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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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