Acute Coronary Syndromes (1)

 Definition : constellation of symptoms

Compatible with acute myocardial Ischemia

 Includes
* Unstable angina (UA)
* Acute MI:
- with ST segment elevation
- with no ST-segment elevation (NSTEMI)
- with or without Q waves
 Guidelines cover UA and NSTEMI
Acute Coronary Syndromes (2)

Symptoms of
Myocardial ischemia

Yes Acute MI
ST-segment elevation ? (q-wave, non-Q Wave)

NO
Elevated serum Yes
NSTEMI
biomarkers ?
NO
Unstable angina
 SPECTRUM OF ISCHEMIC HEART DISEASE

 Acute ischemic syndrome

 Unsable angina
 Non-ST elevation myocardial infarction
 ST-segment elevation myocardial infarction
 Prinzmetal’s variant angina
 Sudden cardiac death
 Silent ischemia
 Ventricular dysfunction
 Chronic stable angina
 The WHO, NEW, and REALITY of Classification
of Acute Coronary Syndrome
(Courtesy of Willie Gerhardt, MD, Helsingborg, Sweden)

WHO REALITY NEW

NOT 1. NOT ischemic heart disease NOT
Acute 2. Ischemic heart disease Myocardial
Myocardial 3. Stable angina pectoris Damage
4. Unsable angina pectoris
5. Minor myocardial damage
Acute 6. Non-Q wave infarction Myocardial
Myocardial 7. Q wave infaction Damage
Infarction 8. Postacute infarction
PERAN PETANDA JANTUNG BARU UNTUK DX AMI
BERKAITAN DGN PATOFISIOLOGI ACS
Plague rupture

Asymptomatic for CAD

Markers of inflamation
C-reactive protein

Intracoronary thrombus

Unstable Angina

Myocardial Infarction
Coagulation factors and proteins
Thrombus precursor protein

Reduced blood flow

Perfusion or functional imaging
Acute: use Sestambi imaging
2 D echocardiography
Myocardial ischemia
Early ischemic indicators (GP BB)
ECG: ST segment depression

Myocardial Necrosis
Classical biochemical markers (CK MB, troponin, myoglobin)
ECG: ST segmen elevation
WHO CRITERIA
DIAGNOSIS OF MYOCARDIAL
INFARCTION
Patient History

2 of 3

ECG Changes Serum Markers

 PERKEMBANGAN PETANDA
BIOKIMIAWI UNTUK PEMERIKSAAN
JANTUNG

Monoclonal MB
RIA for myoglobin antibody

Kriteria cTnT in UA
INH for CKMB AMI
WHO cTnI in AMI
cTnT pd
Electroforesis CK & LD Isoform for
AMI
triaging
CK in CKMB
AST in Massa
AMI AMI cTnT & cTnI for
risk stratification

1950 1960 1970 1980 1990 2000

CHARACTERISTIC OF IDEAL
BIOCHEMICAL MARKERS

Fast turnaround time

Becomes positive early
Readily available
Wide temporal diagnostic window
Inexpensive to perform
Predicts outcome
High sensitivity and specificity
Predicts reperfusion
 INDICATIONS FOR CARDIAC
BIOCHEMICAL MARKERS

 Establish diagnosis in AMI

 Determine risk and prognosis in acute ischemic
syndrome
 Rule out AMI with chest pain syndrome
 Rule out AMI in survivors of sudden cardiacdeath
 Rule out periprocedural AMI with PTCA and CABG
 Rule out perioperative AMI in noncardiac surgey
 Assess reperfusion status post thrombolysis
 iONS MACROMOLECULES
eg Potassium eg Enzymes
or Phosphate or Proteins
Blood level

METABOLITES
eg Lactate
or Adenosine

0 6 12 18 24
Hours after the onset of infarction

Concentration vs. time curves

http://www.chestpainsolutions.com/figure1.htm
 CHARACTERISTICS OF CONTEMPORARY MARKERS

Early Release Wide Diagnostic Window

Myoglobulin cTnT
CK-Isoforms cTnl
hFABP LDH
GPBB MLC / MHC

High Specificity Predicts Reperfusion

cTnT Myoglobulin
CTnl CK-MB isoforms
CK-MB CK-MM isoforms
CK-Isoforms

Predicts Outcome
cTnT
cTnl
CK-MB
 Accordingly, three time periods can be defined:
Early (within 1 to 6 hours), middle (6 to 12 hours), and
Late (more than 12 hours).

Early markers include :

Myoglobulin, CK-MB mass,*
CK-MB isoforms, heart-type fatty acid binding protein
(FABP), and glycogen phosphorylase isoenzyme
BB (GPBB).
Middle markers include :
CK-MB mass and the
chardiac troponins (T and I).
Late markers include :
CK-MB mass and the cardiac troponins, with CK-MB mass returning to
pre-infarct levels by 36 to 38 hours, whereas troponin T remains
elevated for 2 to 3 weeks compared with 1 to 2 weeks for troponin T
 Sensitivitas dan Spesifisitas
Cardiac Status CK-MB / Myoglobin

10 0

80

60

40

20

0
0 - 2 jam >2 - 4 jam >4 - 6 jam >6 jam

Sensitivitas Spesifisitas

Metode : + jika CK-MB dan Myo +, n = 277 (52 IMA) Clin Chem 1998: 1865-1869
 Sensitivitas cardiac markers

10 0
90
80
70
%Sensitivity

60
50
40
30
20
10
0
CK CKMB CKMB Mass Myoglobin cTnI cTnT
Aktivity

0 - 2 hrs after AMI 2- 4 hrs after AMI

Morandell et al, Clin. Chem. 1995; 41/9: 1266 - 1272

 Advantages:
CK-MB
 Rapid, cost-efficient, accurate assays

 Ability to detect early reinfarction

 Disadvantages:
 Loss of specificity in setting of sceletal muscle disease or injury,

incl. Surgery
 Low sensitivity during very early MI (<6 hr after symptom

onset (>36 hr) and for minor myocardial damage (detectable

with troponins)
 Recommendation:
 Prior standard and still acceptable diagnostic test in most

clinical circumstances

American Clinical Laboratory, 2001: 31-35

 Advantages:
Myoglobin
 High sensitivity

 Useful in early detection of MI

 Detection of Reperfusion

 Most useful in ruling out MI

 Disadvantages:
 Very low specificity in setting of skeletal muscle injury or disease

 Rapid return to normal range limits sensitivity for later presentations

 Recommendation
 Should not be used as only diagnostic marker because of lack of
cardiac specificity

American Clinical Laboratory, 2001: 31-35

 Cardiac Troponins
 Advantages:
 Powerful tool for risk stratification

 Greater sensitivity and specificity than CK-MB

 Detection of recent MI up to 2 weeks after onset

 Useful for selection of therapy

 Detection of reperfusion

 Disadvantages:
 Low sensitivity in very early phase of MI (<6 hr after symptom onset)

and requires repeat measurement at 8-12 hr if negative

 Limited ability to detect late minor reinfarction

 Recommendation:
 Useful as a single test to efficiently diagnose NSTEMI (incl. Minor

myocardial damage), with serial measurements.

American Clinical Laboratory, 2001: 31-35

A simplistic decision analysis of the use of ECG, myoglobulin, troponin
I/CK-2 mass assays in the diagnosis of myocardial infarction. Each testing
decision is separated by a period of 2 4 hours

Thrombolityc Therapy
EKG (+ve)
None

TnI / CK 2 (+ ve) MI
MI ?
Myoglobulin (+ ve)

TnI / CK 2 ( - ve) Not an MI

TnI / CK 2 (+ ve)
MI

EKG (- ve) Myoglobulin (+ ve)

Myoglobulin ( - ve) TnI / CK 2 ( - ve)

Not an MI
Myoglobulin ( - ve)
Not an MI
 EKG jelas  investigasi tidak perlu diperpanjang
 EKG samar  dievaluasi dgn petanda jantung
(early/6 jam; late/6-9 jam) pd saat masuk RS dan
setelah 2-4, 6-9, 12-24 jam
 Troponin jantung sbg standar baru u/ dx AMI dan
deteksi kerusakan sel otot jantung.
 Laboratorium harus menyediakan px cyto petanda
jantung dgn basis random access dan TAT 1 jam atau
kurang.
Pelayanan Rutin Cardiac Status
CK-MB/Myoglobin/Troponin I

 Pemeriksaan POCT
 Cabang pelaksana: Jakarta, Medan, Surabaya, Denpasar dan Malang (per 19
Agustus 2002)
 Frekuensi kerja: setiap hari
 Spesimen: darah heparin, plasma heparin atau serum
 Stabilitas spesimen:
 24 jam pada 2 - 8 ctg
 Lebih dari 1 hari pada –20 ctg atau lebih rendah