Dr. Dasdo Antonius Sinaga, SpJP, FIHA. 3rd Pekanbaru Cardiology Update, August 24th 2013. Pangeran Hotel Pekanbaru. Learn more at PerkiPekanbaru.com

1. Cardiac Biomarkers in
Acute Coronary Syndrome
Dasdo Antonius Sinaga
Cardiologist

2. 4
1 2 3 4 5 6
Presentation
Working Dx
ECG
Cardiac
Biomarker
Final Dx
UA
NQMI QwMI
No ST Elevation
NSTEMI
Ischemic Discomfort
Acute Coronary Syndrome
Unstable
Angina
Myocardial Infarction
ST Elevation
Modified from Libby. Circulation 2001;104:365,
Hamm et al. The Lancet 2001;358:1533 and
Davies. Heart 2000;83:361.

3. Detection of a rise/fall of cardiac biomarkers (preferable Troponin)
with at least one value above the 99th percentile upper reference
limit, with at lest one of the following:
Symptoms of ischemia
New of presumed new significant ST-T Change or new Left Bundle
Branch Block
Development of pathological Q wave
Imaging evidence of new loss of viable myocardium or new regional wall
motion abnormality
Identification of an intracoronary thrombus by angiography or autopsy

4. What is a BIOMARKER ?
BIOMARKER =
a traceable substance that is introduced into an organism
as a means to EXAMINE ORGAN FUNCTION or other aspects
of health.
RENAL function Serum Ureum & Creatinine
Glomerular Filtration Rate
LIVER function Transaminase (SGOT-SGPT)

5. MYOFILAMEN
STRUCTURE

6. Various possibilities during myocardial infarction:
Release of structural proteins from the myocardium,
including normal turnover of myocardial cells,
Apoptosis,
Cellular release of troponin degradation products,
increased cellular wall permeability,
Formation and release of membranous blebs, and
Myocyte necrosis

8. Cardiac-specific troponins should be used as the
optimum biomarkers for the evaluation of patients
with STEMI who have coexistent skeletal muscle
injury.
For patients with ST elevation on the 12-lead ECG
and symptoms of STEMI, reperfusion therapy
should be initiated as soon as possible and is not
contingent on a biomarker assay.
Biomarkers of Cardiac Damage
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
Alpert et al. J Am Coll Cardiol 2000;36:959.
Wu et al. Clin Chem 1999;45:1104.

9. 0 1 2 3 4 5 6 7 8
Cardiac troponin-no
reperfusion
Days After Onset of STEMI
MultiplesoftheURL
Upper reference limit
1
2
5
10
20
50
URL = 99th %tile of
Reference Control Group
100
Cardiac troponin-reperfusion
CKMB-no reperfusion
CKMB-reperfusion
Cardiac Biomarkers in MYOCARDIAL INFARCTION
Alpert et al. J Am Coll Cardiol 2000;36:959.
Wu et al. Clin Chem 1999;45:1104.

10. Creatine kinase-MB
A cytosolic carrier protein for high-energy phosphates,
Has long been the standard marker for the diagnosis of MI.
LESS sensitive and LESS specific for MI than the cardiac
troponins.
Low levels of CK-MB can be found in the blood of
healthy persons
Elevated levels occur with damage to skeletal muscle
Tsung SH. Several conditions causing elevation of serum CK-MB
and CK-BB. Am J Clin Pathol 1981;75:711–5

11. TROPONIN
The troponin complex consists of 3 subunits:
Troponin T (TnT),
Troponin I (TnI),
Troponin C (TnC).
Troponin C is expressed by both cardiac and skeletal
muscle, whereas TnT and TnI are derived from heart-
specific genes.
Therefore, the term “cardiac troponins” in these
guidelines refers specifically to either Troponin T or
Troponin I.
Mair J, et al. Equivalent early sensitivities of myoglobin, creatine kinase MB mass, creatine kinase isoform
ratios, and cardiac troponins I and T for acute myocardial infarction. Clin Chem 1995;41:1266–72.
Jaffe AS, Babuin L, Apple FS. Biomarkers in acute cardiac disease:
the present and the future. J Am Coll Cardiol 2006;48:1–11.

12. Cardiac troponin as a biomarker
Highly sensitive and specific in detecting cell necrosis
Because cTnT and cTnI generally are not detected in the
blood of healthy persons, the cutoff value for elevated
cTnT and cTnI levels may be set to SLIGHTLY ABOVE the
upper limit of the performance characteristics of the
assay for a normal healthy population.
Mair J, et al. Equivalent early sensitivities of myoglobin, creatine kinase MB mass, creatine kinase isoform
ratios, and cardiac troponins I and T for acute myocardial infarction. Clin Chem 1995;41:1266–72.
Jaffe AS, Babuin L, Apple FS. Biomarkers in acute cardiac disease:
the present and the future. J Am Coll Cardiol 2006;48:1–11.

15. HIGH SENSITIVITY TROPONIN
Novel testing devices: 5- to 10-fold more sensitive
than existing troponin assays.
Earlier detection of myocardial infarction relative
to the time of presentation
Detect a higher percentage of emergency
department chest pain patients who are at risk for
short-term major adverse cardiac events.
However, use of a high-sensitivity troponin assay
will also result in detection of more patients who
have cardiac necrosis due to a non-ischemic
etiology,

16. MYOGLOBIN
Myoglobin, a low-molecular-weight heme protein
Found in both cardiac and skeletal muscle not
cardiac specific
But it is released more rapidly from infarcted
myocardium than are CK-MB and Troponin
Can be detected as early as 2 hours after the onset of
myocardial necrosis.
However, the clinical value of serial determinations of
myoglobin for the diagnosis of MI is limited by its brief
duration of elevation of less than 24 h.
Eggers KM, Oldgren J, Nordenskjold A, Lindahl B. Diagnostic value
of serial measurement of cardiac markers in patients with chest pain:
limited value of adding myoglobin to troponin I for exclusion of
myocardial infarction. Am Heart J 2004;148:574–81.

17. ONSET of RELEASE of BIOMARKER

18. ADVANTAGES DISADVANTAGES
CARDIAC
TROPONIN
• Highly sensitive &
spesific
• Detection of Myocardial
infarction until 2 weeks
Low sensitivity in early hour of
infarction (> 6 hours)
CKMB Detect Early Infarction (4-
6 hours)
Loss of spesificity in muscle
disease or injury
MYOGLOBIN Early Detection of MI (2-4
hours)
• Loss of spesificity in muscle
disease or injury
• Quickly rapid to normal value

20. Cardiac Troponin in Patients with
Kidney Disease
In good kidney function, Troponin T and Troponin I give
equivalent information
In RENAL dysfunction, TROPONIN I assessment appears
to have a specific role.
Among patients with end-stage renal disease and no
clinical evidence of acute myocardial necrosis,
15% to 53% show increased cTnT,
fewer than 10% have increased cTnI;
Freda BJ, Tang WH, Van Lente F, Peacock WF, Francis GS.
Cardiac troponins in renal insufficiency: review and clinical
implications. J Am Coll Cardiol 2002;40:2065–71.

21. Dialysis increases Troponin T, but but decreases cTnI.
The exact reasons: NOT CLEAR.
An elevation of Troponin in patients with renal
insufficiency is associated with a higher risk of morbidity
REGARDLESS of the presence of cardiac symptoms or
documented CAD.
Freda BJ, Tang WH, Van Lente F, Peacock WF, Francis GS.
Cardiac troponins in renal insufficiency: review and clinical
implications. J Am Coll Cardiol 2002;40:2065–71.

22. PROGNOSTIC VALUE
James SK, Lindahl B, Armstrong P, et al. A rapid troponin I
assay is not optimal for determination of troponin status and
prediction of subsequent cardiac events at suspicion of unstable
coronary syndromes. Int J Cardiol 2004;93:113–20

23. HIGH SENSITIVITY TROPONIN
Novel testing devices: 5- to 10-fold more sensitive
than existing troponin assays.
Earlier detection of myocardial infarction relative
to the time of presentation
Detect a higher percentage of emergency
department chest pain patients who are at risk for
short-term major adverse cardiac events.
However, use of a high-sensitivity troponin assay
will also result in detection of more patients who
have cardiac necrosis due to a non-ischemic
etiology,

24. ROLE OF SERIAL MEASUREMENT
Blood samples for the measurement of Troponin should be
drawn
on first assessment
Repeated 3-6 h later.
The second sample is required if:
Further ischemic episodes occur, or
Timing of the initial symptoms is unclear
To establish the diagnosis of MI, a rise and/or fall in
values with at least one value above the cut-off level
is required.

25. For example, patients with renal failure or HF can
have significant chronic elevations in cTn.
These elevations can be marked, as seen in many
patients with MI, but do not change acutely
no myocardial infarction
But if the serial troponin measurement shows
significantly higher troponin level
Evidence of myocardial infarction

26. Case 1: What would you do?
Man, 55 years old
Risk factors: smoker, hypertension
Complaint: CHEST PAIN since 3 hours prior to admission
CKMB: 20
(cuf off: 24)
Troponin T
low
(Cut off 0.03)

28. Case 2: What would you do?
Woman, 50 years old
Risk factors: Diabetes mellitus for 10 years
Complaint: CHEST PAIN since 2 hours prior to admission
Waiting for
biomarker
results?

30. Case 2: What would you do?
Man, 45 years old
Risk factors: Diabetes mellitus for 10 years, smoker
No spesific complaint. ECG found during routine medical
check up

32. SUMMARY
Diagnosis of myocardial infarction includes Detection of
a rise/fall of cardiac biomarkers (preferable Troponin)
with at least one value above the 99th percentile upper
reference limit.
Several types of cardiac biomarkers/enzymes can be
utilized, namely Troponin, creatine kinase, and
myoglobin.
Troponin is the most spesific biomarker in diagnosing
myocardial infarction.
ONSET of chest pain and biomarker level must be
considered in establishing diagnosis of MI.

33. THANK YOU