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By Dr.Anup Bhandari JR 1 ,Department of Pathology, S.R.T.R.M.C.Ambajogai • “A 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 • preexisting ST-segment elevation because of ventricular aneurysm or by Q waves • Gastroesophageal disease • pacemaker rhythm • Pulmonary embolism • or preexisting or newly developed bundle branch blocks (BBB). • Aortic aneurism • Pericarditis, pleuritis • Chest wall syndromes • Herpes zoster • 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 • • • • • • • CK (CPK) CK-MB Troponin-I/T LD (LDH) Myoglobin ALT/AST Others Test Most cardiac specific Normal Range CK or CPK Creatinine 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 I cTnI Normal < 0.1 ng/ml Not elevated by CRF Timing 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 • 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) • 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) : – 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 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% • Therefore it has good utility for retrospectively diagnosing AMI • Remember, CK-MB returns to baseline by 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 eventfree survival rate and with increased risk of reinfarction heart failure, myocarditis and pericarditis, cardiomyopathy, cardiac contusion, defibrillation and internal or external cardioversion,cardiac procedures 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 • 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 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 Falsepositive Falsenegative heterophile antibodies interference of circulating IgGclass autoantibodies fibrin clots microparticles in specimens analyzer malfunctions IMA GPBB MPO • Increases within 6-10 min • Used with ECG Or troponin • Peaks earlier than CK-MB • More sensitive early marker • Released from WBC granules • Atheromatous plaque instability RBC GP1 • Inverse activity relationship PAPP-A • Eroded or ruptured plaque 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