Lecture 43 Coronary Artery Disease Pathophysiology Klassen INTRODUCTION:

HEART:

Pumps blood through 2 main circuits o Pulmonary circulation o Systemic circulation

Supply (diastolic) vs. demand (systolic)

Heart blood supply: coronary arteries o Oxygenated blood for heart

function

HEART ANATOMY:

Triple (3) layer construction: o Endocardium: inner layer interacting with blood o Myocardium: muscular layer of cardiomyocytes o Epicardium: outer layer of support tissue

Pericardium: double walled sac with minimal fluid b/w layers o Structural and nutritional support o Limit heart volume (overfilling)

END CIRCULATION: limited redundancy in blood supply to heart

Left coronary artery: left ventricle/atrium o Left anterior descending artery: anterior wall/septum (2/3 supply) o Left circumflex artery: left ventricle

Right coronary artery: right ventricle/atrium o Right posterior descending artery: posterior of septum (1/3 supply) o Acute marginal arteries: whole right ventricle o Supply to pacemaker (sinoatrial and atrioventricular nodes)

ISCHEMIC HEART DISEASE:

MYOCARDIAL ISCHEMIA:

Inadequate blood supply (O2) o Imbalance: ischemia = O2 supply < O2 demand

Impact greatest on myocardium (highest O2 demand for function) o Demand: exercise, exertion o Supply: blockage/constriction o Both can occur simultaneously

> 98% from coronary artery disease o Atherosclerosis of coronary artery wall

thickening and blockage

Impairment of heart function o Insufficient oxygen o Limited nutrients o Build of metabolites/waste

IMBALANCE IN SUPPLY VS. DEMAND:

RISK FACTORS: Lifestyle Disease Genetics

Age (men > 60, women > 65)

Stress

Diet

Inactivity

Obesity

Smoking

Stroke

Peripheral vascular disease (vascular damage)

Hypertension (high systolic)

Hypercholesteremia (cholesterol deposits/artery narrowing)

Hyperglycemia (DM)

Family history of CVD

Ethnicity

CLASSIFICATION:

Acute coronary syndrome (ACS) o Unstable angina – changing/worsening

chest pain o Myocardial infarction – heart attack o Sudden cardiac death – heart cessation

Chronic coronary artery disease (CCAD) o Stable angina – chest pain after exertion o Coronary artery disease

Lecture 43 Coronary Artery Disease Pathophysiology Klassen

COMMON MANIFESTATIONS: majority are symptoms initially ANGINA PECTORIS: CHEST PAIN

STABLE/ TYPICAL ANGINA MOST COMMON

Pain comes with exertion (exercise, stress) (increased O2 demand)

Relief occurs when there is:

Decreased demand (rest)

Increased supply (vasodilation)

Prolonged onset (occurs over decades)

Gradual narrowing of coronary artery over time

VARIANT (PRINTZMETAL’S) ANGINA UNCOMMON (2-10%)

Transient pain occurring AT REST

Frequently missed and treated as acute coronary disease

Vasospasm – constriction of artery diameter

Although 30% have concurrent atherosclerosis, variant angina is not from atherosclerosis (unlinked mechanism)

UNSTABLE/ CRESCENDO ANGINA

Pain at rest (64% overnight)

Clinical diagnosis: 1/3 sx

Lasting > 10 min while at rest

New /severe pain within previous month

Crescendo pattern

Abrupt decrease in blood flow

Rupture / blockage by atherosclerotic plaque

S/S:

Burning/pressure on/near sternum

Radiating left side pain: jaw, shoulder, arm

Tight chest

Shortness of breath

ANGINA = CHEST PAIN

Pain caused by decrease/absence of blood flow o Transient: 15 sec – 15 min duration

Weak relationship b/w pain severity & O2 deprivation

Minimal or no tissue damage results from insult

MYOCARDIAL INFARCTION (MI): OVERVIEW:

Necrosis of endo and myo- cardium

Typically in left ventricle

Severe atherosclerotic narrowing

Occurs when multiple coronary arteries occluded

TYPES:

Transmural infarction: full thickness of ventricular wall; complete occlusion of blood supply to region

Subendocardial infarction: inner 1/3 to 1/2 of ventricular wall

MI SYMPTOMS:

Angina (chest pain) o Common sx BUT 20% are silent o Dull radiating pain (left side dominant)

Shortness of breath

Excessive sweating

Nausea/vomiting

FACTORS IMPACTING SIZE OF INFARCT REGION:

Severity & duration of ischemia

Location of block o Main vs. peripheral branches

Metabolic needs of region o Left ventricle requires more O2

Regions with fewer collateral blood vessels have > risk of damage

Heart rate/rhythm/blood pressure o Challenge supply/demand balance

MI CLINICAL COMPLICATIONS:

Contractile dysfunction: irreversible damage to myocardium

Arrhythmia: irregular contraction rhythm

Mural thrombus: perpetual clot on heart chambers that disrupt normal blood passage inefficient/working harder

Myocardial rupture: mechanical weakness in heart wall so there’s increased heart effort to accommodate O2 lack heart bursts/ruptures

Pericarditis: swollen pericardial sac that rubs on heart and chest with beats = chest pain (changes with body position) o Post infarct = 24 hrs post MI

Dressler’s Syndrome: onset week months post MI

CHRONIC MI CARDIAC FAILURE:

Progressive heart failure o Ischemic damage to myocardium o Hypertrophy: enlarged heart & ventricular walls

Compensation for absent/dead cardiomyocytes

Cardiac failure o Insufficient pumping to maintain blood flow to body

SUDDEN CARDIAC DEATH: natural, rapid and unexpected death (can occur w/o sx OR within 1 hr of sx onset) LETHAL VENTRICULAR ARRYTHMIA

Disrupted cardiac conduction/function

Ventricular fibrillation

Leading to cardiac output

AUTOPSY GENERALLY REVEALS:

Severe coronary atherosclerosis

Healed infarct

Limited necrosis

Focal fibrosis

Limited hypertrophy

Lecture 43 Coronary Artery Disease Pathophysiology Klassen

DIAGNOSTICS: ELECTROCARDIOGRAPHY (ECG):

Cardiac electrical conduction & function of myocardium o Indicates timing o Can indicate where an MI occurred

P wave: atrial depolarization

QRS complex: ventricle depolarization

T wave: ventricle repolarization

PR interval: conduction from atrium ventricle

QT interval: duration of ventricular action potential o DIAGNOSTIC INTERVAL

CARDIAC ANGIOGRAM:

Visualize problem

Injected radio-dense dye injected into heart

Visualised by x-rays

STRESS TEST/EXERCISE TOLERANCE TEST:

Examine cardiac function

Detect silent ischemia

At risk screening (gender, age, symptoms)

Effect of exercise/stressors on heart o Exercise: treadmill, stationary bike o Pharmacological: vasodilators

Clinical correlation: disease progression (incidence of angina, acute MI, cardiac death)

CARDIAC ENZYMES/MARKERS:

Damage to and degradation of tissues Cardiac markers Specificity Measurement

Myoglobin Non-specific Any muscle injury in body

Cardiac troponin (cTnT and cTnI)

High specificity for cardiac damage

Levels increase by 2 hrs post MI, spike in 12 hrs, and persist for < 2 weejs

Creatinine Kinase Non-specific Muscle injury or exercise damage

Lactate dehydrogenase

LDH-1 isozyme dominant in heart

High levels during tissue break down, up to 72 hrs post MI