Biochemical Investigations In Heart Disaeses

Overview Myocardial infarction Time-course of plasma enzyme changes Creatine kinase (CK) Lactate dehydrogenase (LDH) Aspartate aminotransferase (AST) Myoglobin Cardiac troponins I and T

Acute Coronary Syndromes Unstable Angina Non-ST-Segment Elevation MI (NSTEMI) ST-Segment Elevation MI (STEMI) Similar pathophysiology Similar presentation and early management rules STEMI requires evaluation for acute reperfusion intervention Unstable angina with or without increase of troponins ECG : include ST elevation, and T wave inversion The increased levels of troponins although not associated by ECG changes indicates increased risk of subsequent cardiac events

What is Myocardial Infarction? Myocardial ischemia results from the reduction of coronary blood flow to an extent that leads to insufficiency of oxygen supply to myocardial tissue When this ischemia is prolonged & irreversible, myocardial cell death & necrosis occurs ---this is defined as: myocardial infarction is the death & necrosis of myocardial cells as a result of coronary prolonged & irreversible ischemia

Previously: WHO criteria for the diagnosis of myocardial infarction ( at least 2/3): Typical history of chest pain Presence of ECG changes Rise of biochemical markers With the advent of troponins, which is more sensitive biochemical marker, new definition:

Types of Biochemical Markers 1- Cardiac Enzymes (isoenzymes): Total CK CK-MB activity CK-MB mass Aspartate aminotransferase (AST) Lactate dehydrogenase (LDH) 2- Cardiac proteins: Myoglobin Troponins

Cardiac Enzymes Total CK (sum of CK-MM, CK-MB & CK-BB) non specific to cardiac tissue (available in skeletal ms.) CK-MB (CK-2) activity more specific than total CK BUT: less specific than troponin I (available in sk. Ms) appears in blood: within 4-6 hours of onset of attack peak: 12 - 24 hours returns to normal: within 2 - 3 days (no long stay in blood) Advantages: - useful for early diagnosis of MI - useful for diagnosis reinfarction Disadvantages: not used for delayed admission (more than 2 days) not 100% specific (elevated in sk.ms damage)

Cardiac Proteins cytosolic protein Myoglobin - not specific for cardiac tissue (also in sk.ms. & renal tissue) - appears in blood EARLIER than other markers (within 1-4 hours) So, with high sensitivity - BUT: Returns to normal in 24 hours So, not for delayed admission cases (after one day of onset of attack)

Cardiac Troponins 100 % cardiac specific Protein complex located on the thin filament of striated muscles consists of 3 subunits: cTn T, cTnI & cTn C with different structures & functions cTnI & cTnT are used are biomarkers for MI diagnosis Cardiac troponins (cTn) are different from skeletal muscle tropnins So, more specific for MI diagnosis cTnI: 100 % cardiac specific With greater sensitivity for diagnosing minor damage of MI Appears in blood within 6 hours after onset of infarction peak: around 24 hours Disappears from blood after about one week (stays longer) So, useful for diagnosis of delayed admission cases Prognostic marker (relation between level in blood & extent of cardiac damage)

Lactate dehydrogenase (LDH) LDH is a tetramer, each chain may be one of two types (H,M) where LDH1 is (H4) while LD5 is (M4) LD1 & LD2 predominates in heart and red cells LDH increases later than CK-Mb and Ck Reaches a max. level in 48 h Remains elevated for 5-6 days after the MI A non-specific marker of tissue injury: * High levels are found in liver, lung, kidney and other diseases

Aspartate aminotransferase (AST) AST is somewhat heart-specific than ALT A non-specific marker of MI It appears in liver and other diseases

Time-course of enzyme changes Plasma enzymes follow a pattern of activities after a MI The initial lag phase lasts for about 3 hours Enzymes rise rapidly to peak levels in 18-36 hours The levels return to normal based on enzyme half-life Rapid rise and fall indicates diagnostic value.

Blood samples collected at:. Baseline (upon admission) Blood samples collected at: * Baseline (upon admission) * Between 12 to 24 hours after the onset of symptoms

Time-Course of Changes Enzyme Detectable (hours) Peak value Duration (days) CK-MB 3-10 12-24 1.5-3 Total CK 5-12 18-30 2-5 AST 6-12 20-30 2-6 LDH (heart specific) 8-16 30-48 5-14 Cardiac troponins 4-6 Up to 10