Biochemical Biochemical Investigations In Investigations In Heart Disaeses Heart Disaeses

OverviewOverview•Myocardial infarctionMyocardial infarction•Creatine kinase (CK)/ CK-MBCreatine kinase (CK)/ CK-MB•Lactate dehydrogenase (LDH)Lactate dehydrogenase (LDH)•Aspartate aminotransferase Aspartate aminotransferase (AST)(AST)•MyoglobinMyoglobin•Cardiac troponins I and TCardiac troponins I and T•Time-course of plasma enzyme Time-course of plasma enzyme changeschanges•Natriuretic peptideNatriuretic 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 is the death & necrosis of

myocardial cells as a result of coronary prolonged & myocardial cells as a result of coronary prolonged & irreversible ischemiairreversible ischemia

PreviouslyPreviously:

• 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:

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

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)

• 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 indexRelative index = CK-MB mass / Total CK X 100 = 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

AST is somewhat heart-specific than ALT

A non-specific marker of MI

It appears in liver and other diseases

Aspartate aminotransferase (AST)

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 myocytesconsists 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)

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

Time-Course of Biochemical Marker 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

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.)