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 Validated as marker for MI. However: Can increase after muscle injury, muscular diseases. Can be found in tongue, intestine, diaphragm, uterus, prostate.

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

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

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

Troponin C Same isoform for both skeletal and cardiac muscles.

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.

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.

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.

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.

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

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.

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.

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.

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%).

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.

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

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

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.

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.

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).

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.

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.