Cardiac marker – Part 1 – Diagnosis of Acute Myocardial Infarction, AMI

Sample
- The best sample is Venous blood to get a clear serum.
- Heparinized plasma can be used.
- Rapid Troponin-T can be done on whole blood (some methods are available).
- Current recommendation on admission with the possibility of acute MI, blood sample should be taken at intervals of:
- Blood sample at admission.
- Second sample at 2 to 4 hours.
- Third sample at 6 to 8 hours.
- Fourth sample at 12 hours.
- Current recommendation on admission with the possibility of acute MI, blood sample should be taken at intervals of:
- The serum can be stored at room temperature for 4 to 8 hours.
- At 4 °C serum is stable for 1 to 2 days.
- For troponin-T serum is stable for 24 hours at 2 to 8 °C.
Precautions
- I/M injection may raise the level of CPK.
- Strenuous exercise and recent surgery may raise the CPK level.
- Early pregnancy may decrease the CPK level.
Definition of Acute Myocardial Infarction
- This is characterized by the ischemia of the myocardial muscles. Also, this myocardial ischemia results in irreversible myocardial cell damage or death (necrosis).
- Or when there is obstruction of the blood supply to any part of the heart and necrosis of the muscles or massive cell death occurs.
- Silent myocardial infarction where 40 to 50% of the patient does not notice the typical signs and symptoms of acute myocardial infarction.
- These are diagnosed on the ECG.
- This is usually seen in diabetic patients and in hypertension.
- The AMI classified on the basis of anatomic, morphologic, and diagnostic clinical data as:
- Nontransmural MI when there is the involvement of only the endocardium or both endo and myocardium.
- Transmural MI when all the three layers endo, myo, and epicardium layers are involved.
Pathophysiology
- There is an increased risk of AMI with the increasing age.
- 4 to 5 times more risk in men between the ages of 45 to 54 years as compared to women.
- The risk is the same in both sexes (men and women) after the age of 80 years.
- Before the acute myocardial infarction takes place there is transient ischemia where the oxygen supply is deprived of muscle and this is called an Anginal attack.
- In angina, there is no necrosis.
- The major cause of AMI is atherosclerotic plaques and thrombus formation.
- Ischemia starts from the endocardium and then spreads outwards.
- Irreversible damage to the muscles occurs when the ischemia is for at least 15 to 20 minutes.
- Vasospasm and platelet aggregation may contribute to coronary occlusion.
- Myocardial necrosis starts:
- The necrosis process starts in 20 to 30 minutes.
- Infarcts start in the subendocardial area.
- After several hours there is a mid and subepicardial area of the myocardium is involved.
- After 3 to 6 hours there is full infarct formation.
- Streptokinase injection can limit the infarct.
- The ischemic necrosis involvement of the heart muscle depends upon the involvement of the anatomical blood vessel occlusion.
- The anterior left descending coronary artery involves the Anterior and apical part of the left ventricle and adjacent interventricular septum.
- The left circumflex coronary artery involves the Lateral wall of the left ventricle.
- The right coronary artery involves a Posterior and basal portion of the left ventricle.
- Risk factors for AMI are:
- Hypertension.
- Tobacco use.
- Diabetes mellitus.Hyperlipidemia.
- Sex when more common in males.
- More common in the case of family history.
Signs and symptoms:
- Chest pain in the mid-thorax, and there is crushing substernal pain.
- Pain may radiate to teeth or jaw, or shoulder, or arm, or back.
- There may be dyspnea or shortness of breath.
- There may be sweating.
- There may be epigastric discomfort with or without nausea and vomiting.
- The patient may go into syncope.
- In 50% of the patient, the AMI is preceded by angina pectoris.
- The pain of AMI is not relieved by nitroglycerin.
Acute Myocardial infarction is characterized by:
- The typical rise of CK-MB.
- Raised level of Troponin.
- ECG changes.
- A coronary angiogram shows coronary artery abnormality.
To diagnose the Acute Myocardial infarction:
- H/O chest pain.
- Changes in the ECG.
- The initial ECG is diagnostic in more than 50% of the cases.
- 15% no initial changes seen in ECG.
- Follow-up for 24 hours shows positive ECG in 75% of the cases.
- These changes are reflected from the ST-segment, T-wave, and enlarged Q-wave.
- Abnormal cardiac enzymes:
- CK.
- CK-MB.
- LDH.
- Myoglobin.
- Troponin T and I.
- SGOT.
CK and CK-MB
- CK Can reflect timing, quantity, and resolution of MI.
- CK has isoenzymes:
- CK-1 =BB
- CK-2 =MB
- CK-3 =MM
- CK has isoenzymes:
- CK-MB is more specific for cardiac muscle injury.
- This also helps in quantifying and give a degree of myocardial injury.
- If there is no further myocardial damage then:
- CK-MB detected in the first 3 to 6 hours.
- The peak level is at 20 to 24 hours.
- This returns to normal in 12 to 48 hours (in another reference becomes normal in 72 hours).
- Serial measurement is more important and diagnosis reaches 100%.
- If there is no further myocardial damage then:
- Total CK may be normal but CK-MB will be raised.
- CK-MB is not as specific as Troponin and there are false-positive reports of non-ischemic cardiac injuries like pericarditis and myocarditis.
- CK-MB is also positive in muscular dystrophy, exercise, and rhabdomyolysis.
- CK-MB usually does not arise in the case of angina, pulmonary embolism, or congestive heart failure.
- CK-MB may be seen rising in case of shock, malignant hyperthermia, myopathies, or myocarditis.
- There is a small amount of CK-MB in the skeletal muscles.
- In case of severe skeletal muscle injury may give rise to a significantly high level of CK-MB.
- CK-MB is more helpful and more specific than Myoglobin when the patient comes with chest pain after 10 to 12 hours.
- CK-MB relative index:
- This is done to avoid skeletal muscle injury with myocardial muscle damage.
- Calculation:
- CPK-MB/total CPK
- If CPK-MB = 3.0 ng/mL
- Relative index = ≥2.5
- This is highly suggestive of myocardial injury.
- If CPK-MB = >3.0 ng/mL
- Relative index = <2.5
- Not diagnostic for myocardial injury.
- If CPK-MB = 3.0 ng/mL
- CPK-MB/total CPK
LDH (lactate dehydrogenase enzyme):
- This is present in the cytoplasm of the cells and the highest concentration seen in the skeletal muscles, heart, liver, RBCs, kidneys, brain, and lungs.
- LD-1 (17 to 27%) has the highest concentration is found in the RBCs, heart, and kidneys. It comes mainly from the heart.
- LDH-2 ( 27 to 37%) comes from the reticuloendothelial system.
- LDH-3 (18 to 25%) comes from the lungs and other tissues.
- LDH-4 (3 to 8%)is present in the kidneys, placenta, and the pancreas
- LD-5 (0 to 5%) has the highest concentration in the skeletal muscles and liver.
- LDH is not tissue-specific because of its distribution throughout the body.
- It is raised in a variety of diseases, including myocardial injury.
- It is also not specific for cardiac diseases.
- LDH in the myocardial infarction:
- Rises within 24 to 48 hours of Acute MI.
- The peak level is 2 to 3 days.
- Returns to normal in 5 to 10 days.
- LDH has significance in other diseases like:
- The elevated level in the urine indicates malignancy or injury to the urinary system.
- LDH also found in the effusions like pleural, cardiac, or peritoneal.
- When effusion LDH / serum LDH ratio is >0.6 indicate exudate in the effusion fluid.
Myoglobin:
- Myoglobin is an oxygen-binding protein of the skeletal and cardiac muscles.
- Myoglobin most sensitive to the cardiac marker and is the earliest marker of acute myocardial infarction.
- But this is the least cardio-specific of cardiac markers.
- This is cardiac and skeletal muscle protein. This can increase after trauma to skeletal muscle or cardiac muscle injury.
- This is not specific for the cardiac muscle injury because it will rise even with there is a minor injury to skeletal muscle.
- It is raised in the trauma, inflammation, or ischemic changes to skeletal muscles.
- But Myoglobin is very sensitive than CK and CK-MB during the first hour of chest pain.
- It starts rising in the first 1 to 4 hours and detectable in 6 to 9 hours.
- If Myoglobin remains within reference range 8 hours after the start of chest pain, then essentially Acute MI can be ruled out.
- Myoglobin is not recommended in patients with renal failure because they will have a raised level due to decreased clearance by the kidneys.
SGOT
- This was the first enzyme marker for MI but it lakes cardiac specificity, so lost its value.
Troponin (Tn) T
- The troponin protein complex is situated on the thin filament of skeletal and cardiac muscles.
- Troponin is highly concentrated in cardiomyocytes.
- The role of Troponin is calcium-mediated contraction through its action with actin and myosin.
- Troponin complex can be separated by the monoclonal antibodies consists of:
- TnT (Troponin – T) is a tropomyosin binding subunit.
- TnI (Troponin – I) is the myosin ATPase inhibiting subunit, block the myosin movement in the absence of calcium.
- TnC (Troponin – C) is the calcium-binding subunit.
- Cardiac troponins are separated by the immunoassay with the help of monoclonal antibodies into:
- Troponin – T.
- Troponin – I.
- Troponin is localized in:
- Myofibrils are 94 to 97%.
- A cytoplasmic fraction is 3 to 6%.
- Troponin -T allows the early and late diagnosis of MI.
- The serum level remains raised beyond 7 days.
- It can be detected as early as 3 hours after the myocardial injury.
- Troponin -T remains elevated for 10 to 14 days.
- Troponin – I remain elevated for 7 to 10 days.
- The sensitivity of Troponin – T is 100% from 12 hours to 5 days after the chest pain.
- The raised level is also significant, because it may go even up to 200 times.
- Serial measurement of Troponin – T, and Troponin – I is advisable and specific for the diagnosis of AMI (myocardial damage).
- Raised levels of Troponin – T in unstable angina predict poor outcomes in some patients.
- Troponin measurement is better than LDH, particularly in patients who seek medical attention more than 24 to 48 hours after the onset of symptoms.
- Troponins are measured by:
- Monoclonal antibody immunoassay.
- Enzyme-linked immunoassay.
- Monoclonal sandwich antibody qualitative technique.
Advantage of Troponin over CK-MB:
Troponins | CK-MB | |
Specificity |
More specifically for cardiac muscle injury. Normal in noncardiac muscle injury |
Increased in skeletal muscle injury, brain, lung, and renal failure |
Increased level | Increased early and remains elevated longer than CK-MB | |
Sensitivity | More sensitive to cardiac muscle injury than CK-MB | Less sensitive to cardiac muscle injury |
Importance | More important for the evaluation of chest pain | Less important for the evaluation of chest pain |
Normal values of cardiac markers:
Source 1
- CK-MB = 0 to 3 ng/mL
- Or 0 to 3 µg/L
Source 2
- Troponin T = <0.2 ng/mL
- Troponin I = <0.3 ng/mL
Source 4
- TRoponin – T = <0.2 ng/mL
- Or <o.2 µg/L
- Troponin – I = <0.35 ng/mL
- Or <0.35 µg/L
- LDH = 140 to 280 U/L
- Myoglobin = <55 ng/mL
Table of cardiac markers:
Marker | Time rise in hours | When detectable in hours | Peak hours | days to become normal |
---|---|---|---|---|
Creatine Kinase | 5 to 8 | 6 to 8 | 24 to 36 hours | 3 to 4 days |
CK -MB | 5 to 15 | 4 to 6 | 12 to 24 hours | 2 to 3 days |
LDH | 2 to 4 | 8 to 12 | 72 to 144 hours | 8 to 14 days |
Myoglobin | 1 to 3 | 6 to 9 hours | 1 day | |
Troponin I | 3 to 8 | 14 to 18 hours | 3 to 10 days | |
Troponin T | 3 to 8 | 72 to 100 hours | 5 to 10 days | |
AST (SGOT) | 3 to 5 | 6 to 8 | 24 to 48 hours | 4 to 6 days |
- Thrombolytic therapy is useful if applied within the first 12 hours of AMI.
- Note: You may find some differences in these tests to become normal in different references.
Critical values
- Troponin I = >1.5 ng/mL