Heart 4: Ischemic Heart Disease

Learning Outcomes
At the end of the lecture ,student will
be able to
• Definition and pathogenesis of IHD
• Classification of IHD

Dr. Maxy A. C. Odike. • Discuss etiology, pathogenesis,

MBBS, MSc, FMCPath, FICS, FCPath (ECSA) morphologic and clinical features of
Professor, Pathology each of the following disorders:
St. James School of Medicine
a. Angina Pectoris: Stable, Unstable,
September 18, 2018
b. Myocardial Infarction,
c. Sudden Cardiac Death (SCD)
d. Chronic IHD
Coronary artery blood flow
• Ischemic Heart Disease
(IHD) is the pathological
condition caused by
imbalance between the
supply (perfusion) and
demand of the heart for
oxygenated blood

• IHD is often termed

coronary artery disease
(CAD) or coronary heart
disease
• Coronary Heart Disease is
extremely common and So it’s a multi-factorial disease
contributes to more than 1.2
million myocardial infarctions
(MIs) and nearly 500,000
deaths in the United States
each year

• It is caused by numerous
modifiable risk factors with
high prevalence, including
physical inactivity,
overweight and obese states,
dyslipidemia, hypertension,
diabetes mellitus, and
tobacco use
Presents as one or more of the following clinical syndromes:
1. Myocardial infarction (MI), where ischemia causes frank cardiac necrosis

2. Angina pectoris (literally “chest pain”), where ischemia is not severe enough to
cause infarction, but the symptoms indicate infarction risk

3. Chronic IHD with heart failure

4. Sudden cardiac death (SCD)

Numbers 1, 2 and 4 make up the Acute Coronary Syndrome

 90% of Myocardial ischemia results from reduced blood flow due to obstructive
atherosclerotic lesions in the coronary arteries

 Rest myocardial ischemia are caused by coronary emboli, myocardial vessel

inflammation, or vascular spasm
Epidemeology
 IHD is the leading cause of death in the United States (one of
every six deaths in 2008; more than 400,000 individuals) and other
developed nations

 Things are improving though due to:

a. Better understanding of the condition
b. Preventive measures that have modified risk factors
c. Diagnostic and therapeutic advances

 Risk factors are very similar to those of atherosclerosis

Causes

(e.g., Fibromuscular dysplasia)

Pathogenesis
• Dominant cause of IHD syndromes is insufficient coronary perfusion relative to
myocardial demand
• Mostly due to chronic, progressive atherosclerotic narrowing of coronary arteries,
which
• May be complicated by acute plaque change, thrombosis, and vasospasm
• Such plaque changes include rupture, superficial erosion, ulceration, fissuring, or
deep hemorrhage
• These are typically associated with intra-lesional inflammation, and the
• Formation of superimposed thrombus that partially or completely occludes the
artery
• Then Myocardial Ischemia

NB: If occlusion grows slowly, it allows time to develop collateral circulation,

and may prevent infarction
Sudden/dynamic morphological changes in the atheromatous plaque.
Angina pectoris
• Characterized by paroxysmal and usually recurrent attacks of sub-sternal or
precordial chest discomfort caused by transient (15 seconds to 15 minutes)
myocardial ischemia that is insufficient to induce infarction.
• Most common in middle-aged and elderly males (women affected after
menopause)
• Within 1 year 20% of people with angina pectoris will develop an myocardial
infarction or unstable angina
• 3 overlapping patterns of angina pectoris are described
Caused by varying combinations of decreased perfusion, increased demand,
and coronary arterial pathology
Stable (Typical), Prinzmetal variant, and Unstable (Crescendo)
Stable (Typical) angina pectoris
 Most common variant of angina
 Causes:
• Fixed, atherosclerotic coronary artery disease - one or more vessels are obstructed-
>70%.
• Aortic valve stenosis or HTN with concentric LVH - O2 supply is not adequate
• Hypertrophic cardiomyopathy
• Cocaine-induced coronary artery vasoconstriction

Clinical findings:
 Exercise-induced substernal chest pain (Other precipitating events include sexual
intercourse, climbing stairs, eating a heavy meal, emotional stress, and cold
temperature)
 Accompanied by shortness of breath, diaphoresis, numbness, and pain in the left inner
arm, shoulder, or jaw
Relieved by resting or nitroglycerin or calcium channel blockers (increasing perfusion)
 Stress test shows ST-segment depression >1 mm
Prinzmetal variant angina
• episodic myocardial ischemia, caused by coronary artery spasm

• attacks are unrelated to physical activity, heart rate, or blood pressure

• Prinzmetal angina generally responds promptly to vasodilators

• Vasoconstriction may be due to an increase in platelet thromboxane A2 OR an increase

in endothelin

• Clincally – Chest pain, Stress test shows ST-segment elevation (transmural ischemia).
Unstable (Crescendo) angina
• a pattern of increasingly frequent, prolonged (>20 min), or severe angina or chest
discomfort that is precipitated by progressively lower levels of physical activity or even
occurring at rest

• mostly caused by the disruption of an atherosclerotic plaque with superimposed partial

thrombosis and possibly embolization or vasospasm (or both)

• is an early warning for myocardial infarction

Clinical findings
• Frequent bouts of chest pain occur at rest or with minimal exertion
• It may progress to an acute myocardial infarction (AMI)
Myocardial Infarction; aka “Heart attack”
 Roughly 1.5 million individuals in the United States suffer an MI annually

 Most common cause of death in adults in the United States

 Prominent in males between 40 and 65 years old; but occurs at virtually any
age (nearly 10% of myocardial infarcts occur in people younger than age 40,
and 45% occur in people younger than age 65)

 No predominant sex predilection after menopause; no racial differences

 At least 25% of Acute MIs are clinically unrecognized

Pathogenesis
• Approximately 90% of cases
result from typical coronary
atherothrombosis (diagram)

• In the rest 10% of cases, MI

results from vasospasm, emboli,
or idiopathic

• Idiopathic cases may be from

vasculitis, vascular amyloid,
hypotension (e.g., shock), drugs
(e.g., cocaine use) or inadequate
myocardial “protection” during
cardiac surgery
Morphologic Classification of Myocardial Infarcts
A. Depending on the thickness of myocardium involved
Transmural Sub-endocardial (Non-transmural)
Area of Ischemic necrosis of the entire Ischemic necrosis of inner one-third to one-
Necrosis thickness of the ventricular half of the ventricular wall.
wall

Causes • chronic coronary • Occurs due to plaque disruption followed

atherosclerosis, by a coronary thrombus, which
• acute plaque change undergoes lysis
• superimposed thrombosis • prolonged, severe reduction in systemic
blood pressure. For example, shock
superimposed on chronic, coronary
stenosis
B. Depending on the age of the infarct: Recent (fresh) or old (healed).

C. Depending on the anatomic region involved: Anterior, posterior, lateral, septal, and
combinations, like posterolateral.
Multifocal microinfarction.
• Involves only smaller intramural vessels

• Occur in the setting of microembolization, vasculitis, or vascular spasm,

for example, due to endogenous catecholamines (epinephrine) or drugs
(cocaine or ephedrine)

• Possible outcome:
o sudden cardiac death (usually caused by a fatal arrhythmia), or
o ischemic dilated cardiomyopathy, so-called takotsubo cardiomyopathy
(also called “broken heart syndrome” because of the association with
emotional stress).
Pattern of infarct according to the frequencies of occlusion of
various
Left anteriorcoronary arteries
Anterior and apical left ventricle;
descending
coronary artery 40% to 50% Anterior two thirds of the interventricular
septum

Right coronary Posterior wall of the left ventricle;

artery posterior one third of the interventricular
30% to 40% septum (in persons with right-dominant
coronary circulation), posterior and lateral
walls of right ventricle

Left circumflex Lateral wall of left ventricle (may also

coronary artery 15% to 20% involve the posterior wall in persons with
left-dominant coronary circulation

• Collateral circulation may develop over time if there is slow occlusion of the vessels by
atherosclerosis.
• Protective effect on preventing an acute myocardial infarction (AMI)
Morphology
Macroscopy
• Within first 12 hours: No identifiable/apparent gross changes are seen. Triphenyl
tetrazolium chloride (a histochemical stain) can grossly identify infarct within 2 to 3 hours
after onset.
• Non-infarcted myocardium appears brick-red (lactate dehydrogenase activity is
preserved).
• Infarcted area remains unstained pale (loss of dehydrogenases).
• Old infarcts appear white and glistening.
Acute myocardial infarction, predominantly of
the posterolateral left ventricle,
demonstrated histochemically by a lack of
staining by the triphenyltetrazolium chloride
(TTC) stain in areas of necrosis. The staining
defect is due to the enzyme leakage that
follows cell death. Note the myocardial
hemorrhage at one edge of the infarct that
was associated with cardiac rupture, and the
anterior scar (lower left), indicative of old
infarct.
Evolution of Morphologic Changes in Myocardial Infarction
 border of the infarct is
accentuated by a dark
red zone

Infarct – pale yellow

left ventricular wall

is hypertrophic

MI- 4 to 7 days old

Infarction - anterior portion
and into the septum
By about 2 months, the necrotic myocardium has
been completely replaced by dense scar tissue,
visible here as a thinned gray area in the left
ventricular myocardium
A B C

Microscopic features of myocardial infarction and its repair.

A, One-day-old infarct showing coagulative necrosis and wavy fibers (elongated and
narrow, as compared with adjacent normal fibers at right). Widened spaces between the
dead fibers contain edema fluid and scattered neutrophils.
B, Dense polymorphonuclear leukocytic infiltrate in an acute myocardial infarction that is 3
to 4 days old.
C, Removal of necrotic myocytes by phagocytosis (approximately 7 to 10 days).
 D E

D, Granulation tissue characterized by loose collagen and abundant capillaries.

E, Healed myocardial infarct, in which the necrotic tissue has been replaced by a
dense collagenous scar. The residual cardiac muscle cells show evidence of
compensatory hypertrophy.
Progression of myocardial
necrosis after coronary artery
occlusion.
Necrosis begins in a small zone
of the myocardium beneath
the endocardial surface in the
center of the ischemic zone.

The area that depends on the

occluded vessel for perfusion
is the “at risk” myocardium
(shaded). Note that a very
narrow zone of myocardium
immediately beneath the
endocardium is spared from
necrosis because it can be
oxygenated by diffusion from
the ventricle.
Diagnosis of MI
It is based on
(1) Clinical symptoms
(2) Electrocardiographic changes- most important tool in the initial evaluation and triage
of patients in whom an acute coronary syndrome (ACS)
(3) Laboratory findings.
Clinical Symptoms
1. Severe, retrosternal chest pain that can radiate to neck, jaw, epigastrium or left arm.
2. Rapid, weak pulse.
3. Profuse sweating (diaphoresis), anxiety, and hypotension
4. Nausea and vomiting are common, and can suggest involvement of the posterior-inferior
ventricle with secondary vagal
5. Dyspnea due to impaired contraction of the ischemic myocardium and the resultant
pulmonary edema.
6. Asymptomatic in about 10% to 15% of cases (“silent” MIs). Common in elderly and in
patients with diabetes mellitus; also in people who have a high pain threshold)
Laboratory evaluation

Based on measuring the blood levels of proteins that leak out of irreversibly damaged
myocytes:
• The most sensitive and specific biomarkers of myocardial damage are cardiac-specific
proteins, troponins, particularly cTnT and cTnI
• Creatine kinase, composed of two isoforms (M and B). While MM homodimers are found
predominantly in cardiac and skeletal muscle, and BB homodimers in brain, lung, and
many other tissues, MB heterodimers are principally localized to cardiac muscle
• Myoglobin: an oxygen-carrying respiratory protein found only in skeletal and cardiac
muscle. It is the earliest marker of MI, the level rises within 1 to 3 hours, peaks in about 8
to 12 hours and return to normal in about 24 to 36 hours.
• Lactate dehydrogenase (LDH): is not a specific marker. It starts rising after 24 to 48
hours, remains high for many days and returns to normal in 7 to 14 days.
FABP:
There is rapid release of heart-type fatty-acid-binding
protein (h-FABP) (15 kDa) into plasma during ischemia
which peaks at 4-6 hours and disappears in 24hrs
Complications of MI

1. Cardiogenic shock.
2. Arrhythmias
3. Heart block
4. Congestive heart failure
5. Rupture- occurs between 1–10 days)
• Anterior wall rupture
a. Produces cardiac tamponade
b. Associated with thrombosis in the LAD coronary artery
• Posteromedial papillary muscle rupture
• acute onset of mitral valve regurgitation and LHF
• Interventricular septum (IVS) rupture
• (a) Most often associated with a thrombosis in the LAD coronary artery
• (b) Produces a left-to-right shunt, causing RHF
6. Mural thrombus
• associated with LAD coronary artery thrombosis.
• Danger of peripheral embolization
7. Fibrinous pericarditis with or without effusion
• Most often occurs between day 1 to 7 of a STEMI.
• Presents with substernal chest pain
• Precordial friction rub is present on auscultation-due to increase
8. Autoimmune pericarditis (Dressler syndrome)
• Usually occurs 1 to 8 weeks after a STEMI infarction.
• Autoantibodies are directed against the damaged pericardial antigens (type II
hypersensitivity reaction).
• Fever and a precordial friction rub are present.
9. Ventricular aneurysm
• Clinically recognized within 4 to 8 weeks after a STEMI. a late complication
• Begins to develop in the first 48 hours
• Clot formation and embolization.
• Rupture is uncommon
 Ruptured papillary muscle usually occurs
within 2 weeks, it results in the acute onset
of Mitral Regurgitation & LV failure

A, Anterior myocardial rupture in an acute infarct (arrow). B, Rupture of the ventricular septum (arrow). C, Complete
rupture of a necrotic papillary muscle. D, Fibrinous pericarditis, showing a dark, roughened epicardial surface overlying an
acute infarct. E, Early expansion of anteroapical infarct with wall thinning (arrow) and mural thrombus. F, Large apical left
ventricular aneurysm. The left ventricle is on the right in this apical four-chamber view of the heart.
Chronic Ischemic Heart Disease (CIHD)

• Describes progressive congestive heart failure as a consequence of accumulated

ischemic myocardial damage and/or inadequate compensatory responses

• In most instances there has been prior MI and sometimes previous coronary arterial
interventions and/or bypass surgery

• Due to replacement of myocardial tissue with noncontractile scar tissue

Clinical findings include:

a. Biventricular CHF
b. Angina pectoris
c. Evolution into a dilated cardiomyopathy
d. Arrhythmia
Sudden Cardiac Death (SCD)
• Describes unexpected death from cardiac causes either without
symptoms, or within 1 to 24 hours of symptom onset

• Approximately 70% of sudden natural deaths have a cardiac cause, and

80% of those are attributable to chronic ischemic heart disease.

Risk factors
(1) Ischemic heart disease (most important risk factor)
(2) Obesity, glucose intolerance, hyperlipidemia, Left Ventricular
Hypertrophy, Hypertension, smoking
(3) Congenital heart lesions (may have been undiagnosed)

• Most frequently occurs in the morning hours (8 am to 11 am) and late

afternoon to evening hours (4 pm to 7 pm).
Non–coronary artery causes of SCD syndrome include:
• (1) Cardiomyopathy (all types)
• (2) Aortic Valve stenosis
• (3) Mitral valve prolapse, cocaine use, myocarditis,
conduction defects (Wolff-Parkinson- White
syndrome)

Causes of SCD in children include:

• (1) Aortic Valve stenosis (most common cause)
• (2) Cardiomyopathies (hypertrophic cardiomyopathy
is the most common cause)
• (3) Wolff-Parkinson-White syndrome
Schematic for the causes and outcomes of
ischemic heart disease (IHD), showing the
interrelationships among coronary artery
disease, acute plaque change, myocardial
ischemia, myocardial infarction, chronic
IHD, congestive heart failure, and sudden
cardiac death.
 References
• Hurst’s The heart 13th edition
• Understanding pathophysiology Sue Huether Kathryn McCance
fifth edition
• Porths pathophysiology-concepts of altered health states
• Robbins Pathological basis of disease 9th edition
• Rapid review Pathology 4e-Goljan
• Text book of pathology 7e Harsh Mohan
• Exam Preparatory Manual For Undergraduates-general and
Systemic Pathology