A view of Novel Cardiac Biomarkers in Heart Failure

Sequence of presentation

Background Current status in Heart Failure (HF) Candidate biomarkers in HF Criteria to evaluate utility of cardiac biomarkers Recent review of some HF biomarkers Summary

Background

Diagnosis, predicting risk and prognosis Role in guiding therapy Biomarker testing in HF – An elective supplement A contrast approach New lines of investigation – genomics,

metabolomics.

Current status in Heart Failure HF a major burden in health care A promising avenue for evaluating novel biomarkers Considering established biomarkers in new ways Correct diagnosis can be challenging

Current status in Heart Failure A heterogenous group of different syndromes Biomarkers use restricted for diagnosis Can biomarkers be utilized to establish risk Rising interest in HF biomarkers

Role of BNP (Can BNP guide therapy?)Determination of biological standards for

diagnosis, prognosis & treatment of HF.BNP & NT–pro BNP for diagnosing HFUseful in predicting outcomesTo guide treatment out of reach for now.

Candidate Biomarkers in HFInflammation

C–reactive protein Tumour necrosis factor α LP–PLA2 Adiponectin

Oxidative Stress Oxidized LDL Myeloperoxidase Urinary biopyrrins

Extracellular–matrix remodeling MMP2, MMP3, MMP9 TIMP1 Collagen propeptides

Neurohormones Angiotensin II Aldosterone Arginine vasopressin, copeptin Endothelin – I

Myocyte injury and apoptosis Troponins I and T Heart–type fatty acid binding protein Myosin light–chain kinase I Creatine kinase MB fraction

Mycoyte stress BNP, NT–proBNP, MR–pro ANP s ST2 GDF–15

Extracardiac involvement Cystatin–C, β–trace protein NGAL, NAG, KIM-I Triiodothyronine

Criteria to evaluation utility of cardiac biomarkers

Measurability Can it measure a specific pathology with known ref

limits and high myocardial Specificity? High accuracy, precision & reproducibility? High sensitivity & Specificity? High throughput & short turnaround time? Reasonable Cost? Pre – analytical issues?

Incremental value Linear relationship in multiple studies? Predicting risk, early diagnosis or correlating with

disease – Is the marker superior? Validation of decision limits? Evaluation in diverse population?

Patient management Does a change in the marker alter patient

management? Evidence of Biomarker–guided triage or monitoring

improves care?

Aide in selecting therapy, stratifying risk, monitoring response to therapy?

Detecting sub–clinical disease?Patient Impact

Better understanding of disease or risk? Healthier patient behaviors?

NACB goals for a biomarker in HFIdentify possible underlying causes of HFConfirm the presence or absence of HF

syndromeEstimate the severity of HF & risk of disease

progression

Recent view of some HF biomarkers

None of the presently available or studied biomarkers meet the standards except Natriuretic peptides

Evaluation is a complex processNatriuretic peptides, soluble ST2 & Galectin-3

hold considerable promise

The processing cascade of Natriuretic peptides

Natriuretic peptidesDiagnosing & excluding HF, predicting

outcome in diagnosisResults of a recent metaanalysisNatriuretic peptide–guided therapyMR pro–ANP assay

ST 2 Membrane bound (ST2L) and soluble form

(sST2)Stimulated by myocardial strainAssociated with ventricular remodelingPowerfully prognosticGuide to HF therapyAssay for sST2

Galectin–3 (Gal–3)Secreted by activated macrophagesGal–3 is increased in patients with HFPredictor of intermediate and Longer

prognosis in HFComparative data are lacking

Clinical relevance of promising novel biomarkers

SummaryBiomarkers will play increasing role in

diagnosisUntil recently biomarkers playing a peripheral

role in evaluation & management of HF syndromes

Emerging applications with established markers

Novel markers & limitation of widespread application of novel tests.