Atherosclerotic Heart Disease Part I: Angina Pectoris

1. Atherosclerotic Heart DiseasePart I: Angina Pectoris Humayun J. Chaudhry, D.O., M.S., S.M., FACP, FACOI Chairman, Department of Medicine and Assistant Dean for Health Policy New York College of Osteopathic Medicine of NYIT September 20, 2005

2. Case Study • A 48 year-old man with a history of tobacco abuse is admitted to the hospital for elective bronchoscopy. On the evening of his admission, he tells the nurse visiting his room that he has been having substernal chest pain for the previous 15 minutes • As the medical resident on call that night, you are contacted first by the nurse • How urgent is this complaint? What do you do?

3. Case Study • Is there a prior history of ASHD? Does the current chest pain resemble previous episodes of angina pectoris? • What is the location, quality and severity of the pain? Is there Levine’s sign? Is there radiation of the pain? Is there SOB? Is there diaphoresis? Is there nausea? • What precipitated the pain? • Has there been any recent trauma, falls?

4. Differential Diagnosis (DDx) • Acute Myocardial Infarction (MI) • Pain generally persists longer than 30 minutes • More than 50% of deaths occur in first 2 hours • Angina Pectoris • Typically lasts less than 20 minutes • Is there unstable angina? • Angina at rest • New-onset angina • Worsening angina (“crescendo-decrescendo” angina: more frequent, more severe, or prolonged) • Causes: ASHD, coronary artery spasm, aortic stenosis, thyrotoxicosis, anemia, low diastolic blood pressure

5. Differential Diagnosis (DDx) • Acute Pericarditis • Pain is frequently pleuritic, worsened by recumbency, relieved by sitting up • Causes: Infection, Post-MI (e.g. Dressler’s syndrome), Uremia, Malignancy, Connective tissue diseases (e.g. Systemic Lupus Erythematosus) • Acute Aortic Dissection • See excruciatingly severe pain at onset that is tearing in nature

6. Differential Diagnosis (DDx) • Pulmonary Causes • Pulmonary embolism with infarction • Pneumothorax, Traumatic • Pneumonia • Gastrointestinal (GI) Causes • Gastroesophageal Reflux Disease (GERD) • Esophageal Spasm, Gastritis, Biliary Colic • Peptic Ulcer Disease (PUD), Pancreatitis • Musculoskeletal Causes • Costochondritis, Muscle straim/spasm, Rib fracture(s)

7. Unstable Angina and Intermediate Syndrome • Unstable angina represents a constellation of symptoms that usually indicates transient myocardial ischemia • It is an acute dynamic syndrome that is considered intermediate between chronic stable angina and acute MI • 750,000 hospitalizations annually in the U.S. • Progresses to acute MI in 15% of cases • Mortality in the first year after diagnosis is 10%

8. Unstable Angina • Up to 57% of patients undergo coronary revascularization within a year of presentation • Defined by its clinical presentation in the absence of EKG and cardiac enzyme changes diagnostic of an MI • Prinzmetal’s, or variant angina, can present similarly to unstable angina and is due to coronary artery spasm

9. Etiology and Pathophysiology of Unstable Angina • Imbalance in myocardial oxygen supply-demand ratio • Coronary vasoconstriction and platelet aggregation and/or thrombosis are key elements in this supply imbalance • Coronary endothelial plaque ruptures are independent factors • Anatomic location of lesion - areas of high shear stress are more susceptible • Lipid pool size • Amount of infiltrative macrophages within the plaque • Sympathetic tone • Neurohumoral environment • Impaired fibrinolysis

10. Angiography of a patient with unstable angina • Note the large thrombus formation in the RCA causingthe high grade stenosis and atheromatous ulcer • Rupture of the plaque is highly likely in the tortuous areas of the vessel

14. Atherosclerotic Heart Disease • One million deaths per year among Americans are the result of ASHD • More than two out of every five deaths in the U.S. are the result of ASHD • Of the current US population, 1 in 4 suffer from some form of ASHD • Prevalence increases markedly with age

15. Reduction in mortality ofASHD Deaths • Reduction of modifiable risk factors • Hypertension (better control) • Diabetes Mellitus (early diagnosis, better control) • Hyperlipidemia/Dyslipidemia (diet and/or statins) • Inprovement of socioeconomic circumstances • New methods of diagnosis and treatment • Enhanced access to care

16. Once upon a time… • In the late 1940s, if a 50 year-old man presented to a U.S. hospital emergency room complaining of chest pain and had EKG changes suggestive of myocardial ischemia or infarction, the following would be offered… • Sublingual Nitroglycerin to relieve the pain • Supplemental oxygen, as needed for hypoxia • Aspirin for analgesia • Absolute quiet • If the patient survived, he was kept in the hospital for four weeks for rest and rehabilitation

17. Vascular Injury • Vascular endothelial injury is the critical initiating event in atherogenesis • This injury leads to • Lipid accumulation • Release of various growth factors • Migration and proliferation of smooth muscle cells

20. Stary Classification “regression” possible I Isolated macrophage foam cells II Mainly intracellular lipid accumulation, “Fatty Streak” III Extra-cellular lipid pools, intra- and extra-cellularcalcium potentially “vulnerable” IV Core of extra-cellular lipids, “Atheroma” V Lipid core covered by fibrous cap Fibroatheroma (Va)/Mainlycalcific(Vb)/Mainly fibrotic (Vc) VI Surface defect (VIa)/Hematoma-hemorrhage (VIb)/Thrombus (VIc)

22. Proposed scenario of EDRF and Endothelin during ischemic syndromes

24. ASHD Risk Factors • Age (greater than 40 in males) • Male • Obesity (BMI greater than 30.0) • Tobacco Smoking • Hypertension • Diabetes Mellitus • Family History of Premature Heart Disease • Hyperlipidemia/Dyslipidemia

25. Approach to Patients with ASHD • History • Physical Exam • EKG • Cardiac enzymes – CPK-MB, AST, LDH, Troponin, Myoglobin • Admit to the hospital • Definitive treatment with pharmacologic and other interventions

26. Approach to Patients with ASHD • Stress test, as tolerated • Gradual exercise stress test • Regular stress test, exercise or pharmacological • Stress echocardiography or pharmacological • Cardiac catheterization (“cath”) – angiography • Percutaneous transluminal coronary angioplasty (PTCA) with stenting • Coronary artery bypass surgery (CABG)

27. Sudden Cardiac Death in Ischemic HD • A. Between 300,000-400,00 deaths a year • B. Accounts for 50% of all US cardiac deaths and approximately 25% of natural deaths • C. Cardiac arrest may be the first manifestation in many patients with ASHD and ½ of all sudden deaths occur in patients without a prior history of ischemic heart disease • D. Other causes of sudden death • 1. Dilated or hypertrophic cardiomyopathy-10-15% • 2. Valvular heart disease-5% • 3. WPW, long QT syndrome, and idiopathic V-fib

28. Sudden Cardiac Death-Treatment • A. Beta-blockers • B. ACE-Inhibitors • C. Anti-arrhythmics - Amiodarone • D. Automated Implantable Cardioverter Defibrillator (AICD) – the most effective tool at reducing incidence of sudden death • E. Revascularization to decrease ischemia

30. Adenosine • Is thought to act on the coronary vasculature via stimulation of the adenosine A2 receptors on smooth muscle cells which activates adenylate cyclase to produce cyclic adenosine monophosphate (cAMP) and smooth muscle relaxation • At pharmacological doses , adenosine can cross the endothelium lining and stimulate the receptors on the smooth muscle directly in an endothelium-independent mechanism • Adenosine also acts predominantly on vessels less than 150 microns in diameter

31. Nitroglycerine • A vasodilator that acts directly on smooth muscle through a cGMP mechanism – a non endothelial-dependent vascular response • Because coronary microvessels contain the enzyme needed to convert nitroglycerine into nitric oxide, nitroglycerine creates a dose related dilation of coronary vessles >200 microns in diameter

32. Coronary Stenosis • With coronary stenosis, the microvasculature dilates to compensate • During increased myocardial demand, the capacity of the microvasculature to dilate further is limited (the vessels are already maximally dilated), resulting in myocardial ischemia

35. “Hibernating” Myocardium • Hibernating Myocardium • Areas of myocardium supplied by severely stenosed coronary arteries that, over time, develop impaired left ventricular contractility despite the presence of viable myocardium • Clinical importance is that if blood flow is improved to these areas, there is improvement in contractility, which is associated with decreased heart failure symptoms and improved survival

36. Stunned Myocardium • Stunned Myocardium • Areas of myocardium that develop post- ischemic dysfunction in the absence of, or with, minimal necrosis • Stunning is seen following acute myocardial infarction or repeated episodes of angina

37. Stunned and Hibernating Myocardium • Both stunned and hibernating myocardium are characterized by severe wall motion abnormalities in the presence of living or viable myocardium • Dysfunctional stunned myocardium is more acute and will regain function over time without intervention • Hibernating myocardium is more chronic. Rigorous restoration of blood flow by revascularlization (CABG / PCTA with stenting) is needed in order to restore contractility

38. Bayes’ Theorem for Non-invasive Testing • The predictability of a given test depends on the prevalence of the disease in the study population (e.g., low likelihood, low probability; high likelihood, high probability) • Therefore, routine testing on asymptomatic individuals without significant cardiac risk factors should be avoided because such tests will result in more false positives than true positives • Diagnostic invasive testing is best applied to the group with an intermediate probability of coronary artery disease, such as patients with multiple risk factors and atypical chest pain or patients with typical chest pain but no risk factors

39. Who benefits from diagnostic testing? • A patient with a low pre-test probability of disease will continue to have a low likelihood of disease regardless of a (-) test • A patient with a high pre-test probability of disease will continue to have a high likelihood of disease regardless of a (-) test • Diagnostic testing is most beneficial for those patients with intermediate probability for disease

40. The Role of Diagnostic Testing • Once the diagnosis of ASHD has been made, or the patient has stable anginal symptoms, non-invasive testing remains useful in • stratifying patients into high risk and low risk groups • monitoring changes in patient status • drug management

41. Nuclear Imaging • The value of nuclear perfusion imaging using Thallium or Sestamibi (Technetium) has been well established for over the last 20 years • In comparison to exercise treadmill testing, perfusion imaging is more sensitive and provides better localization and identification of multi-vessel disease. Technically adequate studies are obtained in nearly all patients.

44. Medical Management of Chronic Ischemic Heart Disease • In the U.S., more than six million Americans have a history of ASHD and an estimated 11 million are affected to some degree with coronary plaque formation

45. Silent Ischemia • 30-40% of patients with myocardial ischemia due to ASHD are asymptomatic: they do not experience ischemic cardiac symptoms • Risk of MI and sudden death is as great as those experiencing symptoms (angina) • Evaluation includes • 1. Exercise testing • 2. Ambulatory ST segment monitoring • 3. Other non-invasive studies • Incidence post-infarction is approximately 30% • Treatment is similar to patients with symptoms

48. Treatment • Nitrates – • Dilate vessels and improve flow • Reduce afterload and preload • Preload = volume – end diastolic volume (EDV) • Afterload = amount of pressure generated to push blood out of the heart • Contractility can be improved by decreasing preload and afterload but if too vigorous this will decrease contractility • In LaPlace’s Law, Tension = Pressure X Resistance • As the preload pressure decreases and the radius goes down, wall tension becomes less, and the heart does not need to push as hard

49. Treatment of Chronic Ischemic ASHD (and Stable Angina Pectoris) • Beta-blockers • Decrease contractility, therefore decrease myocardial oxygen demand by decreasing wall tension • Calcium channel blockers • Platelet inhibitors • ASA (Aspirin) 50-500mg • Clopidogrel- for those who are ASA-intolerant • High dose ASA greater than 1000mg may not result in platelet inhibition