1. Biochemical Markers for Diagnosis of Myocardial Infarction

2. 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

3. Biochemical Changes in Acute Myocardial Infarction (mechanism of release of myocardial markers) ischemia to myocardial muscles (with low O 2 supply) anaerobic glycolysis increased accumulation of Lactate decrease in pH activate lysosomal enzymes disintegration of myocardial proteins cell death & necrosis release of intracellular contents to blood BIOCHEMICAL MARKERS clinical manifestations (chest pain) ECG changes

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

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

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

7. Cardiac Enzymes Total CK (sum of CK-MM, CK-MB & CK-BB)Total CK (sum of CK-MM, CK-MB & CK-BB) non specific non specific to cardiac tissue (available also in skeletal muscles) CK-MB (CK-2) activityCK-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 bloodearly Appears in blood: within 4 - 6 hours of onset of attack (used for early cases) Reaches maximum peak within Reaches maximum peak within: 12 - 24 hours Returns to normalno not Returns to normal: after 2 - 3 days of onset (no long stay in blood. So, not for delayed admissions) early Advantages: - useful for early diagnosis of MI reinfarction - useful for diagnosis reinfarction not Disadvantages: not used for delayed admission (more than 2 days) not 100% specific not 100% specific (elevated in skeletal muscle damage)

8. CK-MB massCK-MB mass earlier more sensitive - Appears one hour earlier than CK-MB activity (more sensitive) early cases & reinfarction - So, useful for diagnosis of early cases & reinfarction not - 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 Cardiac Enzymes cont.

9. Lactate dehydrogenase (LDH)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 LD1 & LD2 predominates in heart Detected in bloodnot Detected in blood: 18-16 hours after onset of MI attacks (not for early cases) Reaches a maximum peak level Reaches a maximum peak level: in 48 h Remains elevated for Remains elevated for: 5-6 days after MI (may remain elevated up to 14 days) Disadvantages Disadvantages: non-specific marker A non-specific marker of as it is also elevated in diseases of liver, lung, kidney, RBCs etc Cardiac Enzymes Cardiac Enzymes cont.

10. Aspartate aminotransferase (AST) Aspartate aminotransferase (AST) non-specific marker of MI 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 bloodnot Detected in blood: 6-12 hours after onset of MI attacks (not for early cases) Reaches a maximum peak level Reaches a maximum peak level: in 30 hours Returns to normal Returns to normal : after 2 - 6 days after MI Cardiac Enzymes Cardiac Enzymes cont.

11. Cardiac Proteins MyoglobinMyoglobin - Non specific - Non specific for cardiac tissue (as it is elevated also in skeletal muscle & renal tissue) earlier within 1-4 hours - Appears in blood earlier than other markers (within 1-4 hours) high sensitivity So, with high sensitivity BUT - BUT: Returns to normal in 24 hours NOT for delayed admission So, NOT for delayed admission cases (after one day of onset of attack)

12. Cardiac TroponinsCardiac Troponins Protein complex located on the thin filament of striated muscles cTn T, cTn I & cTn C consists of 3 subunits: cTn T, cTn I & cTn C with different structures & functions cTnI & cTnT biomarkers for MI diagnosis cTnI & cTnT are used are biomarkers for MI diagnosis Cardiac troponins (cTn) Cardiac troponins (cTn) are different from skeletal muscle troponins more specific for MI diagnosis So, more specific for MI diagnosis Cardiac Proteins Cardiac Proteins cont.

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

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

15. MarkerDetectable(hours) Peak value (hours)Duration(days) cTn I 4 - 6 12 - 24 Up to 10 CK-MB 3 - 10 12 - 24 1.5 - 3 Myoglobin 1 - 4 121 Total CK 5 - 12 18 - 30 2 - 5 AST 6 - 12 20 - 30 2 - 6 LDH 8 - 16 30 - 48 5 - 14 Time Course for Biomarkers of Myocardial Infarction

16. Diagnosis of Heart Failure Heart failure is a complex clinical condition in which the heart ‘s ability to pump is compromised. The prognosis is poor if untreated, with a two-year survival rate of under 50% The diagnosis can be difficult, especially the presenting symptoms can be due to many diseases. The definitive diagnosis is best by echocardiography ( which can be limited or delayed

17. Diagnosis of Heart Failure  -natriuretic peptide (BNP) BNP is a neurohormone secreted by cardiac myocytes in response to volume expansion & pressure overload, It plays a role in circulatory homeostasis (natriuresis, diuresis & vasodilatation). In heart failureIn heart failure, it increases. So we can differentiate between breathlessness due to cardiac disease or pulmonary cause. The accuracy of its measurement is greatest in patients with more severe disease and poorest in those already receiving treatment