7. Ischemic Heart Disease

Question 1

Definition of ischemic heart disease

Answer 1

Generic designation for a group of pathophysiologically related syndromes resulting from myocardial ischemia due to an imbalance between supply & demand of the heart for oxygenated blood; also referred to as coronary heart disease (as majority of cases are due to underlying atherosclerotic lesions of coronary vessels)

Question 2

Causes of ischemic heart disease

Answer 2

1. Atherosclerosis of coronary vessels (90-95%)
2. Embolism
3. Ostial stenosis in syphilitic aortitis
4. Dissecting aneurysms
5. Direct trauma
6. Arteritis
7. Anomalous origin of left coronary artery
8. Hypoxaemia or insufficient oxygen content of blood
   (anemia, carbon monoxide poisoning, hypotensive crises)

Question 3

Pathogenesis of ischemic heart disease (mainly due to atherosclerosis)

Answer 3

1. Chronic Progressive Atherosclerotic Stenosis
   a. Growing atherosclerotic plaque in coronary arteries
   occlude lumen progressively
   b. Require about 75% occlusion for symptomatic
   ischemia precipitated by exercise
   c. Require about 90% occlusion for inadequate
   coronary perfusion even at rest
2. Acute Plaque Change
   a. Acute plaque change (rupture/fissure, erosion/ulceration) can lead to the formation of a thrombus which can partially or completely occlude the lumen of the coronary artery
   b. Thrombus formed may also embolize to occlude downstream coronary vessels
   c. Occlusion can be further exacerbated by vasoconstriction (due to stimuli such as adrenergic stimulation)
3. Other non-atherosclerotic factors:
   a. [Inadequacy of supply] decreased availability of
   blood oxygen content (anemia, CO poisoning, pulmonary disease, left-to-right shunts)
   b. [Increased demand] exercise, infection, pregnancy,
   hyperthyroidism, myocardial hypertrophy

Question 4

Consequences of ischemic heart disease

Answer 4

Manifests as one or more of the following 4 clinical syndromes:

1. Angina pectoris
2. Myocardial infarction
3. Chronic ischemic heart disease
4. Sudden cardiac death

Question 5

Definition of angina pectoris

Answer 5

Literally meaning ‘chest pain’, characterized by paroxysmal and usually recurrent attacks of substernal or precordial chest discomfort (constricting, choking, squeezing, knife-like) caused by transient myocardial ischemia that falls short of inducing myocyte necrosis

Question 6

Types of angina

Answer 6

1. Stable (typical) angina
2. Unstable (crescendo/pre-infarction) angina
3. Prinzmetal angina

Question 7

Stable (typical) angina

Answer 7

1. An episodic chest pain caused by imbalance between increased demand for myocardial work and impaired coronary blood flow
2. Impaired coronary blood flow in stable angina is due to chronic progressive stenosis atherosclerosis
   - Forms a fixed atheromatous obstruction
   - Typically at least 75% occlusion is present before
   stable angina surfaces
3. Increased demand for myocardial work can be due to:
   - Physical activity
   - Emotional excitement

4. Modifiable (i.e. angina resolves) with rest & coronary
vasodilating drugs (nitroglycerin)

Question 8

Unstable (Crescendo/Pre-infarction) Angina

Answer 8

1. A pattern of increasingly frequent chest pain often of
   prolonged duration, that is precipitated by progressively lower levels of physical activity or that even occurs at rest
2. Usually due to an acute plaque change with superimposed thrombosis & possibly embolization &/or vasospasm
3. Manifestion of acute coronary insufficiency, hence leading to an increased risk of myocardial infarction & arrhythmias (which may result in sudden cardiac death)
   - Note: unlike in myocardial infarction, unstable angina does not give rise to elevation of serum cardiac troponin (ischemia is still sublethal)

Question 9

Prinzmetal Variant Angina

Answer 9

1. An episodic chest pain caused by coronary artery spasm which is unrelated to physical activity, heart rate or blood pressure
2. Responds to nitroglycerin & calcium-channel blockers

Question 10

Definition of myocardial infarction

Answer 10

Death of cardiac muscle due to prolonged severe ischemia

Question 11

Causes of myocardial infarction

Answer 11

1. Coronary artery occlusion by acute plaque event (90%)
   - Acute plaque event exposes thrombogenic plaque contents or subendothelial basement membrane, initiating platelet aggregating and subsequent coagulation cascade
   - Thrombus evolves to completely occlude the lumen
   - Also, platelet & injured endothelial cell-derived mediators induce local vasospasm
2. Coronary artery occlusion in absence of coronary vascular pathology (10%)
   - Vasospasm (in associated with other causes of platelet aggregation or cocaine abuse)
   - Emboli (from atrial fibrillation, left-sided mural thrombus, vegetations or infective endocarditis)
   - Others (vasculitis, shock, vascular dissection, amyloidosis, sickle cell disease)

Question 12

Pathogenesis of myocardial infarction – Myocardial Response To Coronary Occlusion

Answer 12

1. Reversible Phase (Early Changes) – first 20-30 minutes
   - Cessation of aerobic metabolism within seconds with progressive accumulation of potentially noxious
   metabolites (e.g. lactic acid)
   - Exquisite dependence of myocardial function on oxygen results in loss of myocardial contractility within 60 seconds (which can precipitate acute heart failure even before myocardial infarction occurs)
   - However, myocyte damage at this stage is reversible
2. Irreversible Phase
   - Following severe ischemia for 20-30 minutes, irreversible damage to myocytes occur (starting with the subendocardial myocytes which are normally the least perfused in the heart)
   - Wavefront of cell death moves through the myocardium, eventually involving the full transmural thickness & breadth of the ischemic zone
   - Permanent damage by 2-4 hours, complete necrosis of ischemic zone by 6 hours
   - Note: in individuals with chronic ischemia, collateral coronary arterial circulation may have had sufficient time to develop, hence progression of necrosis in myocardial infarction may be more protracted
3. Infarct Modification By Reperfusion
   - Via coronary intervention (thrombolysis, angioplasty with stent placement, coronary artery bypass graft)
   - Helps to salvage reversibly injured myocytes, limiting the area of ischemic necrosis
   - Reperfusion injury (due to ROS, influx of neutrophils)

Question 13

Regional subendocardial infarct

Answer 13

Ischemic necrosis of inner one third or half of the wall supplied by occluded vessel (due to lysis of thrombus before necrosis progresses through full thickness of wall)

Question 14

Regional transmural infarct

Answer 14

Ischemic necrosis of full thickness of wall supplied by occluded vessel

Question 15

Circumferential subendocardial infarct

Answer 15

Ischemic necrosis of inner one third or half of the entire wall (due to general hypoperfusion due to hypotension)

Question 16

ECG alterations of subendocardial infarcts

Answer 16

Non-ST elevation infarcts

Question 17

ECG alterations of transmural infarcts

Answer 17

ST elevation infarcts

Question 18

Occluded left anterior descending coronary artery

Answer 18

Anterior wall of LV near apex + anterior 2/3 of IV septum

Question 19

Occluded right coronary artery

Answer 19

Inferoposterior wall of LV + posterior 1/3 of IV septum + posterior wall of RV

Question 20

Occluded left circumflex coronary artery

Answer 20

Lateral wall of LV

Question 21

0-12 hours post myocardial infarct

Answer 21

1. No visible micro- or macroscopic changes
2. Use of triphenyltetrazolium chloride (stains cardiac LDH brick-red) to stain viable heart muscle (appear darker than dead myocardium)

Question 22

12-24 hours post myocardial infarct

Answer 22

1. [Gross] pale with blotchy discoloration

2. [Histology] area of infarct brightly eosinophilic, myocytes anucleate (coagulative necrosis), interstitial edema

Question 23

24-72 hours post myocardial infarct

Answer 23

1. [Gross] Soft, pale, yellow

2. [Histology] neutrophilic infiltrate

Question 24

3-10 days post myocardial infarct

Answer 24

1. [Gross] Hyperemic border around yellow area

2. [Histology] Granulation tissue (macrophages) in periphery of infarct, progresses towards centre

Question 25

6-8 weeks post myocardial infarct

Answer 25

Fibrous scar

Question 26

Clinical features of myocardial infarction

Answer 26

1. Symptoms
   - Chest pain that does not go away with rest
   - Rapid weak pulse, profuse sweating (diaphoresis)
   - Dyspnea (secondary to pulmonary congestion)
2. ECG Changes
   - Transmural infarcts:
   a. Acute phase: ST segment elevation
   b. Post-infarct: appearance of Q wave
   - Subendocardial infarcts:
   a. T wave inversion

3. Laboratory findings: 
Raised serum levels of:
- Troponin I & T
- Cardiac creatine kinase (CK-MB)
- Cardiac lactate dehydrogenase (LDH)
- Myoglobin

Question 27

Pathological effects & complications of myocardial infarction

Answer 27

1. Left-sided heart failure
   - Forward failure: hypotension, cardiogenic shock
   - Backward failure: pulmonary venous hypertension
2. Cardiac Dysrhythmias
   - Sinus bradycardia, heart blocks (especially with posterior infarcts), ventricular premature contractions, fibrillation
3. Myocardial Rupture
   - Ventricular free wall → hemopericardium
   - Ventricular septum → left-to-right shunt formation
   - Papillary muscle → post-infarct mitral regurgitation
4. Mural Thrombus Formation
5. Pericarditis
   - Dressler syndrome (fibrinous or fibrinohemorrhagic pericarditis due to underlying myocardial inflammation)
6. Ventricular Aneurysm
   - Thin scar tissue wall undergoes paradoxical bulging
   during systole (which may compromise cardiac
   output and contribute to heart failure)
7. Recurrent Myocardial Infarction
   - Causes infarct extension
8. Chronic Ischemic Heart Disease

Question 28

Definition of chronic ischemic heart disease

Answer 28

Descriptive term referring to progressive heart failure as a consequence of ischemic myocardial damage (aka ischemic cardiomyopathy)

Question 29

Pathogenesis of chronic ischemic heart disease

Answer 29

1. Myocardial infarction leads to decrease in viable myocardial mass
2. Increased myocardial workload (exacerbated by paradoxical bulging of ventricular aneurysm if present) on remaining viable myocytes induces compensatory hypertrophy to maintain cardiac output
3. Functional decompensation results in hypertrophied myocardium over time, leading to eventual heart failure

Question 30

Definition of sudden cardiac death

Answer 30

Unexpected death from cardiac causes in individuals without symptomatic heart disease or early after symptom onset; usually the consequence of lethal arrhythmias

Question 31

Causes of sudden cardiac death

Answer 31

1. Acute myocardial ischemia
2. Congenital structural or coronary arterial abnormalities
   - Right coronary artery arising from root of left coronary artery (hence compressed between aorta & pulmonary trunk)
3. Cardiac hypertrophy or dilation of any cause
   - Valvular disease (aortic stenosis, mitral prolapse)
   - Hypertension
   - Dilated or hypertrophic cardiomyopathy
4. Myocarditis
5. Hereditary or acquired causes of cardiac arrhythmias
   - Long QT syndrome
   - Brugada syndrome
   - Short QT syndrome
   - Catecholaminergic polymorphic ventricular tachycardia
   - Wolff-Parkinson-White syndrome
   - Congenital sick sinus syndrome
   - Isolated cardiac conduction disease
6. Miscellaneous
   - Systemic metabolic and hemodynamic alterations
   - Catecholamines
   - Drug abuse (cocaine & methamphetamine)