Download Congenital heart disease

Cardiac Function Tests
• Heart diseases
• Laboratory diagnosis of AMI
• Markers of inflammation and coagulation
• The role of the lab in monitoring heart
disease
Case-1
An 83-year-old man with known severe coronary artery
disease, diffuse small vessel disease, and significant
stenosis distal to a vein graft from previous CABG
(coronary artery bypass graft) surgery, was admitted when
his physician referred him to the hospital after routine
office visit.
His symptoms included edema, jugular vein distention and
heart sound abnormalities. Significant laboratory data
obtained upon admission were as follows:
Urea nitrogen
53
6-24 mg/dl
Creatinine
2.2
0.5-1.4 mg/dl
Total protein
5.8
6.0-8.3 g/L
Albumin
3.2
3.5-5.3 g/L
Glucose
312
60-110 mg/dl
Calcium
4.1
4.3-5.3 mEq/L
Phosphorus
2.4
2.5-4.5 mg/dl
Total CK
134
54-186 U/L
CK-MB
4
0-5 ng/L
Myoglobin
62
<70g/L
Troponin T
0.2
0-0.1 g/L
 Questions:
1. Do the symptoms of this patient suggest AMI?
2. Based on lab data, would this diagnosis be
AMI? why or why not?
3. Based on the lab data, are there other organ
system abnormalities present?
4. What are the indicators of these organ system
abnormalities?
5. Is there a specific lab data that might indicate
congestive heart failure in this patient?
Heart diseases

Is the primary cause of illness and death in the US

50 000 000 patients have hypertension.

7 600 000 patients suffer a myocardial infarction each year.

4 900 000 patients have been diagnosed with congestive heart
failure.

Improved detection of heart disease  can save lives.

Blood tests detect substances that normally are not present or measure
substances that, when elevated above normal levels, indicate either a
disease or a future risk of the development of a disease.

Selection of appropriate cardiac markers that provide the most effective
and clinically useful indicators of myocardial function is critical.
Heart anatomy
Symptoms of heart disease
Symptoms of heart disease

Patients with cardiac disease are often asymptomatic until a relatively late stage in their
condition.
1. Dyspnea:

Dyspnea is a difficulty in breathing.

The most frequent symptoms manifested in heart disease.

It can be a result of cardiac or respiratory disease and is a normal response during
exercise in healthy individuals.
2. Cyanosis:

A bluish discoloration of the skin.

Result of dyspnea and is caused by an increased amount of nonoxygenated
hemoglobin in the blood.
Symptoms of heart disease
3. Angina pectoris:

Is the most common symptom associated with ischemic
heart disease.

It is a gripping or crushing, central chest pain that may
be felt around or deep within the chest.

The pain may radiate to the neck or jaw.

It is typically worsened by exercise and relieved by rest.

The pain is most often caused by a lack of oxygen to the
myocardium as a result of inadequate coronary blood
flow.
4. Palpitation:

A palpitation may be an increased awareness of a
normal heartbeat or the sensation of a slow, rapid, or
irregular heart rate.
Symptoms of heart disease
4. Syncope:

Partial or complete loss of consciousness with interruption of
awareness of oneself and ones surroundings.

It is temporary and there is spontaneous recovery.

The most common syncopal attacks are vasovagal in nature
(simple faints) and not a result of serious disease.

Without warning, the patient falls to the ground with a slow or
absent pulse and, after a few seconds, the patient recovers
consciousness.
5. Fatigue:

Is a common, but nonspecific, cardiac symptom.

Lethargy (abnormal drowsiness) is associated with heart
failure, persistent cardiac arrhythmia.

It may be a result of both poor cerebral and peripheral
perfusion and poor oxygenation of blood.
Symptoms of heart disease
5. Edema:

Retained fluid accumulates in the feet and ankles of patients.

The edema associated with heart disease is often absent in the
morning because the fluid is reabsorbed when lying down, but
becomes progressively worse during the day.
6. Unusual symptoms

A cough may be the primary complaint in some patients with
pulmonary congestion.

Nocturia (is the need to get up during the night in order to
urinate, thus interrupting sleep) is also common in patients
with congestive heart failure.

Anorexia, abdominal fullness, and weight loss are seen in
patients with advanced heart failure but are rare in mild or
early heart disease.
Heart diseases
1. Congenital heart diseases.
2. Congestive heart failure.
3. Infective heart disease.
Congenital heart disease

Congenital heart defects are important cause cardiac disease and occur
in about 8% of live births. It is a common cause of death in the first
year of life

Congenital heart disease includes:

Valvular defects that interfere with the normal blood flow.

Septal defects that allow mixing of oxygenated blood from the
pulmonary circulation with unoxygenated blood from the
systemic circulation.

Shunts, abnormalities in position or shape of the aorta or
pulmonary arteries.

Tetralogy of Fallot.

or a combination of these conditions.

Many variations and degrees of severity are possible.
Congenital heart disease
 The etiology of congenital cardiac disease is often unknown.
 However, most defects appear to be multifactorial and reflect a combination
of both genetic and environmental influences.
 The rubella virus, the causative agent of German measles.
• Infection of the mother during the first 3 months of pregnancy is
associated with a high incidence of congenital heart disease in the baby.
 Fetal alcohol syndrome is often associated with heart defects, as alcohol
affects the fetal heart by directly interfering with its development.
 Chromosomal abnormalities are associated with several developmental
syndromes, many of which include heart disease, the best-known example is
Down syndrome.
Congenital Cardiac Disease
 The symptoms of congenital heart disease may be
 Evident at birth or during early infancy.
 Or they may not become evident until later in
life.
 Signs and symptoms common to many congenital
heart diseases include cyanosis, pulmonary
hypertension, clubbing of fingers, embolism or
thrombus formation, reduced growth, or syncope.
Cyanosis
Congestive heart failure
Congestive heart failure results when the
heart is unable to pump blood effectively.
 Congestive heart failure may occur if the
heart muscle is weak or if the heart is
stressed beyond its ability to react.
 It is characterized by fluid accumulation,
initially in the lungs and subsequently
throughout the body.
 When the heart is unable to pump
efficiently, cardiac output decreases.
Congestive heart failure
 When the left side of the heart fails  excess fluid accumulates
in the lungs, resulting in pulmonary edema  reduced output to
the systemic circulation  The kidneys respond to this decreased
blood flow with excessive fluid retention  making the heart
failure worse.
 When the right side of the heart fails  excess fluid accumulates
in the systemic venous circulatory system and generalized edema
results. There is also diminished blood flow to the lungs and to the
left side of the heart, resulting in decreased cardiac output to the
systemic arterial circulation.
Causes of congestive heart failure
1. Coronary artery disease:
 Is the most common cause of heart
failure in the United States.
 Atherosclerosis of coronary arteries
leads to ischemia  a process that
replaces active cardiac muscle with
fibrous tissue that does not function
as cardiac muscle.
 Obstruction of the cardiac vessels reduces blood flow and forces the
heart muscle into anaerobic metabolism, producing waste products that
can also damage the tissue cells.
Risk factors for development of arterial plaques
•
Age
•
Sex
•
Family history
•
Hyperlipidemia
•
Smoking
•
Hypertension
•
Sedentary lifestyle
•
Diabetes mellitus
•
Response to stress
Causes of congestive heart failure
2. Cardiomyopathies
 A weakening of the heart muscles or structural changes in these muscles. The
heart is unable to contract efficiently.
 They are grouped as dilated cardiomyopathies, restrictive cardiomyopathies, or
hypertrophic cardiomyopathies.
Causes of congestive heart failure
3. Arrhythmia:
 Malfunction of the cardiac conduction system, may also result in congestive
heart failure.
 Arrhythmia may be caused by ischemia, infarction, electrolyte imbalances, or
chemical toxins.
Congestive heart failure
 Clinical indications of congestive heart failure range from mild
symptoms that appear only on effort to the most advanced
conditions in which the heart is unable to function without
external support.
 Congestive heart failure is readily detectable if it involves a
patient with myocardial infarction, angina, pulmonary problems,
or arrhythmia.
 Congestive heart failure is most commonly investigated because
of dyspnea, edema, cough, or angina.
 Other symptoms, as exercise intolerance, fatigue, and weakness,
are common.
Infective heart disease
 The most common infectious diseases involving the heart are
rheumatic heart disease, infectious endocarditis, and
pericarditis.
 Rheumatic fever is an inflammatory disease of children and
young adults that occurs as a result of complications from
infection with group A streptococci.
 Rheumatic fever is not caused by a direct infection or toxin but
because of the antibodies against the streptococcal antigens
cross-react with similar antigens found in the heart and initiate a
cell-mediated immune response involving macrophages and
lymphocytes.
Ideal Marker?
1.
The marker should be absolutely heart specific to allow reliable diagnosis
of myocardial damage in the presence of skeletal muscle injury.
2.
The marker should be highly sensitive to detect even minor heart damage.
3.
The marker should be able to differentiate reversible from irreversible
damage.
4.
In acute myocardial infarction, the marker should allow monitoring of
reperfusion therapy and estimation of infarct size and prognosis.
5.
The marker should be stable and the measurement rapid, easy to perform,
quantitative, and cost effective.
6.
The marker should not be detectable in patients who do not have
myocardial damage.
Lab diagnosis of AMI
• Enzymes
AST, LD
Creatinine kinase, CK-MB
• Cardiac proteins
Myoglobin
Troponin T and troponin I
Lab diagnosis of AMI
Enzymes:
AST and LD
 These enzymes were used as indicator for MI but they are no
longer used in diagnosis because of lack of specificity to
cardiac cells.
Creatine kinase (CK)
 Creatine kinase (CK) is a
cytosolic enzyme involved
in the transfer of energy in
muscle metabolism.
 It is a dimer comprised of
two subunits (the B, or
brain form, and the M, or
muscle form), resulting in
three CK isoenzymes.
Creatine kinase (CK)
 CK-BB isoenzyme is of brain origin and only found in the
blood if the blood-brain barrier has been breached.
 CK-MM isoenzyme accounts for most of the CK activity in
skeletal muscle.
 CK-MB has the most specificity for cardiac muscle, even
though it accounts for only 3-20% of total CK activity in the
heart, it can be used as a marker of early AMI.
CK-MB
 CK-MB is a valuable tool for the diagnosis of AMl
because of its relatively high specificity for cardiac
injury.
 It takes at least 4-6 hours from onset of chest pain
before CK-MB activities increase to significant levels
in the blood.
 Peak levels occur at 12-24 hours, and serum activities
usually return to baseline levels with 2-3 days
CK-MB
 CK-MB activity assays have been increasingly replaced by CK-MB mass
assays that measure the protein concentration of CK-MB rather than its
catalytic activity.
 These laboratory procedures are based on immunoassay techniques using
monoclonal antibodies and have fewer interferences and higher analytic
sensitivity than activity-based assays.
 Mass assays can detect an increased concentration of serum CK-MB about 1
hour earlier than activity-based methods.
 To increase specificity of CK-MB for cardiac tissue, it has been proposed that
that a ratio (relative index) of CK-MB mass/CK activity be calculated  If
this ratio exceeds 3, it is indicative of AMI rather than skeletal muscle damage.
 CK isoforms may be effectively used as indicators of reperfusion after
thrombolytic therapy in patients with confirmed AMI.
Cardiac Proteins
Myoglobin:
 An oxygen-binding heme protein.
 It is rapidly released from striated muscles (both skeletal and cardiac muscle)
when damaged.
 Because of the abundance of myoglobin in cardiac and skeletal muscle tissue,
the upper reference limit of serum myoglobin directly reflects the patient's
muscle mass and, therefore, varies with gender, age, and physical activity.
 However, because of its small size, myoglobin is rapidly cleared by the kidneys,
making it an unreliable long term marker of cardiac damage.
Myoglobin
 Myoglobin is significantly more sensitive than CK and CK-MB activities during the first
hours after chest pain onset:
 It rises 1-4 hours
 Peaks 6-9 hours
 Returns to normal 18-24 hours
 If myoglobin concentration remains within the reference range 8 hours after onset of
chest pain, AMI can essentially be ruled out.
 CK-MB determinations are preferable over myoglobin in:
 patients who are admitted later than 10-12 hours after chest pain onset because the
myoglobin concentration may have already returned to reference ranges within that
time frame.
 patients with renal disease (renal failure) because myoglobin will be consistently
increased as a result of decreased clearance by the diseased kidneys.

Myoglobin can be used as an indicator of reinfarction.
 A persistently normal concentration will rule out reinfarction in patients with recurrent chest
pain after AMI.
Troponins
 Enzymes, electrolytes, and proteins are integrated to convert the chemical
energy of ATP to into mechanical work and allow the muscle to contract.
 Actomyosin, ATPase, calcium, aktin, myosin, and a complex of three proteins
known as troponin complex are major participants in muscle contraction.
 The three polypeptides of the troponin complex are troponin T, troponin I, and
troponin C.
 Troponin C is not heart specific.
 Unlike CK-MB, the serum troponins are not found in the serum of healthy
individuals.
 The cardiac troponins may be released in reversible ischemia as well as
irreversible myocardial necrosis.
Troponin T
Troponin T (TnT)
 Allows for both early and late diagnosis of AMI.
 Serum concentrations of TnT:
 Begin to rise within a few hours of chest pain onset and peak by day 2.
 A plateau lasting from 2 to 5 days.
 The serum TnT concentration remains elevated beyond 7 days before
returning to reference values.
 The early appearance of TnT gives no better diagnostic information than CKMB or myoglobin concentrations within the first 4 hr, but the sensitivity of TnT
for myocardial infarct is 100% from 12 hours to 5 days after chest pain onset.
 Also, the degree of elevation of TnT after AMI is significant, often up to a 200fold increase over the upper limit of reference intervals.
Troponin T
 TnT concentrations are particularly useful for diagnosing myocardial
infarction in patients:
 Who do not seek medical attention within the usual 2- to 3-day window
during which total CK and CK-MB are elevated.
 It is also useful in the differential diagnosis of myocardial damage in
patients with cardiac symptoms as well as skeletal muscle injury because
the TnT results will clearly and specifically indicate the extent of the
cardiac damage.
 Cardiac TnT also has value in monitoring patients after reperfusion of an
infarct-related coronary artery.
 The degree of elevation of TnT on days 3-4 after AMI can also be used as a
practical and cost-effective estimate of myocardial infarct size.
Troponin I
 Troponin I (TnI) is only found in the myocardium making it extremely specific for
cardiac disease.
 It is also found in much higher concentrations than CK-MB in cardiac muscle,
making it a sensitive indicator of cardiac injury.
 TnI is not found in detectable amounts in the serum of patients with multiple
injuries or athletes after strenuous exercise, in patients with acute or chronic
skeletal muscle disease, in patients with renal failure, or in patients with elevated
CK-MB, unless myocardial injuries are also present.
 TnI is a good biochemical assessment of cardiac injury in critically ill patients,
those with multiple organ failure, and situations in which CK/CK-MB elevations
may be difficult to interpret.
 Time profile
 Increases above the reference range 4 and 6 hours after the onset of chest pain
 Peaks 12-18 hours
 Returns to reference values in about 6 days
Markers of inflammation and coagulation
disorders
 Studies have evaluated several acute phase proteins as potential
markers for cardiovascular risk assessment.
 There is evidence that C-reactive protein (CRP) is a reliable predictor
of acute coronary syndrome risk.
 CRP is an acute phase reactant produced primarily by the liver.
 CRP is a sensitive marker for ongoing chronic inflammation that is not
affected by ischemic injury.
 It rises significantly in response to injury, infection, or other
inflammatory conditions.
 is not present in appreciable amounts in healthy individuals.
hs-CRP
 Reliable, automated high sensitivity assays for CRP (hs-CRP) exist that allow detection
of the small increases of CRP often seen in cardiac disease
 Epidemiologic data document a positive association between hs-CRP and the prevalence
of coronary artery disease.
 Elevated baseline levels of hs-CRP are correlated with higher risk of future
cardiovascular morbidity and mortality among those with and without clinical evidence
of vascular disease.
 hs-CRP also demonstrates prognostic capacity in those who do not yet have a diagnosis
of vascular disease
 The level of CRP has been shown to correlate with future risk as follows:
CRP level less than 1mg/L: lowest risk
CRP levels of 1 to 3mg/L: intermediate risk
CRP greater than 3mg/L: highest risk
D-Dimer
 D-Dimer is the end product of the ongoing process of thrombus formation and
dissolution that occurs at the site of active plaques in acute coronary syndromes.
 Because this process precedes myocardial cell damage and release of protein
contents, it can be used for early detection.
 It remains elevated for days so it may be an easily detectable physiologic marker of
an unstable plaque even when the troponins or CK-MB are not increased,
potentially identifying high-risk patients
 D-Dimer lacks specificity for cardiac damage as it is increased in other conditions
that cause thrombosis.
 Elevations of D-Dimer have been shown to be useful in predicting risk for
future cardiac events.
Markers of congestive heart failure
 Brain-type, or B natriuretic peptide (BNP), is a peptide hormone
secreted primarily by the cardiac ventricles.
 Diagnosis of congestive heart failure (CHF) is difficult because
of its nonspecific symptoms, as well as the lack of a specific
biochemical marker:
Patients with a BNP < 20 pmol/L are unlikely to have CHF
Patients with BNP > 20 pmol/L have a high probability of
CHF
 BNP may also be clinically relevant in determining the prognosis
of patients.
The role of lab in monitoring heart disease
The laboratory's role in monitoring heart function primarily involves:
 Measuring the effects of the heart on other organs, such as the lungs, liver and kidney.
 Arterial blood gases measure the patient's acid-base and oxygen status 
determine the respiratory acidosis and elevated carbon dioxide levels that are often
seen in patients with heart disease.
 Osmolality: The patient with cardiac disease may develop edema and fluid retention
and ionic redistribution.
 Serum electrolyte determinations, including sodium, potassium, chloride, and
calcium, are important to monitor diuretic and drug therapy in patients with heart
disease.
 Elevations of AST, ALT and ALP are often seen in patients with chronic right
ventricular failure and GGT value elevated in congestive heart failure, suggesting
liver congestion and damage.
The role of lab in monitoring heart disease
 Lipid evaluation will assess risk for coronary artery disease:
 Maintenance of near normal HDL-cholesterol, LDLcholesterol, and triglyceride
levels is highly recommended for cardiac patients.

Determination of a lipoprotein similar to LDL may also be indicated as it is an
independent risk factor associated with development of premature coronary artery
and vascular disease.
 The patient who has secondary heart failure due to thyroid dysfunction can be identified by
a highly sensitive thyroid-stimulating hormone assay.
 The laboratory is also invaluable for monitoring therapeutic drugs following the diagnosis
of heart disease.
 The routine blood count:
 Important for detecting anemia and infection
 Blood cultures:
 To identify infections associated with pericarditis, endocarditis and valvular problems
The End