9/16/2016 1 Role of Biomarkers in Heart Failure Diagnosis and Prognosis James C. Fang, MD University of Utah Health Sciences Salt Lake City, UT Biomarkers for Clinical Practice • “Definition of a biomarker includes virtually any measurement that can be made on a biological system…” • “…restricted to substances measured in the blood other than genetic markers, electrolytes, and commonly used markers of hepatic or renal function.” Braunwald EB, JACC 2013
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9/16/2016
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Role of Biomarkers in Heart FailureDiagnosis and Prognosis
James C. Fang, MD
University of Utah Health Sciences
Salt Lake City, UT
Biomarkers for Clinical Practice
• “Definition of a biomarker includes virtually any measurement that can be made on a biological system…”
• “…restricted to substances measured in the blood other than genetic markers, electrolytes, and commonly used markers of hepatic or renal function.”
Braunwald EB, JACC 2013
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Biomarkers for Clinical Practice
• Must be easily available with rapid turnaround and inexpensive.
• Should provide information not available from careful clinical assessment.
• Aid in medical decision making, e.g. diagnosis, prognosis, identify healthy people at risk.
Braunwald EB, JACC 2013
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Ahmed T, et al. JACC 2013
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Biomarkers in Heart FailureJust a few to pick from…
Braunwald’s Textbook of Heart Failure 2014
Yancy C et al. 2013 ACC AHA HF guidelines
What Our Colleagues SayACC/AHA Guidelines 2013
(Troponins)
(sST2, Galectin-3)
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proBNP 1-108
BNP 77-108
NT-proBNP 1-76
BNP is Lower in HFpEF Relative to HFrEF
Iwanaga Y, et al. JACC 2006;47:742
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Natriuretic Peptides Improve Diagnostic Ability
Januzzi JL, et al. AJC 2005
NP-Guided HF ManagementMultiple Studies with Conflicting Results
N Age HFPEF NP target NP <C ? Tx ≠C ?
STARBRITE 130 60 No BNP at d/c No Yes
TIME-CHF 499 77 No NTP 400/800 No Yes
BATTLESCARRED 364 76 Yes NTP 1270 No Yes
PRIMA 345 72 Yes NTP at d/c No No
SIGNAL 252 78 No NTP 50% No No
Troughton, et al. 69 70 No NTP 1735 Yes Yes
STARS-BNP 220 65 No BNP 100 ? Yes
Berger, et al. 278 71 No NTP 2200 Yes Yes
PROTECT 151 63 No NTP 1000 Yes Yes
Januzzi JL. JCF 2011;17:622-625
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NP-guided HF ManagementActionable biomarker data?
Porapokkham P, et al. Arch Int Med 2010
NP guided ManagementA Way to Optimizing GDMT?
Porapokkham P, et al. Arch Int Med 2010
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Using Biomarkers to Profile HF
Biomarkers in HFMultimarker Approach
BNP sfltMPO hsCRPST2 TnIUACr
Ky B, et al. CircHF 2012
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Ky B, et al. CircHF 2012
Net reclassification improvement: 25.2%; 95%CI 14.2–36.2%; p<0.001
Biomarkers in HFMultimarker Approach
HFrEF, HFpEF, and HFrecEFPersistent CV risk
Basuray A, et al. Circulation 2014
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Biomarkers in HFPEFRemission versus Recovery?
Basuray A, et al. Circulation 2014
Creatinine is insensitive marker of renal function
Mishra J, et al. Lancet 2005
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Renal Biomarkers in HF
Tubulointerstitial• N-acetyl glucosaminidase
(NAG)• Kidney Injury Molecule (KIM-
1)• Neutrophil gelatinase-
associated lipocalin (NGAL)
Glomerular• eGFR• Cystatin C• albuminuria
GFR insensitive to abnormalities in tubular function in HF
Damman K, et al. Heart 2010
GFR <60 cc/min/1.73m2
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GFR Does Not Tell the Whole StoryTubulointerstitial biomarkers in GISI-HF
Damman K, et al. EHJ 2011
Van Rooij E, et al. PNAS 2006
MiRs in Heart FailureNew era in biomarkers?
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Cell 153:828-839
Blood Urea NitrogenImportant marker of HF prognosis
Fonorow G, et al. JAMA 2005
1) BUN >43 mg/dL2) SBP <115 mmHg3) SCr >2.75 mg/dl
1) BUN
2) SBP
3) SCr
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Anker SD, et al. Circulation. 2003
Uric AcidAn Oxidative Stress Biomarker
Summary
• Natriuretic peptides and troponins provide strong independent prognostic value in chronic LV dysfunction
• A Multimarker approach can improve prognostic power
• Use of renal and new cardiac biomarkers is evolving
• May help guide assessment of true myocardial recovery