Atherosclerotic and Ischemic Heart Disease

1. Atherosclerotic and Ischemic Heart Disease Howard L. Sacher, D.O. Chief, Division of Cardiology New York College of Osteopathic Medicine Adjunct Clinical Associate Professor of Medicine, New York College of Osteopathic Medicine

2. Teaching Objectives • To understand the pathogenesis of atherosclerosis and assess coronary flow reserve • To properly diagnose and manage stunned and hibernating myocardium • To make appropriate decisions in non-invasive testing processes and medical management of chronic ischemic heart disease, including the use of coronary angioplasty and coronary artery bypass grafts (CABG).

3. Teaching Objectives (cont) • To manage secondary prevention of coronary artery disease • To manage unstable angina, variant angina and silent myocardial ischemia • To review special considerations for the woman patient with heart disease

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

5. Reduction in mortality of CAD Deaths • Reduction of risk factors • Hypertension • Diabetes • Hyperlipidemia • Inprovement of socioeconomic circumstances • New methods of diagnosis and treatment • Enhanced access to care

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

8. Pathophysiology • Classification of vascular injury is divided into 3 types: • Type I functional alteration • Type II  Endothelial and Intimal damage, the internal elastic lamina is preserved • Type III  Deep injury involving the intima and media. The lamina is not preserved

9. After Type I injury, note the endothelium’s ability to release intrinsic relaxing substances

11. Proposed scenario of EDRF and Endothelin during ischemic syndromes

12. Endothelium • Decrease in vasodilitory substances such as EDRF (nitric oxide) with associated anti-proliferative properties • Release of vasoconstrictive substances, such as endothelin, with associated migration properties • Critical balance between nitric oxide and endothelin may be major determinant in regulatory system and regional hemodynamic function and cellular proliferation

13. CAD Risk Factors • Age • Male / Female • Obesity • Smoking • Hypertension • Diabetes • Family History • Hyperlipidemia

14. Approach to Patients with CAD • History • Physical Exam • Treatment • EKG • Cardiac enzymes – CPK-MB, Troponin • Admit to hospital

15. Approach to Patients with CAD (cont) • Stress test • Gradual exercise stress test • Regular stress test, exercise or pharmacological • Stress echocardiography or pharmacological • Coronary and cardiac catheterization – angioplasty • Percutaneous transluminal coronary angioplasty (PTCA) with stenting • Coronary artery bypass surgery (CABG)

18. Smooth Coronary artery segment that shows EDRF dependent dilation to ACh (will also dilate with exercise). When evaluating coronary segments that where irregular and stenosed, however, they did not show EDRF dependent dilation to ACH. These did not dilate with exercise

20. Adenosine • Thought to act on the coronary vasculature by stimulating the Adenosine A2 receptors on the smooth muscles. • Adenosine crosses the endothelial barriers to stimulate the Endothelial Independent Pathway for vasodilatation

21. 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 micrometers in diameter and therefore mainly assesses its changes in the coronary resistance vessels

22. Nitroglycerine • A vasodilator that acts directly on smooth muscle through a cGMP mechanism – a non endothelial-dependant 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

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

25. 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

26. Treatment (cont) • Beta Blockers • Decrease contractility, therefore decrease myocardial oxygen demand by decreasing wall tension • ACE- I (Angiotensin Converting Enzyme Inhibitors) • Lipid Lowering Agents • Aspirin

28. “Stunned” and “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

29. Stunned and Hibernating Myocardium (cont) • 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

30. Stunned and Hibernating Myocardium (cont) • 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 and rigorous restoration of blood flow by revascularlization (CABG / PCTA with stenting) is needed in order to restore contractility

31. Stunned and Hibernating Myocardium (cont) • Stunning can follow hibernation if the residual stenosis is sufficiently severe. If the area is necrotic, revascular-ization will not improve ventricular function.

32. The hypokinetic inferior and akinetic apical wall is shown to improve several months after revascularization

34. Bayes’ Theorum for Non-invasive Testing • The predictability of a given test depends on the prevalence of the disease in the study population. 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.

36. Who benefits from diagnostic testing from this last graph? • A Pt with a low pre-test probability of disease will continue to have a low likelihood of disease regardless of a (-) test • A Pt 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 Pt’s with intermediate probability for disease

37. Normal MIBI – uniform tracer uptake globally on SA slices

38. Ischemia that is a result of Stress is dynamic with cascade of events. Pain and ECG changes are seen late in the game

39. The Role of Diagnostic Testing • Once the diagnosis of CAD 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 and drug management.

40. Nuclear Imaging • The value of nuclear perfusion imaging using Thallium or Sestamibi (Technetium), has been established for over 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.

41. Sudden Cardiac Death in Ischemic HD • A. Between 300,000-400,00 deaths per year. • B. Accounts for 50% of all US cardiac deaths and approximately 25% of natural deaths. • C. Cardiac arrest may be first manifestation in many patients with CAD 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

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

43. Moral of story is to revascular for the greatest reduction in long term mortality