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Cardiac
Function
The Heart
The heart is a muscular organ
responsible for pumping blood
through the blood vessels by
repeated, rhythmic
contractions.
 Size of human fist
 Weighs 250-350 g

o The primary function of the heart is to
pump blood in order to generate and
sustain an arterial blood pressure necessary
to provide adequate perfusion of organs.
Pathologic Conditions Of The Heart
Cardiovascular disease (CVD) is a
condition that affects an estimated 80
million adults in the US.
 CVD is responsible for the deaths of
approximately 2,400 Americans daily.
 Timely and accurate diagnosis is essential,
 But even today, this is difficult due to the
lack of tests available to provide
information quickly enough to be
beneficial to those presenting with chest
pain.

Role of Laboratory
 The
laboratory has been used
primarily:

to assess cardiac disease, such as acute
myocardial infarctions (AMIs),

and offer body chemistry information to
aid supportive cardiac therapy.
 Use
of laboratory results still supports
diagnosis of AMI but also assesses risk
for future cardiac disease
Role of Laboratory
 This
is performed through analysis of
body chemistry metabolites, such as:

total cholesterol,

high-density lipoprotein

cholesterol,

and high-sensitivity C-reactive protein.
 Risk
factor assessment enables
health-care professionals to educate
the patient and to start activities that
will reduce risk for an AMI.
Common Symptoms of Heart Disease
 Dyspnea
‫ضيق التنفس‬
 Chest pain
 Cyanosis ‫الزرقة‬
 Palpitations ‫الخفقان‬
 Fatigue ‫التعب‬
 Edema
Heart Diseases


Congenital heart disease or Congenital
Cardiovascular Defects (CCVDs)

Abnormalities arising from the abnormal
formation of the heart or its major blood vessels

There are a number of genetic tests available
that may assist in the diagnosis of CCVDs
Congestive heart failure

Clinical syndrome that results from any disorder
that impairs the ability of the ventricle to fill with
or eject blood
Heart Diseases

Hypertensive heart disease
a general term used to describe heart diseases
caused by direct or indirect effects of elevated BP
 Hypertension is defined as persistent systolic blood
pressure (BP) of at least 140 mm Hg and/or
diastolic pressure of at least 90 mm Hg
 Data have established that death from ischemic
heart disease and stroke increases progressively
and linearly
 every 20 mm Hg systolic or 10 mm Hg diastolic
increase in BP, there is a doubling of mortality from
ischemic heart disease and stroke.

Heart Diseases
 Acute

Coronary Syndromes
A general term used to describe the
following series of events:
 Angina
(‫(الذبحة الصدرية‬, reversible tissue
injury, myocardial infarction (MI), and
extensive tissue necrosis.

The major cause of ACS is
atherosclerosis
Heart Diseases
 Infective


heart disease
Infectious agents have been associated
with a variety of heart diseases
The most common heart diseases
caused by infectious agents are:
rheumatic heart disease,
 infective endocarditis,
 and pericarditis.

Diagnosis of Heart Disease


Single diagnostic laboratory test that assess
cardiac function does not exist
The ideal marker for heart disease should
have the following criteria:
1.
2.
3.
4.
5.
It should be absolutely heart specific.
It should be highly sensitive to detect even minor
heart damage.
It should be able to differentiate reversible from
irreversible damage.
In acute myocardial infarction "AMI" the marker
should estimate infarct size and prognosis.
The marker should be stable, rapid and easy to
perform and cost effective.
Laboratory Diagnosis of AMI
 Enzymes

Creatine kinase "CK"
 Involved
in the transfer of energy in
muscle metabolism.
 Isoenzymes
 CK-MB
CK-BB, CK-MB & CK-MM
"CK2" isoenzyme is the most
specific for cardiac muscle eventhough
it accounts for only 20% for total CK
activity in the heart.
Laboratory Diagnosis of AMI- CK enzyme
Total CK activity in early AMI has great
specificity "80%".
 CK-MB takes 4-6 h from onset of chest pain
before it can be detected in significant levels.
 Peak levels occur at 12-24 h, it returns to normal
in 2-3 days.
 Calculation of a relative index (CK-MB mass
assay/total CK × 100) may be used as an
indicator of MI.
 Allows the distinction between increased total
CK due to myocardial damage and that due to
skeletal or neural damage.
 A relative index exceeding 3 is indicative of AMI.

Laboratory Diagnosis of AMI- CK enzyme
 CK-MB mass assay
 It measures the protein concentration of CKMB rather than its catalytic activity.
 Laboratory procedures are based on
immunoassay techniques using monoclonal
antibodies.
 It is more sensitive and have fewer
interferences than activity-based assays.
 Mass assays can detect an increased serum
concentration of CK-MB about 1 h earlier than
activity-based assay.
Cardiac Proteins
 Myoglobin




It is more sensitive than CK and CK-MB
activities during the first hours after chest
pain onset.
It starts to rise within 2-4 h and is
detectable in all AMI patients between 69 h from chest pain onset.
It returns to baseline levels within 18-24 h.
If conc. remain within the reference range
8 hours after the onset of chest pain, AMI
can essentially be ruled out.
Cardiac Proteins - Myoglobin
 Myoglobin
is rapidly cleared by
the kidneys as it is small in size
 Myoglobin should not be used for
early diagnosis of AMI in patients
with renal disease because of its
decreased clearance.
Cardiac Proteins
Troponin


The preferred biomarkers for assessment of
myocardial necrosis
Complex of 3 proteins that
bind to filaments of striated
muscle (cardiac & skeletal)




Troponin T (TnT)
Troponin I (TnI)
Troponin C (TnC)
The major function of
troponins is to bind calcium
and regulate muscle
contraction.
Cardiac Proteins - Troponin

Troponin T "TnT"






It allows for both early and late diagnosis of AMI.
Serum concentrations of TnT begins to rise within
4-10 hours of chest pain onset and peak by day
2, a plateau lasting from 2-5 days usually follows.
It remains elevated beyond 7 days before
returning to reference values.
Unlike CK-MB, the serum troponins are not found
in the serum of healthy individuals.
The sensitivity of TnT for detecting AMI is 98% from
12 h – 5 days after chest pain onset.
It is useful for diagnosis of AMI in patients who do
not seek medical attention within 2-3 days.
Cardiac Proteins - Troponin
 Troponin



I "TnI"
TnI increases within 4 - 6 hours after chest
pain onset,
Peaks at 12-18 hours, and returns to
within reference limits in about 6 days
TnT tends to remain elevated longer and
maintain higher sensitivity after day 7
after infarct than TnI.
Markers of Inflammation and
Coagulation Disorders
Inflammation plays a role in
atherosclerotic plaque formation, and
acute coronary syndrome.
 Inflammatory cells, cytokines, and other
biomolecules have been considered as
potential markers for the assessment of risk
for the development of such events
 several studies have identified such
biomarkers of inflammation over recent
years including high-sensitivity C-reactive
protein (hsCRP)

Markers of Inflammation and
Coagulation Disorders
 High




Sensitivity Assay for CRP ”Hs-CRP”
CRP is an acute-phase reactant
produced primarily by the liver.
It increases rapidly with inflammation.
It rises in response to injury, infection, or
other inflammatory conditions, it is
nonspecific.
CRP may be considered as a risk factor
marker for cardiovascular disease.
Markers of Inflammation and Coagulation Disorders
High Sensitivity CRP ”Hs-CRP”



There is evidence that CRP is a reliable
predictor of acute coronary syndrome
risk.
A positive association between hs-CRP
and the prevalence of coronary artery
disease.
A mild elevation of baseline levels of hsCRP among apparently healthy
individuals is associated with higher longterm risk for future cardiovascular events.
Markers of Congestive Heart Failure
"CHF"
 Brain-type Natriuretic Peptide "BNP"
 BNP is a peptide hormone secreted primarily by
the cardiac ventricle.
 BNP acts on the renal glomerulus to stimulate
urinary excretion of Na (similar to atrial natriuretic
peptide)
 Plasma concentrations of BNP are increased in
diseases characterized by an expanded fluid
volume e.g renal failure, primary aldosterodism
and CHF.
 Patients with a BNP concentration < 20 pmol/L
are unlikely to have CHF and those with results
above this concentration have a high probability
of CHF.
Other markers

Glycogen phosphorylase isoenzyme BB





It is an isoenzyme of glycogen phosphorylase.
This isoform of the enzyme exists in cardiac (heart)
and brain tissue.
Improve early diagnosis in acute coronary
syndrome.
A rapid rise in blood levels can be seen in
myocardial infarction.
Heart Fatty Acid-Binding Protein.

small cytoplasmic protein (15 kDa) released from
cardiac myocytes following an ischemic episode
Other markers

Homocysteine:



Formed from metabolic demethylation of
methionine
Many studies demonstrated the link between high
levels of homocysteine and increase risk of CVD
Mechanisms include:



Induce damage to vascular endothelium
Accelerate thrombin formation
Promotion of lipid peroxidation
Case Study




Joe is an overweight 57-year-old male who was
mowing his lawn when he experienced a sharp
chest pain along with pain in his left arm.
His wife rushed him to the hospital, fearing that he
was having a heart attack.
In the clinic, the physician examined Joe and
sent him for electrocardiogram (ECG) and blood
work.
The blood is processed in the clinical laboratory
and the serum is tested for troponins, creatine
kinase (CK), and creatine kinase isoenzyme MB
(CK-MB).
Investigations & Comment
All of these cardiac biomarkers are
elevated.
 There is a high likelihood that Joe had a
myocardial infarction.
 These results, combined with ECG, history,
and physical examination, were used to
make the diagnosis of AMI.

Case Study




A 62-year-old woman was admitted to the ED
by ambulance. Her husband says she fell down
some stairs and injured her right leg.
He also reveals that she had some chest pain
and discomfort in her left arm a couple of days
ago, but did not let him call her physician.
She thought she might have some indigestion
and so brushed away her husband’s concerns.
They order a chemistry metabolic profile, a
CBC, and right leg x-rays to determine what
may be wrong with her. The treating physician
also requests cardiac markers on Lindsey.
Investigations & Comments
 Her
troponin level was elevated,
indicating that she had experienced
an AMI but delayed in seeking
diagnosis.
Comments
Because of the time frame, troponin was
the only cardiac marker that still showed a
clear indication that an MI had occurred.
 The CK-MB was within normal limits
because it returns to normal level after
peaking 18 to 24 hours post-MI.
 The LD flip was not clear cut, although the
LD1 was at the same level as the LD 2,
indicating that the LD1 was elevated.
 The troponin level is clearly above the
upper limit of the reference range and so
demonstrates that an MI has occurred.
