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