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.