Biochemical Markers for Diagnosis of Myocardial Infarction

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

clinical manifestations BIOCHEMICAL MARKERS ECG Biochemical Changes in Acute Myocardial Infarction (mechanism of release of myocardial markers) ischemia to myocardial muscles (with low O2 supply) anaerobic glycolysis increased accumulation of Lactate decrease in pH activate lysosomal enzymes disintegration of myocardial proteins cell death & necrosis clinical manifestations (chest pain) release of intracellular contents to blood BIOCHEMICAL MARKERS ECG changes

Diagnosis of Myocardial Infarction 1- Clinical Manifestations 2- ECG 3- Biochemical Markers

Criteria of ideal markers for myocardial infarction 1- Specific: to myocardial muscle cells (no false positive) 2- Sensitive: - rapid release on onset of attack (diagnose early cases) - so, can detect minor damage - no miss of positive cases (no false negative) 3- Prognostic: relation between plasma level & extent of damage 4- Persists longer: so, can diagnose delayed admission 6- Reliable: procedure depends on evidenced principle 5- Simple, inexpensive: - can be performed anywhere by low costs - no need for highly qualified personnel 7- Quick: low turnaround time

Types of Biochemical Markers for Diagnosis of Myocardial Infarction 1- Cardiac enzymes (isoenzymes): Total CK CK-MB activity CK-MB mass LDH AST 2- Cardiac proteins: Myoglobin Troponins

Cardiac Enzymes Total CK (sum of CK-MM, CK-MB & CK-BB) non specific to cardiac tissue (available also in skeletal muscles) CK-MB (CK-2) activity More specific than total CK BUT: less specific than cardiac troponin I (as CK-MB is also available in skeletal muscles) Appears in blood: within 4 - 6 hours of onset of attack (used for early cases) Reaches maximum peak within: 12 - 24 hours Returns to normal: after 2 - 3 days of onset (no long stay in blood. So, not for delayed admissions) 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 skeletal muscle damage)

Cardiac Enzymes cont. CK-MB mass - Appears one hour earlier than CK-MB activity (more sensitive) - So, useful for diagnosis of early cases & reinfarction - BUT: not for diagnosis of delayed admission cases & less specific than cardiac troponin I Relative index = CK-MB mass / Total CK X 100 more than 5 % is indicative for MI

Cardiac Enzymes cont. 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) 5 isomers are available, but, each predominates in a certain organ. LD1 & LD2 predominates in heart Detected in blood: 8-16 hours after onset of MI attacks (not for early cases) Reaches a maximum peak level: in 48 h Remains elevated for: 5-6 days after MI (may remain elevated up to 14 days) Disadvantages: A non-specific marker of as it is also elevated in diseases of liver, lung, kidney, RBCs etc

Cardiac Enzymes cont. Aspartate aminotransferase (AST) A non-specific marker of MI as it appears also in liver & other organs diseases (N.B. AST is somewhat more heart-specific than ALT) Detected in blood: 6-12 hours after onset of MI attacks (not for early cases) Reaches a maximum peak level: in 30 hours Returns to normal : after 2 - 6 days after MI

Cardiac Proteins Myoglobin - Non specific for cardiac tissue (as it is elevated also in skeletal muscle & 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 Proteins cont. Cardiac Troponins Protein complex located on the thin filament of striated muscles consists of 3 subunits: cTn T, cTn I & cTn C with different structures & functions cTnI & cTnT are used are biomarkers for MI diagnosis Cardiac troponins (cTn) are different from skeletal muscle troponins So, more specific for MI diagnosis

Cardiac Proteins cont. Cardiac Troponin I (cTn I) 100 % cardiac specific With greater sensitivity for diagnosing minor damage of MI Appears in blood: within 6 hours after onset of infarction Reaches maximum peak: around 24 hours Disappears from blood: after about 10 days (stays longer) So, useful for diagnosis of delayed admission Prognostic marker : Matching relation between level in blood & extent of cardiac damage

Recommendations for use of biochemical markers for diagnosis of myocardial infarction 1- Recommended for all patients complaining of chest pain (with clinical examination & ECG) 2- Sample Type: plasma Timing: i. on admission ii. serial ( at least every one hour in a period 6-9 hours) should be referenced to admission & onset of pain 3- Test should be with low turnaround time Less than one hour (accepted) Less than half an hour is preferred 4- Types of Markers used: Early markers: as Myoglobin: Appears in blood early (within less 4 fours) BUT not specific & not persists for long period (less than 2 days) Definitive markers: Troponin: Appears in blood later than myoglobin (within 6 hours) BUT 100% specific, prognostic & stays longer (one week) 5- Troponin is currently the marker of choice should be available in all cardiac & emergency centers (if not, CK-MB mass is the second choice)

Time Course for Biomarkers of Myocardial Infarction Detectable (hours) Peak value Duration (days) cTn I 4 - 6 12 - 24 Up to 10 CK-MB 3 - 10 1.5 - 3 Myoglobin 1 - 4 12 1 Total CK 5 - 12 18 - 30 2 - 5 AST 6 - 12 20 - 30 2 - 6 LDH 8 - 16 30 - 48 5 - 14