CARDIAC PROFILE: CARDIAC LESIONS, CARDIAC MARKERS - MEDICINE - 2024

The cardiac profile is made up of a series of biochemical markers, some more specific than others, which help to make the diagnosis of some cardiac ischemic events.

The American Heart Society reports that approximately every 30 seconds a person dies from cardiovascular disease. Out of 6 million visits a year for chest pain in emergency rooms in the United States, only 1 in 5 patients is diagnosed with an acute myocardial infarction by means of the electrocardiogram.

Image by Jefty Matricio at www.pixabay.com

The evaluation of cardiac markers makes it possible to rule out or diagnose acute myocardial infarction in the absence of electrocardiographic patterns. For more than twenty years the standard form of diagnosis has included measuring levels of the creatine kinase isoenzyme (CK-MB or CK-2) and cardiac troponin proteins.

Along with these enzymes, other enzymes and substances have been used as cardiac markers, among which LDH (lactic dehydrogenase and its isoforms) and myoglobin, etc. can be named. These last markers do not have a high specificity for cardiac lesions.

It is important to note that in 1998 the American Society for Clinical Chemistry recommended the use of cardiac troponins as a precise and specific method for the diagnosis of acute myocardial infarction and other cardiac ischemic injuries.

Cardiac injuries

Myocardial heart diseases or disorders can be broadly grouped into: (1) ischemic heart diseases, (2) cardiomyopathies, (3) arrhythmias, and (4) congenital and valvular heart diseases.

Commonly, cardiac ischemia can occur as a result of coronary arteriosclerosis, which can lead first to angina and reversible ischemic lesions of the heart tissue. If left untreated, unstable angina can develop leading to myocardial damage and heart attack.

As a result of myocardial cell damage, inappropriate muscle contractions occur, such as those described in many cardiomyopathies. Some cardiomyopathies can also be secondary to pathological processes of different origins.

Chest pain (Image from Pexels at www.pixabay.com)

Abnormal heart contractions and arrhythmias are due to anatomical changes in the heart muscle that interrupt or alter the proper transmission of electrical impulses in the heart. This can lead to low or high frequency rhythms or irregular rhythms that are classified as bradycardias, tachycardias, and arrhythmias, respectively.

When congenital and / or valvular heart diseases are not corrected they can cause a deficit in the blood supply that can cause damage to the myocardium and other heart tissues. Increased cardiac workload under these conditions can lead to angina and heart failure.

Thus, irreversible damage to cardiac tissue releases enzymes and contractile proteins into the bloodstream that can be identified and measured and, on many occasions, allow the corresponding diagnosis to be made.

These substances are called "cardiac markers" and the more specific the markers used, the more accurate the diagnosis and prognosis for each case. For this, serial measurements are used to evaluate the release and blood levels of these markers.

Cardiac markers

When evaluating the diagnostic results of cardiac ischemic processes, especially myocardial infarction, the temporal phases of the process must be considered. The temporary progression of a myocardial infarction goes through the following phases:

- Acute phase (first hours to 7 days)

- Healing phase (7 to 28 days) and

- Healing phase (more than 29 days)

The tests used to evaluate and confirm the diagnosis of these ischemic processes can be divided into four groups:

- electrocardiographic studies

- measurement of cardiac markers (cardiac profile)

- cardiac echocardiographic images and

- nonspecific indices of inflammation and tissue necrosis

Historically, the most widely used markers were glutamic oxaloacetic transaminases (GOT), which are nonspecific, and myoglobin, which is an intramuscular oxygen transporter and is not specific for cardiac muscle, as it is also found in other tissues such as skeletal muscle.

Also used are creatine kinase (CK), which is an enzyme that promotes the formation of ATP (Adenosine-Tri-Phosphate) from phosphocreatine, and lactate dehydrogenase (LDH), which transforms pyruvic acid (pyruvate) into lactic acid. These enzymes as such are not specific, but some of their isoforms are.

- Specific markers and release periods

After a myocardial infarction certain proteins called "cardiac markers" are released in large quantities from necrotic areas into the bloodstream. The release rate of these proteins differs depending on their intracellular location, their molecular weight, and local blood and lymphatic flow.

The temporal patterns of release of these markers are very important for diagnosis and for making immediate decisions for reperfusion strategies. There are very quick tests that are done in the patient's bed and that only require a small sample of whole blood.

These markers should be measured at the time of patient admission. Then between 6 to 9 hours after admission. Finally 12 to 24 hours later, if the diagnosis is still uncertain.

Phosphocreatine kinase and its isoform

Phosphocreatine kinase (CK) rises in the first 4 to 8 hours, then decreases and returns to normal levels after 48-72 hours. This enzyme is not specific and can be elevated by skeletal muscle trauma such as an intramuscular injection, for example.

This ambiguity can lead to misdiagnosis in patients who have received intramuscular injections of narcotics to treat non-cardiac chest pain.

Other causes of elevated CK and possible diagnostic problems include:

1. Diseases that affect skeletal muscle such as muscular dystrophy, myopathies, and polymyositis
2. Electrical cardioversion
3. Hypothyroidism
4. Surgeries
5. Secondary skeletal muscle damage from trauma, seizures, or prolonged immobilization

The isoform of CK called CK-MB has the advantage that it is not found in significant amounts in extra-cardiac tissues, and is therefore considered more specific. However, cardiovascular surgery, electrical cardioversion, and myocarditis frequently elevate CK-MB.

Cardiac troponin

The specific cardiac troponins are troponins T and I and are named by the abbreviations cTnT and cTnI, respectively. These troponins have different amino acid sequences than skeletal muscle, so they are specific to heart muscle.

These differences have made it possible to develop tests with specific monoclonal antibodies that are very easy to apply. Since there is no cardiac troponin in the blood under normal conditions, its appearance is of great diagnostic utility and is currently the cardiac marker of choice for myocardial infarction.

Cardiac troponins are particularly important when skeletal muscle damage is suspected or when myocardial infarction affects very small areas and the levels of the other marker proteins are below the sensitivity of measurement methods such as CK or CK- MB.

After a myocardial infarction, cTnT and cTnI levels remain elevated for 7 to 10 days. If other infarcts occur during this period, this method will not be able to detect them, since troponins are already elevated, so another marker will be required to do so.

In these cases, myoglobin can be used as a marker, since it only remains elevated for a few hours after the ischemic event and is one of the first proteins to rise after the infarction; it is rapidly excreted in the urine and its levels return to normal within 24 hours.

Thus, many hospitals now routinely use cardiac troponin measurements, but if recurrent ischemic episodes are suspected after the initial episode, then markers that rise more briefly than troponin are required.

In these cases and especially when these recurrent episodes are not accompanied by obvious electrocardiographic alterations, use is made of the CK-MB or myoglobin markers because their levels increase rapidly but also normalize within a few hours.

References

1. Aydin, S., Ugur, K., Aydin, S., Sahin, İ., & Yardim, M. (2019). Biomarkers in acute myocardial infarction: current perspectives. Vascular health and risk management, 15, 1.
2. Fauci, AS, Kasper, DL, Hauser, SL, Jameson, JL, & Loscalzo, J. (2012). Harrison's principles of internal medicine (Vol. 2012). DL Longo (Ed.). New York: Mcgraw-hill.
3. Fitzgerald, RL, Frankel, WL, & Herold, DA (1996). Comparison of troponin-T with other cardiac markers in a VA hospital. American journal of clinical pathology, 106 (3), 396-401.
4. Keffer, JH (1997). The cardiac profile and proposed practice guideline for acute ischemic heart disease. American journal of clinical pathology, 107 (4), 398-409.
5. McCance, KL, & Huether, SE (2018). Pathophysiology-E-book: the biologic basis for disease in adults and children. Elsevier Health Sciences.
6. Rosales, JL (1999). The clinical utility of cardiac markers. Laboratory Medicine, 30 (10), 668-673.