remains speculative.
support to these retrospective, observational data, the Improved
Management of Patients with Congestive Heart Failure (IMPROVE- NT-proBNP is also a strong prognostic marker among patients with
CHF)
79
study recently demonstrated the importance of NT-proBNP stable coronary artery disease (CAD). In one study,
96
after adjustment
testing to optimise the evaluation and management of those with for independent predictors of cardiac risk the median NT-pro-BNP level
acutely destabilised HF. In the trial, a prospective, randomised study of was significantly lower among patients who survived rather than died
dyspnoea evaluation with or without NT-proBNP values, the use of NT- (120pg/ml [ng/l] [interquartile range 50–318] versus 386pg/ml [ng/l]
proBNP levels for diagnosis and management was associated with a [146–897]; p<0.001). In another study,
97
an association between NT-
21% reduction in time spent in the emergency department, and 60- proBNP levels and cardiovascular end-points including myocardial
day re-hospitalisation rates decreased by 35% (with concomitant infarction, stroke, HF and death existed among patients with stable
reductions in costs). These data argue the value of NT-proBNP for the CAD, even after adjustment for all prognostic indicators. These
evaluation and management of the dyspnoeic patient with HF. findings indicate potential utility for NT-proBNP to identify those at
highest risk of adverse outcomes from ischaemic heart disease, and
Chronic Heart Failure the potential for the marker to assist in more aggressive therapeutic
In chronic HF, NT-proBNP levels are strongly prognostic. As intervention accordingly.
demonstrated,
80
this risk increments over time when concentrations
rise, suggesting that serial NT-proBNP measurement could be used as Besides acute and stable CAD, NT-proBNP has prognostic value in
an important prognostication tool for chronic HF patients, particularly acute pulmonary embolism, presumably due to release of natriuretic
as tools with favourable effects on HF – such as loop diuretics, peptide in the context of dilation/strain of the right ventricle.
angiotensin-converting enzyme (ACE) inhibitors, β-adrenergic blockers Importantly, in addition to rising in the context of pulmonary
and spironolactone – also tend to lower NT-proBNP embolism, Kutcher et al.
98
demonstrated that NT-proBNP levels
concentrations.
81–84
Troughton et al.
84
demonstrated that an NT- <500ng/l had a negative predictive value of 97% for adverse clinical
proBNP level below approximately 1,700ng/l was associated with outcome, and was an independent prognostic predictor (OR 14.6,
fewer combined events of HF decompensation, hospitalisation and 95% CI 1.5–139.0; p=0.02) after adjusting for severity of pulmonary
mortality (19 versus 54; p=0.02) during a median 9.5 months of embolism, age, troponin T levels and a prior history of HF. Lutz Binder
follow-up of stable HF patients. Importantly, this study was small and et al.
99
observed that an NT-proBNP cut-point of 1,000ng/l had a
the medical management was not optimal, particularly in relation to β- negative predictive value of 95% for death and in-hospital
blockers. Although several studies
85–87
that achieved natriuretic complications, and of 100% for in-hospital deaths.
peptide concentrations below ‘target’ levels have only just been
published or are ongoing, the use of natriuretic peptides to ‘tailor’ The measurement of NT-proBNP has been shown to have prognostic
outpatient HF remains an exciting prospect. significance among critically ill patients patients admitted to intensive
72 ASIA-PACIFIC CARDIOLOGY
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