1. Ischemic Heart Disease William J Hunter MD

2. Types of Heart Disease Acquired Heart Disease Acquired Heart Disease Congenital Heart Disease Congenital Heart Disease

3. Acquired Heart Disease Ischemic Heart Disease Ischemic Heart Disease Hypertensive Heart Disease Hypertensive Heart Disease Valvular Heart Disease Valvular Heart Disease Myocardial Heart Disease Myocardial Heart Disease

4. Ischemic Heart Disease Supply of oxygen in the coronary arterial blood is inadequate to provide for the oxygen demands of the heart. Supply of oxygen in the coronary arterial blood is inadequate to provide for the oxygen demands of the heart.

5. Epidemiology of ischemic heart disease 500,000 die 500,000 die Overall rate has fallen since 1980 Overall rate has fallen since 1980 Prevention - working on risk factors: smoking, hypertension, cholesterol, better diabetic control, aspirin prophylaxis Prevention - working on risk factors: smoking, hypertension, cholesterol, better diabetic control, aspirin prophylaxis Therapeutic advances- new medications, coronary care units, thrombolysis, angioplasty, stents and coronary bypass surgery Therapeutic advances- new medications, coronary care units, thrombolysis, angioplasty, stents and coronary bypass surgery

6. Results of Ischemic HD Angina Pectoris - ASVD Angina Pectoris - ASVD Stable angina Stable angina Prinzmetal’s angina - spasm Prinzmetal’s angina - spasm Preinfarction (unstable) angina - MI Preinfarction (unstable) angina - MI Myocardial Infarct- myocardial necrosis Myocardial Infarct- myocardial necrosis Sudden cardiac death Sudden cardiac death Chronic ischemic HD with heart failure- ‘focal fibrosis’ or presbycardia Chronic ischemic HD with heart failure- ‘focal fibrosis’ or presbycardia

7. Acute Coronary Syndromes The new ‘in’ word- TV ads The new ‘in’ word- TV ads A spectrum -from unstable angina to acute myocardial infarct A spectrum -from unstable angina to acute myocardial infarct Atherosclerotic plaque disruption and associated platelet-fibrin thrombus formation Atherosclerotic plaque disruption and associated platelet-fibrin thrombus formation Sudden death Sudden death

8. Acute coronary Syndrome

9. Etiology of Ischemic HD 95-98% Atherosclerotic Narrowing with plaques 95-98% Atherosclerotic Narrowing with plaques Coronary embolism (rare) Coronary embolism (rare) Dissecting aneurysm (rare) Dissecting aneurysm (rare) Arteritis (polyarteritis, rheumatoid, Kawasaki Disease) (rare) Arteritis (polyarteritis, rheumatoid, Kawasaki Disease) (rare) Syphilis (rare) Syphilis (rare) Cocaine abuse Cocaine abuse

10. Coronary Atherosclerosis 90% have at least one 75% occlusion- the key is acute change of the plaque 90% have at least one 75% occlusion- the key is acute change of the plaque Hemorrhage into the atheroma Hemorrhage into the atheroma Rupture of the plaque with thrombosis Rupture of the plaque with thrombosis Erosion or ulceration of the plaque with thrombosis Erosion or ulceration of the plaque with thrombosis Most have two arteries involved Most have two arteries involved Most blocks are in the epicardial arteries Most blocks are in the epicardial arteries

11. Atherosclerotic plaque

12. Hemorrhage into plaque compromises lumen

14. Cut section of a coronary artery with complete occlusion

15. Histologic section with recent thrombosis

16. Rupture of Plaque

17. Progression of Myocardial necrosis after occlusion

18. Myocardial Infarct Most have Most have >75% occlusion of coronary by plaque >75% occlusion of coronary by plaque multi-vessel disease multi-vessel disease 80% have recent thrombus 80% have recent thrombus LAD most commonly involved LAD most commonly involved

19. Typical MI Most have multivessel disease Most have multivessel disease Ulcerative stenotic plaque or hemorrhage into the plaque Ulcerative stenotic plaque or hemorrhage into the plaque Platelets aggregate Platelets aggregate Tissue thromboplastin released Tissue thromboplastin released Vasoactive amines released Vasoactive amines released Thrombosis and spasm occur Thrombosis and spasm occur Ischemic necrosis Ischemic necrosis

20. Arteries involved LAD (40 - 50%) Anterior wall, apex, Anterior 2/3 septum LAD (40 - 50%) Anterior wall, apex, Anterior 2/3 septum RCA (30- 40%) Post wall, post 1/3 septum RCA (30- 40%) Post wall, post 1/3 septum LCA (15- 20%) Lateral wall LCA (15- 20%) Lateral wall

22. Role of Hemodynamic Changes Sudden drop in BP Sudden drop in BP Must be difference in pressure between coronary ostia and coronary sinus Must be difference in pressure between coronary ostia and coronary sinus

23. Role of Vasospasm Vasospasm documented in angina Vasospasm documented in angina Spasm can cause rupture of plaques Spasm can cause rupture of plaques Rare cases of MI after spasm Rare cases of MI after spasm

24. Role of Platelet Rupture of Plaques > adherence Rupture of Plaques > adherence The aggregation contributes to blockage The aggregation contributes to blockage Thromboxane, histamine, serotonin => vasospasm Thromboxane, histamine, serotonin => vasospasm ASA helps ASA helps

25. Supply of O2 in the Blood Anemia Anemia CO and cyanide CO and cyanide O2 demand O2 demand Hypertension Hypertension Valvular disease Valvular disease Hyperthyroidism Hyperthyroidism Fever Fever Catecholamines Catecholamines (? personality types) (? personality types)

26. Role of acute Plaque Change in MI Hemorrhage into the atheroma - expanding its volume Hemorrhage into the atheroma - expanding its volume Rupture or fissuring, exposing the highly thrombogenic plaque constituent Rupture or fissuring, exposing the highly thrombogenic plaque constituent Erosion or ulceration Erosion or ulceration Note that the original plaque may not have been a significant lesion (no critical stenosis Note that the original plaque may not have been a significant lesion (no critical stenosis

27. Time of Day Peak incidence of MI: 6am to noon Peak incidence of MI: 6am to noon Adrenergic stimulation of awakening can put more stress on the plaque Adrenergic stimulation of awakening can put more stress on the plaque Surge of blood pressure at same time frame Surge of blood pressure at same time frame

28. Key Events in Ischemic Damage FeatureTime Onset of ATP depletion seconds Loss of contractility < 2 min ATP reduced to 50% to 50% 10 min to 10% to 10% 40 min Irreversible cell injury 20 -40 min Microvascular injury > 1 hr

29. Gross Changes of MI Up to 5 hours- no changes Up to 5 hours- no changes 6-24 hour- pallor 6-24 hour- pallor 24-48 hours- central pallor - hyperemia at margins 24-48 hours- central pallor - hyperemia at margins 2-5 days - hyperemic border, yellow band, soft dull center 2-5 days - hyperemic border, yellow band, soft dull center 5-10 days- broader yellow border and thin new pink border 5-10 days- broader yellow border and thin new pink border 10 days-3 wks - islands of red brown tissue surrounded by red-purple granulation tissue 10 days-3 wks - islands of red brown tissue surrounded by red-purple granulation tissue 3-6 weeks - fibrosis 3-6 weeks - fibrosis

30. Acute myocardial infarct

32. Acute MI - 4 days

33. Acute MI

34. Myocardial changes

35. Histology of MI 0-6 hours - none (? waviness) 0-6 hours - none (? waviness) 6-24 hours- eosinophilia, loss of cross striation 6-24 hours- eosinophilia, loss of cross striation 24-48 hours- coagulative necrosis, PMN 24-48 hours- coagulative necrosis, PMN 2-5 days- phagocytosis, granulation tissue 2-5 days- phagocytosis, granulation tissue 10 days - 3weeks increasing fibrosis, PMN’s disappear 10 days - 3weeks increasing fibrosis, PMN’s disappear 3-6 weeks - maturing fibrosis 3-6 weeks - maturing fibrosis

36. Normal myocardium – note central nuclei and intercalated disks

37. Early ischemia- contraction bands

38. Early MI – coagulation necrosis. Pyknosis and karyolysis of nuclei

39. Early coagulation necrosis- loss of myocyte nuclei

40. MI 4days

41. Later coagulation necrosis – infiltration of neutrophils

42. Remote infarct – fibrous scar

43. Complications of MI Arrhythmias (90%) Arrhythmias (90%) CHF 60% CHF 60% Cardiogenic shock 10% Cardiogenic shock 10% Rupture (wall, septum, PAP M.) 5-10% Rupture (wall, septum, PAP M.) 5-10% Mural thrombus and embolism Mural thrombus and embolism Pericarditis Pericarditis Ventricular Aneurysms Ventricular Aneurysms Papillary muscle dysfunction Papillary muscle dysfunction

44. Complications of MI – Hemopericardium due to rupture

45. Rupture of myocardial infarct hemopericardium Area of infarct

46. MI with rupture

47. Rupture of myocardial infarct

48. Rupture of ventricular septum– giving rise to Acute right heart failure

49. Rupture of papillary muscle

50. Infarct of papillary muscle – leading to mitral valve dysfunction

51. Mural thrombus

52. Ventricular aneurysm due to MI - with mural thrombus thrombus

53. Diagnosis of MI Symptoms and signs Symptoms and signs 1/2 may be silent 1/2 may be silent EKG- New Q-wave, S-T segment and T-wave changes EKG- New Q-wave, S-T segment and T-wave changes Enzymes, CK, (CKMB), Troponins Enzymes, CK, (CKMB), Troponins Drs. Lynch & Baltaro will talk more about this Drs. Lynch & Baltaro will talk more about this

54. Subendocardial Infarct- non Q wave infarct severe ASCD severe ASCD no critical stenosis no critical stenosis Multifocal or bridges arterial zones Multifocal or bridges arterial zones diabetes diabetes Dangerous Dangerous

55. Infarct Modification After Reperfusion Reperfusion early- may prevent most necrosis Reperfusion early- may prevent most necrosis Hemorrhage - leaky damaged vessels Hemorrhage - leaky damaged vessels Necrosis with contraction bands Necrosis with contraction bands Increased oxygen free radicals Increased oxygen free radicals

56. Effects of reperfusion