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Coronary Artery Disease by Duber (9/30/02)Pathogenesis Abruptly changing disorder During on, develop atherosclerotic plaque with a lipid core, smooth muscle cells, and collagen. The artery will subsequently expand to accommodate for this change. The progression of the disease depends on the stability versus the vulnerability of the plaque More collagen, more smooth muscle cells, less lipid in the plaque the more stable Thinner plaque more likely to rupture Thicker plaque less likely to rupture The plaque composition is a more important determining factor of disease versus the degree on obstruction (very unpredictable, not a gradually progressive disorder) There is initial dilation (inflammation) of the smooth muscle to compensate for obstruction plaque gets larger rupture of the plaque and release mediating factors Factors which can initiate inflammation and plaque rupturing: 1) Stress 2) Increase BP 3) Previous Infections (Chlamydia) 4) C-Reactive Protein 5) Platelets 6) Thrombosis Most likely to rupture at the shoulder of the capMyocardial Ischemia Demand for oxygen exceeds the supply Factors determining demand: 1) Myocardial Tension 2) Myocardial Contractility 3) Extrinsic Factors (i.e. exercise, fever, etc.) 2. Factors determining supply : 1) Fixed Coronary Obstruction 2) Dynamic Obstruction (spasm); endothelial dysfunction 3) Extrinsic Factors (i.e. GI bleed, carbon monoxide poisoning, etc.)Possible Risk Factors (other than those listed on handout) 1) Infection 2) Second-hand smoke ; air pollution 3) Enzyme deficiences 4) Stress 5) Sedentary Activity/ObesityManifestations of CAD 1) Clinical Spectrum (angina pectoris) 2) Electrical: Cardiad arrhythmias 3) Hemodynamic: Myocardial dysfunction In about 25% of persons, the first symptom is sudden deathAngina Pectoris Classification of Angina Pectoris (see second to last page of handout) Keep in mind of the patients age and physical activity when classifying patients Evaluation of Chest Pain 1) Location/radiation 2) Character/intensity 3) Onset/frequency/duration 4) Precipitating/relieving factors Levines Sign: Diffuse discomfort, often deep in the center in the chest Usually radiates to many areas Often described as: heavy pressure, burning, etc. (not poking, piercing sensation) Stable angina: No change for at least 60 days Indicates a stable plaque Usually the discomfort lasts for minutes at a time (5-20 minutes) Unstable Angina: Prone to having plaque rupture total occlusion myocardial infarction 3. Common Etiologies on Chest Pain (differential diagnosis): 1) Myocardial Ischemia 2) Pericardial and/or Pleural Inflammation 3) Dissecting Thoracic Aortic Aneurysm 4) Neuromuscular 5) Gastrointestinal Source 6) Anxiety Causes of Angina Pectoris 1) CAD (atherosclerosis, etc.) 2) Aortic Valvular Disease 3) Hypertrophic Cardiomyopathy 4) Excessive Imbalance between supply and demand Symptoms of Angina 1) Chest Pain 2) Shortness of Breath 3) Exertional Fatigue When ischemia produces HYPOKINESIA (decreased contractility) of the muscle, and this leads to the symptoms listed above Silent Myocardial Ischemia: Ischemia with no presenting symptoms More common in diabetics Progression of Myocardial Ischemia: Supply/demand dysfunction abnormal wall motion diastolic dysfunction systolic dysfunction EKG abnormalities anginaDiagnostic Evaluation of CAD 1) History and physical (see table on last page of handout) 2) Resting Electrocardiogram (50% of the time it will be normal) 3) Chest Xray 4) Laboratory Evaluation 5) Electron Beam Computerized Tomography a. If normal CT scan 2% or less chance of CAD b. Not predictive of coronary events 6) Provocative Testing a. Routine Exercise Electrocardiography (45% sensitive/85% specific) i. Problem: Not sensitive nor specific enough to be diagnostic b. Pharmacological Induction

of Ischemia (good if cant exercise) i. IV Dobutamine: Stress 1. Increases myocardial contractility Induce CAD ii. Adenosine: Coronary Steal 4. 1. Coronary Vasodilator (normal arteries) See ischemia in abnormal arteries because it is stolen away by the normal ones c. Supplemental Imaging i. Nuclear: Myocardial perfusion (Thallium, Technetium, etc.) 1. Give agent, have patient exercise, anterior wall will become ischemia, see perfusion defect in anterior wall ii. Nuclear: Wall motion iii. Echocardiography: Wall motion 7) Invasive Evaluation a. Coronary Angiography: Gold standard for diagnosis of CAD Typically reserved for more severe cases Mitral Valve Regurgitation due to papillary muscle dysfunction (another reason for myocardial ischemia) Hypertension: Most common cause of Left Ventricle hypertrophyRisk Stratification of CAD 1) Left Ventricular function 2) Anatomic extent/severity of CAD a. How many vessels affected? 3) Stable versus Unstable (vulnerable) plaque a. Difficult to see how stable the plaque is. Best determined by history 4) General health/ co-morbidity a. Age, other health problems, etc.Therapy for Chronic CAD 1) Behavioral modification a. Diet (lower LDL cholesterol, raise HDL, restrict salt intake) b. Exercise (helps stabilize plaques, reduces likelihood of coronary event) c. Alcohol (drink 1-2 drinks a day have a reduced risk) d. Treat associated medical conditions (i.e. diabetes, hypertension) e. Modifiable Risk Factors in CAD i. Cigarette smoking ii. Hypercholesterolemia iii. Hypertension iv. Diabetes mellitus v. Glucose intolerance vi. Low levels of HDL/high total cholesterol 2) Medications to prevent coronary occlusion a. Aspirin & Anti-Platelet Agents i. If plaque ruptures inflammation and plaque formation occurs 5. ii. Want to stop this with the anti-platelets b. Anti-Coagulants (Warfarin) i. May not be that effective c. Lipid Therapy (Statins) i. Changes the composition of the atherosclerotic plaque 1. Lower lipid core, more collagen more stable 3) Modifications to decrease ischemia a. Nitrates (avoid tolerance) i. Potent venodilators less blood to heart and less tension ii. Reduce Preload/Afterload iii. Increase collateral flow iv. Spasm blocked v. Problem: Severe headaches, but otherwise well-tolerated b. Beta-Blockers i. Decrease heart rate, contractility, systolic blood pressure decrease oxygen demand ii. Reduces the likelihood of a coronary event (especially sudden death) iii. Contraindicated: Pulmonary diseases, bradycardia c. Calcium Antagonists i. Improve coronary blood flow ii. Reduced Afterload iii. Slightly reduced preload & contractility iv. Spasm prevented v. Decrease coronary vascular resistance vi. SHOULD BE USED WITH A BETA-BLOCKER 4) Coronary Revascularization (increase oxygen supply) a. Percutaneous b. Transthoracic c. Investigational i. EECP ii. Atherogenesis (gene therapy, etc.) 5) Secondary Prevention of CAD a. Behavioral modification b. Medications to prevent coronary occlusion 1) Aspirin, anti-platelets 2) Lipid Reduction Therapy 3) ACE Inhibitors For people with previous CAD, diabetics, peripheral vascular diseaseCoronary Vasospasm (Printzmetals Angina/Variant Angina) 1) Extremely RARE disorder 2) Transient reduction in coronary blood flow due to spasm 3) Diagnostic: ST segment elevation DURING pain (difficult to diagnose) 4) Problem with supply, not demand. So Beta-Blockers are not effective