Pathophysiology of Coronary Artery Disease

Stable CAD

Oxygen imbalance that does not result in plaque rupture

Referred to as “stable ischemic heart disease (SIHD)” or “chronic coronary disease (CCD)”

Acute Coronary Syndrome (ACS)

Rupture of unstable atherosclerotic plaque in coronary arteries

Constellation of clinical symptoms that correspond to acute myocardial ischemia - Unstable Angina (UA), Myocardial Infarction (MI) or “Heart Attack”: NSTEMI (Non-ST-Segment Elevation MI); STEMI (ST-Segment Elevation MI)

Major players of the Platelet

Thrombin (Factor II)

Fibrin

PAR-1 Receptor

P2Y12 (ADP) Receptor

Thromboxane (TXA2)

Glycoprotein (GP) IIb/llla

Atherothrombosis - Adhesion

Plaque rupture exposes endothelial tissue factor (TF), activating the coagulation cascade via extrinsic pathway - potentiates thrombin production

Platelets adhere to exposed collagen on endothelium via surface glycoproteins (GP) and von Willebrand factor (vWF)

After adhesion, platelets activate and release substances promoting further platelet activation and vasoconstriction - Serotonin (5-HT), Adenosine diphosphate (ADP), Thromboxane A2 (TXA2)

Atherothrombosis – Activation

ADP and TXA2 - Induce platelet activation/recruitment which leads to change in platelet conformation; serves as surface for activation of clotting factors X and II

Promote vasoconstriction and upregulation of inflammatory cytokines

Conversion of GP IIb/IIIa receptor into active form

Thrombin - Most potent platelet activator, stimulates protease-activation receptor (PAR)-1

Atherothrombosis – Aggregation

Activated GP IIb/IIIa receptor - Potentiates platelet aggregation and spreading of platelets across extracellular matrix; Facilitates formation of fibrinogen “bridge” between activated platelets

Thrombin converts fibrinogen into fibrin - stabilizes interlocking platelets, creating a fibrin mesh-work

Platelet “plug” has formed

Unstable Angina (UA)

Partial occlusion of coronary artery

NSTEMI (Non-ST-Segment Elevation Myocardial Infarction)

Unstable plaque causing ischemia

STEMI (ST-Segment Elevation Myocardial Infarction)

Unstable plaque causing infarction

Requires immediate intervention to clear blockage

Signs of CAD

S: EKG changes, presence of biomarkers

Less important signs - Diaphoresis, Syncope, Hypotension, Hypertension, Tachycardia, Bradycardia

Symptoms of CAD

Sx: Angina pectoris (Chest pain)

Less important Sx - Pain radiating to left arm, nausea, vomiting, dyspnea at rest or upon exertion, atypical symptoms

Angina Pectoris

Cardiac chest pain - Symptomatic manifestation of ischemia

Substernal chest discomfort with a characteristic quality and duration, that can be provoked by exertion or emotional stress

Chronic stable angina (CSA) is relieved by rest or nitroglycerin

Change in any of the following warrants a call to EMS: Quality of chest pain, Location, Duration, Precipitating/relieving factors

Atypical Presentations of Angina Pectoris

Women

Diabetes mellitus

Elderly

Silent MI

Zone of Infarct (No ECG Manifestations)

ECG Changes

ST segment changes - Depression, elevation

T wave inversions

Q-waves

New Left Bundle Branch Block (LBBB)

Cardiac Biomarkers

Drawn from blood, Indicative of dying tissue

Troponin - Most specific, High-sensitivity troponin testing is now available

Myoglobin

Creatine kinase – myocardial band (CK-MB)

Assessment of CAD - Cardinal Symptoms and signs

Ischemic chest pain – angina pectoris (CARDINAL SYMPTOM)

ECG changes - ST-segment depressions, elevations, T wave inversions (CARDINAL SIGN)

Biomarkers (CARDINAL SIGN)

SIHD/CCD

Coronary Plaque - Stable

Angina - Precipitated by exertion or emotional stress and relieved by rest

Quality of Angina - Consistent

Lack of biomarkers

ST-Segment changes - Transient changes that develop during symptomatic episodes that resolves when the patient becomes asymptomatic

Unstable Angina

Coronary Plaque - Unstable

Angina - Precipitated by exertion or emotional stress and is NOT relieved by rest

Quality of Angina - Changing

Lack of biomarkers

ST-Segment changes - ST-segment changes that may develop during symptomatic episodes that do not resolve

Acute Myocardial Infarction

Coronary Plaque - Unstable

Angina - Precipitated by exertion or emotional stress and is NOT relieved by rest

Quality of Angina - Changing

Positive biomarkers

ST-Segment changes - ST-segment changes that do not resolve when the patient becomes asymptomatic or that develop at rest