Biomarkers for Clinical Practice - OSU Center for ... - Role of Bioma… · Role of Biomarkers in Heart Failure Diagnosis and Prognosis James C. Fang, MD University of Utah Health

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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

• Don’t forget the simple biomarkers

• Stay tuned for NP guided HF management

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