7. Evaluation of a patient
with possible ACS
Hamm CW. Et al. EHJ (2011) 32, 2999-305
8. Timing of serial samples
• AHA guidelines:
– 6-8hrs after symptom onset.
Amsterdam, E. A., J. D. Kirk, et al. (2010). Circulation 122(17):
1756-1776.
• ESC guidelines:
– 3hrs after presentation with hs assay.
Hamm, C. W., J. P. Bassand, et al. (2011). European Heart Journal
32(23): 2999-3054.
• HFA/CS-ANZ guidelines:
– 3hrs after presentation + 6hrs after symptom onset with a hs assay or
– 8+hrs after ‘last episode of pain’ with other cTn assays
Chew, D. P., C. N. Aroney, et al. (2011) Heart Lung Circ 20(8):
487-502
9. CPK-MB
▪ 15% of cardiac CPK, small amount in
skeletal muscle
▪ Validated as marker for MI.
However:
▪ Can increase after muscle injury, muscular
diseases.
▪ Can be found in tongue, intestine,
diaphragm, uterus, prostate.
16. Troponin T & I
▪ Require myocardial necrosis for release
from sarcomere.
▪ Early rise (4-12 hours after symptom).
▪ Peak 12-24 hours.
▪ Continuous release up to 10-14 days 2nd to
constant release/necrotic sarcomeres.
▪ Unclear excretion pathway.
17. Troponin I
▪ Only 1 isoform.
▪ The cardiac isoform of troponin I is only
found in cardiac muscles.
▪ Highly bound to the tropomyosin complex
in the sarcomere.
▪ <5% in cytosol.
18. Troponin I
▪ N ,C terminus and central portion.
▪ Myocardial necrosis: cleavage of the
terminus (more unstable).
▪ Different assays with antibodies
measuring different terminus (6 assays).
▪ Strong binding with troponin C (calcium
dependent) may affect measurement.
▪ Assays also affected by other protein
kinases and fibrinogen levels.
19. Troponin T
▪ Cardiac troponin T: 4 isoforms.
▪ Fetal skeletal muscle: + cardiac troponin
isoform.
▪ Muscle injury, myopathy, renal failure:
reexpression of cardiac troponin T in
muscles.
20. Troponin T
▪ Two monoclonal antibodies:
▪ 1 for capture (M11.7) and 1 for detection
(M7).
21. Troponin T
▪ Only 1 manufacturer: Roche Boeringer
▪ Possible false + with first generation assay
in renal failure.
▪ M11.7 and M7 isoforms have to be both
present for 2nd and 3rd generation assays
to be detected.
22. How do Troponin compare with EKG in
ACS?
▪ Negative troponin and normal EKG,
mortality 1%.
▪ Negative troponin and ischemic EKG:
mortatity 4% at 1 month.
▪ Troponin and EKG changes
complementary.
23. TIMI score
1. Age ≥ 65 years.
2. ≥ 3 risk factors for CAD.
3. Coronary stenosis ≥ 50%.
4. ASA use in past 7 days.
5. Severe angina ≤ 24 hours
6. + cardiac markers.
7. ST deviation ≥ 0.5 mm.
Each point scores 1.
Intermediate:3-4 (14-days events:13-20%).
High: 6-7 (14-days events: 40%).
Thrombolysis in Myocardial infarction
C-Coronary
stenosis
A-Age
R-Risk Factors
D-Deviations in ST
segment
I-Increased Angina
A-ASA in use
C-Cardiac markers
24.
25. Troponin and GPIIbIIIa inhibitors
▪ Substudies of clinical trials: patients
with troponin rises benefit more from
GPIIbIIIa inhibitors.
▪ ACC/AHA recommend these
medications in + troponins.
▪ No prospective study examining the
role of initiating these medications as
per troponin levels.
37. Accelerated Diagnostic Protocol (ADP)
-ve if all of the following:
• Pre-test probability assessment (TIMI risk score
= 0)
• No new Ischemic ECG changes
• All 0 and 2hourpoint-of-care cardiac
biomarkers negative:
– TnI (Alere Triage)
– CK-MB
– Myoglobin
45. Finding Balance
Speed
Overcrowding is dangerous
Long ED stays are dangerous
Differences in assays
– Lack of standardization
– Key differences exist in POC platforms and their performance
– for some difficult to differentiate normal from abnormal at
low values
– Maintain accuracy (both sensitivity and specificity)
48. Troponins in ESRD
733 patients Troponins T & I
2-year mortality:
▪ T: <0.01=8.4%
▪ T 0.01-<0.04= 26%.
▪ T 0.04-0.1= 39%.
▪ T ≥0.1= 47%
▪ I<0.1= 30% and I≥ 0.1=52%.
▪ RR for TnT: 5.0 and TnI: 2.1.
49. Troponin in renal failure and ACS
▪ GUSTO IV: 581 patients:
▪ Creat clearance >58 ml/min, + TnT odds
ratio: 1.7.
▪ Creat clearance <30 ml/min, + TnT odds
ratio: 2.5.
▪ TnT +: >0.1 ug/l.
50. Troponin T and renal failure
▪ Can have chronic elevation.
▪ Not related with frequency and efficacy
of dialysis or creatinine level.
▪ Predict increased adverse outcomes in
stable patients.
▪ ACS: also increased adverse outcomes.
Serial measurements important. (>50%
increase=MI).
51. Troponins and congestive heart failure
▪ May have chronic elevation of both TnT
and TnI.
▪ As low as TnT<0.05 predicts increased
risk.
▪ Diagnosis of ACS require serial
measurement.
52. Conclusions
▪ Troponins T and I important clinical tools.
▪ Problems with TnI: variability of assays.
▪ Complement clinical risk factors and EKG
changes.
▪ May help decision to initiate GPIIb/IIIa
blockade.
▪ POC Troponin reduce ED stay and fasten up ED
disposal decisions
▪ POC is Accurate and Rapid