Cardiac Markers in Cardiac Markers in Acute Coronary Acute Coronary

SyndromesSyndromes

NilratNilrat WannasilpWannasilpDepartment of Clinical Department of Clinical

PathologyPathology

ScopeScope

Acute coronary syndromeAcute coronary syndromeWHO criteriaWHO criteriaIdeal cardiac markersIdeal cardiac markersCardiac markersCardiac markersClinical uses of cardiac markersClinical uses of cardiac markersNew criteria for diagnosis ACSNew criteria for diagnosis ACSSummarySummary

ACSACS

Unstable angina pectoris (UAP) Unstable angina pectoris (UAP) Acute myocardial infarction (AMI): Acute myocardial infarction (AMI):

NonNon--Q wave MI, QQ wave MI, Q--wave MIwave MICardiac (coronary) sudden deathCardiac (coronary) sudden death

WHO criteria WHO criteria 19791979

History of chest pain consistent History of chest pain consistent with myocardial ischemiawith myocardial ischemia

ElectrocardiographicElectrocardiographic (ECG) (ECG) changes consistent with AMIchanges consistent with AMI

Typical myocardial infarction Typical myocardial infarction plasma or serum enzyme changes plasma or serum enzyme changes

Ideal Cardiac MarkersIdeal Cardiac Markers

High sensitivity : abundant in High sensitivity : abundant in cardiac tissuecardiac tissue

High specificity : absent from non High specificity : absent from non cardiac tissuecardiac tissue

Release pattern : rapid, long blood Release pattern : rapid, long blood half lifehalf life

Clinical usefulness : influence Clinical usefulness : influence therapy therapy

Analytical performance : Analytical performance : automation automation

CytosolicCytosolic markermarker

Contractile proteinContractile protein

Cardiac MarkersCardiac Markers

CytosolicCytosolic markers : AST, LDH, CK, markers : AST, LDH, CK, myoglobinmyoglobin

IsoenzymeIsoenzyme of CK: CKof CK: CK--MB, MB, isoenzymeisoenzyme of LDHof LDH

Contractile proteins : myosin, Contractile proteins : myosin, troponin troponin

AST AST

AspartateAspartate aminotransferaseaminotransferase

First cardiac markerFirst cardiac marker

Marked increase in Marked increase in

Viral hepatitisViral hepatitisCarbon tetrachloride poisoningCarbon tetrachloride poisoningShock and circulation failure Shock and circulation failure

> 10 times

Mild to moderate increase in Mild to moderate increase in

Myocardial infarction, Myocardial infarction, pericarditispericarditisPulmonary infarctionPulmonary infarctionHepatic diseases: cirrhosis, Hepatic diseases: cirrhosis,

obstructive jaundice, neoplasmobstructive jaundice, neoplasmSkeletal muscle diseases: Skeletal muscle diseases:

progressive muscular dystrophy, progressive muscular dystrophy, dematomyositisdematomyositis, trauma, trauma

Hemolytic anemia Hemolytic anemia

LDH LDH

Lactate dehydrogenaseLactate dehydrogenase

LDHLDH

Increase in : Increase in : megaloblasticmegaloblastic anemia, anemia, metastaticmetastatic carcinoma, CML, carcinoma, CML, pulmonary infarction, hepatic pulmonary infarction, hepatic disease, skeletal muscle disease, disease, skeletal muscle disease, hemolytic anemia hemolytic anemia

CK CK

CreatineCreatine phosphokinasephosphokinase

CK CK

CreatineCreatine phosphate + ADPphosphate + ADP

CreatineCreatine + ATP + ATP

Marked increase in Marked increase in

Progressive muscular dystrophyProgressive muscular dystrophyRhabdomyolysisRhabdomyolysisShock and circulation failure Shock and circulation failure

> 10 times

Mild to moderate increase in Mild to moderate increase in

Myocardial infarctionMyocardial infarctionExercise, intramuscular injection, Exercise, intramuscular injection,

major surgerymajor surgeryAlcoholic Alcoholic myopathymyopathy, delirium , delirium

tremens, acute psychotic reactiontremens, acute psychotic reactionStrokes, brain traumaStrokes, brain traumaHypothyroidismHypothyroidism

CK CK isoenzymeisoenzyme

B (brain) subunit B (brain) subunit M (muscle) subunitM (muscle) subunitCKCK--BB (CKBB (CK11): brain, fast): brain, fastCKCK--MB (CKMB (CK22): cardiac muscle, ): cardiac muscle,

skeletal muscleskeletal muscleCKCK--MM (CKMM (CK33): skeletal muscle, ): skeletal muscle,

cardiac muscle, slowcardiac muscle, slow

CKCK--MBMB

Cardiac muscle > skeletal muscleCardiac muscle > skeletal muscleIncrease in cardiac disease: After Increase in cardiac disease: After

cardioversioncardioversion, cardiac surgery, , cardiac surgery, PericarditisPericarditis, , myocarditismyocarditis, after , after PTCA, AMI PTCA, AMI

CKCK--MB: increase in non MB: increase in non cardiac diseasecardiac disease

Skeletal muscle injurySkeletal muscle injurySkeletal muscle disease: Skeletal muscle disease:

dermatomyositisdermatomyositis, , polymyositispolymyositis, , rhabdomyositisrhabdomyositis, Duchene’s , Duchene’s muscular dystrophymuscular dystrophy

Reye’s syndromeReye’s syndromeHypothyroidismHypothyroidismChronic renal failureChronic renal failureLabor and Labor and peripartumperipartum period period

CKCK--MB: increase in non MB: increase in non cardiac diseasecardiac disease

Laboratory artifact: Laboratory artifact: hemolysishemolysis, , hyperbilirubinemiahyperbilirubinemia, drugs, macro, drugs, macro--CKCK

Tumor: lung cancerTumor: lung cancer

CKCK--MB: MB: ลักษณะที่บอกวาลักษณะที่บอกวา มาจากกลามเนื้อลายมาจากกลามเนื้อลาย

Appropriate clinical setting Appropriate clinical setting (History: trauma, skeletal muscle (History: trauma, skeletal muscle disease)disease)

No rise and fall patternNo rise and fall pattern%CK%CK--MB < 10MB < 10--15% of total CK15% of total CKTotal CK Total CK incraseincrase > 20> 20--30 times 30 times

MyoglobinMyoglobin

HemeHeme proteinproteinMuscle cellMuscle cellStorage and transport OStorage and transport O22

ขึ้นเร็วขึ้นเร็ว และลงเร็วและลงเร็ว

TroponinTroponin

Contractile proteinContractile proteinContraction of muscleContraction of muscleSkeletal and cardiac troponinSkeletal and cardiac troponinCardiac troponin T and cardiac Cardiac troponin T and cardiac

troponin I troponin I

cTncTn: increase in cardiac : increase in cardiac diseasedisease

Primary ischemic cardiac injury: Primary ischemic cardiac injury: ACSACS

Secondary ischemic cardiac injury: Secondary ischemic cardiac injury: coronary intervention, pulmonary coronary intervention, pulmonary embolus, coronary artery spasm, embolus, coronary artery spasm, vasculitidesvasculitides, end state renal failure, , end state renal failure, acute heart failure, exerciseacute heart failure, exercise

MyocarditisMyocarditis, cardiac trauma, cardiac trauma

cTncTn: increase in non cardiac : increase in non cardiac diseasedisease

Metabolic toxicMetabolic toxicRhabdomyolysisRhabdomyolysisHypertensive emergencyHypertensive emergencyAcute Acute neurologicneurologic diseasediseaseSepsisSepsisHematologicHematologic malignanciesmalignanciesEndocrine diseaseEndocrine diseaseIntubatedIntubated patients patients

Clinical Use of Cardiac Clinical Use of Cardiac MarkersMarkers

TimeTime

Marker Rise(xULN)

Start (Hr) Peak (Hr) Return(days)

CK 5-8 3-8 10-24 3-4

CK-MB 5-15 3-8 10-24 2-3

LDH 2-4 8-12 72-144(3-6 days)

8-14

Myoglobin 1-3 6-9 1

cTn 3-8 24-48 (1st)72-100(2nd)

4-10

Diagnostic PerformanceDiagnostic Performance

Markers Sensitivity SpecificityCK 94 57CK MB 90.7 99.6LDH/AST 64 92Myoglobin 86.5 (97) 90.2 (57)cTn 86.5 96.4

AST/LDHAST/LDH

Advantage Limitation

1. Low cost, available indeveloping country

2. Rapid

1. Low specificity2. Low sensitivity

CKCK--MBMB

Advantage Limitation

1. Rapid, cost efficient,accurate assay

2. Ability to detect earlyreinfarction

1. Low specificity2. Low sensitivity during

early (<6 hr aftersymptom onset) or laterafter symptom onset (>36hr) and for minormyocardial damage

MyoglobinMyoglobin

Advantage Limitation

1. High sensitivity2. Useful in early detection

of MI3. Detection of reperfusion4. Most useful in ruling out

MI

1. Very low specificity insetting of skeletal muscleinjury or disease

2. Rapid return to normalrange limits sensitivity forlater presentations

Cardiac troponinCardiac troponin

Advantage Limitation

1. Powerful tool for riskstratifiation

2. Greater sensitivity andspecificity than CK-MB

3. Detection of recent MI upto 2 weeks after onset

4. Useful for selection oftherapy

5. Detection of reperfusion

1. Low sensitivity in veryearly phase of MI andrequires repeatmeasuremen at 8-12 hr, ifnegative

2. Limited ability to detectlate minor reinfarction

New criteria: ACC/ESC New criteria: ACC/ESC 20002000

Rise and flow pattern of Rise and flow pattern of cTncTn or or CKCK--MB: MB: รวมกับความผิดปกติตอไปนี้อยางนอยรวมกับความผิดปกติตอไปนี้อยางนอย 1 1 ขอขอ: :

Symptom of AMISymptom of AMIECG: pathologic Q wavesECG: pathologic Q wavesECG: ischemiaECG: ischemiaCoronary interventionCoronary interventionPathologic finding: AMIPathologic finding: AMI

New criteria: British New criteria: British Cardiac Society 2004Cardiac Society 2004Increase Increase TnTTnT and/or CKand/or CK--MB or MB or

AccuAccu TnITnIECG: ST elevation or ST ECG: ST elevation or ST

depression or T inversion depression or T inversion

Patient with suspected ACS

ECG-ST elevation MI No ECG-ST elevation MI

Q wave MI Non-Q wave MI Unstable Angina

Immediate consideration of reperfusion therapy

Evaluation for myonecrosis(CK-MB or troponin)

Evidence of myonecrosis(Non-Q wave

MI)

No myonecrosis

Anti-plt therapy

Anti-thrombotic

Early invasive therapy

Anti-plt therapy

Risk stratification

Consideration alternate diagnosis:

No ACS

Tn+

Tn+

Tn-

Tn-

FrequencyFrequency

AHA: First: admit, Second 6AHA: First: admit, Second 6--12 hr 12 hr after onsetafter onset

ESC/ACC: first admit, Second 6ESC/ACC: first admit, Second 6--9 9 hr after onset, Third 12hr after onset, Third 12--24 hr after 24 hr after onset of chest painonset of chest pain

SummarySummary

Acute coronary syndromeAcute coronary syndromeWHO criteriaWHO criteriaIdeal cardiac markersIdeal cardiac markersCardiac markersCardiac markersClinical uses of cardiac markersClinical uses of cardiac markersNew criteria for diagnosis ACSNew criteria for diagnosis ACS

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