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Anything that you want to know about troponins but never ask

Anything that you want to know about troponins but never ask. Thao Huynh & Roland Sabbagh Division of Cardiology MUHC. WHO classification of MI. 2/3 these criteria: Ischemic symptoms EKG changes. Increased serum markers. CPK-MB. 15% of cardiac CPK, small amount in skeletal muscle

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Anything that you want to know about troponins but never ask

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  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

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

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

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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

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

  13. 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.

  14. 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.

  15. 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.

  16. 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%).

  17. 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.

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

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

  20. 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.

  21. 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.

  22. 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).

  23. 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.

  24. 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.

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