Amino-Terminal Pro-Brain Natriuretic Peptide, Brain Natriuretic Peptide, and Troponin T for Prediction of Mortality in Acute Heart Failure

HYPERTENSIONHYPERTENSION CAD CAD ARRHYTHMIA CARDIAC DISEASES CARDIAC HYPERTROPHY CONGENITAL & VALVULAR HEART DISEASE CARDIOMYOPATHY CARDIOMYOPATHY HEART FAILURE

A Cardiac Marker is definded as a clinical laboratory test useful for detecting AMI or minor myocardial injury. Most useful when patients have nondiagnostic ECG tracing.

Markers differ in their… 1. Location in/out of the myocytes 2. Release kinetics of damage 3. Clearance from the circulation 4. Chemical Structure and conformation

Myocardial necrosis (ACS markers) Ischemia Hypervolemic status Plaque rapture Renal Function Thrombogenesis Genetics Apoptosis Antherosclerotic Inflammatory process

An Ideal Marker for Myocardial Injury (action in acute conditions) Time after chest pain ECG Abnomality Marker 0-4hrs 4-48hrs >48hrs Anytime No Yes No Rapid Persist long shortfall Serial monitoring Monitoring therapy thrombolytic

Predicting morbidity and mortality An Ideal Marker for Myocardial Injury (in chronic conditions)

Release of Cardiac Markers in Myocardial Infarction

PROTEIN MARKERS Myo / (HFABP & CK-MM or CA) ratio helps to differentiate Cytoplasmic  rapid release 1. Location in/out of the myocytes 2. Release kinetics of damage 3. Clearance from the circulation 4. Chemical Structure and conformation Myoglobin Oxygen binding protein of cardiac and skeletal muscle Cardiac and skeletal muscle  nonspecific Renal   GFR increases Myo small  rapid release

ENZYME MARKERS Creatine Kinase MB isoenzyme Cytoplasmic  fast release 1. Location in/out of the myocytes 2. Release kinetics of damage 3. Clearance from the circulation kidneys   GFR increases CK-MB Cardiac (10-20% of total CK activity) and skeletal muscle (2-5% of total CK activity)  nonspecific % CK-MB (mass:total CK activity) helps to differentiate Activity and Mass

ENZYME MARKERS Creatine Kinase MB isoenzyme 4. Chemical Structure and conformation At least 4 isoforms Only two forms CK-MB1 and CK-MB2 used diagnostically Activity and Mass

PROTEIN MARKERS Cardiac Troponin I and T Regulatory proteins of myofibril 94-97% myofibril, 3-6% cytoplasmic  delayed release, persist 1. Location in/out of the myocytes 2. Release kinetics of damage 3. Clearance from the circulation Cardiac and skeletal muscle isoforms

PROTEIN MARKERS 4. Chemical Structure and conformation Complex of three subunits C(calcium binding), I (inhibitory) and T (tropomyosin-binding): association/dissociation Mutiple modifications: C and N terminal degradation Phosphorylation Oxidation, reduction cTnI has additional posttranslational 31-aa NT residues than skeletal muscle TnI, very specific cTnT has additional posttranslational 11-aa NT residues than skeletal muscle TnT, also expressed in skeletal muscle under certain circumstances Cardiac Troponin I and T Regulatory proteins of myofibril

PEPTIDE MARKERS NT-pro BNP and BNP Regulatory hormone in response to cardiac stresses, particularly cardiac stretch No storage in cardiomyocytes Not a marker for acute conditions 1. Location in/out of the myocytes 2. Release kinetics of damage 3. Clearance from the circulation Heart ventricles and brain→ nonspecific NT-proBNP: kidneys   GFR increases NT-pro BNP BNP: Receptor-mediated clearance (neutral endopeptidase)

PEPTIDE MARKERS NT-pro BNP and BNP Regulatory hormone in response to cardiac stresses, particularly cardiac stretch 4. Chemical Structure and conformation myocyte preproBNP (134aa) proBNP(108aa) Signal peptide (26aa) BNP-32 (77-108aa)NT-proBNP(1-76aa) Wall tension LV stretch

MISCELLANEOUS MARKERS Antherosclerotic process  hsCRP Serum amyloid protein A sCD40 ligand Cytokines Inflammatory responses Myeloperoxidase Phospholipase A2 oxLDL Placental growth factor Isoprostanes Nourin Adhesion molecules Homocysteine Choline (phospholipase D)

MISCELLANEOUS MARKERS Thrombogenesis  Unbound free fatty acid Ischemia modified albumin Secreted platelet granular substances Urinary thromboxane Tissue plasminogen activator antigen Matrix metalloproteinases Ischemia Pregnancy associated plasma protein A Plaque rapture 

MISCELLANEOUS MARKERS Heart-type cytoplasmic fatty acid-binding protein (H-FABPc) Early Detection of MI?  Glycogen phosphorylase isoenzyme BB (GPBB)

Cardiac troponin I or T CK-MB mass Total CK 1. Early release kinetics similar to CK-MB Although none of them sensitive enough for early detection. 2. Long interval of increase, replaced LD in detecting late-presenting patient. Although can not differentiate new and recurrent MI. 3. Cardiac tissue specificity ESC/ACC Acute Coronary Syndrome

Heart Failure Pathophysiological condition in which an abnormality of cardiac function is responsible for the failure of the heart to pump sufficient blood to satisfy the requirements. 1. Impairment from ACS 2. Cadiac stiffness 3. High output heart failure BNP & NT-proBNP

Diagnosis of HFMonitoring HF therapies Prognosis of CAD, HF High sensitivity Low specificity Insufficient evidence to show  after therapy Independent predictor Comparison & Combination with other markers Insufficeint accuracy to be a screening test

6mo 1yr AUC P=0.05 P=0.35

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