THE UTILITY OF B-TYPE NATRIURETIC PEPTIDE IN HEART FAILURE: Is it Ready For Prime Time?

1. THE UTILITY OFB-TYPE NATRIURETIC PEPTIDEIN HEART FAILURE:Is it Ready For Prime Time? Resident Grand Rounds Robert B. Preli November 13, 2001

2. Overview • Clinical Case/Question • Heart Failure - Diagnosis • B-Type Natriuretic Peptide - Physiology • Evidence • Primary Care Setting • Urgent Care Setting • Costs and Timing • Conclusions

3. Clinical Case - History • 74 yo wf presents with a 2-week hx of SOB/DOE. • Denies Chest Pain/PND/Orthopnea/Edema • + non-productive cough • PMHx: Hypertension • Meds: Atenolol, Amlodipine, aspirin • ROS: as above, otherwise negative.

4. Clinical Case - Physical Exam • BP 160/93 P93 R16 T97.3 SaO2 95% on RA • No JVD • Lungs - Clear • Heart - RRR without abnormal heart sounds • No peripheral edema • EKG - Non-specific T-wave changes • CXR - Emphysema, no edema

5. Clinical Case - Questions • Does this patient have congestive heart failure? • Would a B-type Natriuretic Peptide be helpful in determining the etiology of this patient’s dyspnea?

6. Heart Failure - Diagnosis • Sometimes difficult • Symptoms are insensitive and non-specific - especially if only a few are present • Echocardiography - gold standard, but may be impractical in certain clinical settings: • Emergency Department • Primary Care Physician’s Office

7. Heart Failure-Signs & Symptoms

8. What About a Blood Test? • Similar to a WBC for infection or Troponin for myocardial infarction • May be useful in ER or office setting • Would not replace echocardiography • May help guide therapy or further work-up

9. Natriuretic Peptides • The subject of investigation for > 20 years • Neurohormones • Internal compensatory mechanism for intravascular volume changes • Three types: • Atrial Natriuretic Peptide (ANP) • Brain-type Natriuretic Peptide (BNP) • C-type Natriuretic Peptide (CNP)

10. Natriuretic Peptides

11. Natriuretic Peptides

12. The Evidence • EBM Concepts • BNP in Primary Care Settings/Referral • BNP in the Acute Care Setting

13. The Origin of EBM

14. ROC Curves • Shows the tradeoff between sensitivity and specificity • “Northwest” • Area Under Curve (AUC) quantifies the overall test accuracy • 1.0 > AUC > 0.5

15. ROC Curves • Some examples of AUC’s for different screening tests • Pap Smear = 0.70 • Mammogram = 0.85 • PSA = 0.94

16. Cowie • Design - Prospective observational case-series • Subjects - 122 patients referred to a heart failure clinic. 59 males, 63 females, age range 24 - 87 • Subjects did not have a history of heart failure

17. Cowie - Methods • All patients had H&P, blood sampling, EKG, Echo, CXR • HF defined as Echo “abnormality” + signs and symptoms • Panel of 3 cardiologists determined HF cases • Panel blinded to serum BNP measurements

18. Cowie - Results • BNP values available for 106/122 • 29% were defined as having HF • 86% with HF had NYHA Class II-III • 14% with HF had NYHA Class IV

19. Cowie - Results GroupMean BNP (pmol/L) Heart Failure 63.9 Normal 13.9 For BNP > 22.2 pmol/L • Sensitivity = 97% • Specificity = 84% • LR(+) = 6.1 • LR(-) = 0.04

20. Cowie - ROC CurveBNP AUC = 0.96

21. Cowie - Conclusions • BNP may be a useful tool in a primary care setting to aid in decisions about referrals • BNP should NOT be used as a diagnostic tool alone nor should it be a substitute for clinical judgment

22. Cowie - Limitations • Specific echo criteria for heart failure were not given • No confidence intervals • Small number of patients

23. Krishnaswamy • Design - Prospective observational study to evaluate the ability of BNP to predict left ventricular dysfunction • Subjects - 400 patients referred for echo at a VA Hospital • Subjects were both inpatients and outpatients • Some patients had a history of heart failure

24. Krishnaswamy - Methods • Clinical heart failure defined by Framingham Criteria • Echo criteria for heart failure: • Normal EF > 50% • Abnormal EF < 50% • All patients sampled for BNP • Investigators blinded to BNP values

25. Krishnaswamy - Results forClinical Criteria of CHF • For BNP > 107 pg/ml • Sensitivity = 86% • Specificity = 70% • LR(+) = 2.9 • LR(-) = 0.2

26. Krishnaswamy - Results forEcho Criteria of CHF • Normal LV function (n=147) • BNP = 30 +/- 36 pg/ml • Abnormal LV function (n=253) • BNP = 416 +/- 413 pg/ml • For a BNP > 75 pg/ml • Sensitivity = 85% • Specificity = 97% • LR(+) = 28.3 • LR(-) = 0.15

27. Krishnaswamy - ROC Curve

28. Krishnaswamy - Conclusions • BNP may be a useful way of identifying people with LV dysfunction.

29. Krishnaswamy - Limitations • VA Hospital - predominantly male subjects • Both inpatients and outpatients • BNP value confidence intervals extremely broad - not discussed by authors • Different cut-points used for different criteria

30. Maisel • Design – Prospective observational study of BNP as a screening test for LV dysfunction • Subjects – 200 consecutive patients referred for echo with no prior history of LV dysfunction • Exclusion criteria – referral for assessment of valvular disease or r/o cardiac cause of stroke • 24% of the population were inpatients • Mostly male patients (189/200) • Average age = 65

31. Maisel - Methods • All subjects had echocardiography and BNP measurements • Strict criteria defined for LV dysfunction: • Systolic - EF < 50% • Diastolic • Systolic + Diastolic

32. Maisel - Results

33. Maisel - Results

34. Maisel - Results

35. Maisel – ROC Curve

36. Maisel – Conclusions • BNP may be useful as a supplement in the screening for heart failure when trying to decide whom to refer for further evaluation • BNP should not replace echocardiography, but rather complement it

37. Maisel - Limitations • Study done at a single VA Hospital • Patients referred for echo were not necessarily symptomatic secondary to heart failure

38. McClure • Design – Prospective observational trial using BNP to identify LV dysfunction in survivors of myocardial infarction • Subjects – 134 “long-term” survivors of MI recalled for echo. • Subjects • Mean age 67 (range 43 – 89) • 63% men • 29% with symptoms of heart failure • 38% with hypertension • 57% with angina

39. McClure - Methods • All subjects had the following: • History and Physical • 12-Lead EKG • BNP measurement • Echocardiogram • LV dysfunction: • Mild • Moderate • Severe • Echo measurements made without knowledge of BNP levels

40. McClure - Results

41. McClure - Conclusions • BNP was only useful in identifying the small subgroup of patients with severe LV dysfunction • All subjects had an “abnormal” heart and were on cardiovascular medications • 45% of patients were on beta-blockers (may confound BNP levels)

42. McClure - Limitations • Subjects were all status post MI • Considerable overlap between the ranges of values for all subjects • “Long-term survivor” not defined

43. BNP in Primary Care - Summary

44. BNP in Primary Care - Summary

45. BNP in Acute Care • Evaluation of dyspnea of unclear etiology • Urgent care or emergency room settings • Can it aid in the diagnostic work-up?

47. Dao et. Al. • Design – Prospective observational trial of patients presenting to an urgent care facility with SOB as a prominent complaint • Subjects – 250 patients at a VA • Eligibility based on SOB as a main complaint • Trauma, tamponade, acute MI excluded • 30% had a history of heart failure • 40% had a history of CAD • Average age = 63 • 94% male

48. Dao - Methods • ED physicians assessed probability of HF as low, medium, or high • Available data at presentation included H&P, CXR, and blood tests (except BNP) • In patients with a history of HF, physicians determined if an exacerbation explained dyspnea • Gold standard of heart failure was two cardiologists reviewing medical records (blinded to the BNP values)

49. Dao - Results

50. Dao - Results