Troponin: what is it, etiology, epidemiology, pathophysiology

Introduction

Diagnosis of urgent cardiac conditions is one of the most important tasks of an emergency doctor. The broad differential diagnosis of chest pain must be narrowed down quickly and accurately in order to fulfill the vital procedures required by patients. Along with the history and physical examination, there are a number of important diagnostic tools that are used to differentiate between different causes of chest pain. One of the tools that has become an important component of cardiac examinations and diagnostics is troponin measurement. Troponin interval measurements have revolutionized the practice of emergency medicine and the diagnosis and treatment of myocardial ischemia.

Etiology and epidemiology

Troponins Are cardiac regulatory proteins that are found in the cytoplasm of cardiac myocytes. When calcium binds to a protein complex, the structure of troponin changes and this triggers an interaction between actin and myosin filaments. This interaction leads to contraction of the heart muscle. The troponin complex consists of 3 subunits: cTnC, cTnI, and cTnT. cTnI and cTnT are subunits that are identified in laboratory tests aimed at detecting damage to the heart muscle. It has been shown that cTnI is present exclusively in the heart muscle. Studies have not been able to identify cTnIs in any tissue of the body at any stage in the development of the newborn. Small amounts of cTnT have been identified in skeletal muscle, but are found at much higher concentrations in cardiac muscle. In clinical studies, no statistically significant differences were found with cTnI versus cTnT in troponin assays.

Prior to the advent of troponin, there were a number of different cardiac biomarkers that were used to identify myocardial ischemia. In the 1960s and 1970s, biomarkers were used such as aspartate transaminase (AST), lactate dehydrogenase (LDH) and creatine kinase (CK), but their use has ceased due to the lack of specificity for cardiac muscles. The next generation of biomarkers was more specific for cardiac muscle and included CK-MB and LDH 1 + 2. However, these markers still had an unacceptably high false-positive rate and a new, more specific biomarker was required. Troponins were first identified in 1965, but a reliable immune test to determine their blood levels was not developed until the late 1990s. Troponin measurements have been found to have almost 100% sensitivity when checked 6-12 hours after the onset of pain in the chest and have significantly improved specificity for cardiac muscle damage compared to previous biomarkers. Because of its clinical utility, troponin serial testing has been added to the third universal definition myocardial infarctionwhich is currently the definition used by the American College of Cardiology.

Pathophysiology

Myocardial infarction occurs when blood flow is blocked in the coronary vessels that supply oxygen to the heart muscle. This causes a mismatch when the oxygen supply does not meet the oxygen demand of the myocytes, resulting in cell necrosis and death. During this process, cell membranes are ruptured, causing intracellular contents to spill into the extracellular space, eventually entering the bloodstream. If these cellular substances, including troponins, are spilled in sufficiently large quantities, then they can be found in the circulating blood.

Most of the troponin found in the bloodstream of healthy people is associated with the normal turnover of cardiac myocytes. For the troponin measured to indicate pathophysiological muscle damage, it must be greater than the 99th percentile of the normal range, which is approximately 3 standard deviations from the mean. According to the third universal definition of myocardial infarction, there should also be a characteristic rise and fall in troponin levels, measured over several hours and days. Troponin levels usually begin to rise in the bloodstream within 2 to 3 hours after the onset of chest pain. During this time, levels will continue to rise until a peak is reached, usually between 12 and 48 hours. Troponin levels will then begin to drop over the next 4-10 days to normal levels.

Diagnostic tests

In the emergency department, it is impossible to fully monitor troponin levels from rise to peak to fall. When a patient complains of chest pain, a diagnostic decision must be made immediately. To aid in decision making in emergency situations, myocardial infarction is divided into 2 categories based on ECG data; ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (STEMI). With STEMI, patients will have elevated troponin as well as one of the following ECG changes: (1) ST segment elevation greater than 1 mm in adjacent leads with reciprocal changes, (2) new signs of left bundle branch block or (3) ST segment elevation marked on the posterior ECG. In this case, the diagnostic and therapeutic solutions are simple. The patient probably has a severe blockage of the coronary artery and requires emergency coronary catheterization if there is one, or thrombolytic therapy to open the blocked vessel and reperfuse the heart muscle.

STEMI is defined as damage to the heart muscle that results in elevated troponin levels, but does not have the ECG changes that determine STEMI. NSTEMIs usually present less damage to myocardial tissue than STEMIs, and there is no need for emergency coronary catheterization in the beginning. STEMI is usually treated with medication, including dual antiplatelet therapy, as well as complete anticoagulant therapy such as heparin. NSTEMIs are a challenging problem for the emergency room physician. It is possible that a patient with chest pain may initially have negative troponin without ECG changes, but all may still have STEMI because troponin levels do not start to rise until at least 2-3 hours after the initial stroke. This highlights the importance of serial troponin production at 3 to 6 hour intervals for patients suspected of having an ischemic event but having troponin that is initially normal.

Interfering factors

One problem with the use of troponins to diagnose acute myocardial infarction is that troponin levels can be elevated in other conditions. Anything that causes damage to the heart muscle can cause troponin to enter the bloodstream. The most common cause of injury is the inadequacy of oxygen supply and consumption, which is observed in acute myocardial infarction. However, this mismatch can arise from many other conditions and, therefore, to an increase in troponin levels. For example, tachycardia may cause a decrease in perfusion due to a decrease in diastolic time when coronary blood flow occurs and oxygen demand increases. Patients able to shock may also have a mismatch in oxygen supply and consumption due to low blood volume, and elevated troponin levels in these patients have been shown to indicate poorer outcomes.

Another cause of elevated troponin levels is damage to the heart muscle from non-ischemic causes. Direct blunt trauma to the chest can cause significant myocardial damage and, in turn, lead to increased troponin levels. In a study of 333 patients with blunt chest trauma, elevated troponin was found in 144 (44%) patients. Inflammatory conditions such as viral myocarditis and infiltrative diseases such as sarcoidosis also cause elevated troponin levels. Leakage of troponin can also occur during processes outside the heart. For example, an increase in troponin levels has often been observed in patients with acute strokealthough they have no signs coronary heart disease. One of the supposed mechanisms of this phenomenon is a violation of the autonomic function after a violation cerebral circulation, which can cause an increased catecholamine reaction that affects the heart myocytes.

Another problem that makes it difficult to determine troponins for the diagnosis of acute myocardial infarction is chronic kidney disease (CKD). Patients with CKD have been found to have elevated troponin levels above the 99th percentile without evidence of heart disease. Although the mechanism for the increase in troponins is not fully understood, it is assumed that it is associated with major structural abnormalities of cardiac tissue and chronic myocardial damage. There have also been studies that suggest that the kidneys play a role in clearing troponin from the circulation, although there is no evidence that troponin is found in urine. This can make it difficult to diagnose a CKD patient who presents to the emergency department with chest pain due to elevated troponin levels.

A meta-analysis of 14 different studies showed that the specificity of elevated troponin levels above the 99th percentile decreased dramatically in patients with CKD. In these patients, it is very important to know if troponins change over time to see if there is an increase or decrease in levels. Troponin levels in patients with CKD are usually stable, so an increase and decrease in troponin will be more indicative of a cardiac cause of elevated troponin. One of the accepted guidelines is that if a change is observed during serial testing troponin levels by 20%, this is probably due to a cardiac cause, although the studies for this recommendation absent.

Clinical significance

Accurate diagnosis and treatment heart attacks Is an important component of working in the emergency department. The development and implementation of troponin testing has had a tremendous impact on emergency care. When using troponin testing, it is important to be aware of the shortcomings and potential errors and to consider the entire clinical picture when making medical decisions. Troponin testing has changed the way emergency care is delivered, and a deep understanding of its clinical implications is key to the success of emergency physicians.