Troponin in Emergency departments

Dr.Venugopalan P P DA,DNB,MNAMS,MEM[GWU]

Director , Emergency Medicine Aster DM Health care – India

WHO classification of MI

2/3 these criteria: ✓ Ischemic symptoms ✓EKG changes. ✓ Increased serum markers.

CHEST PAIN IN THE EMERGENCY DEPARTMENT

Chest Pain presentations   Numerous causes …

Acute coronary syndrome – AMI Aortic dissection Pericarditis Pulmonary embolism Pneumothorax Pneumonia GI - esophageal spasm, PUD etc Musculoskeletal

Chest pain ED presentations: ACS  

Other diagnoses

ACS related 20-25%  

Non ACS related 75-80%

Chest Pain  

ED presentations: ACS  

Evaluation of a patient with possible ACS  

Hamm CW. Et al. EHJ (2011) 32, 2999-3054.

Timing of serial samples

• AHA guidelines: – 6-8hrs after symptom onset.

Amsterdam, E. A., J. D. Kirk, et al. (2010). Circulation 122(17): 1756-1776.

  • ESC guidelines:

– 3hrs after presentation with hs assay.

Hamm, C. W., J. P. Bassand, et al. (2011). European Heart Journal 32(23): 2999-3054.

  • HFA/CS-ANZ guidelines:

– 3hrs after presentation + 6hrs after symptom onset with a hs assay or

– 8+hrs after ‘last episode of pain’ with other cTn assays

Chew, D. P., C. N. Aroney, et al. (2011) Heart Lung Circ 20(8): 487-502

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

Troponins

Cardiac troponins:

1. Troponin C: binds with calcium. 2. Troponin T: binds with tropomyosin. 3. 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.

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 score1. Age ≥ 65 years. 2. ≥ 3 risk factors for CAD. 3. Coronary stenosis ≥ 50%. 4. ASA use in past 7 days. 5. Severe angina ≤ 24 hours 6. + 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%).

Thrombolysis in Myocardial infarction

C-Coronary stenosis A-Age

R-Risk Factors D-Deviations in ST

segment I-Increased Angina

A-ASA in use C-Cardiac markers

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.

What is the advantage of POC

• results?

TIME!

Time-critical conditions •Hypoglycaemia •Ventricular arrhythmias •Sepsis •Heart Failure •Hypoxia •Myocardial infarction •Haemorrhage

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

POC devices

POC testing Analytical time in various systems

Accelerated Diagnostic Protocol (ADP) -ve if all of the following:

 

• Pre-test probability assessment (TIMI risk score = 0)

 

• No new Ischemic ECG changes

• All 0 and 2hour point-of-care cardiac biomarkers negative:

– TnI (Alere Triage)

– CK-MB

– Myoglobin

Study outcomes •30 day MACE = 3 (0.85%).

Study outcomes •30 day MACE = 3 (0.85%)

1 in 10 patients could be safely discharged for outpatient testing or have accelerated inpatient investigations.

OPTIMISING USE OF POC TROPONIN TESTING

Am J Emerg Med 2012. 30; 1639-49.

Am J Emerg Med 2012. 30; 1639-49.

Am J Emerg Med 2012. 30; 1639-49.

Finding Balance

Speed Overcrowding is dangerous

Long ED stays are dangerous

  Differences in assays

– Lack of standardization

– Key differences exist in POC platforms and their performance – for some difficult to differentiate normal from abnormal at low values

– Maintain accuracy (both sensitivity and specificity)

Finding Balance •Risk stratification processes

Individualize strategy with specific POC assay

Troponin is non-Cardiac scenarios

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.

Troponin 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. ▪ POC Troponin reduce ED stay and fasten up ED

disposal decisions ▪ POC is Accurate and Rapid

Thank you for listening

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