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CARDIAC TROPONIN ASSAY-UTILITY IN DIAGNOSIS OF ACUTE CORONARY SYNDROME
By Dr.Anup Bhandari JR 1 ,Department of Pathology, S.R.T.R.M.C.Ambajogai
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Definition “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
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WHY WE NEED BIOMARKER STUDY IN ACUTE CORONARY SYNDROME ?
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It’s because; neither the clinical presentation nor the ECG had adequate clinical sensitivity and specificity for detecting MI without the use of biomarkers
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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
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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
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Which Biomarkers? CK (CPK) CK-MB Troponin-I/T LD (LDH) Myoglobin
ALT/AST Others
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CARDIAC ENZYMES (BIOMARKERS)
Test Normal Range CK or CPK Creatinine Phosphokinase Normal U/L CK-MB < 5% MB Myoglobin Normal < 85 ng/ml LDH (Lactate dehydrogenase) Normal 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 I cTnI Normal < 0.1 ng/ml Not elevated by CRF Most cardiac specific
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Timing Summary TEST ONSET PEAK DURATION CK/CK-MB 3-12 hours
Troponins Up to 10 days Myoglobin 1-4 hours 6-7 hours 24 hours LDH 6-12 hours 24-48 hours 6-8 days
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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)
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TROPONIN 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)
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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
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Troponin Use Troponin Early Rise(hrs) Peak (Hrs) Duration (Days) Specficity Sensitivity Tn T 3-4 10-24 80% >98% Tn I 4-6 1-24 4-7 95% Therefore it has good utility for retrospectively diagnosing AMI Remember, CK-MB returns to baseline by 48 hours
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Troponin Influence on Prognosis
detectable 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 risk of reinfarction
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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
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Lab Details SAMPLE PATIENT SERUM CHEMICAL REACTION IMMUNOASSAY
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SOS repeated 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
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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
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False-positive False-negative
heterophile antibodies fibrin clots microparticles in specimens analyzer malfunctions False-negative interference of circulating IgG-class autoantibodies
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New molecules being studied;
IMA Increases within 6-10 min Used with ECG Or troponin GPBB Peaks earlier than CK-MB More sensitive early marker MPO Released from WBC granules Atheromatous plaque instability
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RBC GP1 activity Inverse relationship PAPP-A Eroded or ruptured plaque
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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
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Thank you !
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