Download Clinical Utility of Blood Natriuretic Peptide Levels

Research Section
Clinical Utility of Blood Natriuretic Peptide Levels
a report by
Pe t e r A M c C u l l o u g h , M D , M P H , FA C C , FA C P , F C C P , FA H A
Consultant Cardiologist and Chief, Division of Preventive Medicine, Willliam Beaumont Hospital
Heart failure (HF) is a common condition and carries a
considerable age-dependent all-cause mortality.1 As a
leading cause of hospitalization in adults, ~50% of
patients discharged with a diagnosis of HF are
readmitted within six months, and the one-year
mortality rate is 20% after an initial diagnosis is
established. There is currently a chronic HF epidemic
with a rapidly expanding prevalence pool of HF
patients, which has accounted for increased rates of
hospitalization over the past two decades.1–3
Accordingly, much effort has been directed toward
understanding the pathophysiology of HF, as well as
improving diagnostic and therapeutic strategies. The
recognition of the natriuretic peptides, in particular
B-type natriuretic peptide (BNP), as a marker for the
diagnosis, prognosis, and severity of HF has been a
major breakthrough.4 This article will focus on the latest
advances in the clinical utility of BNP in a variety of
applications (see Figure 1).
N at r i u re t i c Pe p t i d e s — I m p o r t a n t ‘ H e a r t
Hormones’
There are three major natriuretic peptides, all sharing a
common 17-amino-acid ring structure—atrial natriuretic
peptide, BNP, and C-type natriuretic peptide.5 B-type
natriuretic peptide is synthesized and stored in the
ventricular myocardium as a precursor prohormone.
Cleavage of the 32 amino acid sequence by the enzyme
corin from the C-terminal end of ProBNP results in the
active BNP peptide hormone and the inactive Nterminal fragment of proBNP (NT-proBNP). B-type
natriuretic peptide is secreted into the circulation in a
pulsatile fashion through the coronary sinuses in response
to left ventricular (LV) wall stretch and multiple
neurohumoral factors. It has a half-life of 22 minutes and
is metabolized by neutral endopeptidase (~30%), and
receptor-mediated endocytosis (~70%), which occurs
predominantly in the kidney. Normally, BNP levels are
slightly higher in women compared with men.6
Additionally, in the obese, BNP levels are 30% to 50%
lower than those of normal body weight, either because
of impaired BNP production or increased peripheral
clearance of BNP.6 Both BNP and NT-proBNP have
been found in urine. NT-proBNP is not cleared by
neutral endopeptidase or by the clearance receptors,
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hence its clearance is more dependent on glomerular
filtration with incomplete resorption, resulting in
considerable quantities found in the urine.7 These urinary
levels are high enough to be used as a urinary test for HF.7
Plasma BNP levels reflect the decompensated state of
circulatory congestion and correlate with LV end
diastolic pressure and pulmonary capillary wedge
pressure. Due to the fact that BNP reflects volume status
and has a short half-life, levels reflect dynamic changes in
volume attributed to diuresis, making the assay an
attractive marker for a variety of conditions associated
with LV and right ventricular (RV) dysfunction.8 The
majority of the published studies on clinical applications
have utilized BNP; BNP levels will therefore be
considered the focus of this article.
Po p u l at i o n S c re e n i n g
As a general rule, a normal BNP value should be less
than half the chronological age of the patient.
Multiple population screening studies indicate that a
cut-point of 20pg/ml would be appropriate for a
population with a mean age in the fourth or fifth
decade.9–11 Although the reason for mild elevations in
BNP in women compared with men is unknown, it
is speculated that ventricular stiffening is more
pronounced in women at all ages.11 All current studies
of screening support the notion that clinical
information such as cardiac risk factors, age, gender,
and subtle symptoms should trigger the BNP test in
practice. Blanket asymptomatic population screening
with BNP would likely lead to over-utilization of
resources including cardiology consultation and
echocardiography (ECG).
Decompensated HF
HF has two major subtypes, systolic and diastolic failure,
which each account for half the cases in the HF
prevalence pool.12 The pivotal Breathing Not Properly
Multinational Study (BNPMS) evaluated 1,586 patients
who presented to the emergency department (ED) with
acute dyspnea and demonstrated that BNP >100pg/ml
or more had a sensitivity of 90%, and a specificity of 76%
in differentiating between dyspnea due to HF (either
systolic or diastolic), and dyspnea related to other
Peter A McCullough, MD, MPH, FACC,
FACP, FCCP, FAHA, is a Consultant
Cardiologist and Chief of the
Division of Nutrition and Preventive
Medicine at William Beaumont
Hospital in Royal Oak, Michigan. He
has been in practice for 17 years
and is board-certified in internal
medicine and cardiovascular disease.
He has senior rank of Fellow in
American Heart Association (AHA),
the American College of Cardiology
(ACC), the American College of
Physicians (ACP), and the American
College of Chest Physicians (ACCP).
Dr McCullough served as Director
for the Henry Ford Hospital
Cardiovascular Diseases Fellowship
Training Program. He has published
over 200 medical communications,
including over 100 peer-review
original articles and reviews, and
has led large epidemiologic studies,
as well as multicenter randomized
trials. He serves as an editorial
consultant for the Journal of the
American College of Cardiology and
is an Associate Editor of Reviews in
Cardiovascular Medicine. Dr
McCullough received his medical
degree at the University of Texas
Southwestern. He went on to
complete his residency in internal
medicine at the University of
Washington in Seattle and his
internship in cardiology at William
Beaumont Hospital. He earned a
master’s degree in public health at
the University of Michigan.
1
Research Section
Figure 1: Conceptualization of the Hub and Spoke of
Applications with Blood BNP Testing
Adapted with permissions from Silver M A, Maisel A,Yancy C W et al. BNP Consensus
Panel, “BNP Consensus Panel 2004: A clinical approach for the diagnostic, prognostic,
screening, treatment monitoring, and therapeutic roles of natriuretic peptides in
cardiovascular diseases” Congest. Heart Fail. (September–October 2004);10(5 suppl.
3): pp. 1–30.
causes.13 In determining the correct diagnosis, adding
BNP to clinical judgment would have increased the
diagnostic accuracy from 74% to 81%.14 A proposed
algorithm for using BNP in the acute evaluation of
dyspnea is given in Figure 2.15 Due to the fact that BNP
levels were found to correlate negatively with estimated
glomerular filtration rate (eGFR), the optimum cutpoint for diagnosing HF rose to 200pg/ml for patients
with eGFR less than 60ml/min.16
2
Due to the fact that BNP is a reflection of LV wall
tension, it follows that BNP levels would identify
patients with dyspnea related to HF with diastolic HF,
where the primary abnormality is decreased LV
compliance and increased end-diastolic pressure.
Lubien et al. reported on BNP levels in 294 patients
referred for ECG to evaluate ventricular function
with careful classification of diastolic filling patterns.17
Transmitral pulsed Doppler velocity recordings were
used to derive the deceleration time. Short
deceleration times are known to be highly associated
with LV end diastolic pressures >25mmHg. In this
analysis, BNP levels were higher in patients with
deceleration times <160ms (249±43pg/mL), in
comparison with the near normal BNP levels
(70±13pg/mL) in patients with normal deceleration
times.17 Similarly, the BNPMS reported the median
BNP of patients with diastolic HF was 413pg/mL, in
comparison with 34pg/mL in patients with dyspnea
not due to HF. B-type natriuretic peptide levels did
not separate patients with systolic HF from those
with diastolic HF, although levels trended higher in
patients with systolic HF (821pg/mL), likely related
to this cohort’s higher New York Heart Association
(NYHA) functional classification status.18
Prognosis of HF
Prognosis in HF is dictated by the complex interplay of
neurohumoral, mechanical, electrical, and multi-organ
derangements. Koglin et al. evaluated the prognostic
power of BNP in 78 patients referred to their HF
clinic.19 Levels of BNP were significantly correlated
with the HF survival score. Patients with high levels of
BNP were much more likely to develop clinical
deterioration or die over a median 398-day follow-up
period.19 As nearly half of the HF mortality in these
and other trials is felt to represent sudden cardiac
death, Berger et al. investigated the association of BNP
with future cardiac death in 452 patients with LV
ejection fraction (LVEF) ≤35%.20 Forty-four (10%) of
the patients developed sudden death over a period of
592 days, with equal distribution between ischemic
and non-ischemic HF etiology. Among all baseline
variables, BNP was the most important predictor of
sudden death. The sudden-death free survival rate
among patients with high BNP levels (defined as log
BNP >130pg/mL) was 81%, compared with 99% in
patients with low BNP levels.20 B-type natriuretic
peptide has consistently been found to be the best
predictor of survival in HF, when compared with all
other clinical variables.21
Multiple blood marker approaches have recently been
reported for HF prognosis. Horwich et al. studied the
combination of BNP and cardiac Troponin I (cTnI) levels
upon initial heart transplantation evaluation in 98 patients
with ischemic and non-ischemic cardiomyopathy.
Independently, detectable levels of blood cTnI due to
accelerated myocyte apoptosis were associated with a
two-fold increased mortality risk. The combination of
detectable cTnI and high BNP levels (≥485pg/mL)
portended a 12-fold relative risk of death.22 These studies
support the notion that a multi-marker approach may
provide incremental prognostic information in patients
with advanced HF.
P r e d i c t i n g Tr e a t m e n t O u t c o m e s a n d
Guiding the Management of HF Patients
Several recent studies support the usefulness of
changes in BNP levels, as well as predischarge BNP
levels, as important markers to optimize the care of
patients hospitalized with HF. Bettencourt et al.
investigated the ability of changes in BNP levels
during hospitalization to track clinical outcomes in 50
consecutive patients hospitalized with decompensated
HF.23 B-type natriuretic peptide levels decreased in
most patients, although to a significantly greater
degree in those who remained free of readmission for
CV causes and death. Of the seven patients with
increases in BNP levels during hospitalization, only
one patient was event-free at six months. Within the
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Clinical Utility of Blood Natriuretic Peptide Levels
subgroup of patients with declining BNP levels during
hospitalization, the degree of change in BNP tracked
six-month outcomes. In patients without six-month
hospital readmission or death, BNP levels fell from
619±491pg/mL to 328±314pg/mL (p<0.0001).
In comparison, reductions in BNP levels were
less pronounced in those who suffered events, with
BNP levels decreasing from 779±608pg/mL to
643±465pg/mL (p=0.08) in this group. Consistent
with these data, Cheng et al. reported that BNP levels
increased by 233pg/mL in hospitalized patients who
went on to die or be re-hospitalized in the next 30
days.24 Finally, Logeart et al. demonstrated that HF
patients who had a pre-discharge BNP level
>700ng/L had an ~80% rate of death or
hospitalization at 120 days (relative risk (RR)=15.2).25
Conversely, those with BNP values <350ng/L had a
<10% rate of death or rehospitalization over the same
period (see Figure 3).25
These small, single-center studies were validated in
out-patients who participated in the Valsartan in
Heart Failure Trial (Val-HeFT).26 The Val-HeFT trial
evaluated the role of valsartan in moderate to severe
HF, and represents the largest collection of
neurohumoral data in HF patients. B-type natriuretic
peptide was measured in all patients at randomization,
with follow-up values measured at four, 12, and 24
months thereafter. Patients with a BNP level above
the median had a relative risk of 2.1 for mortality, and
2.2 for first morbid events, in comparison with those
with BNP levels below the median. Furthermore,
there was an incremental increase in relative risk of
mortality and morbidity throughout each quartile of
BNP levels (see Figure 4).There are several important
inferences from this analysis:
• approximately half of well-treated HF patients
had BNP levels <100pg/ml when measured
as out-patients;
• the lowest quartile of BNP (<50pg/ml) had the
lowest all-cause mortality;
• the highest quartile (>238pg/ml) had the highest
mortality of ~32% at 30 months.
Importantly, change from baseline and the per cent
change of BNP level over a four- and 12-month period
were also evaluated. This analysis demonstrated a direct
relationship between per cent change from baseline
BNP levels and four-month mortality. Highest mortality
was seen in patients with the largest per cent increase in
BNP, while the lowest mortality was observed in those
with the largest per cent decrease in BNP.26
These compelling data raise the argument that
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Figure 2: Cumulative Incidence of Death (Panel A) and
HF (Panel B), According to the Plasma BNP Level at
Baseline—Age 59
A
Cumulative incidence of death
0.08
0.06
0.04
Highest third 0.02
Middle third
Lowest third
0.00
0
1
2
3
4
5
6
1,051
959
945
959
882
865
697
673
666
331
369
361
3
4
5
6
957
878
850
695
670
653
331
368
355
Years
No. at risk
Lowest third
Middle third
Highest third
B
1,191
1,073
1,082
1,188
1,070
1,073
1,160
1,053
1,047
Cumulative incidence of heart failure
0.04
0.03
0.02
Highest third 0.01
Middle third
Lowest third
0.00
0
1
2
Years
No. at risk
Lowest third
Middle third
Highest third
1,191
1,073
1,082
1,188
1,068
1,068
1,160
1,050
1,038
1,050
957
932
The lowest-third, middle-third, and highest-third of plasma BNP levels were 4pg/ml or less,
4.1–12.7pg/ml, and 12.8pg/ml or more, respectively, for men and 5.9pg/ml or less,
6–15.7pg/ml, and 15.8pg/ml or more, respectively, for women. Reprinted with permission
from Wang T J, Larson M G, Levy D et al., “Plasma natriuretic peptide levels and the risk
of cardiovascular events and death”, N. Engl. J. Med. (February 12 2004);350(7): pp.
655–663.
neurohormonal levels, in particular BNP levels, may be
useful in actively guiding the treatment of patients with
HF. Mueller et al. randomized 452 patients who
presented to the ED with acute dyspnea, to a diagnostic
strategy including a single measurement of BNP level
versus the use of a standard diagnostic strategy without
the aid of BNP level.27 Serial measurements of BNP
were not performed in either group.The measurement
of BNP level in the ED resulted in reduced time to
discharge (eight compared with 11 days (p=0.001)),
reduced rate of hospitalization (75% compared with
85% (p=0.008)), less frequent admission to the intensive
care unit (15% compared with 24% (p=0.01)), and
improved total cost of treatment (US$5,410 compared
with US$7,264 (p=0.006)).27 These data suggest that a
single measurement of BNP level improves the
in-patient care of patients with dyspnea.
3
Research Section
Figure 3: Algorithm for Using BNP as Part of the Initial
Evaluation of Dyspnea and HF
Patient with dyspnea or
other HF signs/symptoms
History/physical
examination/ECG/chest X-ray
Diagnostic for CHF
Acute/chronic
HF management
(ECG, if not carried
out previously)
First BNP blood test
with laboratory admission
Positive (>500pg/ml)
Non-diagnostic
ëGreyzone’ (100–500pg/ml)
• CHF
• PE
Negative (<100pg/ml) • Ischemia
Second BNP blood
• Sepsis
test before D/C
Evaluate for non-CHF etiologies
• Renal Failure
(ECG usually not indicated)
• Cor Pulmonate
First BNP blood test
drives decision
Figure 4: Prognosis Based on Discharge Levels of BNP in Patients Admitted with
HF
treatment.29 The treatment target in the BNP group
was an N-BNP level <70pg/ml, and the target for the
clinical group was based upon an objective
standardized HF scoring system. If patients did not
meet target, pharmacotherapy (ACE inhibitors,
diuretics, digoxin, and vasodilators) was up-titrated in
a prespecified protocol, with repeat assessment in two
weeks. In the BNP group, BNP levels fell by an
average of 273.5pg/ml from baseline, in comparison
with a 10.4pg/ml rise in the clinical group. More
importantly, after a 9.5-month follow-up there were
more events (CV death, hospital admission for any
CV event, and out-patient decompensated HF) in the
clinical group than the BNP group (54 compared
with 19 events, respectively, (p=0.02)). 29 The
improvement in outcome seen in the BNP group was
attributed to a statistically significant increase in
dosage of conventional, oral HF medications.29 These
important studies suggest that there may be an active
role for a neurohumoral guided approach to titration
of drug therapy in HF.
Mor tality in Acute Coronary Syndromes,
Pulmonary Embolism, and Sepsis
Death or readmission
100%
p <0.0001
15.2
75%
50%
p <0.0001
It has been reported in multiple studies that BNP can
be elevated in acute cardiopulmonary emergencies that
have cardiac dysfunction as part of the syndrome. In
these circumstances, BNP is elevated in only a minority
of cases; however, when found, the elevated BNP level
indicates a higher mortality rate in ACS, pulmonary
embolism, and sepsis.
5.1
25%
1
0%
0
30
60
Pre-discharge BNP>700ng/l
n=41, events=38
90
120
Follow-up (days)
Pre-discharge BNP350–700ng/l
n=41, events=30
150
180
Pre-discharge BNP<350ng/l
n=41, events=18
Hazard ratios of second
and third versus first
BNP range
Reprinted with permission from Logeart D,Thabut G, Jourdain P et al.,“Predischarge B-type natriuretic peptide assay for identifying patients
at high risk of re-admission after decompensated heart failure”, J.Am. Coll. Cardiol. (February 18 2004);43(4): pp. 635–641.
4
In this out-patient setting, self-reported quality of life
has little relation to the blood BNP level, since
quality of life is continually resetting to lower levels as
disease progresses.28 BNP is therefore a useful and
independent measure of disease severity obtained in
the out-patient clinic.28 To date, there have been three
small randomized controlled trials supporting the
out-patient use of BNP to guide the medical
management of HF.29–31 As an example, the first trial of
69 patients with symptomatic HF (NYHA class II-IV;
LVEF <40%) hospitalized with decompensated HF or
referred from cardiology clinics were randomized
between N-BNP guided treatment (BNP group) and
standardized clinically guided (clinical group)
De Lemos et al. found that a BNP level >137.8pg/ml
occurred only in 25% of ACS patients (fourth
quartile), but when at this level predicted higher rates
of all-cause mortality at 30-days and six months.32
Above a threshold of 80pg/ml, there were higher rates
of death, new or progressive HF, and recurrent MI. It
has been shown that BNP can be elevated in cases of
unstable angina without evidence of infarction, and
again, it is predictive of acute and longer term
mortality.33 It is believed that BNP elevations reflect
underlying cardiac decompensation due to the size of
the infarct or ischemic zone and/or the overall lack of
compensatory hyperkinesis of the reference segments,
and therefore these processes are critically linked to the
survival of the patient.34
Acute pulmonary embolism is known to increase levels
of BNP produced from the RV.Wolde et al. found BNP
was elevated (>75.1pg/ml) in one-third of 110 patients
with angiographically proven pulmonary emboli.35 It
was this group that had the highest mortality (25%)
over the next 80 days. Conversely, those patients with
BNP levels <8.7pg/ml had no deaths reported.
Echocardiographic evaluation has correlated RV
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Clinical Utility of Blood Natriuretic Peptide Levels
Figure 5: All-cause Mortality by BNP Level in Stable
Out-patients with Systolic HF
Survival probability
1
Mortality %
BNP (pg/ml)
0.8
9.7
14.3
<41
41–97
0.7
20.7
98–238
32.4
>238
0.9
0.6
0.5
0
10
20
30
Time since randomization (months)
predictor of post-operative atrial fibrillation. Hutfless
reported higher pre-operative BNP levels in patients
who died within one year (357pg/ml compared with
184pg/ml).41 Finally, Chello et al. reported on 31
patients with LV dysfunction, and found that BNP
dropped from 133.2pg/ml to 77.5pg/ml, as the mean
ejection fraction improved from 29% to 39%, preoperatively and at 10 months, respectively.42 These data
suggest that BNP is not only predictive of postoperative complications, but that a fall in BNP
measured in the months after surgery indicates recovery
of LVEF after revascularization.
40
Data adapted from Anand I S, Fisher L D, Chiang Y T et al., “Changes in brain natriuretic
peptide and norepinephrine over time and mortality and morbidity in the Valsartan Heart
Failure Trial (Val-HeFT)”, Circulation (2003);107: pp. 1,278–1,283.
dysfunction with elevations in BNP and subsequent
mortality. In 50 patients with confirmed pulmonary
embolism, Kruger found that the mean BNP levels
were 340pg/ml and 55pg/ml for those with and
without RV dysfunction, respectively (p<0.0001).36 The
best discriminating mortality level for BNP in
pulmonary embolism was found to be 90pg/ml.
In sepsis, endotoxin has been shown to induce the
synthesis of mRNA for BNP. Sepsis is known to be a
cardiotoxic state with subtle reductions in LV
performance attributed to circulating cytokines and
myocardial depressants. In sepsis, BNP levels are
correlated to the severity of the sepsis state and shortterm mortality.37 There are too few data to identify a
critical cut-point for BNP and survival in sepsis to date.
In the population of patients with dyspnea, sepsis is
fairly uncommon. In the BNPMS, there were 717
patients without HF and only 40 (5.6%) of those had
BNP levels >500pg/ml, with the majority having
underlying renal dysfunction. Sepsis was thought to be
a cause of the elevation in a minority of cases.37
BNP and Cardiac Surgery
All of the cardiac natriuretic peptides rise acutely with
cardiac surgery, and then decline over the following
three to five post-operative days. Atrial natriuretic
peptide is best correlated with moment-to-moment
elevations in left atrial and pulmonary capillary wedge
pressure and are not predictive of outcomes.39 Elevated
pre-operative BNP levels have been associated with the
development of atrial fibrillation and death after
coronary artery bypass surgery (CABS). Wazni et al.
measured BNP pre-operatively in 187 patients (mean
ejection fraction 42%) and found the mean BNP was
615pg/ml and 444pg/ml in those who did and did not
development post-operative atrial fibrillation,
respectively.40 The pre-operative BNP was the strongest
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C h ro n i c Va l v u l a r H e a r t D i s e a s e
The chronic valvular lesions of aortic stenosis (AS),
aortic regurgitation (AR), and mitral regurgitation
(MR) have all been associated with elevations of BNP.
In general, if the baseline BNP value is known over
time, then a significant increase in BNP value is thought
to precede ECG changes in LV function, and hence
might be a useful guide in the timing of valvular
surgery. Gerber et al. found that BNP levels were
31.2pg/ml and 96.9pg/ml for those with asymptomatic
(aortic valve area=0.99cm2) and symptomatic (aortic
valve area=0.71cm2) AS, respectively (p<0.0001).43 A
cut-point of 48.5pg/ml was the best discriminator for
symptomatic AS. Qi et al. demonstrated that the BNP
levels more closely reflected the pulmonary capillary
wedge pressure and LV function than the severity of
AS.44 Importantly, it has recently been shown that a preoperative BNP level >130pg/ml predicted higher event
rates and need for aortic surgery in patients with severe
AS by ECG (see Figure 5).45 In patients with AI, the data
are similar, with BNP levels averaging 152.3 and
24.2pg/ml in symptomatic and asymptomatic patients
with moderate to severe AI.46 There are analogous data
in the setting of chronic MR where Sutton et al.
reported the mean BNP values were 58.5pg/ml and
24.6pg/ml in those with and without symptoms.47 The
chronology of how BNP rises over the course of
chronic valvular heart disease is unclear, but it likely
rises before there are changes seen on the ECG and
possibly before symptoms develop. As a general rule, a
doubling of BNP over time may be the first signal in
AS, AR, or MR that a clinician could detect indicating
cardiac decompensation; however, there are too few data
to identify critical cut-points for each lesion. When a
patient has been selected for valvular surgery, then the
pre-operative BNP level predicts long termsymptom-free survival, much like the way LVEF
predicts outcome.
Caveats
While data continue to emerge with respect to the
clinical meaning of BNP levels in given patients, the
5
Research Section
Figure 6: Integrated Approach of Using BNP Throughout the Continuum of HF as a Chronic Disease State
At Risk for Heart Failure
Heart Failure
Stage A
Stage B
Stage C
Stage D
At high risk for HF but
without structural heart
disease or symptoms of HF
Structural heart disease
but without signs or
symptoms of HF
Structural heart disease
with prior or current
symptoms of HF
Refractory HF requiring
specialized interventions
e.g. patients with:
• hypertension
• atherosclerotic disease
• diabetes
• obesity
• metabolic syndrome
or patients:
• using cardiotoxins
• with Fhx CM
e.g. patients with:
• previous MI
• LV modelling including
LVH and low EF
• asymptomatic valvular
disease
e.g. patients with:
• known structural heart
disease
• shortness of breath and
fatigue
• reduced exercise tolerance
Structural
heart disease
Development of
symptoms of HF
Refractory
symptoms of
HF at rest
e.g. patients:
who have marked symptoms
at rest despite maximal medical
therapy (e.g. those who are
recurrently hospitalized or
cannot be safely discharged from
the hospital without specialized
interventions)
Therapy
Therapy
Therapy
Goals:
• treat hypertension
• encourage smoking cessation
• treat lipid disorders
• encourage regular exercise
• discourage alcohol intake,
illicit drug use
• control metabolic syndrome
Drugs:
ACEI or ARB in appropriate
patients (see text) for
vascular disease or diabetes
Goals:
• all measures under Stage A
Drugs:
• ACEI or ARB in appropriate
patients (see text)
• beta-blockers in appropriate
patients (see text)
BNP Normal
<50% age in pg/ml
BNP >20pg/ml
Screening cutpoint
Goals:
• all measures under Stages A and B
• dietary salt restriction
Drugs for routine use:
• diuretics for fluid retention
• ACEI
• beta-blockers
Drugs in selected patients:
• aldosterone antagonist
• ARBs
• digitalis
• hydralazine/nitrates
• devices in selected patients:
• biventricular pacing
• implantable defibrillators
BNP optimally managed to <100pg/ml
Rises to 500–5,000pg/ml with decompensation
Therapy
Goals:
• appropriate measures under
Stages A, B and C
• decision re. appropriate
level of care
Options:
• compassionate end-of-life
care/hospice
Extraordinary measures:
• heart transplant
• chronic inotropes
• permanent mechanical support
• experimental surgery or drugs
Persistent BNP over 250pg/ml
Adapted from “ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: A Report of the American College of Cardiology/American Heart Association Task Force on Practice
Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure) 2005”, by the American College of Cardiology Foundation and the American Heart Association, Inc. BNP=Btype natriuretic peptide; FHx CM=family history of cardiomyopathy; ACEI=angiotensin converting enzyme inhibitors; ARB=angiotensin receptor blocker.
following caveats need to be emphasized. The blood
level should be interpreted in context with the
patient, their gender, age, renal function, degree of
adiposity, and underlying LVEF. It appears that BNP at
particular cut-points may be useful for predicting or
anticipating clinical events but does not replace
clinical judgement.
These caveats and suggestions for clinical use have
been summarized in the 2004 BNPMS Consensus
Panel document and in the most recent update to the
American College of Cardiology (ACC)/American
Heart
Association
(AHA)
Heart
Failure
Guidelines.15,48 An integrated approach to using BNP
in the continuum of HF, a disease process, is shown in
Figure 6.
Conclusion
BNP levels can facilitate the proper diagnosis of patients
with HF, and add valuable information to the physician
faced with the assessment of patients with and without
known HF. When BNP is elevated in acute coronary
syndromes, pulmonary embolism, and sepsis, subclinical
LV and/or RV dysfunction is present and a higher
mortality can be expected. Elevated BNP levels before
cardiac surgery are associated with higher rates of atrial
fibrillation and death. After bypass surgery, as LV
function improves, the BNP level can be expected to
fall. Lastly, in patients with AS, AR, and MR, BNP
elevates and is associated with the development of
symptoms—it can possibly serve as a trigger for
additional evaluation or intervention. ■
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