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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 10 6 cases
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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?????
Peptide Primary Origin Stimulus of Release ANP Cardiac atria Atrial distension BNP Ventricular myocardium Ventricular overload CNP Endothelium Endothelial stress Natriuretic Peptides: Origin and Stimulus of Release 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
6 0.0 0.2 0.4 Change per hour 0.6 4 0.8 1.0 BNP 0 2 PAW (mm Hg) 10 R= 0.729 P< .05 20 30 0 40 0 1 2 3 4 5 6 7 PAW BNP (pg/ml) Relationship between BNP Concentration and Pulmonary Artery Wedge Pressure Maisel, A., Kazenegra, R. et al. J Cardiac Failure, Vol. 7, No. 1, 2001
BNP vs. NYHA Classification 12.3 95.4 221.5 459.1 1006.3 (pg/mL)
100 BNP < 73 pg/ml 80 p < 0.0001 Cumulative Survival (%) 60 40 BNP > 73 pg/ml 20 0 Months 0 10 20 30 40 50 Cumulative Survival Rates in CHF Patients With Left Ventricular Dysfunction Stratified on Median Plasma BNP Concentration Tsutamoto T. et al. Circulation 1997;96:509-516
Is it specific? BNP Levels in Patients With Dyspnea Secondary to CHF or COPD N=56 N=94 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
Inclusion Criteria: 18 Years of Age or Older CHF Diagnosed by Either Cardiologist or E.D. Physician Patient Requires Treatment for CHF Exclusion Criteria 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 R.E.D.H.O.T. Study Design (Continued)
Patient Characteristics N=464 Age Male Female Caucasian African American Hx CHF Hx COPD 63.4% 53.9% 46.1% 32.5% 63.4% 76.5% 21.7% PND JVP Rales S3 Peripheral Edema 59.0% 42.6% 74.8% 19.6% 75.0%
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 78% of discharged patients have BNP 400 pg/ml
Discharged patients: NYHA class and Subsequent mortality 30 day follow-up 90 day follow-up
Perceived NYHA Class in patients Ultimately admitted from the ED 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 30 day follow-up 90 day follow-up
REDHOT BNP Values & Patient Disposition • 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.
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.
11% Reduction $506mm Reduction “BNP Guided” E.D. Discharge @ 200pg/ml: Annual Economic Impact Potential: DRG 127 • 680,106 Admissions in ‘01 • 5.27 Day L.O.S. • $5,414.68 Cost per Patient • Medicare = 80% Total Costs $4,600,000,000.00 Total U.S. Inpatient Cost
BNP Levels in Patients With Dyspnea Secondary to CHF or COPD N=56 N=94 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 N=44 N=44 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
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 clinical and economic value of BNP measurement • 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