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 !