Ischemic Heart Disease William J Hunter MD

Types of Heart Disease Acquired Heart Disease Acquired Heart Disease Congenital Heart Disease Congenital Heart Disease

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

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.

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

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

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

Acute coronary Syndrome

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

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

Atherosclerotic plaque

Hemorrhage into plaque compromises lumen

Cut section of a coronary artery with complete occlusion

Histologic section with recent thrombosis

Rupture of Plaque

Progression of Myocardial necrosis after occlusion

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

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

Arteries involved LAD ( %) Anterior wall, apex, Anterior 2/3 septum LAD ( %) 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

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

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

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

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)

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

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

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 min Microvascular injury > 1 hr

Gross Changes of MI Up to 5 hours- no changes Up to 5 hours- no changes 6-24 hour- pallor 6-24 hour- pallor hours- central pallor - hyperemia at margins 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

Acute myocardial infarct

Acute MI - 4 days

Acute MI

Myocardial changes

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 hours- coagulative necrosis, PMN 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

Normal myocardium – note central nuclei and intercalated disks

Early ischemia- contraction bands

Early MI – coagulation necrosis. Pyknosis and karyolysis of nuclei

Early coagulation necrosis- loss of myocyte nuclei

MI 4days

Later coagulation necrosis – infiltration of neutrophils

Remote infarct – fibrous scar

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

Complications of MI – Hemopericardium due to rupture

Rupture of myocardial infarct hemopericardium Area of infarct

MI with rupture

Rupture of myocardial infarct

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

Rupture of papillary muscle

Infarct of papillary muscle – leading to mitral valve dysfunction

Mural thrombus

Ventricular aneurysm due to MI - with mural thrombus thrombus

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

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

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

Effects of reperfusion