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 HF Useful in predicting outcomes To guide treatment out of reach for now.

Candidate Biomarkers in HF Inflammation 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 ST 2 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 HF Identify possible underlying causes of HF Confirm the presence or absence of HF syndrome Estimate 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 process Natriuretic peptides, soluble ST2 & Galectin-3 hold considerable promise

The processing cascade of Natriuretic peptides

Natriuretic peptides Diagnosing & excluding HF, predicting outcome in diagnosis Results of a recent metaanalysis Natriuretic peptide–guided therapy MR pro–ANP assay

ST 2 Membrane bound (ST2L) and soluble form (sST2) Stimulated by myocardial strain Associated with ventricular remodeling Powerfully prognostic Guide to HF therapy Assay for sST2

Galectin–3 (Gal–3) Secreted by activated macrophages Gal–3 is increased in patients with HF Predictor of intermediate and Longer prognosis in HF Comparative data are lacking

Clinical relevance of promising novel biomarkers

Summary Biomarkers will play increasing role in diagnosis Until 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.