Biomarkers of Cardiac Injury

 The diagnosis of acute myocardial infarction (AMI) involves multiple clinical tools including physical assessment, ECG, and the evaluation of cardiac biomarkers. Electrocardiography produces a physiological signal that is frequently used for diagnosing heart problems, but it is incapable of adequately diagnosing AMI. Myoglobin, B-type natriuretic peptide (BNP), creatine kinase isoenzyme MB (CK-MB), and cardiac troponin T (cTn-T) are cardiac biomarkers frequently used for evaluating cardiac risk factors.

Biomarker History

Biomarkers have been in use since the 1960s and have continually improved to become more reliable when used to diagnosis a cardiac event.

Aspartate Transaminase (AST)

The first biomarker identified was Aspartate Transaminase (AST), and it was used frequently in the 1960s but was not cardiac muscle specific.

Lactate Dehydrogenase (LDH) and Creatine Kinase (CK)

Lactate dehydrogenase (LDH) and creatine kinase (CK) were used in the 1970s, and even though neither was absolutely specific for cardiac muscle, CK was more specific for AMI than LDH.

Myoglobin

Myoglobin is a small globular oxygen-carrying protein found in the heart and striated skeletal muscle1 and was first used in 1978. Myoglobin rises after acute myocardial injury, and it became a useful cardiac biomarker in the differential diagnosis of suspected AMI. It appears in the blood 1 hour after myocardial infarction, peaks at 4-12 hours, and then returns to the baseline level.

B-Type Natriuretic Peptide (BNP)

BNP is a cardiac neurohormone that is synthesized in cardiac cells. It is used as a diagnostic biomarker for congestive heart failure and can predict outcomes in patients with AMI (Wiviott). Some studies have shown that BNP can be a useful biomarker for estimating mortality in acute coronary syndrome (ACS).

CKMB

Advancements led to the development of isoenzymes of CK and LDH, CK-MB and LDH 1 + 22. CK-MB levels increase in the serum 4-9 hours after chest pain begins, reach peak values within 24 hours, and return to baseline values within 48-72 hours. CK-MB is not sensitive enough for diagnosis within 4 hours from the time of symptom onset, but test sensitivity rises 6 hours or more after the onset of chest pain.

Troponin

In 1965, a new protein constituent of the cardiac myofibrillar apparatus was discovered, which subsequently came to be known as troponin, and in the late 1990s, a sensitive and reliable radioimmunoassay was developed to detect it in the serum. Since then, the role of cardiac troponins as diagnostic biomarkers of myocardial injury in the context of the acute coronary syndrome (ACS) has been well established. Troponin levels appear in the serum 4-10 hours after the onset of AMI, peak at 12-48 hours, and remain elevated for 4-10 days.

Cardiac troponin (cTn) is a complex comprising three subunits:

• troponin C acts as the calcium-binding site (skeletal and cardiac muscle);
• troponin I inhibit interaction with myosin heads in the absence of sufficient calcium ions (cardiac myocytes);
• troponin T attaches the troponin complex to the actin filament (cardiac myocytes).

Troponin I and T isoforms are highly specific and sensitive to cardiac myocytes and, therefore, are known as cardiac troponins (cTn). The detection of cTn-I or cTn-T in the bloodstream is, therefore, a highly specific marker for cardiac damage.

Even though increased cTn-T levels are highly indicative of a cardiac event, it is still not 100% specific. There are six mechanisms that have been proposed to explain the release of troponin into the bloodstream: normal cell turnover, myocyte necrosis, apoptosis or programmed cell death, proteolytic fragmentation, increased cell membrane permeability, and membranous blebs.

Cardiac biomarkers for diagnosis of AMI have become more and more sensitive in recent decades, but the perfect test to diagnose AMI still does not exist. Clinicians need to use every option given to them to quickly and accurately determine what is happening with their patients. Clinical assessment, 12-lead ECG, and cardiac troponin (cTn) I or T form the diagnostic cornerstones of patients with acute onset chest pain.

Why do I need this test?

You may need this test if your healthcare provider thinks you're having or have recently had a heart attack. You may also need this test if you have symptoms of coronary artery blockage.

Symptoms of coronary blockage may include:

• Chest pain or pressure that lasts for more than a few minutes
• Pain or discomfort in your shoulders, neck, arms, or jaw
• Chest pain that gets worse
• Chest pain that doesn’t get better by rest or by taking nitroglycerin

Other symptoms that may happen along with chest pain:

• Sweating, cool, clammy skin, or paleness
• Shortness of breath
• Nausea or vomiting
• Dizziness or fainting
• Unexplained weakness or fatigue
• Rapid or irregular pulse

What other tests might I have along with this test?

Your healthcare provider may order other tests to measure other factors in your blood, or in your heart, or both. These include:

• Blood gases or other tests to measure oxygen in the blood
• Complete blood count
• Electrolytes (sodium, potassium, chloride)
• Blood lipids (cholesterol and triglycerides)
• Blood sugar (glucose)
• Electrocardiogram (ECG)
• Echocardiogram or ultrasound of the heart muscle
• Cardiac catheterization or coronary angiogram
• B-type natriuretic peptide (BNP). This is to find stress in the heart or heart failure after a heart attack.

What do my test results mean?

Test results may vary depending on your age, gender, health history, the method used for the test, and other things. Your test results may not mean you have a problem. Ask your healthcare provider what your test results mean for you. 

Results are given in nanograms per milliliter (ng/mL). People who are young and healthy usually have little or no cardiac troponin in their blood.

Normal-level results vary. But people with levels of cardiac troponin at or above 0.01 ng/mL are twice as likely to have life-threatening cardiac disease.

How is this test done?

The test is done with a blood sample. A needle is used to draw blood from a vein in your arm or hand. 

Does this test pose any risks?

Having a blood test with a needle carries some risks. These include bleeding, infection, bruising, and feeling lightheaded. When the needle pricks your arm or hand, you may feel a slight sting or pain. Afterward, the site may be sore. 

What might affect my test results?

Other factors aren't likely to affect your results.

How do I get ready for this test?

You don't need to prepare for this test. Be sure your healthcare provider knows about all medicines, herbs, vitamins, and supplements you are taking. This includes medicines that don't need a prescription and any illicit drugs you may use. 

Thanks & regards

Vikas Tiwari