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ISCHAEMIC HEART

DISEASE
Prof Kamani Samarasinghe

Definition

IHD is defined as acute or chronic form


of cardiac disability arising from an
imbalance between
the myocardial supply
and
demand for oxygenated blood.

IHD is the leading cause of death in


developed countries.

Etiopathogenesis

IHD is invariably caused by disease


affecting the coronary arteries

IHD=Coronary Artery Disease

Atherosclerosis accounting for


more than 90% of cases
Other causes are responsible for
less than 10% of cases.

Aeitiology
(1) Coronary atherosclerosis
(2)Superadded changes in
coronary
atherosclerosis.
(3) Non-atherosclerotic causes

Coronary atherosclerosis

Distribution- involve one or more of the


three major coronary arterial trunks.
Highest incidence Anterior
descending branch of left coronary
artery
Right coronary
Circumflex branch of left coronary
artery

1/3 has single vessel disease,most


often left ant. descending
involvement
1/3 2 vessel disease
1/3 3 major vessel disease.

Location- Almost all adults show


atherosclerotic plaques scattered
throughout the coronary arterial system.

Significant stenotic lesions that may


produce myocardial ischaemia show more
than 75% (3/4) reduction in the cross
sectional area of a coronary artery.

Most often severe involvement is about 34cm from the coronary ostia at or near
the bifurcation of the arteries.

Fixed atherosclerotic plaquesAtherosclerotic plaques in coronary


arteries are more often
eccentrically located.
Occasionally there may be
concentric thickening of the wall,
producing luminal narrowing that
will eventually lead to fixed
coronary obstruction.

Superadded changes in
coronary atherosclerosis

The attacks of acute coronary


syndromes (MI,Unstable angina
,sudden ischaemic death) are
precipitated by sudden changes in
chronic plaques

Acute changes in chronic


plaque
(a)
(b)
(c)
(d)
(e)
(f)

Plaque hemorrhage
Fissuring
Ulceration
Thrombosis
Embolization of atheromatous debris
Local platelet aggregation and
coronary artery spasm.

Coronary artery
thrombosis

Coronary artery
thrombosis

Coronary artery
thrombosis

Coronary atherosclerosis
with hemorrhage

Non-atherosclerotic causes

In less than 10% of cases.


(a) Vasospasm
(b) Stenosis of coronary ostia
extension of syphilitic aortitis

(c )Arteritis- Polyarteritis nodosa Burgers disease


Takayasu disease Kawasaki disease

(d) Embolism Infective endocarditis

e) Thrombotic diseases PRV ,sickle cell


anaemia ,TTP

(f) Aneurysm
(g)Trauma
(h) Compression -tumours

Effects of Myocardial
Ischaemia
There is a wide range of coronary
ischaemic manifestations.
- Asymptomatic state
- Angina
- Myocardial infarction
-Chronic ischaemic heart disease
- Sudden cardiac death

Angina Pectoris

Episodic ischemic cardiac pain


constricting, squeezing, choking, or
knifelike)
Substernal /precardial
Resulting from transient myocardial
ischaemia (15 sec.15 min)
Reduced perfusion, but NO infarction
3 types of angina

Angina Pectoris
(a)

Stable or Typical angina

(b)

Prinzmetals angina

(c)

Unstable or crescendo angina

Stable angina

Most common
Pain following physical exersion or
emotional excitement and relieved
by rest and nitrates.

Chest pain caused by the build up of


lactic acid and irritation to the
myocardial nerve fibers.

The pathogenesis is chronic stenosing


coronay atherosclerosis

During the attack there is depression


of ST segment in ECG due to poor
perfusion of subendocardial region
Enzymes are not elevated

Variable/Prinzmetal/Spasm

uncommon
Transient ischemia that occurs
unpredictably and almost always at rest.

caused by coronary artery spasm

ST segment elevations due to


transmural ischaemia will be noted.

Although individuals with Prinzmetal


variant angina may well have
significant coronary atherosclerosis,
the anginal attacks are unrelated to
physical activity, heart rate, or
blood pressure.

Prinzmetal angina generally


responds promptly to vasodilators,
such as nitroglycerin and calcium
channel blocker

Unstable /crescendo
increasingly frequent pain,
angina

of prolonged duration
precipitated by progressively lower levels of
physical activity or that even occurs at rest.
Tends to last greater than 15 minutes.
This results in reversible myocardial
ischemia but is a sign that an infarct is soon
to come.
ECG will reveal ST segment depression and T
wave inversion.

Caused by the disruption of an


atherosclerotic plaque with
superimposed partial thrombosis
and possibly embolization or
vasospasm or both.

Serves as a warning that an acute


MI may be imminent; indeed, this
syndrome is sometimes referred to
as preinfarction angina.

Coronary Artery Pathology in Ischemic Heart Disease


Plaque
Plaque-Associated
Stenose Disruptio
Thrombus
s
n
Stable angina
Unstable
angina
Syndrome
Transmural MI

>75% No
Variabl
e
Variabl
e

Frequen
t
Frequent

Subendocardial Variabl
e
MI
Sudden death Usually

Variabl
e

severe

Frequent

No
Nonocclusive
Occlusive
Widely variable, may be
absent, partial/complete, or
lysed
Often small platelet
aggregates or thrombi
and/or thromboemboli

Myocardial Infarction
Heart attack

Most important consequence of


coronary artery disease.

Many patients may die within the


first few hours while the remainder
suffer from effects of impaired
cardiac function.

MI can occur at virtually any age


Nearly 10% of myocardial infarcts occur in
people under age 40
45% occur in people under age 65.
Throughout life, men are at significantly
greater risk than women.
women are protected against MI and other
heart diseases during the reproductive years.
Following menopause IHD is the most
common cause of death in women.

Etiopathogenesis

Sudden change in an atheromatous plaque


(intraplaque hemorrhage, erosion or ulceration
rupture ,fissuring)
exposed to subendothelial collagen and
necrotic plaque contents
platelets adhere
become activated
release their granule contents, and aggregate
to form microthrombi.

Vasospasm is stimulated by
mediators released from platelets.

Tissue factor activates the


coagulation pathway, adding to the
bulk of the thrombus

Within minutes, the thrombus


evolves to completely occlude the
lumen of the vessel.

myocardial ischemia
Cessation of aerobic metabolism within
seconds
inadequate production of ATP
Accumulation of potentially noxious
metabolites such as lactic acid
Severe ischemia induces loss of
contractility within 60 seconds.
can precipitate acute heart failure long
before myocardial cell death.

Severe ischemia lasting 20 to 30


minutes or longer leads to irreversible
damage (necrosis) of cardiac
myocytes.

Ultrastructural evidence of irreversible


myocyte injury develops only after
prolonged, severe myocardial ischemia
(such as occurs when blood flow is 10%
or less of normal).

MYOCARDIAL
RESPONSE

Feature

Time

Onset of ATP depletion

Seconds

Loss of contractility

<2 min

ATP reduced

to 50% of normal

10 min

to 10% of normal

40 min

Irreversible cell injury

2040 min

Microvascular injury

>1 hr

In most cases of acute MI, permanent damage


to the heart occurs when the perfusion of the
myocardium is severely reduced for about 2 to
4 hours
This delay in the onset of permanent
myocardial injury provides the rationale for
rapid diagnosis in acute MIto permit early
coronary intervention, the purpose of which is
to establish reperfusion and salvage as much
at risk myocardium as possible.

PROGRESSION OF
NECROSIS

Necrosis begins in a small zone of the


myocardium
beneath
endocardial surface in
Progression
ofthe
myocardial
the center of the ischemic zone.
necrosis after coronary artery
The area that depends on the occluded vessel for
occlusion
perfusion
is the at risk myocardium
A very narrow zone of myocardium immediately
beneath the endocardium is spared from necrosis
because it can be oxygenated by diffusion from
the ventricle.

Areas of myocardium perfused


by the three major coronary
arteries
Left anterior descending branch of
the left coronary artery (LAD) -apex
of the heart ,the anterior wall of the
left ventricle, and the anterior two
thirds of the ventricular septum.
Coronary artery that perfuses the
posterior third of the septum is
called dominant).

In a right dominant circulation


present in approximately four fifths
of individuals, the LCX perfuses only
the lateral wall of the left ventricle,
RCA supplies the entire right
ventricular wall, the posterobasal
wall of the left ventricle, and the
posterior third of the ventricular
septum.
Thus, occlusions of the RCA can
cause left ventricular damage

Morphology

There are 2 types of MI with


different morphology and clinical
significance.
Transmural infarct- 90-95%
Subendocardial infarct- 5-10%

Transmural infarct
Ischaemic necrosis involves the
full thickness or nearly full
thickness of the ventricular wall in
the distribution of a single
coronary artery.

Cont..

In about 90% of cases transmural


infarcts are associated with
- severe coronary atherosclerosis
- acute atheromatous plaque change
- build up of a platelet mass giving
rise to embolism or thrombosis
- vasospasm

In a minority (10%) transmural


infarcts are due to non
atherosclerotic causes.
eg: arteritis
embolism
vasospasm
coronary ostial stenosis

Subendocardial (laminar)
Infarcts

Ischaemic necrosis is limited to the


inner 1/3 or inner of the ventricular
wall, often extending laterally beyond
the perfusion territory of a single
coronary artery.
Subendocardial zone is normally the
least well perfused region and therefore
most vulnerable to any reduction in
coronary blood flow.

In great majority of subendocardial


infarcts there is stenosing coronary
atherosclerosis and global
reduction in coronary blood flow
without acute plaque change.

However, subendocardial infarcts can also


result from prolonged, severe reduction in
systemic blood pressure, as in shock
superimposed on chronic, otherwise
noncritical, coronary stenoses.
The subendocardial infarcts that occur as
a result of global hypotension, myocardial
damage is usually circumferential, rather
than being limited to the distribution of a
single major coronary artery.

Transmural
infarct

Subendocardial
infarct

1.Definition

Full thickness

Inner 1/3-1/2

2.Frequency

90-95%

Less frequent

3.Distribution

Area of a
coronary
artery

circumferential

4.Pathogenesi Athero. with


s
acute plaque
change

hypoperfusion

5.Coronary
thrombosis

Less common

common

6.pericarditi Common

none

Characteristic ECG
changes
Transmural infarcts are often referred
to as ST elevation infarcts
Subendocardial infarcts are known as
non-ST elevation infarcts

Frequencies of critical
narrowing and

Pathologic changes
Changes vary according to the age of the
infarct and survival of the patient
Gross appearance
Most occur singly and vary in size.

Found most often in the ventricle.

Transmural infarcts have a thin rim of


preserved subendocardial myocardium.

Subendocardial infarcts produce less well


defined gross changes.

TIMING of Gross and Microscopic Findings

GROSS
4 hr

None

412 hr

Occasionally dark
mottling
Dark mottling

1224
hr

13 days Mottling with yellow-tan


infarct center
37 days Hyperemic border;
central yellow-tan
softening
710 daysMaximally yellow-tan
and soft, with
depressed red-tan
margins
1014 days
Red-gray
depressed
infarct borders

MICROSCOPIC
Usually none; variable waviness of fibers at
border
Beginning coagulation necrosis; edema;
hemorrhage
Ongoing coagulation necrosis; pyknosis of
nuclei; myocyte hypereosinophilia;
marginal contraction band necrosis;
beginningnecrosis,
neutrophilic
Coagulation
with infiltrate
loss of nuclei and
striations; interstitial infiltrate of
neutrophils
Beginning disintegration of dead myofibers,
with dying neutrophils; early phagocytosis
of dead cells by macrophages at infarct
border
Well-developed phagocytosis of dead cells;
early formation of fibrovascular granulation
tissue at margins
Well-established granulation tissue with new
blood vessels and collagen deposition

28 wk Gray-white scar, progressiveIncreased collagen deposition, with decreased


from border toward core
cellularity
of infarct
>2 mo

Scarring complete

Dense collagenous scar

Myocardial Infarction(1-2
days)

Myocardial infarction (3-4


days)

Myocardial infarction

Myocardial infarction (1-2


weeks)

Old subendocardial infarct

MIs less than 12 hours old are usually not


apparent on gross examination.
If the patient died 2 to 3 hours after the
infarct it is possible to highlight the area of
necrosis by immersion of tissue slices in a
solution of triphenyltetrazolium chloride.
This histochemical stain gives a brick-red
color to intact, noninfarcted myocardium
where lactate dehydrogenase activity is
preserved.
Because dehydrogenases leak out from
dead cells, an infarct appears as an
unstained pale zone

1 day (pyknosis, waviness)


3-4 days (neutrophils)
7 days (macrophages)
Weeks (organization)
Months (fibrosis)

Salvage in early infarcts

Ischaemic injury to myocardium is


reversible if perfusion is restored
within 30 mits
Methods1) Thrombolytic therapy with
various fibrinolytic agents such as
streptokinase and tissue
plasminogen activator

Percutaneous transluminal
coronary angioplasty (PTCA)
Stent placement
Coronary artery bypass surgery

Reperfusion

Thrombolytic therapy.

Thrombolysis re-establishes the


patency of the occluded artery.

Reperfusion

Grossly-reperfused infarcts are


hemorrhagic
Microscopy-irreversibly injured myocytes
often have necrosis with contraction
bands.
These are produced by hypercontraction
of myofibrils in the dying cell that has
damaged membranes after ischaemia
due to exposure to plasma calcium ions.

Reperfusion injury

reperfusion injury may be mediated by


oxidative stress,
calcium overload,
inflammation
Reperfusion-induced microvascular injury
causes not only hemorrhage but also
endothelial swelling that occludes capillaries
and may limit the reperfusion of critically
injured myocardium (called no-reflow).

Biochemical abnormalities may also


persist for a period of days to several
weeks in myocytes that are rescued
from ischemia by reperfusion.
Due to stunned myocardium, a state of
reversible cardiac failure that usually
recovers after several days.
Reperfusion also frequently induces
arrhythmias.

Myocardium that is subjected to


chronic ischemia may also enter into a
state of lowered metabolism and
function that is referred to as
hibernation.
The function of hibernating
myocardium may be restored by
revascularization (e.g., by CABG
surgery, angioplasty, or stenting).

Paradoxically, repetitive short-lived


transient severe ischemia may
protect the myocardium against
infarction (a phenomenon known
as preconditioning) by
mechanisms that are not
understood.

Diagnosis of MI

Clinical feature

ECG changes

Serum enzyme levels

Signs and Symptoms

Signs and symptoms are unique to


each individual patient.
Ranging from no symptoms to
sudden cardiac arrest.

Chest Pain

The most common initial manifestation


is chest pain or discomfort.
This is not relieved by rest, position
change or nitrate administration.
Pain is described by heaviness,
pressure, fullness and crushing
sensation.
Not everyone experiences this
sensation.

Chest Pain

PQRST assessment for chest pain


P- Precipitating events
Q- Quality of pain
R- Radiation of pain
S- Severity of pain
T- Timing

Nausea and Vomiting

Not everyone will experience this.


Vomiting results as a reflex from
severe pain.
Vasovagal reflexes initiated from
area of ischemia.

Sympathetic Nervous
System Stimulation

During an MI increased catecholamines


are released. This results in diaphoresis
and vasoconstriction of peripheral blood
vessels.

rapid, weak pulse and profuse sweating


(diaphoresis). Dyspnea due to impaired
contractility of the ischemic myocardium and
the resultant pulmonary congestion and
edema is common

Silent MIs are particularly


common in elderly patients and in
the setting of diabetes mellitus

Serum enzyme changes

CPK-MB 2

LDH

Cardiac specific troponins T and I -most


sensitive and specific

Myoglobins

Elevated troponin levels persist for


approximately 7 to 10 days after
acute MI
Unchanged levels of CK-MB and
troponin over a period of 2 days
essentially excludes the diagnosis
of MI.

Serum Cardiac Markers

Normal Sinus Rhythm

Normal ECG

Myocardial Infarct

Elevation of the ST segment above the


isoelectric line within a few hours, representing
an abnormal electrical potential associated with
acute injury. The T wave becomes inverted, and
in transmural infarction the dead muscle acts as

Other changes

Increased ESR
Neutrophil leucocytosis
Increased acute phase reactant
proteins

Complications

80-90% develop one or more major


complications
Immediate mortality(sudden
cardiac death)25%

Complications of MI

Arrhythmias
Congestive cardiac failure
Cardiogenic shock
Mural thrombosis and thromboembolism
Cardiac rupture
Cardiac aneurysm
Pericarditis
Post myocardial infarction syndrome

Arrythmias

Abnormalities in the rhythm


Most common complication
Due to Ischaemic irritation of
conducting system
Leakage of K
Lactic acid in tissue fluid

Thromboembolism

Cardiac
Venous

Cardiac rupture-5%

Ventricular wall
Septum
First week

Cardiac aneurysm-5%

Pericarditis

Second day
Transmural infarcts
Fibrinous pericarditis
Pericardial effusion

Post myocardial infarction syndrome


(Dresslers syndrome)

1-6 weeks after


?autoimmne

Chronic ischemic heart


disease

Focal/diffuse fibrosis
Erisodes of angina attacks of MI
years back
Develop CHF

Regarding an MI
Quiz Time
1. The subendocardium is the least
susceptible to hypoxia
2. Are most often transmural
3. Morphological changes are visible
after 12 hours
4. In 30% there is no atheroma in
coronary arteries
5. Cardiac rupture occures in first 24
hours

Regarding myocardial infarction

Microscopic changes are not visible in


the first 12 hours
Coagulative necrosis manifests as a
loss of striations of the myocytes
Fibrinous pericarditis is a complication
Heart block is a sequel of anterior
myocardial infarcts
Systemic embolism is a known
complication

Regarding Myocardial
infarction

Colliquative type of necrosis is seen


Heals be regeneration of myocardial
fibres
Lymphocytic infiltration is seen within
48 hours
Will extend when re-perfused after 48
hours
Pale in colour

Regarding MI

Ischaemic necrosis of the myocardium is due


to lack of blood supply
Is always due to complete or partial block of
coronary arteries
Shows colliquative necrosis in the
myocardium
Transmural type is commoner than
subendocardial type
When treated with streptokinase after 8 hours
it is known to produce reperfusion injury in
heart muscle
Macroscopic changes can be seen
immediately after infarction

What are the pathological changes


you may find in a heart of a patient
who died 72 hours following MI?

Pale infarct surrounded by


haemorrhagic margin
Calcification of infarcted muscle
Patches of fibrosis
Atheroma occluding coronary
artery
Myomalasic cordis

Complications of myocardial
infarction include

Myocardial rupture
Pericarditis
Prinzmetal angina
Ventricular fibrillation
Dissecting aneurysm of aorta

1) List the aetiological factors of


myocardial infarction (50 marks)
2) Describe the morphological
changes of an infarction during the
first 7 days (50 marks)
3) Describe the complications of
myocardial i infarction (15 marks)

A 55 year old male presented to the emergency


treatment unit with sudden onset of severe
retrosternal chest pain associated with sweating. 72
hours later he developed severe heart failure and died
wit. He had a past history of chest pain relieved by
rest.

i) Describe the macroscopic and microscopic


changes you would expect to see in this patients
heart (60 marks)
ii) Briefly describe the pathogenesis of this condition
(15 marks)
iii) Mention four biochemical changes which can occur
in this condition (10 marks)
iv) Write a short note on reperfusion injury (15 marks)