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Marc A. Silver, MD Clinical Professor and Chairman, Department of Medicine Director, Heart Failure Institute Advocate Ch

Update on Clinical Approaches for the Use of Natriuretic Peptides in Cardiovascular Disease Outpatient BNP Testing. Marc A. Silver, MD Clinical Professor and Chairman, Department of Medicine Director, Heart Failure Institute Advocate Christ Medical Center

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Marc A. Silver, MD Clinical Professor and Chairman, Department of Medicine Director, Heart Failure Institute Advocate Ch

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  1. Update on Clinical Approaches for the Use of Natriuretic Peptides in Cardiovascular Disease Outpatient BNP Testing Marc A. Silver, MD Clinical Professor and Chairman, Department of Medicine Director, Heart Failure Institute Advocate Christ Medical Center Systemwide Physician Leader, Heart Failure Advocate Healthcare

  2. A B C D Obesity Diabetes Hypertension Abn. Sleep Diastolic Dysfunction LVH Systolic Dysfunction Heart Failure Syndrome Death Hypertension Smoking Lipids Diabetes MI LV Remodels Time Decades Time Months

  3. Stages A-B Onset Stage C

  4. Evidence-Based Approach to Left Ventricular Dysfunction Monitor Therapy / Disease Modification X X X X Moderate CHF Severe CHF ALVD Mild CHF Pre- Heart Failure ALVD=asymptomatic left ventricular dysfunction.

  5. Evidence-Based Approach to Left Ventricular Dysfunction Choose Therapy / Monitor Disease Regression Moderate CHF Severe CHF ALVD Mild CHF Pre- Heart Failure ALVD=asymptomatic left ventricular dysfunction.

  6. Current and Potential Roles Of BNP Measurement(s) • Screening of High Risk Patients (Stage A) • Determination of use of more costly screens • Early Detection of Disease Progression (Stage A-C) • Monitoring/Guiding Adequacy of Therapy • In-patients (Need for admission /timing of D/C) • Out-patients / clinic • Prognosis • Determination of escalation / application of • limited resources (ICD’s) • Risk Stratification for CAD/ SD

  7. Framingham Study: Asymptomatic LV Dysfunction (ALVD) 1.0 Stage A 0.8 No ALVD (EF >50%) and noHF history 0.6 Stage B Survival 0.4 Mild ALVD (EF 40% to 50%) P<.0001 0.2 Moderate-to-severe ALVD (EF <40%) Systolic HF (EF 50%) 0.0 0 2 4 6 8 10 12 Years Wang TJ et al. Circulation. 2003;108:977-982.

  8. 233 Community Dwelling Individuals with Risks for HF Hyperlipidemia (48%) Hypertension (48%) Age > 65 years (45%) Tobacco Use (45%) CAD DM But NO HF! 91 % had > 1 Risk Silver M, et al. Congestive Heart Failure 2003, 9:127-132

  9. Screening for Heart Failure Role of BNP Levels On day of screening 48% had systolic hypertension 59% had diastolic hypertension 82% had 1 symptom that could be attributable to HF Silver M, et al. Congestive Heart Failure 2003, 9:127-132

  10. Screening for Heart Failure Role of BNP Levels BNP Levels Ranged from 0 to 479 pg/ml (mean 40 pg/ml) (Men mean 39 pg/ml; Women 42 pg/ml) 24 (10.3%) had levels > 100 pg/ml 32 (13.7%) had levels > 80 pg/ml No significant difference in the number of risk Factors and the BNP level Silver M, et al. Congestive Heart Failure 2003, 9:127-132

  11. Screening for Heart Failure Role of BNP Levels Silver M, et al. Congestive Heart Failure 2003, 9:127-132

  12. NEJM 2004 ;350:655-63

  13. Death NEJM 2004 ;350:655-63 HF Lowest 1/3 < 4.0 pg/ml Middle 1/3 4.1 to 12.7 pg/ml Highest 1/3 > 12.8 pg/ml

  14. Conclusions • In this community-based sample, plasma natriuretic peptide levels predicted the risk of death and cardiovascular events after adjustment for traditional risk factors • Excess risk was apparent at natriuretic peptide levels well below current thresholds used to diagnose heart failure

  15. BNP Levels in Patients With Dyspnea Secondary to CHF or COPD N=56 N=94 Maisel, A. et al. J. American College of Cardiology, Vol 37, No. 2, 2001

  16. Consensus Statement 8: BNP Screening in Higher-Risk Populations 8.1 At this time, BNP testing is not appropriate for screening asymptomatic, low- risk populations for LV systolic dysfunction. 8.2 There may be some value in using plasma BNP to screen high-risk subgroups of the population such as post-MI patients, diabetic patients, or those with an extended history of uncontrolled hypertension. It is important to note that echocardiography is likely to remain the main method of assessing LV function in this setting.

  17. 100 80 y=-0.7, p<0.001 60 LVEF (%) 40 20 0 0 1.0 2.0 3.0 Log BNP (pmol/l) BNP vs. EF by Echocardiography Davis et al. Lancet 1994;343:440-4.

  18. Heart Failure Diagnostic Algorithm Patient with dyspnea or other CHF signs/symptoms Diagnostic for CHF History/physical exam/ECG/chest x-ray Acute/chronic CHF management (echocardiography, if not done previously) Nondiagnostic Positive BNP blood test Negative Evaluate for non-CHF etiologies (echocardiography usually not indicated) Adapted from Maisel A. RevCardiovasc Med. 2002;3(suppl 4):S10–S17.

  19. Discriminate Function of BNP Maisel, A. et al. J. American College of Cardiology, Vol 37, No. 2, 2001

  20. Causes of Hospital Readmission for Congestive Heart Failure Diet Noncompliance 24% Rx Noncompliance 24% 16% Inappropriate Rx 17% Other 19% Failure to Seek Care Vinson J Am Geriatr Soc 1990;38:1290-5

  21. BNP Algorithm: Wet BNP level versusdry BNP level Decompensated CHF: volume overload BNP ≥ 1000 pg/ml (wet) Inpatient Rx: Rx: diuretics vasodilators Goal: Relief of symptoms euvolemia BNP levels:  to < 500 reflecting “dry-weight” BNP Uptitrate ACE, B-blockers BNP Monitoring for Early Detection of Decompensation Outpatient Rx: Discharge Goal: Reverse remodeling • from “dry-weight” BNP 100-200 pg/ml preferable BNP levels:

  22. “In the one published trial of outpatient treatment of heart failure guided by plasma BNP, 69 patients (LVEF < 40%, NYHA II-IV) were randomised to treatment according to plasma peptide levels or a clinical score. The primary end point of total cardiovascular events was reduced in BNP-guided patients (19 versus 54 events) with p < 0.001 in a multivariate analysis. The natriuretic peptides and particularly plasma BNP and aminoterminal proBNP promised to provide an objective guide for optimising treatment in heart failure.” Mark Richards BNP Guided Therapy Lancet 2000 Heart Failure Reviews, 2003 Eur J Heart Fail. 2004 Mar 15;6(3):351-4

  23. The hope is that RABBIT / BATTLE SCARED /STAR will not only demonstrate that BNP levels can guide therapy, but perhaps can help us monitor the type of drugs we use and how far to titrate that drug

  24. Another Genie About to Get Out of the Bottle…… BNP

  25. Is B-type natriuretic peptide-guided heart failure management cost-effective? • Int J Cardiol. 2004 Aug;96(2):177-81 • Intervention was BNP measurement once every 3 months (BNP group) or no BNP measurement (clinical group). Clinical and utility data were retrieved from published studies. Cost-effectiveness was measured by $ per quality-adjusted life year (QALY). • RESULTS: The baseline analysis during the 9-month period after hospitalization showed the QALY to be longer for the BNP group and the costs were also lower for the BNP group ($9577 and 10,131). The dominance of the BNP group continued during the 1-year follow-up. • CONCLUSIONS: Introduction of BNP measurement in heart failure management may be cost-effective.

  26. Clinical features and medical therapy at discharge in 521 post-MI patients Tapanainen JM et al. J Am Coll Cardiol 2004; 43:757-763.

  27. Clinical features and medical therapy at discharge in 521 post-MI patients Tapanainen JM et al. J Am Coll Cardiol 2004; 43:757-763.

  28. Clinical features and medical therapy at discharge in 521 post-MI patients Multivariate predictors of SCD*

  29. Wash. Dog Gets Heart Defibrillator By THE ASSOCIATED PRESS Filed at 1:12 p.m. ET PULLMAN, Wash. (AP) -- Honus the dog lacked that old spark, and the solution was a heart defibrillator. Doctors at Washington State University's veterinary hospital operated on the canine Thursday to insert the device, similar to the one that regulates the heart of Vice President Dick Cheney.

  30. B-Type Natriuretic Peptide as a marker for Sudden Death Risk Berger Circulation 2002;105:2392-2397

  31. B-Type Natriuretic Peptide as a marker for Sudden Death Risk (> 130 pg/ml) Berger Circulation 2002;105:2392-2397

  32. Stretch Activation of Maladptive Genes Increased Wall Stress MR Increased Afterload Increased O2 Consumption Episodic Subencardial Ischemia EF = 60 % EF = 40 % EF = 20 % SV = 100 ml SV = 100 ml SV = 100 ml Progressive LV Dilation

  33. Stretch Receptor (?) Signal Transduction Cascade Gene Expression Gene Expression Adverse Remodeling Adverse Remodeling Signal Transduction 101 Agonist Receptor Signal Transduction Cascade

  34. Am J Cardiol 2004;94:740-745

  35. Am J Cardiol 2004;94:740-745

  36. BNP During(On1), Short-term Discontinuation(Off) and Reinitiation (On2) of CRT p < 0.001 p < 0.001 382 BNP (pg/ml) 282 262 Off On1 On2 Sinha AM et al, Am J Cardiol. 2003, 15;91:755-8

  37. BNP and Guidelines Documents 9 Measurement of B-type natriuretic peptide (BNP) should be considered in the evaluation of patients presenting in the urgent care setting where the clinical diagnosis of the cause of dyspnea is uncertain. (Level of Evidence: B) 4 Measurement of BNP may be considered in the outpatient evaluation of patients where the clinical diagnosis of heart failure is uncertain or ambiguous. (Level of Evidence: C) 1 The value of serial measurements of BNP to guide therapy for patients with HF is unknown. (Level of Evidence: C).

  38. Prevention Early Diagnosis Differential Diagnosis, further Dx Management strategy Differential treatment Treatment adjustment/ optimization Community based screening after AMI diabetes Chemo Hptn Patients with dyspnea Patients with LVD AS / MR BBlockersDiuretics ACE-Inhib Digoxin Treatment optimization Alternatives BNP Providing actionable health information Treatment/ recurrence monitoring Predisposition screening Targeted screening Treatment stratification Diagnosis Prognosis

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