Biochemical Investigations In Heart Disaeses

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

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:

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

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)

- appears one hour earlier than CK-MB activity (more sensitive) 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 troponin I Relative index = CK-MB mass / Total CK X 100 more than 5 % is indicative for MI

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

Cardiac Proteins Myoglobin cytosolic protein - 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)

Troponins Troponins are structural proteins in cardiac myocytes Involved in the interaction between actin and myosin for contraction Troponins are also present in cytosol of cardiac myocytes consists of 3 subunits: cTn T, cTnI & cTn C with different structures & functions

cTn( I & T) are structurally different than muscle troponins . The existence of the cardiac –specific isoform makes them the most specific of all biochemical markers for cardiac damage. Highly specific markers of detecting MI In human heart the cTn are largely insoluble, but 3-5% exits as a soluble cytoplasmic pool.

This gives the biphasic response of troponins with a rapid rise and prolonged elevation. Appears in plasma in 3-4 h after the MI Remains elevated for up to 10 days After a MI, cytosolic troponins are released rapidly into the blood (first few hours) Structurally bound troponins are released later for several days MI can be diagnosed several days after the onset of chest pain

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)

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.

Time-Course of Biochemical Marker 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

Blood samples collected at:. Baseline (upon admission) Blood samples collected at: * Baseline (upon admission) * Between 6 to 12 hours after the onset of symptoms

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

So: B-natriuretic peptide (BNP) It is a neurohormone secreted by cardiac myocytes in response to volume expansion and pressure overload , It plays a role in circulatory homeostasis ( natriuresis, diuresis and vasodilatation). In 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

Reference Book Lecture Notes on Clinical Biochemistry by Geoffry Beckett , Simon Walker ( 7th ed.)