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

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

2. HEART FAILURE CARDIAC DISEASES HYPERTENSION CAD ARRHYTHMIA CARDIAC HYPERTROPHY CONGENITAL & VALVULAR HEART DISEASE CARDIOMYOPATHY

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

4. 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

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

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

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

10. Release of Cardiac Markers in Myocardial Infarction

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

12. ENZYME MARKERS Creatine Kinase MB isoenzyme Activity and Mass 1. Location in/out of the myocytes 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 2. Release kinetics of damage Cytoplasmic  fast release 3. Clearance from the circulation kidneys GFR increases CK-MB

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

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

15. PROTEIN MARKERS Cardiac Troponin I and T Regulatory proteins of myofibril 4. Chemical Structure and conformation 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 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

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

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

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

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

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

21. Acute Coronary Syndrome ESC/ACC 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 Cardiac troponin I or T CK-MB mass Total CK

22. 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

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

26. 1yr 6mo 1yr 6mo AUC 0.67 0.61 0.68 P=0.05 0.67 0.64 0.61 P=0.35

27. NT-proBNP < < < > > < > > BNP

28. < < < > > < > > NT-proBNP < < < > > < > > BNP Hazard=1/(N-K+1)