CARDIAC TROPONIN ASSAY-
UTILITY IN DIAGNOSIS OF
ACUTE CORONARY SYNDROME
CARDIAC TROPONIN ASSAY-
UTILITY IN DIAGNOSIS OF
ACUTE CORONARY SYNDROME
ByDr.Anup Bhandari
JR 1 ,Department of Pathology,
S.R.T.R.M.C.Ambajogai
ByDr.Anup Bhandari
JR 1 ,Department of Pathology,
S.R.T.R.M.C.Ambajogai
DefinitionDefinition
• “A biomarker is a substance used as an indicator of a biologic state.
• It is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.”
• --Wikipedia
WHY WE NEED
BIOMARKER STUDY IN ACUTE CORONA
RY SYNDRO
ME ?
WHY WE NEED
BIOMARKER STUDY IN ACUTE CORONA
RY SYNDRO
ME ?
It’s because;It’s because;
neither the clinical presentation nor the ECG had adequate clinical sensitivity and specificity for detecting MI without the use of biomarkers
CONFOUNDING FACTORS
CONFOUNDING FACTORS
For ECG
• preexisting ST-segment elevation because of ventricular aneurysm or by Q waves
• pacemaker rhythm
• or preexisting or newly developed bundle branch blocks (BBB).
For clinical presentation
• Gastroesophageal disease
• Pericarditis, pleuritis
• Chest wall syndromes
• Pulmonary embolism
• Aortic aneurism
• Herpes zoster
What biomarkers are good for
What biomarkers are good for
• Diagnosing AMI/ACS• Detecting myocardial damage whether due
to AMI or other cardiac process• Risk-stratifying patients• Commenting on Prognosis
– In ACS, pre and post PCI/reperfusion therapy– Renal Disease
• Stressing interns, confusing residents and worrying cardiology fellows
Which Biomarkers?
Which Biomarkers?• CK (CPK)• CK-MB• Troponin-I/T• LD (LDH)• Myoglobin• ALT/AST• Others
CARDIAC ENZYMES (BIOMARKERS)
CARDIAC ENZYMES (BIOMARKERS)
Most cardiac specific
Test Normal Range
CK or CPKCreatinine Phosphokinase
Normal 25-170 U/L
CK-MB < 5% MB
Myoglobin Normal < 85 ng/ml
LDH(Lactate dehydrogenase)
Normal 100-200 U/L LDH-1 -5 LDH- 1 is found primarily in heart muscle and red blood cells.
Troponin cTnT
Normal < 0.01ng/ml May be elevated by CRF
Troponin IcTnI
Normal < 0.1 ng/ml Not elevated by CRF
Timing SummaryTiming Summary
TEST ONSET PEAK DURATION
CK/CK-MB 3-12 hours 18-24 hours 36-48 hours
Troponins 3-12 hours 18-24 hours Up to 10 days
Myoglobin 1-4 hours 6-7 hours 24 hours
LDH 6-12 hours 24-48 hours 6-8 days
Diagnosis Of Acute Myocardial Infarction
Diagnosis Of Acute Myocardial Infarction
• Typical rise and gradual fall (troponin) or more rapid rise and fall (CK-MB) of biochemical markers of myocardial necrosis with at least one of the following:
• ischemic symptoms;• development of pathologic Q waves
on the ECG;• ECG changes indicative of ischemia
(ST segment elevation or depression);
• coronary artery intervention (e.g., coronary angioplasty)
TROPONINTROPONIN• Troponin is a complex of three
regulatory proteins that is integral to non-smooth muscle contraction in skeletal as well as cardiac muscle
• Troponin is attached to the tropomyosin sitting in the groove between actin filaments in muscle tissue
• three subunits, TnC, TnT, and TnI– Troponin-C (calcium ions) – Troponin-T (tropomyosin)– Troponin-I (actin)
MORE ABOUT TROPONIN
MORE ABOUT TROPONIN
• Laboratory range definition:
– Cutoff is set at 99th percentile of a normal reference population,
variation of less than 10%– Since troponin levels are
virtually undetectable in normal subjects, this 99th percentile corresponds to
<0.01(cTn T) ,0.1(cTn I)– -heparin in sample can result
in lowered values
Troponin UseTroponin Use
• Therefore it has good utility for retrospectively diagnosing AMI
• Remember, CK-MB returns to baseline by 48 hours
Troponin
Early Rise(hrs)
Peak (Hrs)
Duration
(Days)
Specficity
Sensitivity
Tn T 3-4 10-24 10-24 80% >98%
Tn I 4-6 1-24 4-7 95% >98%
Troponin Influence on
Prognosis
Troponin Influence on
Prognosisdetectable levels
chronic disease even if not acute myocardial damage
72-96 hour
peak TI value
infarct size
time to peak
troponin >11
hours
a lower cardiac event-free survival
rate and with increased riskof reinfarction
Other than M.I. conditions
Other than M.I. conditions
• Cardiac conditions- heart failure, myocarditis and pericarditis,
cardiomyopathy, cardiac contusion, defibrillation and internal or external cardioversion,cardiac procedures
• Non-cardiac conditions- critical illnesses such as sepsis, Several toxins
and venoms, Carbon monoxide poisoning , primary pulmonary hypertension, pulmonary embolism and acute exacerbations of chronic obstructive pulmonary disease (COPD), Seizures, end-stage renal disease, Strenuous endurance exercise
Lab DetailsLab Details
SAMPLE PATIENT
SERUM
CHEMICAL REACTION• IMMUNOASSAY
•SOS•repea
ted at 2 and 72 hours later
•Assay times range from 5 to 30minutes
•TAT<60 min
•cTn T >0.1 ng/ml
•cTn I >1.0 ng/ml
An immunoassay is a biochemical test that measures the concentration of a substance in serum or urine, using the reaction of a specific antibody (often monoclonal Ab) or antibodies to bind to its antigen. To determine a numerical result (as in cardiac biomarkers), the response of the fluid being measured must be compared to standards of a known concentration. One of the most common methods is to label either the antigen or the antibody with an enzyme (EIA), radioisotope (RIA), magnetic labels (MIA) or fluorescence
False-positive
heterophile antibodies
fibrin clots
microparticlesin specimens
analyzer malfunctions
False-negative
interference of circulating IgG-
class autoantibodies
New molecules being studied;
New molecules being studied;
•Increases within 6-10 min
•Used with ECG Or troponin
IMA
•Peaks earlier than CK-MB
•More sensitive early marker
GPBB
•Released from WBC granules
•Atheromatous plaque instability
MPO
•Inverse relationship
RBC GP1
activity
•Eroded or ruptured plaque
PAPP-A
Edge over other biomarkers
Edge over other biomarkers
• improved time dependent sensitivity and improved specificity
• first peak value 40 times the detection limit Vs CK-MB only 6-9 times
• prognostic value of troponin in unstable angina,reperfusion therapy
• Corelates with infarct size• Reducing false positives
Thank you !
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