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.