Biochemical Biochemical Investigations In Investigations In Heart Disaeses Heart Disaeses

OverviewOverview•Myocardial infarctionMyocardial infarction•Time-course of plasma enzyme Time-course of plasma enzyme changeschanges•Creatine kinase (CK)Creatine kinase (CK)•Lactate dehydrogenase (LDH)Lactate dehydrogenase (LDH)•Aspartate aminotransferase Aspartate aminotransferase (AST)(AST)•MyoglobinMyoglobin•Cardiac troponins I and TCardiac troponins I and T

Acute Coronary Syndromes

Similar pathophysiology

Similar presentation and early management rules

STEMI requires evaluation for acute reperfusion intervention

Unstable Angina

Non-ST-Segment Elevation MI (NSTEMI)

ST-Segment Elevation MI (STEMI)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):

1.Typical history of chest pain2.Presence of ECG changes3.Rise of biochemical markers With the advent of troponins, which is

more sensitive biochemical marker, new definition:

Types of Biochemical Markers1- 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

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)

Cardiac Troponins

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

AST is somewhat heart-specific than

ALT

A non-specific marker of MI

It appears in liver and other diseases

Aspartate aminotransferase (AST)

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 enzyme changes

• 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(hours)

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 12-24 Up to 10