Cardiac Markers PDF

Cardiac Biomarkers Chest pain Acute Coronary Syndrome (ACS) is one of the most dangerous causes of chest pain. However, non-cardiac reason of chest pain can also occur by : Pulmonary embolism, gall bladder disease or even indigestion. D-Dimer is an early diagnostic marker of coronary ischemia...

Cardiac Biomarkers Chest pain Acute Coronary Syndrome (ACS) is one of the most dangerous causes of chest pain. However, non-cardiac reason of chest pain can also occur by : Pulmonary embolism, gall bladder disease or even indigestion. D-Dimer is an early diagnostic marker of coronary ischemia in patients with chest pain. It is a protein fragment that is made when a blood clot dissolves in our body. This represents a significant dilemma for emergency departments physicians because they must quickly determine which chest pain symptoms are cardiac in origin and which are not.  Acute coronary syndrome (ACS) ACS includes several related conditions, all of which are caused by the inability to provide enough nourishment to the heart muscle due to abruptly decreased blood flow to the heart (cardiac ischemia). Acute coronary syndrome includes: Myocardial Infarction (also known as heart attack) in which heart muscle is damaged Unstable angina pectoris (UA) Silent ischemia  Pathogenesis of ACS The most common cause for acute heart diseases is due to atherosclerosis of cardiac arteries and the rupture of unstable atherosclerotic plaque in a coronary artery. It causes subsequent formation of a thrombus causing partial occlusion of coronary arteries leading to unstable angina or complete occlusion of coronary arteries leading to acute myocardial infarction. Cardiac Markers and Chest Pain Diagnosis The initial evaluation of patients presented with chest pain usually involves four steps: Step 1: Medical history, including relevant risk factors for coronary artery disease Step 2: Physical examination Step 3: Electrocardiogram (ECG) Step 4: Blood tests including cardiac markers  CARDIAC MARKERS Cardiac markers or cardiac enzymes are proteins originating from cardiac tissue and detected in the blood. These proteins are released into the bloodstream when damage to the heart occurs (in response to ischemia) as in the case of a myocardial infarction.  CARDIAC MARKERS The ideal cardiac marker is: Present in high concentration in the myocardium Appears soon after onset of ischemia Should be absent in non myocardial tissue and blood The aim of diagnostic cardiac markers is: To identify patients with acute myocardial infarction even when there is no evidence of myocyte necrosis.  When should cardiac markers be used? Almost all cardiology associations and clinical biochemistry academies recommend an emergency departments protocol that yields physical examination and ECG within 10 minutes and cardiac markers determination within 30 minutes. Patients with suspected acute coronary syndrome should be treated within one hour following admission to the emergency room. Therefore, sensitive and specific serum cardiac marker tests must be performed on a continuous basis, with a target turnaround time of 1 hour or less after patient admission for emergency diagnosis of myocardial damage in Acute Coronary Syndrome.  Serial sampling of an early (myoglobin) and a late cardiac marker (troponin) at T0, T2 - T4 hours and T8 hours is recommended. Additional sampling at T12-T24 hours, although optional, is often highly useful. IMPORTANT CARDIAC MARKERS Until the 1980s, the enzymes AST (SGOT) and LDH were used to assess cardiac injury. aspartate aminotransferase (serum glutamic-oxaloacetic transaminase) Then it was found that proportional elevation of the MB subtype of the enzyme creatine kinase (CK) was very specific for myocardial injury. Important cardiac markers include: Myoglobin CK-MB Cardiac Troponin  Troponins: Troponin T and I The troponin complex consists of 3 different sub-units (I, C and T) which regulate the contraction of cardiac muscle. Both Troponin I and Troponin T have cardiac specific isoforms. They are referred to as cardiac Troponin I (cTnI) and cardiac Troponin T (cTnT). As such, cTnI and cTnT are the preferred biomarkers for myocardial damage and for acute coronary syndrome diagnosis, especially in the absence of clear ECG changes.  What are Troponins Troponins: Troponin T and I Troponins acts as a contractile protein complex of the myofibril that regulates the calcium-dependent interaction of myosin and actin to contract striated muscle. They also enable the detection of minor myocardial damage. These markers appear relatively early (on average, 4 to 6 hours) after cardiac muscle damage and may be present for several days after acute myocardial infarction. The cardiac isoforms are very specific for cardiac injury and are not present in serum of healthy people.  cTnI has never been reported to be expressed in skeletal muscle, therefore making it entirely specific for cardiac damage. Troponin I (cTnI) or T (cTnT) are measured by immunoassay methods. Troponin kinetics after myocardial infarction Rises 3 - 12 hours after injury Peaks in 24 - 48 hours cTnI stays elevated for 5-10 days cTnT stays elevated for 5-14 days As elevations in cTnT and cTnI after acute MI persist for up to 10 days, this helps in late diagnosis.  Differential diagnosis other than MI It is important to note that cardiac troponins are markers of all heart muscle damage, not just myocardial infarction. Other conditions that directly or indirectly lead to heart muscle damage can also therefore increase troponin levels: Cardiac: Non-cardiac: Cardiac surgery & heart transplant Critical illness e.g. sepsis Defibrillation High–dose chemotherapy Cardiomyopathy Pulmonary hypertension Heart failure Pulmonary embolism Myocarditis Renal failure Supraventricular tachycardia Very heavy exercise (marathon)  Creatine kinase It is a cystosolic carrier protein that catalyzes the transfer of phosphate between creatine phosphate and ADP that is released from cells when damaged. In most of the cell, the CK enzyme consists of two subunits, which can be either B (brain type) or M (muscle type). There are, therefore, three different isoenzymes: CK-MM, CK-BB and CK-MB. The genes for these subunits are located on different chromosomes. This enzyme is found in: - Heart muscle (CK-MB), - Skeletal muscle (CK-MM), and - Brain (CK-BB) Creatine kinase (CK-MB), is increased in over 90% of myocardial infarctions.  Creatine kinase CK-MB sensitivity is approximately 95%, with high specificity. However, sensitivity and specificity are not as high as for troponin levels, and the trend has favored using troponins for the diagnosis of MI. CK-MB also can be increased in other conditions such as: - Muscle trauma - Myocarditis - Muscle dystrophy - Physical exertion - Postoperatively - Convulsions - Malignant hyperthermia  CK-MB Kinetics after myocardial infarction It begins to rise in 3-12 hours Peaks 24 hours Returns to normal in 2-3 days Thus, CK-MB cannot be used for late diagnosis. However, new elevations can be used to detect re-infarction. Males: < or = 7.7 ng/mL Females: < or = 4.3 ng/mL CK-MB Kinetics after myocardial infarction  Myoglobin Myoglobin, a low molecular weight heme protein found in cardiac and skeletal muscle, is valuable in the early evaluation of chest pain patients. It may appear in the blood in abnormal level as early as 1 to 3 hours after onset of myocardial ischemia. So, it can help in the earlier identification of an MI. While Myoglobin is not specific to cardiac muscle, it is useful in the detection of MI in the absence of skeletal muscle trauma or other factors that may be associated with a non-cardiac related increase. Myoglobin has also been demonstrated to be statistically more sensitive than CK-MB but not specific. It has false positives with skeletal muscle injury and renal failure, and it is expensive. Myoglobin kinetics after myocardial infarction Rises fast (2 hours) after myocardial infarction Peaks at 6 - 8 hours Returns to normal in 20 - 36 hours  Lactate dehydrogenase Usually LDH-2 is the predominant form in the serum. A LDH-1 level higher than the LDH-2 level, suggests myocardial infarction (damage to heart tissues releases LDH, which is rich in LDH- 1, into the bloodstream). LDH kinetics after Myocardial infarction: Peaks at 3-4 days Returns to normal 10 days. LDH are not used anymore for cardiac diagnosis and are replaced by troponins.