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Congestive Heart Failure What the Latest

VIEWS: 3 PAGES: 35

									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:
   55,000 new cases/year
   5500 cases/year/province roughly
   2000 cases per year in Calgary…or about 7 per day
Cost:
   $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
    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                Ventricular myocardium               Ventricular overload
        CNP                Endothelium                          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
           6                                                                   Change per hour
                                                                              0.0
                                                                              0.2
           4                                                                  0.4
                                                                              0.6
     BNP




                                                                              0.8
                                                                              1.0
           2                                                                        PAW (mm Hg)
                                                                               0
                                                              R= 0.729
                                                                              10
                                                              P< .05
           0                                                                  20
               0       1        2         3        4         5        6   7   30
                                                                              40
                                           PAW                                      BNP (pg/ml)
Maisel, A., Kazenegra, R. et al. J Cardiac Failure, Vol. 7, No. 1, 2001
BNP vs. NYHA Classification

1200

1000

 800

 600
                                                               Median
 400

 200

   0
       Normal   Class I   Class II   Class III Class IV
       12.3      95.4      221.5      459.1     1006.3    (pg/mL)
Cumulative Survival Rates in CHF Patients With Left Ventricular
  Dysfunction Stratified on Median Plasma BNP Concentration
          Cumulative Survival (%)



                                    100                         BNP < 73 pg/ml

                                     80
                                                                                 p < 0.0001
                                     60

                                     40
                                                        BNP > 73 pg/ml

                                     20

                                     0
                                          0   10   20    30      40       50      Months
Tsutamoto T. et al. Circulation 1997;96:509-516
But is it specific?
   Is it specific? BNP Levels in Patients
    With Dyspnea Secondary to CHF or
                    COPD
                             1200                                                   1076 +/- 138

                             1000
                 BNP pg/mL




                             800
                             600
                             400
                                                86 +/- 39
                             200
                               0
                                                COPD                                  CHF
                                                N=56                     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
   Mortality
   Hospital Readmission
     R.E.D.H.O.T. Study Design
            (Continued)

Inclusion Criteria:          Exclusion Criteria
   18 Years of Age or          BNP Levels Equal to or
                                 Less Than 100 pg/ml
    Older
                                Patients with Current
   CHF Diagnosed by             M.I. Or ACS with ST
    Either Cardiologist or       Elevation of 1mm or
    E.D. Physician               greater
   Patient Requires            Patients with Renal
    Treatment for CHF            Failure Requiring
                                 Hemodialysis
 Patient Characteristics
  N=464
Age         63.4%      PND          59.0%
Male        53.9%      JVP          42.6%
Female      46.1%      Rales        74.8%
Caucasian   32.5%      S3           19.6%
African                Peripheral
American    63.4%      Edema        75.0%

Hx CHF      76.5%
Hx COPD     21.7%
  Decision for admission

              Admit   Discharge
Initial
              68.3%    31.7%
Intent


              Admit   Discharge
Final
              90.3%     9.7%
Disposition
     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       I       II      III    IV      Total
    Home
    BNP<400
                    2       6       2       -       10
    pg/ml
    BNP400
                    1      12      21       1       35
    pg/ml
       78% of discharged patients have BNP  400 pg/ml
Discharged patients: NYHA class and
Subsequent mortality
                 70%
                                                           63%
                 60%
                 50%
NYHA III, IV %




                 40%
                 30%
                 20%
                         20%                   100%
                 10%          NYHA III, IV %
                                               80%    30 day follow-up
                  0%
                                               60%
                       D<400pg/ml                       D≥400pg/ml
                                               40%
                                                                               10%
                                               20%                                                        9.0%
                                                           0%                  8%    90 day follow-up
                                                                                          0%
                                                0%

                                                              NYHA III, IV %
                                                        D<400pg/ml 6%                  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
                 1      14      18      11         44
pg/ml
BNP200
                10     103     168     93         374
pg/ml

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
                  72%

                  70%
                                                            70%
 NYHA III, IV %




                  68%

                  66%
                          66%                  6%
                                                    30 day follow-up
                  64%                                                                         4%
                              NYHA III, IV %


                                               4%
                        A<200pg/ml                       A≥200pg/ml
                                               2%
                                                                                 10.0%
                                                                                                              9.0%
                                                           0%                    8.0%
                                                                                         90 day follow-up
                                               0%

                                                                NYHA III, IV %
                                                        A<200pg/ml 6.0%                    A≥200pg/ml
                                                                                 4.0%

                                                                                 2.0%
                                                                                              2.0%

                                                                                 0.0%
                                                                                            A<200pg/ml      A≥200pg/ml
                 REDHOT BNP Values
                 & Patient Disposition
           976
1000                           Previous Data Link High BNP to
 900                   767     Morbidity & Mortality
 800
 700
 600                           Actual BNP Values Blinded to
 500                           E.D. Physician
 400
 300
 200
                               BNP Median Values ~22%
 100                           Higher in Patients Discharged
   0                           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:
   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:
                                              11% Reduction
                                            $506mm Reduction
DRG 127
                                   $4,600
 680,106 Admissions in „01
 5.27 Day L.O.S.                                $4,094
 $5,414.68 Cost per Patient
 Medicare = 80% Total Costs


   $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

                             1200                                                   1076 +/- 138

                             1000
                 BNP pg/mL




                             800
                             600
                             400
                                                86 +/- 39
                             200
                               0
                                                COPD                                  CHF
                                                N=56                     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
                         1200                                                        1038 +/- 163
                         1000
             BNP pg/mL




                         800
                         600
                         400
                         200                   63 +/- 16

                           0
                                             No CHF                                        CHF
                                             N=44                                   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

								
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