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Biomarkers In Heart Failure Heart Failure Teleconference  ●  June 25, 2011
Biomarker:  Definition ,[object Object],NIH Biomarkers Definition Working Group.  Atkinson, et al.  Clin Pharmacol Ther  2001 Discovery Confirmation Validation & Refinement Adoption Identification Established relevance to population Identify clinical utility
Monitoring Heart Failure:  Necessary Pre-requisites ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Whellan et al,  Am Heart J Suppl  2007
Objectives of Biomarker Testing in Heart Failure ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Condition X Outcome A Outcome B Biomarker Intervention
Non-Specific Blood Biomarkers in Heart Failure  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Tang W,  Biomarkers Med  2009;  Braunwald, HF Clin NA 2009
Biomarker Discovery De Couto et al,  Nat Rev Cardiol  2010
Natriuretic Peptide Testing in Acute Heart Failure Januzzi et al,  AJC  2006 Maisel et al  N Engl J Med  2002 Biosite BNP (pg/ml) Roche NT-proBNP Negative Predictive Value >90%
Confounders of Plasma BNP Levels ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Troughton et al,  J Am Coll Cardiol  2004
Incremental Benefit with Natriuretic Peptide Testing in Acute Heart Failure Muller et al,  N Engl J Med  2003  Moe et al,  Circulation  2007 IMPROVE-CHF BASEL Biosite BNP (pg/ml) Roche NT-proBNP (pg/ml)
Incremental Benefit with Natriuretic Peptide Testing in Acute Heart Failure Muller et al,  N Engl J Med  2003  Moe et al,  Circulation  2007 IMPROVE-CHF BASEL Biosite BNP (pg/ml) Roche NT-proBNP (pg/ml) HFSA 2010 Guideline Recommendation 4.6:  It is recommended that BNP or NT-proBNP levels be assessed in all patients suspected of having HF, especially when the diagnosis is not certain. (Strength of Evidence = A)
Risk Stratification:  BNP in Acute Heart Failure Logeart et al,  J Am Coll Cardiol  2004 Biosite BNP (pg/ml)
Risk Stratification:  Concordance with Clinical Status Morrow et al,  JAMA  2005 Bayer ADVIA BNP (in pg/ml) High BNP at Month 4 Low BNP at Month 4
Current FDA-Cleared Indications for NPs ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Refinement:  Criteria for a Clinically Useful Biomarker ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Morrow & Braunwald,  Circulation  2007
Biomarker-Guided Strategies in Heart Failure ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Samara & Tang,  Heart Fail Rev  2011
Risk Stratification:  Multimarker Strategy (Serial) Miller et al,  Circulation  2007 Shionogi BNP (pg/ml)
Natriuretic Peptide-Guided Therapy:  BATTLE-SCARRED Richards et al,  JACC  2009
Natriuretic Peptide-Guided Therapy:  PROTECT Januzzi et al , AHA Late-Breaking Clinical Trial (2010)
Natriuretic Peptide-Guided Therapy:  PROTECT Januzzi et al , AHA Late-Breaking Clinical Trial (2010) ,[object Object],[object Object],[object Object],[object Object]
Monitoring Progression Towards Heart Failure Adapted from Jessup et al,  Circulation  2009; and Aamer et al,  Circulation  2007
Screening:  Echocardiographic Abnormalities (Olmsted County) McKie et al,  Hypertension  2006 Roche NT-proBNP (pg/ml)
Screening:  Echocardiographic Abnormalities (Olmsted County) McKie et al,  Hypertension  2006 Roche NT-proBNP (pg/ml) HFSA 2010 Guideline Recommendation 4.3:   Routine determination of plasma B-type natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP) concentration as part of a  screening evaluation  for structural heart disease in asymptomatic patients is  not recommended .  (Strength of Evidence = B)
Prognostic Value of “Screening” Natriuretic Peptides McKie et al,  Hypertension  2006 Lowest third <13.4 pg/mL Middle third 13.4–39.7 pg/mL Highest third >39.7 pg/mL Lowest third <36.7 pg/mL Middle third 36.7-109.0 pg/mL Highest third >109.0 pg/mL
Subclinical Myocardial Damage and CV Risk Tang et al,  Art Thromb Vasc Biol  2010 Cardinale et al,  Circulation  2006 ,[object Object],[object Object],No ACE-I ACE-I LVEF (%)
Linking Biomarkers to Therapy Hare et al,  J Am Coll Cardiol  2008 Liggett et al,  Nature Med  2008
[object Object],[object Object]

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Biomarkers in Heart Failure

  • 1. Biomarkers In Heart Failure Heart Failure Teleconference ● June 25, 2011
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  • 6. Biomarker Discovery De Couto et al, Nat Rev Cardiol 2010
  • 7. Natriuretic Peptide Testing in Acute Heart Failure Januzzi et al, AJC 2006 Maisel et al N Engl J Med 2002 Biosite BNP (pg/ml) Roche NT-proBNP Negative Predictive Value >90%
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  • 9. Incremental Benefit with Natriuretic Peptide Testing in Acute Heart Failure Muller et al, N Engl J Med 2003 Moe et al, Circulation 2007 IMPROVE-CHF BASEL Biosite BNP (pg/ml) Roche NT-proBNP (pg/ml)
  • 10. Incremental Benefit with Natriuretic Peptide Testing in Acute Heart Failure Muller et al, N Engl J Med 2003 Moe et al, Circulation 2007 IMPROVE-CHF BASEL Biosite BNP (pg/ml) Roche NT-proBNP (pg/ml) HFSA 2010 Guideline Recommendation 4.6: It is recommended that BNP or NT-proBNP levels be assessed in all patients suspected of having HF, especially when the diagnosis is not certain. (Strength of Evidence = A)
  • 11. Risk Stratification: BNP in Acute Heart Failure Logeart et al, J Am Coll Cardiol 2004 Biosite BNP (pg/ml)
  • 12. Risk Stratification: Concordance with Clinical Status Morrow et al, JAMA 2005 Bayer ADVIA BNP (in pg/ml) High BNP at Month 4 Low BNP at Month 4
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  • 16. Risk Stratification: Multimarker Strategy (Serial) Miller et al, Circulation 2007 Shionogi BNP (pg/ml)
  • 17. Natriuretic Peptide-Guided Therapy: BATTLE-SCARRED Richards et al, JACC 2009
  • 18. Natriuretic Peptide-Guided Therapy: PROTECT Januzzi et al , AHA Late-Breaking Clinical Trial (2010)
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  • 20. Monitoring Progression Towards Heart Failure Adapted from Jessup et al, Circulation 2009; and Aamer et al, Circulation 2007
  • 21. Screening: Echocardiographic Abnormalities (Olmsted County) McKie et al, Hypertension 2006 Roche NT-proBNP (pg/ml)
  • 22. Screening: Echocardiographic Abnormalities (Olmsted County) McKie et al, Hypertension 2006 Roche NT-proBNP (pg/ml) HFSA 2010 Guideline Recommendation 4.3: Routine determination of plasma B-type natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP) concentration as part of a screening evaluation for structural heart disease in asymptomatic patients is not recommended . (Strength of Evidence = B)
  • 23. Prognostic Value of “Screening” Natriuretic Peptides McKie et al, Hypertension 2006 Lowest third <13.4 pg/mL Middle third 13.4–39.7 pg/mL Highest third >39.7 pg/mL Lowest third <36.7 pg/mL Middle third 36.7-109.0 pg/mL Highest third >109.0 pg/mL
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  • 25. Linking Biomarkers to Therapy Hare et al, J Am Coll Cardiol 2008 Liggett et al, Nature Med 2008
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