Biochemistry of chest pains

Question 1

Which tests are ordered when a patient presents with chest pains?

Answer 1

Troponin

FBC

LFT

Glucose

Cholesterol

Question 2

What are two ways to risk stratify patients with chest pain?

Answer 2

Perform a 12-lead ECG

Look at troponin levels

Question 3

What is a 12-lead ECG the main diagnostic test for?

Answer 3

Main diagnostic test for acute MI

Question 4

What are troponin levels the main primary tests for?

Answer 4

Look for damage to the myocytes

Question 5

What is troponin?

Answer 5

Cardiac enzyme involved in cardiac contraction

Released by the cardiac myocytes into the circulation when damaged

Question 6

What are the two forms of troponin subunits?

Answer 6

cTnI

cTnT

Question 7

What is the normal concentration of cTnT and cTnI in healthy population?

Answer 7

Very small or undetectable quantities in the blood

Question 8

What happens to the blood concentration of cTnT and cTnI in MI?

Answer 8

Concentration is proportional to the level of damage to the heart

Causes detectable increase in cTnI and cTnT 3-6 hours after the onset of chest pain

Reaching a peak 8-28 hours

Remains elevated 3-10 days

Question 9

What are the advantages of measuring troponin?

Answer 9

cTnI and cTnT are more sensitive and specific for heart injury that other markers like creatine kinase-MB or myoglobin

Remain elevated for longer periods of time

Question 10

What sample is used to measure cardiac troponin levels?

Answer 10

Sample: serum or plasma

Collected by venipuncture in either

• a serum separating tube - gold top
• heparin vacutainer - green-top

Question 11

What type of test is used to measure troponin levels?

Answer 11

High sensitivity troponin-T assays can detect raised levels 3 hours after the onset of chest pains

Question 12

How is the blood sample sent from the A&E to Clinical Biochemistry?

Answer 12

By air-tube system

Marked urgent

Question 13

What lab analyses troponin levels in blood or plasma?

Answer 13

Clinical Biochemistry

Question 14

What is the turnover time for measuring troponin levels?

Answer 14

1 hour

Question 15

What machine measures cardiac troponin?

Answer 15

Automated analyser

Machine with immunoassays

Uses chemiluminescence and magnetism to measure the concentrations of different proteins and molecules

Question 16

What is CMIA?

Answer 16

Chemiluminescent Magnetic Immunoassay

Uses antibodies to bind to molecules and measures the light emitted from them

Question 17

How does a CMIA measure troponin levels?

Answer 17

An immune complex sandwich is made from two types of cTnT antibody complexes, using cTnT protein from the sample as the filling

50 microlitres of the serum/ plasma sample is incubated with

• biotinylated cTnT antibody
• cTnT antibody labelled with a ruthenium complex

Streptavidin-coated magnetic microparticles are added, which bind the sandwich complex via the interaction between the biotinylated-cTnT and streptavidin

The mixture is transferred to the measuring cell, where the microparticles are magnetically captured onto the surface of an electrode

Unbound substances are washed away with a buffer solution

Application of voltage through the electrode generates an unstable excited electron state in the ruthenium complex

Upon relaxation to the lower-level state photons are released
The amount of light generated is proportional to the amount of cTnT in the sample

The amount of light measured by a photomultiplier, and from this the instrument calculates the troponin concentration using a calibration curve

Question 18

What is the peak time where there is the highest troponin levels?

Answer 18

6-8 hours

Question 19

When is troponin-T chronically elevated?

Answer 19

Patients with renal or heart failure

Question 20

What is the first step to diagnosis when patients present to the A&E with chest pain?

Answer 20

Careful clinical history

Examination

ECG

Chest X-ray

Investigations to diagnose other causes of chest pain and evaluate clinical likelihood of evolving ACS

Question 21

What happens if the troponin levels are negative whilst having clinical presentations of MI?

Answer 21

Repeat troponin test

3 hours after presentation and at least 6 hours after the onset of symptoms

Question 22

What characterises a positive result of troponin levels the second time troponin levels are measured?

Answer 22

> 50% increase in troponin concentration

Question 23

Does one positive measurement at the start of clinical presentation conclude acute MI?

Answer 23

No

Repeat troponin to evaluate cause of troponin elevation 6 hours after presentation

If there is not change in troponin levels = not early MI (late MI or other causes of chronic troponin elevation)

If there is a significant change in troponin level then MI is likely

Question 24

What are the next steps following MI diagnosis?

Answer 24

Look for definitive treatment - angiogram

ROMANCE

Reduce risk factors - secondary prevention

• lowering cholesterol
• start on beta blocker
• lower weight