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HEART
DISEASES
HEART DISEASES (HD)
FIVE MAJOR TYPES
 Ischemic HD
 Hypertensive HD
 Valvular/Endocardial HD
 Cardiomyopathy HD
 Congenital HD
 Others: pericarditis, tumor, et al.
ISCHEMIC HEART
DISEASE
Myocardial ischemia
Myocardial ischemia is a condition in
which oxygen deprivation to the heart
muscle is accompanied by inadequate
removal of metabolites because of
reduced blood flow or perfusion.
Ischemic Heart Disease
Ischemic heart disease (IHD) is the generic
designation for a group of closely related
syndromes resulting from ischemia–
an imbalance between the supply and demand
of the heart for oxygenated blood.
.

An imbalance occurs between
myocardial oxygen supply and
demand.

“Supply” ischemia
 Acute reduction of oxygen supply secondary to
increased coronary vascular tone (ie, coronary
vasospasm) or by marked reduction or cessation
of coronary flow as a result of platelet aggregates
or thrombi.
 Responsible for myocardial infarction (MI)
 Most episodes of unstable angina (UA)
 In many circumstances, ischemia results from
both an increase in oxygen demand and a
reduction in supply.

“Demand" ischemia
In the presence of coronary obstruction,
an increase of myocardial oxygen
requirements caused by exercise,
tachycardia, or emotion leads to a
transitory imbalance.
 Responsible for most episodes of chronic
stable angina


Ischemia may manifest as
(1) anginal discomfort,
 (2) ST-segment deviation on ECG,
 (3) reduced uptake of thallium 201 or
technetium 99 in myocardial perfusion
images,
 (4) regional or global impairment of
ventricular function.

Supply
Demand

Determinants of myocardial oxygen
consumption
Heart rate
 Contractility
 Systolic wall tension
 Maintenance of cell viability in basal state
 Depolarization
 Activation
 Maintenance of active state
 Direct metabolic effect of catecholamines
 Fatty acid uptake


Ischemia comprises not only
insufficiency of oxygen (hypoxia,
anoxia), but also reduced availability of
nutrient substrates and inadequate
removal of metabolites.

Because coronary artery narrowing or obstruction
owing to atherosclerosis underlies myocardial
ischemia in the vast majority of cases, IHD is
often termed coronary artery disease (CAD) or
coronary heart disease (CHD).
The acute coronary syndromes of
 unstable angina,
 acute myocardial infarction, and
 sudden death
share a common pathophysiologic basis,
with coronary atherosclerotic plaque
rupture as the pathologic hallmark and
associated intraluminal platelet-fibrin
thrombus.
The dominant influence in the
causation of the IHD syndromes :
 Fixed atherosclerotic narrowing of the
coronary arteries,
 Intraluminal thrombosis overlying a
ruptured or fissured atherosclerotic
plaque,
 Platelet aggregation,
 Vasospasm.
Role of Fixed Coronary Obstructions

More than 90% of patients with IHD
have advanced stenosing coronary
atherosclerosis (“fixed” obstructions).

Although only a single major coronary
epicardial trunk may be affected, more
often two or all three are involved .
Role of Acute Plaque Change
Acute myocardial ischemia is often precipitated by
disruption of previously only partially stenosing
atherosclerotic plaques with hemorrhage, fissuring,
or ulceration.
 This is often followed by mural or total thrombosis.
 Such vascular injury is fundamental to the
development of the acute coronary syndromes–
unstable angina, acute myocardial infarction, or sudden
ischemic death–in most patients.
 High-grade but slowly developing occlusions probably
stimulate well-developed collateral vessels over time

Role of Coronary Thrombus
Coronary thrombosis, partial or total,
plays a critical role in acute coronary
syndromes.
 In myocardial infarction, the added
thrombus converts a disrupted, partially
stenotic plaque to a complete stenosis.
 Thrombus is a potent activator of multiple
growth-related signals in smooth muscle
cells; both platelet-mediated and smooth
muscle cell-mediated events contribute to

Role of Vasoconstriction

Transient vasoconstriction may be
induced at a site of plaque disruption
and thrombosis.
Terminology: Ischemic Heart Disease
• Ischemia - Insufficient blood supply  injury  Angina (reversible)
or MI (irreversible)
• Angina (Angina=Strangulation Pectoris=Chest)
• Myocardial infarction (MI) - Death of myocardial cells (irreversible)
• Cardiac failure : Impaired pumping ability of the heart
• Cardiogenic shock : Shock due to cardiac failure
• Arrhythmias: cardiac rhythm disturbances
Coronary circulation
Rich Blood supply
 High Oxygen consumption (A-V19-9ml/100ml)
 Two coronary arteries-225 ml/min
 Direct branch from aorta
 End arteries – few collaterals
 Phasic blood flow- during diastole
 Local metabolism is primary controller of
coronary blood flow

Left Coronary Artery
Coronary
Arteries
•Anterior Descending
•Circumflex
LCx
LAD
Right Coronary Artery
Abnormalities of O2 supply
 Increased

O2 demand
High heart rate, BP, Contractility
 Insufficient

O2 supply
Anemia and Hypoxia
 Coronary
Vessels
 Intermittent (Spasm, Congenital)
 Permanent (Atherosclerotic Plaque)
Ischemic syndromes
Depending on the rate of development and
ultimate severity of the arterial narrowing(s)
and the myocardial response, four ischemic
syndromes may result:
(1) angina pectoris
(2) myocardial infarction
(3) chronic ischemic heart disease
(4) sudden cardiac death

1. Angina Pectoris

Stable (classic, typical, Heberden) angina

Unstable (pre-infarction, crescendo, acute
coronary insufficiency) angina

Prinzmetal's ("variant") angina
Anginas are caused by varying combinations of
increased myocardial demand and decreased
myocardial perfusion, owing to






fixed stenosing plaques
disrupted plaques
vasospasm
thrombosis
platelet aggregation
embolization
Angina pectoris is a symptom complex of IHD
characterized by paroxysmal attacks of
 substernal or
 precordial chest discomfort (variously described as
constricting, squeezing, choking, or knife-like)

Caused by transient (15 seconds to 15 minutes)
myocardial ischemia that falls short of inducing the
cellular necrosis that defines infarction.
Stable (classic, typical, Heberden) angina
The pathogenesis of typical angina pectoris appears to
be the reduction of coronary perfusion to a critical level
by chronic stenosing coronary atherosclerosis.
 This renders the heart vulnerable to further ischemia
whenever there is increased demand, such as that
produced by
physical activity,
 emotional excitement, or
 any other cause of increased cardiac workload.


Relieved by rest or nitroglycerin, a strong coronary
vasodilator (thereby increasing supply).
Unstable (pre-infarction, crescendo, acute
coronary insufficiency) angina
Refers to a pattern of pain that occurs with
progressively increasing frequency, is precipitated with
progressively less effort, often occurs at rest, and tends
to be of prolonged duration.
 In most cases, this is probably due to a thrombus
developing over a ruptured plaque.

In unstable angina, a relatively small
fissure or disruption of an atherosclerotic
plaque may lead to a sudden change in
plaque morphology, with platelet
aggregation or mural thrombus and
frequently vasoconstriction leading to
transient reduction in coronary blood
flow.
 Untreated, many of these people get an
MI soon.

Prinzmetal's ("variant") angina
This is primarily attributable to vasospasm.
 Perhaps it's the cardiac equivalent of migraine.
 Although individuals with this form of angina may well
have significant coronary atherosclerosis, the anginal
attacks are generally unrelated to physical activity,
heart rate, or blood pressure.
 Prinzmetal’s angina generally responds promptly to
vasodilators, such as nitroglycerin and calcium channel
blockers.

2. Myocardial Infarction
“Heart attack”
• Death of Myocardial muscle due to lack of
blood supply.
• Most common cause is Atherosclerotic
narrowing of coronary arteries.
Pain in Myocardial Infarction
Precordial , intense, constrictive
 Similar to Angina – severe prolonged
 Radiates to shoulder and left arm
 May present in other location-jaw,
epigastrium.
 Often with breathlessness, nausea,
vomiting & perspiration
 Hypotension  Collapse
 Less severe or absent in elderly
 No response to nitrates

Causes of myocardial infarcts

Atherosclerosis: Makes up 90% of coronary artery
disease

Cocaine: The second most common cause of
myocardial infarction and sudden cardiac death
Prinzmetal's coronary spasm
 Vasculitis: (1) lupus; (2) polyarteritis nodosa; (3)

rheumatoid arthritis; (4) Kawasaki's; (5) Takayasu's; (6)
mycotic aneurysms.
Embolization
 Syphilis (mesaortitis syphilitica)
 Dissecting hematoma
 Shock and left-sided failure (subendocardial
infarct )

There are two types of myocardial
infarction, each having differing morphology
and clinical significance:
(1) The transmural infarct (more common
type)
(2) The subendocardial (nontransmural) infarct
The transmural infarct
The ischemic necrosis involves the
full or nearly full thickness of the
ventricular wall in the distribution
of a single coronary artery.
This pattern of infarction is usually
associated with
 coronary atherosclerosis
 plaque rupture
Subendocardial Infarction
 An
area of ischemic necrosis limited to the
inner one-third or at most one-half of the
ventricular wall, often extending laterally
beyond the perfusion territory of a single
coronary artery.
 There is diffuse stenosing coronary
atherosclerosis and global reduction of
coronary flow but neither plaque rupture nor
superimposed thrombosis.
Coronary Arterial Occlusion


At least 90% of transmural acute myocardial infarcts are
caused by an occlusive intracoronary thrombus overlying an
ulcerated or fissured stenotic plaque.
Every acute transmural myocardial infarct, a dynamic
interaction has occurred among several or all of the
following:
 severe coronary atherosclerosis, an acute atheromatous
plaque change (fissuring, ulceration),
 superimposed thrombosis,
 platelet activation, and
 vasospasm.
In the typical case, the following sequence
of events can be proposed (90%):





Sudden change in the morphology of an atheromatous
plaque, i.e., intraplaque hemorrhage, ulceration, or
fissuring.
Platelet adhesion, aggregation, activation, and release of
adenosine diphosphate (ADP), with buildup of a platelet
mass. The platelet mass may give rise to emboli or
potentiate occlusive thrombosis.
Tissue thromboplastin is released.
Adherent activated platelets release thromboxane A2,
serotonin, and platelet factors 3 and 4 (predisposing to
coagulation, favoring vasospasm).
Frequently within minutes, the thrombus evolves to
become completely occlusive.
In the approximately 10% of cases
In some of the cases, the coronary arteries are
free of atherosclerosis by angiography:
 Vasospasm with or without coronary atherosclerosis
may induce the acute perfusion deficit, perhaps in
association with platelet aggregation.
 Emboli from a left-sided mural thrombosis or
vegetative endocarditis or paradoxic emboli from the
right side of the heart or the peripheral veins
(through a patent foramen ovale) could cause
coronary occlusion.
Coronary Atheorsclerosis
LCx
LAD
Right Coronary Artery
Coronary Atheorsclerosis
Myocardial Infarction : Myocardial
Response
Occlusion of a major coronary artery results in ischemia
throughout the anatomic region supplied by that artery
(called area at risk),
 Acutely ischemic myocardium undergoes progressive
biochemical, functional, and morphologic changes, the
outcome of which largely depends on the severity and
duration of flow deprivation.



The principal biochemical consequence of
myocardial ischemia is the onset of anaerobic
glycolysis within seconds,
 leading to inadequate production of high-energy
phosphates (e.g., creatine phosphate and
adenosine triphosphate [ATP ]) and
accumulation of potentially noxious breakdown
products (such as lactic acid).
Myocardial function is exceedingly sensitive to
severe ischemia; striking loss of contractility is
evident within 60 seconds of onset.

Reversible ultrastructural changes develop within
few minutes after onset of ischemia


e.g., cell and mitochondrial swelling, glycogen
depletion.
Although function becomes strikingly abnormal
within few minutes after onset of ischemia,
myocardial coagulation necrosis occurs only after
20 to 40 minutes of severe ischemia.
Irreversible injury of ischemic myocytes
occurs first in the subendocardial zone.
 With more extended ischemia, a
wavefront of cell death moves through
the myocardium to involve progressively
more of the transmural thickness of the
ischemic zone.

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 vascular bed perfused by the obstructed vessels;
(3) the duration of the occlusion;
(4) the metabolic/oxygen needs of the myocardium at risk;
(5) the extent of collateral blood vessels;
(6) the presence, site, and severity of coronary arterial spasm;
(7) other factors
 such as alterations in blood pressure, heart rate, and cardiac
rhythm.
LOCATION
The corresponding sites of myocardial lesions:

Left anterior descending coronary artery (40 to 50%):



Right coronary artery (30 to 40%):




Anterior wall of left ventricle near apex
Anterior two-thirds of interventricular septum
Inferior/posterior wall of left ventricle
Posterior one-third of interventricular septum
Posterior right ventricular free wall in some cases
Left circumflex coronary artery (15 to 20%):

Lateral wall of left ventricle
Classically, the coronary arteries have the following distribution, and their
occlusion will result in transmural infarcts in the corresponding
distribution
1.Left anterior
descending:
Anterior wall,
anterior 2/3 of
septum, apex (4050%)
2.Right: Posteriorinferior wall,
posterior 1/3 of
septum (30-40%)
3.Left circumflex:
Lateral wall (15-20%)
Stuttering infarct
Several infarcts of varying age in the same heart are
frequently found.
 Repetitive necrosis of adjacent regions yields
progressive extension of an individual infarct over a
period of days to weeks–“stuttering infarct.”
 Examination of the heart in such cases often reveals a
central zone of infarction that is days to weeks older
than a peripheral margin of more recent ischemic
necrosis.

Macroscopical findings
Areas of damage undergo a progressive sequence of
changes that consist of typical ischemic coagulative
necrosis, followed by inflammation and repair.
 The appearance of an infarct at autopsy depends on
the duration of survival of the patient following
myocardial infarction onset.
 Early recognition of acute myocardial infarcts by
pathologists is a difficult problem:


particularly when death has occurred within minutes
to a few hours after the onset of the ischemic injury,
because diagnostic morphologic changes lag behind
the actual injury.



Myocardial infarcts less than 6 to 12 hours old are usually inapparent
on gross examination.
It is often possible, however, to highlight the area of necrosis by
histochemical changes that first become apparent after 2 to 3 hours.
Immersion of tissue slices in a solution of triphenyltetrazolium
chloride (TTC) imparts a brick-red color to intact, noninfarcted
myocardium where the dehydrogenase enzymes are preserved.
 Because dehydrogenases are depleted in the area of ischemic
necrosis (i.e., they leak out through the damaged cell membranes),
an infarcted area is revealed as an unstained pale zone (especially
apparent after fixation, when unstained myocardium appears light
brown).
By 12 to 48 hours, the lesion can be identified in
routinely fixed gross slices (including those not stained
with TTC) because of either pallor or a red-blue hue
owing to the stagnated, trapped blood. Progressively
thereafter the infarct becomes a more sharply defined
yellow zone.
 Within10 days to 2 weeks the there is a softened area
rimmed by a hyperemic zone of highly vascularized
granulation tissue.
 Over the succeeding weeks, the injured region evolves
to a fibrous scar.

Microscopical findings
 Using
light microscopy of sections stained by
routine tissue stains, the typical microscopic
changes of coagulative necrosis are not
detectable for at least the first 4 to 12 hours.
 “Wavy fibers” may be present at the periphery
of the infarct;
 it
is thought that these changes result from the
forceful systolic tugs by the viable fibers
immediately adjacent to the noncontractile dead
Morphology
Duration Macro
0-30 m None
4-8 h None
8-12 h None
12-48 h Sharply defined yellow
lesion, Edema
3-7 D Hyperemia and
Hemorrhage
Micro
Loss of glycogen (EM)
EM: Earliest nuclear
changes, Wavy fibers
Contraction bands
Necrosis,
Acute inflammation
Early findings of
Granulation tissue
1-3 W Thin, yellow
Granulation tissue,
Early fibrosis
3-7 W Tough white
Dense Fibrosis
Coronary
Thrombosis
With Infarction
Coronary Atherosclerosis
Coronary Atherosclerosis with Thrombosis
Myocardial Infarction – 3 d
Myocardial Infarction – 1 W
Myocardial Infarction – 2 W
Myocardial Infarction – 3 W
Myocardial Infarction – 5 W
Normal Myocardium
MI 12-48 hr
loss of nucleus, contaction bands, coagulative necrosis.
Contraction bands
(myofibrillar
degeneration) densely
eosinophilic cross-bands
which probably result
from calcium entering
membrane-damaged cells
during reperfusion.
Contraction bands let
you know that a sudden
death is of cardiac
ischemic origin.
Contraction bands can probably result from epinephrine
administration and/or electric shocks in CPR.
MI 3-4 day
MI 1st week
MI 2-3 W
MI >3-7 W
Collagen Scar
If the patient with acute myocardial infarction reaches the
hospital, the likelihood of the most serious complications is as
follows:


Uncomplicated cases (10 to 20% of cases)
Complicated cases (80 to 90% of cases):
 Arrhythmias and conduction defects (75-95% of complicated
cases)
 Extension of infarction, or re-infarction
 Left-sided Congestive heart failure (pulmonary edema)
 Cardiogenic shock (10-15%; high mortality ~70% sudden
death)
 Dressler's pericarditis/postpericardiotomy syndrome
(occurs weeks after an MI or cardiac surgery)
 Mural thrombosis, embolization
 Myocardial wall rupture (tamponade)
 Septum rupture (left-to-right shunt)
 Papillary muscle rupture (mitral regurgitation)
 Ventricular aneurysm
 Chronic ischemic heart disease
Cardiogenic shock
Severe “pump failure” (cardiogenic
shock), which occurs in 10 to 15% of
patients following myocardial infarction
 Generally indicates a large infarct (often
greater than 40% of the left ventricle)
 Cardiogenic shock has a nearly 70%
mortality rate and accounts for two-thirds
of in-hospital deaths

Rupture
The cardiac rupture syndromes result from the
mechanical weakening that occurs in necrotic and
subsequently inflamed myocardium and include ;
(1) rupture of the ventricular free wall (most commonly),
usually with hemopericardium and cardiac tamponade,
(2) rupture of the interventricular septum (less
commonly), leading to a left-to-right shunt;
(3) papillary muscle rupture (least commonly), resulting
in the acute onset of severe acute mitral regurgitation.
MI - Rupture
Tamponade
Pericarditis
A fibrinous or fibrinohemorrhagic pericarditis usually
develops about the second or third day.
 It is most often localized to the region overlying the
necrotic area and usually resolves with healing of the
infarct.
 Pericarditis is the epicardial manifestation of the
inflammation elicited by a direct underlying
transmural infarct.

Aneurysm
The clinical and laboratory diagnosis of
acute myocardial infarction
• Symptoms
• ECG changes
• Elevations of specific
serum enzymes
 Creatinine Kinase
CK- Isoenzymes (Fractions)
Troponins - I & T.
LDH - 1-5 (1 - 2 flip)
Myoglobin
3. Chronic Ischemic Heart Disease
 The
designation chronic ischemic heart
disease (CIHD) is used here for the hearts in
patients, often but not exclusively elderly,
who insidiously develop CHF, sometimes
fatal, as a consequence of ischemic
myocardial damage.
 There has been a history of angina and
usually prior episodes of myocardial
infarction, often as remote as 5 to 10 years
before the onset of the CHF.
Morphology
The pericardial surface of the heart in CIHD may have
adhesions as a result of healing of pericarditis
associated with past myocardial infarcts.
 Invariably there is moderate to severe stenosing
atherosclerosis of the coronary arteries and sometimes
total occlusions resulting from organized thrombi.
 Discrete, gray-white scars of healed previous infarcts
are usually present.
 The mural endocardium is generally normal except for
some superficial, patchy, fibrous thickenings.

 The
major microscopic findings include
 diffuse
myocardial atrophy
 subendocardial vacuolization
 diffuse, interstitial and patchy replacement
fibrous tissue
 large healed scars of previous acute infarcts.

Chronic Ischemic Heart Disease Can Lead to
Cardiomyopathy
 In a minority of patients with severe coronary
atherosclerosis, myocardial contractility is
impaired globally without discrete infarcts, as in
dilated cardiomyopathy.
 This situation usually reflects a combination of
• ischemic myocardial dysfunction,
• diffuse fibrosis,
• multiple small healed infarcts.

Ischemic cardiomyopathy.
4. Sudden cardiac death
Most commonly sudden cardiac death (SCD) is defined
as unexpected death from cardiac causes early (usually
within 1 hour) after or without the onset of symptoms.
 In the vast majority of cases in adults, SCD is a
complication and often the first clinical manifestation of
IHD.


Less frequently SCD is caused by
• a congenital structural abnormality
• aortic valve stenosis
• hereditary or acquired abnormalities of the cardiac conduction
system
• mitral valve prolapse
Morphology
The ultimate mechanism of death is
almost always a lethal arrhythmia (e.g.,
asystole, ventricular fibrillation).
 Long-standing
coronary
atherosclerosis with diffuse
myocardial atrophy,
 Interstitial fibrosis,
 Possibly healed infarcts.
They can impinge on the conduction
In most cases, however, acute myocardial
ischemia with or without plaque fissuring or
myocardial infarction induces irritability of
myocardium distant from the conduction system
and triggers the fatal arrhythmia.
 Marked coronary atherosclerosis with critical
(greater than 75%) stenosis involving more than
one of the three major vessels is present in 80 to
90% of victims;



only 10 to 20% of cases are of nonatherosclerotic
origin.
Usually there are high-grade stenoses (greater than
90%).
 The
precise frequency of acute coronary
changes (i.e., thrombosis, plaque fissuring,
intraplaque hemorrhage) are common (75 to
80%).
 A healed myocardial infarct is present in
about 40%, but in those who have been
rescued by prompt therapy from sudden
cardiac arrest, new myocardial infarction is
found in 25% or less.
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