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

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

WHY WE NEED BIOMARKER STUDY IN ACUTE CORONARY SYNDROME ?

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 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 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? CK (CPK) CK-MB Troponin-I/T LD (LDH) Myoglobin ALT/AST Others

CARDIAC ENZYMES (BIOMARKERS) Test 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 Most cardiac specific

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

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)

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)

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 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

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

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 Details SAMPLE PATIENT SERUM CHEMICAL REACTION IMMUNOASSAY

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

False-positive False-negative heterophile antibodies fibrin clots microparticles in specimens analyzer malfunctions False-negative interference of circulating IgG-class autoantibodies

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

RBC GP1 activity Inverse 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

Thank you !