Amino-Terminal Pro-Brain Natriuretic
Peptide, Brain Natriuretic Peptide, and
Troponin T for Prediction of Mortality
in Acute Heart Failure
HEART FAILURE
CAD
CARDIAC
DISEASES
HYPERTENSION
CARDIOMYOPATHY
CONGENITAL &
CARDIAC
VALVULAR HEART
HYPERTROPHY
DISEASE
ARRHYTHMIA
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
Apoptosis
Antherosclerotic
Inflammatory
process
Genetics
Thrombogenesis
Plaque
rapture
Renal
Function
An Ideal Marker for Myocardial Injury
(action in acute conditions)
ECG
Abnomality
Marker
0-4hrs
No
Rapid
4-48hrs
No
Serial monitoring
>48hrs
No
Persist long shortfall
Anytime
Yes
Monitoring therapy
Time after
chest pain
thrombolytic
An Ideal Marker for Myocardial Injury
(in chronic conditions)
Predicting morbidity and mortality
Release of Cardiac Markers in Myocardial Infarction
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
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
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
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
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
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
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
proBNP(108aa)
NT-proBNP(1-76aa)
Signal peptide (26aa)
LV stretch
Wall tension
BNP-32 (77-108aa)
MISCELLANEOUS MARKERS
hsCRP
Serum amyloid protein A
Cytokines
sCD40 ligand
Myeloperoxidase
Phospholipase A2
 Antherosclerotic process
Inflammatory responses
oxLDL
Placental growth factor
Choline (phospholipase D)
Isoprostanes
Homocysteine
Adhesion molecules
Nourin
MISCELLANEOUS MARKERS
Unbound free fatty acid
Ischemia modified albumin

Ischemia
Urinary thromboxane
 Thrombogenesis
Secreted platelet granular substances
Tissue plasminogen activator antigen
Matrix metalloproteinases
 Plaque
Pregnancy associated plasma protein A
rapture
MISCELLANEOUS MARKERS
Heart-type cytoplasmic fatty
acid-binding protein (H-FABPc)
Glycogen phosphorylase
isoenzyme BB (GPBB)
Early Detection

of MI?
Acute Coronary Syndrome
ESC/ACC
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
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
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
AUC
0.67
P=0.05
0.61
0.68
0.67 P=0.35
0.64
0.61
6mo
1yr
6mo
1yr
NT-proBNP
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BNP
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NT-proBNP
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BNP
Hazard=1/(N-K+1)