Anything that you want to know Anything that you want to know about troponins but never ask about troponins but never ask Thao Huynh & Roland Sabbagh Thao Huynh & Roland Sabbagh Division of Cardiology Division of Cardiology MUHC MUHC
Anything that you want to know Anything that you want to know about troponins but never askabout troponins but never ask
Thao Huynh & Roland SabbaghThao Huynh & Roland Sabbagh
Division of CardiologyDivision of Cardiology
MUHCMUHC
WHO classification of MIWHO classification of MI
2/3 these criteria: Ischemic symptoms EKG changes. Increased serum markers.
CPK-MBCPK-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.
MyoglobinMyoglobin
Rapid riseNon-specific.Cannot be used alone to confirm MI
Tropomyosin:
Troponin T,
Troponin I,
Troponin C.
Actin and tropomyosin
Cardiac troponins:Cardiac troponins:
1. Troponin C: binds with calcium.
2. Troponin T: binds with tropomyosin.
3. Troponin I: inhibites contraction.
Troponin CTroponin C
Same isoform for both skeletal and cardiac muscles.
Troponin T & ITroponin 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 ITroponin 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 ITroponin 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 TTroponin 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 TTroponin T
Two monoclonal antibodies: 1 for capture (M11.7) and 1 for detection
(M7).
Troponin TTroponin 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 ACSTroponins 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 How do troponin compare with EKG in ACS?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 scoreTIMI 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 hours6. + 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%).
Troponin and GPIIbIIIa Troponin and GPIIbIIIa inhibitorsinhibitors
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 1999ACC/AHA/ESC 1999
Myocardial infarction: elevation of serum troponin T/I >0.1.
Bedside testingBedside testing
Trop T and I. 96% concordance with quantitative tests.
Troponins in ESRDTroponins 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.
Troponins in renal failure Troponins in renal failure and ACSand 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 failureTroponin 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 Troponins and congestive heart failureheart 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.
ConclusionsConclusions
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.