Case 5: Novak B. Part 1 - Atherosclerosis + Angina

Coronary Arteries

Branch off from aortic sinuses

• Above aortic valve on ascending aorta

Blood enter during diastole

• Valve open (systole) = Block sinus = No blood flow

• Right: 50% diastole

• Left: 75% diastole (stronger contraction)

Right Coronary Artery (RCA)

Right aortic sinus → Right AV groove

Divide into posterior descending artery (PDA) and marginal branch

RCA: PDA

In posterior interventricular sulcus (between ventricles)

RCA: Marginal

Around acute (right) side of heart

Left Coronary Artery (LCA)

Left aortic sinus → Left AV groove

Divide into left anterior descending (LAD) and circumflex branches

LCA: LAD

In anterior interventricular sulcus (between ventricles)

LCA: Circumflex

Around obtuse (left) side of heart

Coronary Veins

Empty into coronary sinus on posterior AV groove → Into right atrium

Great Cardiac Vein

Parallel LAD

Middle Cardiac Vein

Parallel PDA

Small Cardiac Vein

Parallel marginal branch

Thebesian Cardiac Veins

Smallest

Empty blood into all 4 heart chambers

• Mostly right atrium

Coronary Dominance

Right-Dominant: PDA from RCA

Left-Dominant: PDA from LCA

• Higher risk

• Occlusion = left heart failure

Determinants of Coronary Circulation

Sympathetic innervation

Metabolites

Mechanical compression

Determinants: Sympathetic Innervation

Minor role

Decrease Blood Flow: Release norepi = Bind alpha-adrenoceptors = Vasoconstriction

Increase Blood Flow: Release epi and norepi = Bind beta-adrenoceptors = Vasodilation

• During increased myocardial demand

Determinants: Metabolites

Active Hyperemia: Increased metabolic activity = Increase O2 demand = Release vasodilator substances

Hypoxia: Vasodilation = Increase blood flow

Adenosine: Released from cardiac myocytes = Bind adenosine receptors in coronary vascular smooth muscle = Vasodilation

Determinants: Mechanical Compression

Systole = Occlude/compress blood vessels = Reduce blood flow

Diastole = Reactive hyperemia = Increase blood flow and O2

O2 Use in Muscles

Oxidative phosphorylation convert substrate to energy (ATP)

Low O2 = Anaerobic respiration (glycolysis)

• Glycogen/Glucose → Pyruvate → Lactate

• Produce less ATP

• Ex: Ischemia

Heart Muscle: Energy Substrate

FFA: 70-90%

Other nutrients: 10-30%

• Glucose, lactate

Heart Muscle: O2 Consumption

Directly related to cardiac minute work

• Cardiac Minute Work = CO x Aortic pressure

• Component 1: Volume work (CO)

• Component 2: Pressure work (aortic pressure) → More energy demanding

Greater in LV

• Same CO

• Aortic pressure > Pulmonary pressure

Heart Muscle: Increase Volume Work

Increase CO = Small increase in O2 consumption needs

Ex: Exercise

Heart Muscle: Increase Pressure Work

Increase aortic pressure = Large increase in O2 consumption needs

Ex:

• Aortic stenosis → Increased afterload

  • Stiff aortic valve = Require more pressure to pump into aorta

• Systemic/pulmonary hypertension

  • Increased arterial pressure = Increase aortic/pulmonary trunk pressure

Compensation for Increased Pressure Work

Ventricular hypertrophy

Laplace Law: Increase wall thickness (hypertrophy) = Increase pressure generated (overcome aortic/pulmonary trunk pressure) = Ventricular failure

Heart Muscle: ATP Use

Na+-K+ ATPase: Maintain RMP

Ca2+ pump in sarcoplasmic reticulum: Relaxation

Myosin ATPase: Relaxation (myosin detachment)

Skeletal Muscle: Energy Source

FFA: At rest and light exercise

Carbs: During strenuous exercise

• Glucose, glycogen

Skeletal Muscle: O2 Consumption

Increased myoglobin (O2 reserve) to supplement during low O2

Arterial Wall

3 layers

1. Intima: Innermost

2. Media: Middle

3. Adventitia: Outer

Arterial Wall: Intima

Endothelial cells

Barrier between blood and vessel wall

Arterial Wall: Media

Thickest layer

Contractile and elastic functions

• Systole: Stretch from high pressure

• Diastole: Recoil to propel blood forward

• Contract = Increase resistance = Decrease flow

Contain:

• Elastic fibres

• Smooth muscle cells

• ECM

Arterial Wall: Adventitia

Elastic tissue + collagen

Nerves

Lymphatics

Blood vessels for arterial wall

Larger vs Smaller Arteries

Larger (aorta): Most elastic fibres

Smaller (coronary): Muscular, less elastic fibres

Athersclerosis: Description

Inflammation and plaque buildup in arterial wall

Atherosclerosis: Epidemiology

More common in males

Risk Factors:

• Older age

• Comorbidities

  • Hypercholesteremia

  • Dyslipidemia (high total cholesterol, low HDL)

  • Diabetes

  • Hypertension

• Fam history

• Smoking

Atherosclerosis: Etiology

Lipid, cholesterol, calcium plaques in arteries

Occlude lumen = Decrease blood flow

Athersclerosis: Pathogenesis

1. Chronic stress on arterial endothelium from hypertension and turbulence

2. Endothelial cell dysfunction = Increase permeability

• Increase inflammatory cell invasion

• Platelet adhesion to damaged wall

  • Release inflammatory mediators (cytokines) and platelet-derived growth factors (PDGF)

  • PDGF increase SMC proliferation and fibrosis

3. Chronic inflammation

• Macrophages and SMCs ingest cholesterol (LDL) → Foam cells

4. Foam cells accumulate → Fatty streaks = Early atherosclerosis

5. Foam cells and SMCs increase ECM deposition (collagen) in intima

• PDGF-triggered from platelets and endothelial cells

• Form fibrous plaque (atheroma) under endothelial cells

6. Tunica intima calcifies

• Positive Remodelling: Unstable plaque + Same lumen diameter

  • Thin fibrous cap + large lipid core, prone to rupture, weak outer layer

• Negative Remodelling: Stable plaque + Decrease diameter

  • Thick fibrous cap + small lipid core, not prone to rupture, stiff outer layer

7. Plaque ruptures

• Thrombogenic material (collagen) released into bloodstream → Thrombus

Coronary Atherosclerosis

Plaque formation in coronary arteries

Restrict blood flow to myocardium → Ischemia

Non-Coronary Atherosclerosis

Plaque formation in arteries outside heart (periphery)

Common in:

• Abdominal aorta

• Popliteal arteries

• Carotid arteries

• Circle of Willis (arteries at base of brain)

Atherosclerosis: Investigations

Blood test

Imaging

Atherosclerosis Investigation: Blood Test

Complete lipid profile

• High cholesterol

• High LDL and VLDL

• Low HDL

Atherosclerosis: Imaging

Coronary CT angiography (CCTA)

• Visualize arteries and plaques

• With or without contrast

Carotid ultrasound

• Assess artery thickness and plaques

Atherosclerosis: Clinical Presentation

Coronary: Angina and chest discomfort

Non-Coronary: Decreased O2 reaching brain and retinas

• Transient ischemic attack (TIA): Sudden neurological deficits

  • Unilateral weakness and numbness

  • Speech disturbances

  • Monocular blindness

• Ischemic stroke: Persistent neurological deficits

  • Motor and sensory loss

  • Aphasia (communication disorder)

  • Vision changes

• Bowel ischemia

Atherosclerosis: Treatment/Management

Lifestyle changes

Pharmacological

Athersclerosis: Lifestyle Changes

Life’s essential 8 framework

1. Nutrition: Dietary approaches to stop hypertension (DASH) diet

• Balanced diet

• Low sugar, red meat, added fats

2. Increase physical activity

3. Avoid nicotine

4. Sleep

5. Normal weight

6. Low non-HDL cholesterol

7. Normal blood glucose

8. Decrease BP

Smoking cessation

Atherosclerosis Treatment: Pharmacological

Statins

• + nonstatin lipid-lowering therapy for high-risk

Antiplatelet therapy

• Ex: Aspirin

Atherosclerosis Pharmacological: Statins

Ex: Rosuvastatin

MOA: Inhibit hepatic HMG-CoA reductase = Decrease cholesterol synthesis

Atherosclerosis Pharmacological: Non-Statin Lipid-Lowering Therapy

Ezetimibe: Inhibit cholesterol absorption

PCSK9 Inhibitors: Abs against enzyme degrading LDL receptors

• Ex: Evolocumab, Alirocumab

Bile Acid Sequestrants: Inhibit bile acid reabsorption

• Ex: Cholestyramine, Colesevelam

Atherosclerosis Prevention

ABCDS

A: Aspirin

B: BP control

C: Cholesterol management

D: Diabetes management

E: Exercise

S: Smoking cessation

Angina: Description

Paroxysmal (short, sudden, recurrent) chest discomfort, tightness, and pressure

Angina Types

Stable: Reproducible symptoms

• Predictable severity and frequency

• Symptoms subside with rest/nitroglycerin

Unstable: Longer symptom duration

• No response to rest/nitroglycerin

Variant: Transient

• From coronary artery spasms

Angina: Epidemiology

Risk factor: Atherosclerosis

Angina: Etiology

Myocardial ischemia

Angina: Pathogenesis

Decreased O2 delivery to myocardial tissue from coronary arteries due to plaque formation + coronary artery stenosis

1. Plaque formation from atherosclerosis

• Stable plaque = Stenosis

2. Stiff arteries increase resistance to blood flow = Decrease flow

3. Low O2 delivery = Ischemia

• Reversible: Salvage tissue by restoring O2 supply (angina)

• Irreversible: Tissue necrosis (scarring)

Angina: Investigations

Imaging

ECG

Angina: Imaging

Coronary Angiography: Determine plaques and stenosis

Echocardiogram: Determine heart abnormalities (dilation, hypertrophy, inflammation)

Angina: ECG

Stable: Usually normal

Ischemia: ST-segment depression, T wave inversion

Angina: Clinical Presentation

No chest tenderness

Gradual intensity increase

Radiation to adjacent areas

• Left arm

• Neck 

• Jaw

No changes with respiration

Questions to Ask:

• Nausea

• Dyspnea

• Dizziness

• Sweating (diaphoresis)

Angina: Treatment/Management

Pharmacological

• Nitrates

• Beta-blockers

• Ca2+ channel blockers

Angina Pharmacological: Nitrates

Ex: Nitroglycerin

MOA: Increase NO = Vasodilation = Increase blood flow to heart

Angina Pharmacological: Beta Blockers

Ex: Metoprolol, Propranolol

MOA: Block beta-1 receptors = Vasodilation = Increase blood flow to heart

Angina Pharmacological: Ca2+ Channel Blockers

Ex: Amlodipine

MOA: Block calcium entry into cardiac muscles = Decrease cardiac contraction

Ranolazine: Inhibit late Na+ current = Decrease Na+ and Ca2+ in cell = Increase myocardial relaxation

Acute Coronary Syndrome (ACS): Description

Conditions causing acute myocardial ischemia

• STEMI

• NSTEMI

• Unstable angina

ACS: Clinical Presentation

Acute chest pain (angina)

Dyspnea

Pallor

Nausea and vomiting

Anxiety

Dizziness/lightheadedness and syncope

ACS: Investigations

ECG

Bloodwork

Echo (TTE)

ACS: ECG

STEMI: ST elevation in 2 contiguous leads (same anatomical area)

NSTEMI: ST depression and transient deviations, T wave inversions

ACS: Bloodwork

CBC

Basic metabolic panel

Coagulation panel

Troponin: Increased = Cardiomyocytes under stress (MI)

ACS: Echo

Not routine

For abnormal symptoms

ACS: Treatment/Management

Pharmacological

O2 therapy

ACS Treatment: Pharmacological

Aspirin

Nitroglycerin

Beta-Blocker: Vasodilator

RAAS Inhibitor

NO NSAIDS

ACS Pharmacological: Aspirin

MOA: Anti-platelet = Increase blood flow through stiff/plaque-occluded arteries

ACS Pharmacological: RAAS Inhibitor

ACE Inhibitor (ramipril) or ARB (lorsartan)

MOA: Decrease water retention = Decrease BP

ACS Management: O2 Therapy

Cyanosis

Resp distress/failure

SpO2 < 90%