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Cardiac Markers. Resident Rotation in Clinical Chemistry 2005-2006. Diagnosis of AMI. Based on 2 out of 3 of WHO criteria (Circulation 90:583-612, 1979 ) Prolonged chest pain "Silent infarct”, Painless infarct ECG changes Lacks sensitivity Serum enzyme concentrations
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Cardiac Markers Resident Rotation in Clinical Chemistry 2005-2006
Diagnosis of AMI Based on 2 out of 3 of WHO criteria (Circulation 90:583-612, 1979) • Prolonged chest pain • "Silent infarct”, Painless infarct • ECG changes • Lacks sensitivity • Serum enzyme concentrations • CKMB lacks sensitivity in diagnosis of perioperative MI • Protein markers emerging in the 21st century
Cardiac Markers of the 21Century • MB isoenzyme • CKMM isoforms • CKMB isoforms • Myoglobin • Troponin I • Troponin T
Components in CK • CK Isoenzymes • CK-3 (CK-MM) in Skeletal muscle • CK-2 (CK-MB)10-20% in myocardium<2% in skeletal muscle • CK-1 (CK-BB) • Macro CKs • Type 1Complex formed between CK-BB and immunoglobulin • Type 2Mitochondria CK
MB Index • MB Index = (CKMB /total CK) x 100 • Rationale for using MB Index • Using CKMB alone (RI <4.7 ng/mL) often yields FP results • Combined use with MB Index helps to rule-out patients with skeletal muscle injury • What cut-off value for MB Index to use?
Sensitivity Specificity MB Index Sensitivity & specificity are determined respectively at MB Index of values 0 - 10
Limitations of CKMB • FP incidents in perioperative patients without cardiac injury • False elevations inFalse elevations in: • Skeletal muscle injury • Marathon runners • Chronic renal failure • Hypothyroidism • MI detection not timely enough for thrombolytic intervention. MB peaking takes >12h
Myoglobin & CKMB in typical MI 3 samples drawn within 2 h
MI Concomitant with Renal Failure 3 samples drawn within 2 h
B A = myoglobin or CKMB isoforms B = cardiac troponin C = CKMB D = cardiac troponin after unstable angina A A C A D Marker Responses to AMI
Troponin Release Kinetics • Pattern of release in MI is BIPHASIC. • Detectable in blood 4-12 h, similar to CKMB • Peaks 12-38 h • Remains elevated for 5-10 days
Receiver operating characteristic (ROC) Curve for Tn T • Plot of Sensitivity (TP) vs 1-specificity (FP) • Used for establishing best discriminator for cTnT for predicting AMI • Best discriminator point is 0.2 g/L at 9 h after onset of AMI