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B-type Natriuretic Peptide (BNP) in the Diagnosis of Acute Congestive Heart Failure (CHF)

B-type Natriuretic Peptide (BNP) in the Diagnosis of Acute Congestive Heart Failure (CHF). Scott M Silvers, MD 1 st Annual Pan American Conference Emergency Medicine Clinical Policies November 6 – 7, 2003. Lecture Outline. Introduction to BNP Case Critical Question Literature Search

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B-type Natriuretic Peptide (BNP) in the Diagnosis of Acute Congestive Heart Failure (CHF)

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  1. B-type Natriuretic Peptide(BNP) in the Diagnosis of Acute Congestive Heart Failure (CHF) Scott M Silvers, MD 1st Annual Pan American Conference Emergency Medicine Clinical Policies November 6 – 7, 2003

  2. Lecture Outline • Introduction to BNP • Case • Critical Question • Literature Search • Critical Literature Evaluation • Evidence-based Recommendations

  3. 32-aa polypeptide Found in heart ventricles Produced with  ventricular stretch and volume Results in vasodilation, natriuresis, diuresis, and reduced preload Increases with worsening heart failure Introduction to BNP

  4. Introduction to BNP Maisel AS, et al. N Engl J Med. 2002;347(3):161-167.

  5. Introduction to BNP Morrison LK, et al. J American Coll of Card. 2002;39(2):202-209.

  6. Case Current History: Ms. GM is a 76 yo woman with a history only of obstructive lung disease who presents to the emergency department with 2 days of progressively worsening shortness of breath. Physical Examination T= 37°C HR= 110 BP= 170/90 RR= 40 SO2 (air)= 87% She is unable to speak long sentences. Neck veins: difficult to assess Heart: difficult to hear over her lung sounds Lungs: diffuse wheezing with decreased breath sounds and rales at the bases Abdomen: normal Extremities: warm with moderate pitting edema

  7. Chest X-ray

  8. Critical Question What is the utility of a B-type natriuretic peptide (BNP) measurement in the diagnosis of congestive heart failure among patients presenting to an emergency department with shortness of breath?

  9. Curiosity Poll How many people have a BNP assay available to them where they practice?

  10. Literature Search • Medline January 1995 – Present • Keywords • “Brain natriuretic peptide”, “B-type natriuretic peptide,” “B natriuretic peptide,” or “BNP” • 1, 745 papers • Limits • Human subjects, clinical trials, meta-analyses • 164 papers

  11. Literature Search • Abstracts of clinical studies reviewed • Patients presenting with shortness of breath to “acute care” centers • 5 papers • Reviews and clinical policies 2000 - present (references crosschecked)

  12. Typical Study Methodology Inclusion Criteria • Adult patients presenting to an “acute care” facility • Primary complaint shortness of breath Exclusion Criteria • Obvious non-CHF cause of shortness of breath • Renal Failure • Acute myocardial infarction

  13. Typical Study Methodology • Evaluation by an emergency physician • Assessment of clinical probability of CHF • BNP assay sent • Results not revealed to emergency physician • Patient treated and dispositioned • Physician team blinded to BNP measurement assign final diagnosis after evaluation of case

  14. Typical Study Methodology CHF “Gold Standard” • Clinical findings • Chest x-ray • Echocardiography • Nuclear cardiology • Cardiac Catheterization • Framingham and NHANES scores • Clinical response to therapies

  15. Critical Literature Evaluation:BNP in Diagnosing CHF • 5 published studies to date • 2 report data from the same sample

  16. Critical Literature Evaluation:BNP in Diagnosing CHF

  17. Critical Literature Evaluation:BNP in Diagnosing CHF Maisel et al, (NEJM 2002) • Prospective, multinational; N = 1,586 • All “clinical risk” patients evaluated as one sample • BNP < 22 pmol/L (100 pg/ml) for detecting CHF Sensitivity = 90% Specificity = 76% NPV = 89% PPV = 79% • BNP < 11 pmol/L (50 pg/ml) for detecting CHF Sensitivity = 97% Specificity = 62% NPV = 96% PPV = 71% • Study Grade = 1

  18. Critical Literature Evaluation:BNP in Diagnosing CHF McCullough et al, (Circulation 2002) • Prospective, multinational; N = 1,538 • Excluded 48 patients without “clinical risk” assessement • BNP < 22 pmol/L (100 pg/ml) • “Low and Intermediate” clinical probability (0 – 79%) Sensitivity = 94% Specificity = 70% NPV = 93% PPV = 74% • “High” clinical probability (80 – 100%) Sensitivity = 49% Specificity = 96% NPV = 68% PPV = 91% • Study Grade = 2 (Post-study Analysis)

  19. Critical Literature Evaluation

  20. Critical Literature Evaluation

  21. Critical Literature Evaluation

  22. Critical Literature Evaluation Maisel AS, et al. N Engl J Med. 2002;347(3):161-167.

  23. Critical Literature Evaluation • Possible Limitation of BNP • Among rats given acute CHF, BNP may take over 1 hour to rise. Nakagawa O, et al. J Clin Invest. 1995;96:1280-1287.

  24. Evidenced-based Recommendations Includes • Patients presenting to an emergency department • Primary complaint shortness of breath Excludes • Obvious non-CHF cause of shortness of breath • Renal Failure • Acute myocardial infarction

  25. Evidenced-based Recommendations Level A Recommendations • A BNP < 11 pmol/L (50 pg/ml) may be used to help rule-out the diagnosis of congestive heart failure when the diagnosis is uncertain. (Probability < 4%).

  26. Evidenced-based Recommendations Level B Recommedations • Among low and intermediate “clinical probability” patients, a BNP < 22 pmol/L (100 pg/ml) may be used to help rule-out the diagnosis of congestive heart failure. (Probability < 5%) • Among patients without a history of CHF, a BNP > 88 pmol/L (400 pg/ml) may be used to rule-in the diagnosis of CHF when the diagnosis is uncertain. (Probability > 95%) • A BNP > 220 pmol/L (1,000 pg/ml) may be used to rule-in the diagnosis of acute CHF among patients presenting with a history of CHF. (Probability > 95%)

  27. Evidenced-based Recommendations Level C Recommendations • When evaluating a patient who presents with possible CHF within 1 hour from symptom onset, use caution in the interpretation of a low BNP level as BNP may take over 1 hour to rise.

  28. Key References • Davis M, et al. Plasma brain natriuretic peptide in assessment of acute dyspnea. Lancet. 1994;343:440-444. • Dao Q, et al. Utility of B-type natriuretic peptide in the diagnosis of congestive heart failure in an urgent-care setting. J Amer Coll Card. 2001;37(2):379-385. • Morrison LK, et al. Utility of a rapid B-natriuretic peptide assay in differentiating congestive heart failure from lung disease in patients presenting with dyspnea. J Amer Coll Card. 2002;39(2):202-209. • Maisel AS, et al. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. New Eng J Med. 2002;347(3):161-167. • McCullough PA, et al. B-typenatriuretic peptide and clinical judgement in emergency diagnosis of heart failure – Analysis from breathing not properly (BNP) multinational study. Circulation. 2002;106:416-422. • Nakagawa O, et al. Rapid transcriptional activation and early mRNA turnover of brain natriuretic peptide in cardiocyte hypertrophy. J Clin Invest. 1995;96:1280-1287.

  29. The End

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