Ischemic heart

disease

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● Boys slides
● Girls slides
● Dr’s notes
● Extra
Objectives
Be able to discuss pathology and complications of ischaemic
1 heart diseases with special emphasis on myocardial infarction.

Know how lifestyle modifications can reduce the risk of

2 ischaemic heart disease.

Know how lifestyle modifications can reduce the risk of

3 ischemic heart diseases
 Ischemic Heart Disease -Helpful video
Definition
IHD = A group of closely related conditions/syndromes caused by an imbalance between
the myocardial oxygen demand and blood supply . Usually caused by decreased coronary
artery blood flow (“coronary artery disease”) .
Ischemia: is an insufficient blood supply
The most common cause if IHD is coronary artery atherosclerosis , and Less commonly it
is due to vasospasm and vasculitis .

Related conditions \ syndromes

Epidemiology of Ischemic
Acute myocardial Chronic ischemic Heart syndromes Disease
infarction heart disease
(with e.g necrosis) with CHF

Angina pectoris Sudden

cardiac death ● Peak incidence: 60y for males
(chest pain) (no and 70y for females.
necrosis)
● Men are more affected than
women. (women has
estrogen for protection).
Pathogenesis of IHD
● Contributing factors are same
as that of atherosclerosis e.g.
1 Role of Critical stenosis
or obstruction

2 Role of Acute Plaque

Change Diabetes mellitus Hypertension

3 Role of Coronary
Thrombus Smoking Genetic factors
(direct or indirect)
4
Role of Vasoconstriction High levels of LDL Lack of exercise
(Cholesterol)
5
Role of Inflammation
 Pathogenesis of IHD
(>=75% of the lumen of one or more)
1- Role of Critical stenosis or
(coronary arteries blocked by atherosclerotic
obstruction, Will lead to
plaque).

Disruption of a mildly stenosing plaque leading

2- Role of Acute Plaque Change
to rupture/ ulceration which can lead to:

1 2 exposure of the pro-thrombogenic

basement membrane just below the
hemorrhage into the atheroma which
endothelial cells → thrombosis → the
will expand in volume formed thrombus will further block the
lumen of the blood vessel

So, Acute plaque

change can cause
myocardial ischemia
in the form of:
a. unstable angina
b. acute myocardial
infarction
c. and sudden
cardiac death
 Cont..

3- Role of Coronary Thrombus superimposed on a

Thrombus disrupted partially occluding plaque
can convert the plaque to either

Thrombus in coronary artery can also

embolize .

1.A total occlusion 2. Or a

partial/incomplete/subtotal
leading to acute
occlusion leading to unstable
transmural MI or
angina, acute subendocardial
sudden death.
infarction, or sudden death.

4- Role of Vasoconstriction reduces lumen size and can therefore

Vasoconstriction potentiate plaque disruption (lumen become more narrow)

5- Role of Inflammatory processes play important roles at all stages

Inflammation of atherosclerosis
A: We have fixed coronary obstruction (Typical Angina), Atherosclerotic
Plaque in the intima blocks 70% of the vessel.

B: Severe Fixed coronary artery, more than 70% is blocked (not important)

C: When the Plaque is disrupted it can lead to D AND E .

D: Mural thrombus with a Non complete obstruction (causes Unstable

angina or acute subendocardial myocardial infarction or sudden death.)

E: When a complete obstruction happen it causes Acute transmural

myocardial infarction or sudden death.

Team 439
 Angina pectoris
Definition
Angina pectoris (Chest pain) ,is a type of IHD characterized by
paroxysmal(episodic) and usually recurrent attacks of substernal or precordial
chest discomfort.

● described as constricting, crushing,

squeezing, choking, or knifelike pain.
● The pain can radiate down the left
shoulder, left arm, neck or left jaw
(called as referred pain).

Cause
Angina pectoris is due to inadequate (lack of) perfusion and is caused by
transient (15 seconds to 15 minutes) myocardial ischemia that falls short of
inducing necrosis i.e. duration and severity is not sufficient to cause
infarction(irreversible injury)

Types of Angina
pectoris

Stable Unstable Variant

angina angina angina
 Types of angina pectoris
Stable Angina Unstable or crescendo Variant (prinzmetal)
(Typical Angina) Angina Angina
● uncommon pattern of
- It is an unstable and
● Is the most common form of episodic angina that occurs
progressive condition.
angina at rest and is due to
- Pain occurs with coronary artery spasm.
Is due to a fixed stenosis.
progressively increasing ● Not related to
The chest pain is episodic. frequency, and is precipitated atherosclerotic disease
● Is caused by atherosclerotic with progressively less ● The etiology is not clear
disease with usually ≥70% exertion or even at rest, and ● Prinzmetal angina
narrowing of lumen (i.e. fixed tends to be of more prolonged generally responds
stable critical stenosis). duration. promptly to vasodilators,
● This reduction (due to ≥ 70% - It is induced by disruption or such as nitroglycerin and
stenosis) of blood flow in rupture of an atheroma calcium channel blockers
coronary vessels makes the plaque (acute plaque change)
heart vulnerable, so triggering:
whenever there is increased
● Platelet aggregation
demand e.g. physical activity,
● Vasoconstriction
emotional excitement, or any
● Formation of a mural
other cause of increased
thrombus that may not be Angina pectoris summary
cardiac workload, there is
occlusive.
angina pain.
● Relieved by rest (i.e. - with superimposed ● intermittent chest pain caused
by transient, reversible
decreasing demand) or with thrombosis and partial ischemia

vasodilators like sublingual occlusion of a coronary ● Typical (stable) angina

- pain on exertion
nitroglycerin. vessels. - fixed narrowing of coronary
Unstable angina is often the artery
● Unstable (pre-infarction) angina
precursor of subsequent - increasing pain with less
acute MI. Thus also called as exertion
- plaque disruption and
preinfarction angina. thrombosis
● Prinzmetal (variant) aIngina
- pain at rest
- coronary artery spasm of
unknown etiology
 Myocardial infarction
-Helpful video

Definition
The death of cardiac muscle (coagulative necrosis) resulting from
ischemia. (the severity or duration of ischemia is enough to cause MI)

Risk factors

● Predisposing factors and risk factors : are the same as those of coronary atherosclerosis.
● Atherosclerosis + age + male gender.
● Females are more affected after menopause due to decreased estrogen production

Sequence of events usually occur:

1 Long standing 2 acute plaque change

3 disruption of the plaque
atherosclerotic plaque

4 thrombus formation 5 ischemia 6 Hypoxia

7 irreversible cell 8 Cardiac muscle necrosis

injury

Note: the thrombus usually evolves to

completely occlude the lumen of the
coronary vessel within minutes
 Cont..
MI common locations
In persons with right dominant coronary artery heart (90% of population) the commonly
affected blood vessels are:

40-50%
Left anterior
- Anterior left ventricle
descending
- Anterior septum
artery - Apex

Up to 20%
Left
Infarct involves lateral left
circumflex Ventricle except the apex

30-40%
Right
Posterior left ventricle
coronary
Posterior septum
artery Right ventricular free wall,sometime

Types

subendocardial
transmural
Inner 1/3 of
myocardium
Full thickness(>50% of the wall)
Two mechanisms

1-Fixed atherosclerosis but with increased demand,vasospasm or hypotension

2-Evolving transmural with relieve of the obstruction (often multifocal)
Pathogenesis of MI
Most common cause is thrombosis on a preexisting disrupted
atherosclerotic plaque. In the typical case of MI, the following sequence
of events usually occur:

Acute plaque change

1 (sudden change in the structure of an atheromatous plaque e.g. disruption,
ulceration, rupture or intraplaque hemorrhage).

2 Exposure of the thrombogenic subendothelial basement membrane

resulting in thrombus formation.

3 Frequently within minutes, the thrombus evolves to completely occlude

the lumen of the coronary vessel.

Severity of ischemia

Severe ischemia lasting at least 20 to 40 minutes causes

irreversible injury and myocardial necrosis on the ultrastructural
level (on electron microscopy)

Myocardial necrosis mostly starts in the sub-endocardial region

(because it is less perfused and has high intramural pressure).

The full size of the infarct is usually determined within 3-6 hours of the
onset of severe myocardial ischemia. During this period,lysis
of the thrombus by treatment with streptokinase or tissue plasminogen
activator, may limit the size of the infarct. So any intervention in this time
frame can potentially limit the final extent of necrosis.
 Con..
The precise location, size, and specific morphologic features of an acute
myocardial infarct depend on:

1 The location, severity, and rate of development of coronary

atherosclerotic obstructions

2 The size of the area supplied by the obstructed vessels

3 The duration of the occlusion

4 The oxygen needs of the myocardium at risk

5 The extent of collateral blood vessels

6 Other factors, such as blood vessel spasm, alterations in blood pressure,

heart rate, and cardiac rhythm.

7 In addition reperfusion may limit the size of the infarct.

 Morphologic changes in MI
- Begins with coagulative necrosis and inflammation (initially neutrophils
and later macrophages)
- Followed by formation of granulation tissue
- Heals by formation of fibrous scar

Gross changes Microscopic changes

0-4h None None
4-12h Mottling Coagulation necrosis
12-24h Mottling Coagulation necrosis , neutrophils come in
Neutrophils die, macrophages come to eat
1-7d Yellow infarct center
dead cells
1-2w Yellow centar, red borders Granulation tissue
2-8 w Scar Collagen

Additional information (girls Dr) From Boys slide

B. Acute coronary thrombosis superimposed

A. plaque rupture without on an atherosclerotic plaque with focal
superimposed thrombus in patient disruption of the fibrous cap,
who died suddenly triggering fatal myocardial infarction
 Cont.

C. Nearly complete removal of necrotic myocytes

by phagocytosis (approximately 7 to 10 days).
B. Dense neutrophilic infiltrate in an area of acute
myocardial infarction of 3 to 4 days' duration.

A. One-day-old infarct showing coagulative

necrosis with few neutrophils, wavy fibers with
elongation, and narrowing, compared with
adjacent normal fibers (lower right).

Healed MI with replacement of the necrotic

fibers by dense collagenous scar. Residual
Granulation tissue approximately 3 weeks post MI cardiac muscle cells are present

Laboratory evaluation
Troponins: best marker, TnT, Tnl (more specific).
- Tnl and TnT are not normally detectable in the circulation
1 - After acute MI both troponins become detectable after 2 to 4 hours, peaks at
48 hours. Their levels remain elevated for 7 to 10 days

CK-MB is the second best marker: (for detecting reinfarction)

2 It begins to rise within 2 to 4 hours of MI, peaks at 24 hours and
returns to normal within approximately 72 hours

Lactate dehydrogenase (LD):

3 Rise 24 hrs, peaks 72 hrs, gradually disappears in 5 to 14 days.

4 Myoglobins
 Clinical features of MI
Diaphoresis (sweating) rapid and weak pulse

cardiogenic shock
dyspnea Symptoms
can be seen in massive
MI (>40% of it. ventricle)

ECG shows typical Pain:

findings of ischemia (the ischemia → release of adenosine, bradykinin → pain)

changes :
• Severe crushing sub-sternal chest pain,
- Q waves ( indicating transmural infarct ) which may radiate to the neck, jaw,
- ST-segment abnormalities epigastrium, shoulder or left arm.
- T-wave inversion • Pain lasts for hours to days and is not
relieved by nitroglycerin.
Extra: • No pain (silent) in 20-30% of patients
(diabetics, hypertensive, elderly).
Non-ST-segment elevation MI (NSTEMI)→ST
depression →subendocardial infarct

ST-segment elevation MI (STEMI)→ST

elevation →transmural infarct
 Complications of MI

- No complications in 10-20%.
- 80-90% experience one or more of the following complications:

1. Myocardial infarction lead to sudden death in some cases, even before reaching
the hospital.
2. Cardiac arrhythmia (75-90%): patients have conduction disturbances → sudden
death esp. in ventricular arrhythmia.
3. Left ventricular failure with pulmonary edema (60%).
4. Cardiogenic shock (10%).
5. Myocardial rupture: rupture of free wall, septum, papillary muscle.
6. Thromboembolism (15-49%): the combination of myocardial abnormality in
contractility (causing stasis) and endocardial damage (due to exposure of
underlying thrombogenic basement membrane) can lead to cardiac thrombosis
and embolism.
7. Pericarditis
8. Infarct extension and expansion
9. External rupture of the infarct with associated bleeding into the pericardial
space (hemopericardium).
10. Ventricular aneurysm (ventricle is dilated and the wall is thinned out).
11. Progressive late heart failure in the form of chronic IHD.

Ventricular wall rupture Septal rupture Papillary muscle rupture

Fibrinous pericarditis Mural thrombus Aneurysm

 {ُ ُ ْ َ َ ُ َ ََ ْ َََ َ ‫ } َو‬: ‫ل‬

‫َ ّ زا‬ ‫ أن أ‬: ‫ا‬ ‫لا‬

Cont. ‫زا‬ ‫و وا‬

Laboratory
due to acute coronary
evaluation Summary of MI
● Troponins increase within artery thrombosis
2-4 hours, remain elevated Girls slide ● sudden plaque disruption
for a week. ● platelets adhere
● CK-MB increases within 1 ● coagulation cascade activated
2-4 hours, returns to ● thrombus occludes lumen within
normal within 72 hours minutes
5 Necrosis of the ● irreversible injury/cell death in
heart caused by
2 20-40 minutes
ischemia

Clinical features
complication 4 3 ● Severe, crushing chest pain
● contractile dysfunction ± radiation
● arrhythmias ● Not relieved by
● rupture nitroglycerin, rest
● chronic progressive heart Prognosis ● Sweating, nausea, dyspnea
failure ● Sometimes no symptoms
● depends on remaining
function and perfusion
● Prompt reperfusion can
salvage myocardium

Chronic ischemic heart disease Girls Dr For your level just this

Progressive heart failure due to ischemic injury, either from:

● prior infarction(s) (most common)
● or chronic low-grade ischemia

sudden cardiac death

Definition: Unexpected death from cardiac causes either without symptoms
or within 1 to 24 hours of symptom onset
→ Results from a fatal arrhythmia, most commonly in patients with severe
coronary artery disease

Acute coronary syndrome (boys slide)

● is applied to three catastrophic manifestations of IHD:
- Unstable angina
- Acute MI
- Sudden cardiac death
 Team Leaders
Aya Alhussain Salem Abo Khanjar

Team Members
Amira Alrashedi Dana alsagheir Faisal alshuaibi
Jumana AL-qahtani Majdoly AlKhodair Nawaf Alzaben
Samiah AlQutub Reema Aldekhail Khalid alhamdi
sahar alhakami Shahad Helmi Abdulmajeed Namshah
Mansour Aldhalaan
Layan alhelal Layla Almeshari
Mohammed Alwahibi
Reuf Alahmari Maisa Alaql Ibrahim Al Hazza

Subleader: Lubna Altamimi

Pathology441@gmail.com