Transcript Congestive Heart Failure: What’s the Latest?

BNP: What’s in it for you or
is it “another D-dimer”?
October 7, 2004
Chris Hall
- with the help of Debra Isaac, Bryan Young, a
bunch of cardiology fellows and Adam Oster
CHF: the condition of interest, how
common is it?
USA prevalence 4.6 x 106 cases
USA incidence: 550,000 new cases/year
That translates into Canadian numbers of:
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55,000 new cases/year
5500 cases/year/province roughly
2000 cases per year in Calgary…or about 7 per day
Cost:
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$56 billion/year in USA
$39 billion of that re: hospitalization
Admission rates
75-90% of patients with suspected CHF are
admitted

Graff et al PROVIDE study, Ann Emerg Med 1999
77% of admissions originate in the ED
Absent clinical criteria
Absent lab criteria
BUT…if you are a good clinician, you know who
is in CHF and who isn’t…don’t you?
The problem with signs and symptoms
Poor relationship between symptoms and severity
(more about that later)
BNP levels correlate with both severity and outcome
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Harrison et al Ann Emerg Med 2002: BNP predicts future
events in ED pts
Cheng et al JACC 2001: BNP predicts outcome in admitted
patients
Bettencourt et al Am J Med 2002: BNP predicts outcome
after discharge
Maeda et al JACC 1999: Increased BNP is an independent
predictor of mortality.
So….
BNP should assist with appropriate treatment
and disposition of CHF patients in the ED
What the heck is BNP again?????
Natriuretic Peptides: Origin and
Stimulus of Release
Peptide
Primary Origin
Stimulus of Release
ANP
Cardiac atria
Atrial distension
BNP
CNP
Ventricular myocardium
Endothelium
Ventricular overload
Endothelial stress
ANP = Atrial Natriuretic Peptide
BNP = B-type Natriuretic Peptide
CNP = C-type Natriuretic Peptide
Adapted from Burnett JC, J Hypertens 2000;17(Suppl 1):S37-S43
Relationship between BNP
Concentration and Pulmonary Artery
Wedge Pressure
Change per hour
6
0.0
0.2
0.4
0.6
0.8
1.0
BNP
4
2
R= 0.729
P< .05
0
0
1
2
3
4
5
6
PAW
Maisel, A., Kazenegra, R. et al. J Cardiac Failure, Vol. 7, No. 1, 2001
7
PAW (mm Hg)
0
10
20
30
40
BNP (pg/ml)
BNP vs. NYHA Classification
1200
1000
800
600
Median
400
200
0
Normal
12.3
Class I
Class II
95.4
221.5
Class III Class IV
459.1
1006.3
(pg/mL)
Cumulative Survival (%)
Cumulative Survival Rates in CHF Patients With Left Ventricular
Dysfunction Stratified on Median Plasma BNP Concentration
100
BNP < 73 pg/ml
80
p < 0.0001
60
40
BNP > 73 pg/ml
20
0
0
10
Tsutamoto T. et al. Circulation 1997;96:509-516
20
30
40
50
Months
But is it specific?
Is it specific? BNP Levels in Patients
With Dyspnea Secondary to CHF or
COPD
1076 +/- 138
1200
BNP pg/mL
1000
800
600
400
200
86 +/- 39
0
COPD
N=56
CHF
N=94
Cause of Dyspnea
Dao, Q., Maisel, A. et al. J. American College of Cardiology, Vol 37, No. 2, 2001
So, what’s the ED literature say?
The REDHOT trial:
Ann Emerg Med October 2004
1. To establish whether BNP levels are
associated with outcomes independent of ED
physician assessment (Is there a “disconnect”
between perceived severity of illness and BNP
levels?)
2. To identify BNP levels that might help decide
admission or discharge
R.E.D.H.O.T. Study Design
10 USA Hospitals
BNP Levels Taken Serially
Physicians blinded to BNP Concentrations unless
<100
Key Outcomes Determined at Both 30 & 90 Days
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Mortality
Hospital Readmission
R.E.D.H.O.T. Study Design
(Continued)
Inclusion Criteria:
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18 Years of Age or Older
CHF Diagnosed by
Either Cardiologist or
E.D. Physician
Patient Requires
Treatment for CHF
Exclusion Criteria
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BNP Levels Equal to or
Less Than 100 pg/ml
Patients with Current
M.I. Or ACS with ST
Elevation of 1mm or
greater
Patients with Renal
Failure Requiring
Hemodialysis
Patient Characteristics
N=464
Age
Male
Female
Caucasian
African
American
63.4%
53.9%
46.1%
32.5%
Hx CHF
Hx COPD
76.5%
21.7%
63.4%
PND
JVP
Rales
S3
Peripheral
Edema
59.0%
42.6%
74.8%
19.6%
75.0%
Decision for admission
Initial
Intent
Final
Disposition
Admit
Discharge
68.3%
31.7%
Admit
Discharge
90.3%
9.7%
And of the patients who got
discharged…
If 90% were admitted, everyone sick must have
been admitted…
Not so fast
Perceived NYHA Class in patients
Ultimately discharged home from the ED
Discharge
Home
I
II
III
IV
Total
BNP<400
pg/ml
2
6
2
-
10
BNP400
pg/ml
1
12
21
1
35
78% of discharged patients have BNP  400 pg/ml
63%
20%
100%
D<400pg/ml
80%
60%
40%
20%
0%
30 day follow-up
D≥400pg/ml
10%
0%
NYHA III, IV %
70%
60%
50%
40%
30%
20%
10%
0%
NYHA III, IV %
NYHA III, IV %
Discharged patients: NYHA class and
Subsequent mortality
8%
D<400pg/ml 6%
90 day0%
follow-up
9.0%
D≥400pg/ml
4%
2%
0%
0%
D<400pg/ml
D≥400pg/ml
So, does that mean everyone needs
admission?
Perceived NYHA Class in patients
Ultimately admitted from the ED
I
II
III
IV
Total
BNP<200
pg/ml
1
14
18
11
44
BNP200
pg/ml
10
103
168
93
374
11% of all patients admitted with BNP<200 pg/ml
66% of patients admitted with BNP<200pg/ml
perceived NYHA III,IV
Admitted patients: NYHA class and
Subsequent mortality
70%
70%
68%
64%
66%
6%
4%
A<200pg/ml
30 day follow-up
2%
0%
4%
A≥200pg/ml
10.0%
0%
NYHA III, IV %
66%
NYHA III, IV %
NYHA III, IV %
72%
8.0%
A<200pg/ml 6.0%
4.0%
2.0%
90 day follow-up
9.0%
A≥200pg/ml
2.0%
0.0%
A<200pg/ml
A≥200pg/ml
REDHOT BNP Values
& Patient Disposition
1000
900
800
700
600
500
400
300
200
100
0
976
767
Previous Data Link High BNP to
Morbidity & Mortality
Actual BNP Values Blinded to
E.D. Physician
BNP Median Values ~22%
Higher in Patients Discharged
Home from E.D.
Discharged
Admitted
CONCLUSIONS:
In patients presenting with shortness of breath to
the ED, there is a large “disconnect” between
perceived severity of CHF and the BNP level.
Even in the setting where CHF severity is perceived
as severe, a low BNP level portends a favorable
short and long term prognosis
The Calgary Implementation
Organized plan of implementation to reduce the
D dimer, troponin, “all things ordered at
presentation” effect
Protocol driven approach
Also contribute to the literature in organized
study format
Protocol implementation arranged by billing
group to simplify education of MD’s
Protocol #1: RGH; multicenter trial
sponsored by Roche
Patients suspected to have CHF
Consented for trial (blood draw and chart review)
BNP drawn in ED
Randomized to know results or not
Compare admission rates, test utilization and outcome
in the two groups
Determine the effect of BNP measurement on local
resource utilization and patient outcome
Are USA studies generalizable?
Protocol #2: FMC and PLC
Patients with SOB suspected to be CHF
Consented for involvement in study by ED
Involvement consists of BNP drawn and some patients
with phone follow-up
BNP drawn in ED
BNP values not known to MDs
Usual treatment and disposition of all patients
Phone follow-up only for 300 patients with BNP<100
Determine M&M in 30 and 90 days to determine
“safety” of the 100 cutoff locally
Research-speak
EP considers diagnosis of CHF who demonstrate a BNP level of
<100 pg/ml.
followed for the rates of pre-specified CHF events and CHF
investigative procedures over the 30-day period following their
ED visit.
Endpoints:
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Cardiac endpoints (or Safety endpoints)
investigational or diagnostic procedures endpoints (Resource)
A 30-day follow-up period re: related to index ED visit.
The incidence of Resource endpoints will form the basis for
further study into optimal resource utilization for patients who are
at low risk of adverse CHF events.
Questions?
“BNP Guided” E.D. Discharge @ 200pg/ml:
Annual Economic Impact Potential:
$506mm
11% Reduction
Reduction
DRG 127
 680,106 Admissions in ‘01
 5.27 Day L.O.S.
 $5,414.68 Cost per Patient
 Medicare = 80% Total Costs
$4,600
$4,094
$4,600,000,000.00 Total
U.S. Inpatient Cost
Standard Care
Rapid BNP
BNP Levels in Patients With Dyspnea
Secondary to CHF or COPD
1076 +/- 138
1200
BNP pg/mL
1000
800
600
400
200
86 +/- 39
0
COPD
N=56
CHF
N=94
Cause of Dyspnea
Dao, Q., Maisel, A. et al. J. American College of Cardiology, Vol 37, No. 2, 2001
BNP Levels in Patients With Edema
Diagnosed With CHF or Without CHF
1038 +/- 163
1200
BNP pg/mL
1000
800
600
400
200
63 +/- 16
0
No CHF
N=44
CHF
N=44
Cause of Edema
Dao, Q., Maisel, A. et al. J. American College of Cardiology, Vol 37, No. 2, 2001
Conclusions
BNP levels accurately reflect the cause of
dyspnea and/or edema
BNP levels add additional information to that
gathered by the physician, allowing the correct
diagnosis of congestive heart failure
 clinical and economic value of BNP measurement
 ER
 time and volume issues at play!
 higher percentage of diagnostic dilemmas
 limited access to immediate specialist input
 probably highest potential for economic / resource use
benefit
- reduce cost of “fishing expeditions”
- reduce waiting time for unnecessary consults
- speed up diagnosis; reduced time in ER until
disposition determined
- speed up initiation of appropriate rx