1. Anything that you want to know about troponins but never ask
Thao Huynh & Roland Sabbagh
Division of Cardiology
MUHC

2. WHO classification of MI
2/3 these criteria:
Ischemic symptoms
EKG changes.
Increased serum markers.

3. 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.

4. Myoglobin
Rapid rise
Non-specific.
Cannot be used alone to confirm MI

6. Tropomyosin:
Troponin T,
Troponin I,
Troponin C.
Actin and tropomyosin

7. Cardiac troponins: Troponin C: binds with calcium.
Troponin T: binds with tropomyosin.
Troponin I: inhibites contraction.

8. Troponin C
Same isoform for both skeletal and cardiac muscles.

9. Troponin T & I Require myocardial necrosis for release from sarcomere.
Early rise (4-12 hours after symptom).
Peak hours.
Continuous release up to days 2nd to constant release/necrotic sarcomeres.
Unclear excretion pathway.

10. 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.

11. 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.

12. 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.

13. Troponin T Two monoclonal antibodies:
1 for capture (M11.7) and 1 for detection (M7).

14. 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.

15. Troponins and ACS 7 clinical trials and 19 cohort studies:
For death & MI:
5,360 troponin T: OR 3-5.
6,603 troponin I: OR 3-8.
Comparable accuracy of troponin T & I.

16. 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.

17. TIMI score Age  65 years.  3 risk factors for CAD.
Coronary stenosis  50%.
ASA use in past 7 days.
Severe angina  24 hours
+ cardiac markers.
ST deviation  0.5 mm.
Each point scores 1.
Intermediate:3-4 (14-days events:13-20%).
High: 6-7 (14-days events: 40%).

18. 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.

19. ACC/AHA/ESC 1999
Myocardial infarction: elevation of serum troponin T/I >0.1.

20. Bedside testing
Trop T and I.
96% concordance with quantitative tests.

21. Troponins in ESRD 733 patients Troponins T & I 2-year mortality:
I<0.1= 30% and I 0.1=52%.
RR for TnT: 5.0 and TnI: 2.1.

22. Troponins 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.

23. 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).

24. 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.

25. 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.