122 Wk. 5 Coronary Artery Disease and Stroke

We start with coronary artery disease (or CAD), which includes angina and acute myocardial infarction (commonly referred to as heart attack). CAD is most closely associated with atherosclerosis, thrombosis, and embolism, and therefore to succeed in this topic, you will need to recall what we discussed last week.

The coronary system is responsible for the blood supply of the myocardium.

This is an enormous task as myocardial oxygen demand is high even at rest, and it shows a massive increase in the case of exercise, when myocardial workload greatly increases (because the heart must pump a large amount of blood to active skeletal muscles; i.e., cardiac output must greatly increase).

Under physiological circumstances, there is a fine balance between myocardial metabolic demand and the blood supply to the myocardium. If myocardial metabolic demand cannot be met by coronary blood flow [i.e., an imbalance occurs between myocardial supply (i.e., perfusion) and cardiac demand for oxygenated blood (i.e., blood supply)] myocardial ischaemia develops.

In most cases, myocardial ischaemia is the consequence of coronary atherosclerosis.

You may know that the Latin term 'angina pectoris' translates into 'chest pain'. In this segment, we will define this condition and explore its most common aetiologies. We will also 'meet' William Heberden (aka the 'Father of clinical observations') and Myron Prinzmetal.

Definition of Angina Pectoris: paroxysmal attacks of pain localised on the chest

- Paroxysmal chest pain caused by myocardial ischemia

- Typically recurrent and triggered by physical exertion

Causes of Myocardial Ischemia Blood supply insufficient towards myocardial) Leading to Angina

1. Atherosclerotic coronary artery disease:

   - Fixed atherosclerotic plaques narrowing the coronary arteries

   - Acute plaque changes (e.g., rupture, thrombosis) causing sudden obstruction

2. Coronary artery spasm

3. Increased myocardial oxygen demand without proportional increase in blood flow

   - e.g., severe anemia, carbon monoxide poisoning

Key Principles

- Angina is caused by an imbalance between myocardial oxygen demand and coronary blood supply.

- Atherosclerosis is the most common underlying cause, leading to fixed coronary artery narrowing.

- Significant (e.g., 80-90%) coronary artery stenosis may be asymptomatic at rest but precipitate ischemia during exertion.

- Severe (e.g., 90%) coronary stenosis can cause ischemia even at rest.

Potential Consequences of Myocardial Ischemia

- Angina pectoris

- Acute myocardial infarction ("heart attack")

- Sudden cardiac death

- Chronic ischemic heart disease and heart failure

Types of Angina Pectoris

1. Stable angina

2. Unstable angina

3. Variant (Prinzmetal's) angina (not covered in detail)

  • Induced by vasospasm

Angina Pectoris- caused by transient myocardial ischemia (15 minutes to 15 minutes) that is inefficient to cause necrosis.

- Paroxysmal chest pain caused by transient myocardial ischemia

- Ischemia severe enough to cause symptoms but not cell death

  • Dull and radiates down arm of the jaw

  • Does not worsen with deep breathe

  • Can be associated with shortness of breath, diaphoresis, nausea and vomiting

Decreased blood supply ( Ischemia) leads to Reduced oxygen supply ( Hypoxia) which leads to reduced ATP production therefore Adenosine enters the extracellular space

Stable Angina

- Occurs only with exertion, relieved by rest

- Caused by fixed atherosclerotic coronary artery narrowing

- Resting myocardial oxygen supply meets demand

  • The most common form, typical, effort, classic angina

  • Demand Ischemia

Unstable Angina

- Occurs at rest, not relieved by rest

- Caused by acute changes in atherosclerotic plaque

  (e.g., rupture, thrombosis)

- Resting myocardial oxygen supply does not meet demand

  • Crescendo angina

  • Supply Ischemia

  • Acute Myocardial Infarction may be imminent

ECG Changes in Myocardial Ischemia

- ST segment depression

- T wave inversion

Mechanism of Anginal Pain

- Ischemia leads to decreased ATP production and increased adenosine

- Adenosine stimulates pain receptors and causes vasodilation

Key Differences

- Stable angina is "demand-related" ischemia, unstable is "supply-related"

- Unstable angina carries a higher risk of progressing to myocardial infarction

- ECG changes, while present in both, may be more pronounced in unstable angina

Myocardial Infarction Heart attack — you must have heard this term, and you must know that it is an extremely serious condition. This lecture explains the most common sequence of events that eventually results in ischaemic necrosis of the myocardium.

AMI- Acute Myocardial Infarction

- The most common pathogenesis of acute myocardial infarction (AMI) is the presence of an atherosclerotic plaque in the coronary artery that undergoes acute changes.

- These acute changes often involve damage or disruption of the endothelium covering the plaque, exposing the subendothelial connective tissue to the bloodstream.

- This triggers platelet aggregation and thrombus (blood clot) formation at the site of the damaged plaque.

- The thrombus can completely obstruct blood flow in the affected coronary artery segment, depriving the downstream myocardium of oxygen and nutrients.

- This results in myocardial necrosis, which is the hallmark of acute myocardial infarction.

- Other less common causes of AMI include:

  - Severe coronary vasospasm that obstructs blood flow

  - Embolism of a blood clot formed elsewhere (e.g. in the left atrium) that travels to and blocks a coronary artery

  - Profound myocardial ischemia due to conditions like cardiovascular shock

Other possibilities:

  1. Massive vasoconstriction

  2. Arterial embolism

  3. Ischemia without atherosclerosis (e.g. shock)

The time has come: After having a firm understanding of the aetiology and pathogenesis of AMI, now you are well-equipped to have a go with and understand the main points associated with the three aspects of AMI diagnosis: its clinical appearance as well as its characteristic laboratory and ECG findings.

Clinical manifestations and diagnosis of acute myocardial infarction (AMI):

Clinical Presentation:

- Chest pain that is prolonged (>30 minutes), severe, and associated with a fear of death - unlike the brief, less severe pain of angina

- Rapid, weak pulse due to stress and anxiety

- Profuse sweating, nausea, and vomiting

- Signs of decreased myocardial contractility and perfusion, such as hypotension and edema

- Note that up to 25% of AMI cases may be asymptomatic or have very mild symptoms

Electrocardiogram (ECG):

- The hallmark ECG sign of AMI is ST segment elevation, often described as "tombstoning"

- This indicates myocardial necrosis has occurred, unlike the ST depression or T wave inversion seen in angina (myocardial ischemia)

ST Elevation: indicates myocardial necrosis so pt has myocardial infarction. More frequent through aging.

TIME course:

Laboratory Tests:

- Detection of cardiac-specific proteins like troponin and creatine kinase in the blood

- These proteins are released into circulation when myocardial cells die and their membranes are disrupted

- Their levels show a transient rise and fall, as opposed to a sustained elevation which would indicate a different condition

Necrosis leads to dell of cell so cells that are only supposed to be in myocardial will be detected in blood.  Cells released.

When carrier proteins are detected: they die, these protiens die and no further supply. Transient supply. Indicate AMI

- AMI is diagnosed based on the clinical picture, ECG findings, and laboratory test results

- If any of these three indicate AMI, the patient should be treated as such, as time is critical to salvage as much myocardium as possible

  • Clinical picture, ECG, or laboratory test. All 3 individual indicates AMI. Treat according.

Clinical Picture

  • Prolonged chest pain

  • Crushing, stabbing or squeezing pain of death

  • Dyspnea and oedema

  • Nausea and vomiting

  • However AMI may be asymptomatic in about 25%

Management of acute myocardial infarction (AMI):

Goals of AMI Treatment: Blood clot blocks blood flow

Time is Myocardium

- Prompt restoration of blood flow and myocardial perfusion (reperfusion)

- Reduction of myocardial oxygen demand

- Maintenance of balance between myocardial oxygen supply and demand

- Prevention of thrombus propagation and further myocardial damage

Treatment Strategies:

1. Pain control:

   - Administration of powerful analgesics like morphine

2. Reperfusion: prompt

   - administer Fibrinolytic ("clot-busting", clot busters) drugs to dissolve the occluding thrombus

   - Primary percutaneous coronary intervention (PCI) with balloon angioplasty and stenting

3. Reducing myocardial oxygen demand: to preserve tissue

   - Beta-blockers to decrease (cardiac output) heart rate and contractility

   - ACE inhibitors to reduce afterload

  • Decrease myocardial demand

4. Increasing oxygen supply:

   - Supplemental oxygen administration

5. Preventing thrombus propagation:

   - Antiplatelet agents (e.g. aspirin)

   - Anticoagulants (e.g. heparin)

6. Managing complications:

   - Antiarrhythmic medications to prevent life-threatening arrhythmias

7. Glyceryl trinitrate (GTN):

   - Versatile drug that can achieve multiple goals:

     - Reduce preload and afterload, decreasing myocardial oxygen demand

     - Cause coronary vasodilation, improving oxygen supply

     - Exhibit anti-platelet effects, preventing thrombus propagation

   - Commonly administered sublingually for rapid onset of action

   - However, cannot dilate severely atherosclerotic coronary segments

  • Prevents vasodilation

  • Reduced Venous vasodilation, reduce reload, reduce contractile force which reduces oxygen demand.

  • Reduce Arterial Vasodilation, reduce afterload, reduce contractile force which reduces oxygen demand.

  • Coronary vasodilation, increased coronary perfusion, increased oxygen demand

  • No anti-platelets activities which inhibits thrombus formation.

  • Easy to administer

  • Rapis action

  • Effected can be terminated and bypass liver

  • GTN is converted to nitric oxide which is a powerful vasodilator.

Our second major topic for this week is cerebrovascular disease, and we will explore transient ischaemic attack (TIA) and the two types of stroke. As you will see, ischaemic stroke is most closely associated with atherosclerosis, thrombosis, and/or embolism, whereas haemorrhagic stroke is closely linked to hypertension. These connections further emphasise the importance of Week 4's learning material.

 

If there is anything you need to remember right from the beginning of our quest to understand cerebrovascular disease, here it is: Brain Is Special in every possible sense. It has a very special metabolism, and Mother Nature has equipped the brain with a unique circulatory system, which serves its intended purpose reasonably well but is not foolproof, unfortunately.

 

Why the brain's blood supply is so critical:

- The brain accounts for only about 2% of total body weight, yet receives 15% of the resting cardiac output.

- The brain is responsible for 20% of the body's total oxygen consumption, despite its small size.

- The brain has an extremely high demand for oxygen and glucose, which must be continuously supplied by the blood.

- Unlike other organs, the brain cannot store glucose or oxygen - it relies entirely on a steady blood supply to meet its metabolic needs.

- Impairment of blood flow to the brain, even slightly, can have severe consequences for brain function and lead to tissue damage or death.

- This makes the brain's blood supply and perfusion absolutely critical for maintaining normal brain activity and preventing neurological deficits.

  • 20% of oxygen and 50% of glucose consumed by the entire body.

 

Cerebral blood supply and the circle of Willis:

Importance of Continuous Brain Perfusion:

- The brain has an extremely high demand for oxygen and glucose, which must be continuously supplied by the blood.

- The brain lacks significant stores of oxygen and glucose, so it relies entirely on a steady blood supply.

- Any impairment of cerebral blood flow can rapidly compromise brain function and lead to irreversible brain damage or death.

 

The Circle of Willis:

- Mother Nature's solution to ensure adequate and redundant brain perfusion

Consists of four main arteries that supply blood to the brain:

  - Two internal carotid arteries

  - Two vertebral arteries

- These arteries are interconnected, forming the "circle of Willis" - interconnected system

- Allows blood flow to be redirected if one of the feeding arteries is blocked

 

4 BV coming in and 6 BV coming out

 

Limitations of the Circle of Willis:

1. Cannot compensate for global cerebral ischemia:

   - If overall cerebral blood flow is severely reduced (e.g. in cardiac rest,shock, severe hypertension), the circle cannot provide enough perfusion.

   - Can lead to diffuse brain damage and coma.

 

2. Limited collateral circulation beyond the circle:

   - Once the blood vessels branch off from the circle, there are limited collaterals to compensate for blockages.

   - Certain brain regions like the white matter, basal ganglia, and thalamus are most vulnerable.

 

Importance of the Middle Cerebral Artery: Massive

- Supplies the largest perfusion area of the brain

- Blockage of the middle cerebral artery can cause widespread and severe neurological deficits

  •  

 

So, we have reviewed the basics about the unique features of cerebral metabolism and blood supply — it's time to see what happens if something goes (terribly) wrong. 

 

 

Types of Stroke: necrosis of brain tissue because of lack of brain supply

1. Ischemic Stroke (80% of cases)

   - Caused by obstruction or occlusion of a cerebral artery

   - Leading causes:

     - Embolism (50% of cases), blood clot formed elsewhere which enters through AF and ends up in the arteries supplying the brain.

  • Can be cause by air bubbles.

       - Often from atrial fibrillation-related clots

     - In situ thrombosis (30% of cases) - occurred in particular reason ( atherosclerosis, HTN, Diabetes)

       - Due to atherosclerotic plaque rupture/erosion

     - Other vascular pathologies (20% of cases)

 

2. Hemorrhagic Stroke (20% of cases)

   - Caused by rupture of a cerebral blood vessel

   - Majority are intraparenchymal/intracerebral hemorrhages

     - Often due to hypertension-weakened vessel walls

   - Less common types:

     - Subarachnoid hemorrhage

       - Usually from a ruptured cerebral aneurysm

  • Burst where blood ends up in the brain

 

 

 

 

To be aware of : Subarachnoid hemorrhage: Berry aneurysm.

Between the brain and arachnoidmater ( one of protective layer of brain).

 

 

Consequences of Stroke:

- Ischemic stroke leads to tissue infarction/necrosis

- Hemorrhagic stroke causes direct tissue damage from bleeding

- Both types can lead to increased intracranial pressure and brain herniation

  - Brain moves away from blood which leads to Compression of the brainstem can be fatal

 

Transient ischemic attack (TIA) mini stroke and is similar to agina:

Definition of TIA:

- Temporary episode of decreased blood flow to the brain, spinal cord, or retina

- Does not result in permanent tissue damage or infarction

 

Characteristics of TIA:

- Blood flow is reduced, but not completely blocked

- Neurological symptoms are transient and resolve within minutes to hours

- Resembles a "mini-stroke" in its presentation

- Can be thought of as the "angina of the brain"

 

Significance of TIA:

- Indicates an underlying problem with the cerebrovascular system

- Signals an increased risk of a future full-blown stroke

- Even with proper management, about 10% of TIA patients will go on to have a stroke

 

Implications:

- TIA should be taken seriously, as it is a warning sign of potential stroke

- Patients who experience a TIA require prompt evaluation and management to reduce stroke risk

- TIA is a medical emergency and requires urgent medical attention

 

 

Risk factors for stroke:

Non-Modifiable Risk Factors:

- Sex: Males are at higher risk

- Age: Stroke risk increases with older age

- Genetics/Family history: Genetic factors can predispose to stroke

 

 

Modifiable Risk Factors:

- Smoking

- Obesity, especially abdominal obesity

- Hypercholesterolemia

- Sedentary lifestyle

- Alcohol and drug use

- Stress and anxiety

 

Modifiable disease may lead to … Disease-Related Risk Factors:

- Hypertension

  - Accelerates atherosclerosis

  - Increases risk of hemorrhagic stroke

- Diabetes

  - Promotes atherosclerosis

- Atrial fibrillation

  - Increases risk of thromboembolism and ischemic stroke

 

Importance of Prevention:

- Modifiable risk factors and underlying diseases should be actively managed

- Prevention is key, as brain tissue cannot regenerate once damaged by stroke

- Promoting a healthy lifestyle is crucial to reduce stroke risk

  • Take care of brain.

 

Clinical manifestations of ischemic stroke determined by region of brain affected;

Clinical Presentation of Ischemic Stroke:

- Clinical symptoms depend on the specific brain region affected by the vascular occlusion.

- Major cerebral arteries and their perfusion areas:

  - Anterior cerebral artery: Supplies frontal lobe

    - Cognitive impairment, personality changes, pre frontal cortex is affected

  - Posterior cerebral artery: Supplies occipital lobe

    - Cortical blindness, visual cortex which cause cortical blindness

  - Most common. Single most important area affected by stroke.Middle cerebral artery: Largest perfusion area

    - Motor deficits (contralateral paralysis)

    - Sensory deficits (contralateral)

    - Cortical blindness

    - Aphasia (language disturbances)

 

Diagnosis and Prognosis, Mechanisms of Neurological Deficits:

- Damage to motor cortex leads to contralateral paralysis

- Disruption of sensory pathways causes contralateral sensory deficits

- Involvement of visual pathways results in cortical blindness

- Damage to language centers causes aphasia

 

Importance of Localizing the Affected Arterial Territory:

- Clinical presentation provides clues to which cerebral artery is occluded

- Allows inference of the specific brain regions affected

- Aids in diagnosis and predicting the likely neurological consequences of the stroke

 

We have two more brief recordings to go: the first explores the diagnosis and prognosis of stroke and will underscore (once more) the well-known sentiment associated with stroke management: Time is brain.

 

Diagnosis and prognosis of stroke:

Importance of Early Diagnosis and Management:

- "Time is brain" - Irreversible brain damage occurs within 4-6 minutes of ischemic onset

- Rapid diagnosis and treatment are critical to salvage brain tissue and minimize neurological deficits

  • Aim to save neurons, they don’t necessary die and can improve. Stroke is brain oedema.

Circulatory interruption: 5-8 seconds leads to unconsciousness, 20-25 seconds leads to no electrical activity and 4-6 minutes leads to irreversible brain damage.

 

Clinical Presentation and the "FAST" Acronym:

- F - Face drooping (indicates motor deficits)

- A - Arm weakness (contralateral paralysis)

- S - Speech difficulties (aphasia)

- T - Time is of the essence, call emergency services immediately

 

The Penumbra and Potential for Recovery:

- Penumbra region around the core infarct has disturbed but salvageable neurons

- If blood flow is restored, penumbra neurons may recover function

- Edema resolution can also improve clinical presentation

- Prompt management aims to limit expansion of the infarct core

 

Implications for Prognosis:

- Early diagnosis and rapid treatment can significantly improve outcomes

- Time is the critical factor in maximizing brain tissue salvage and minimizing permanent deficits

- Delayed presentation and management lead to more extensive and irreversible brain damage

 

 

Finally, we will review the most important aspects of stroke management. A word of warning: ischaemic stroke and haemorrhagic stroke require entirely different approaches, and these approaches are not interchangeable. 

 

 

Key Points on Stroke Management. Important to differentiate.

Ischemic Stroke

- Most important goal is to restore blood flow as quickly as possible, usually within 3-6 hours

- This is done through administering fibrinolytic (clot-busting) drugs like tissue plasminogen activator (tPA)

- Also important to prevent further blood clots from forming, so long-term antiplatelet therapy is given

- Manage underlying risk factors like diabetes, smoking, obesity, etc.

  • Long term anti-platelet surgery

  • Management and control of risk factors

  • tPa should not be administered in the area of hemorrhagic. Blood clotting may cause more hemorrhage due to tPa.

 

Hemorrhagic Stroke

- Bleeding is the main issue, so fibrinolytic drugs like tPA are contraindicated as they can worsen bleeding

- If the bleeding site can be accessed, surgical intervention may be needed to stop the bleeding

- Reduce intracranial pressure through diuretics and anti-seizure medication(anti-convulsant to prevent seizures) if needed

- Overall treatment options are more limited for hemorrhagic stroke compared to ischemic

 

 

Summary

- Stroke management depends on whether it is ischemic (blood clot) or hemorrhagic (bleeding)

- For ischemic stroke, the priority is rapid restoration of blood flow through fibrinolytic drugs like tPA

- For hemorrhagic stroke, the focus is on controlling bleeding and reducing intracranial pressure

- Long-term management also involves addressing underlying risk factors in both cases

How's that? I've summarized the key points on the management of ischemic versus hemorrhagic stroke based on the lecture content you provided. Let me know if you need any clarification or have additional requests.