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3. C ARDIOVASCULAR S EQUENCE Kim A. Eagle, M.D. University of Michigan Health System Kim A. Eagle, M.D. University of Michigan Health System Coronary Artery Disease: Chronic Disease Fall 2008

4. O UTLINE Development of CAD Clinical presentation/definitions Concept of myocardial oxygen supply and demand Pathophysiology of chronic ischemia syndromes Diagnosis Treatment strategies Prognosis Development of CAD Clinical presentation/definitions Concept of myocardial oxygen supply and demand Pathophysiology of chronic ischemia syndromes Diagnosis Treatment strategies Prognosis

5. D EVELOPMENT OF CAD AHA C LASSIFICATION OF CAD TYPE I TYPE II Intimal thickening Foam cells Initial Lesion From 1st decade of life From 1st decade of life Clinically silent Clinically silent Initial Lesion From 1st decade of life From 1st decade of life Clinically silent Clinically silent Fatty Streak From 1st decade of life From 1st decade of life Growth by lipid accumulation Growth by lipid accumulation Clinically silent Clinically silent Fatty Streak From 1st decade of life From 1st decade of life Growth by lipid accumulation Growth by lipid accumulation Clinically silent Clinically silent K. Eagle

6. AHA C LASSIFICATION TYPE III Foam cell LipidLipid LipidLipid TYPE IV Foam cell LipidLipid Fibrous cap TYPE V Intermediate From 3rd decade From 3rd decade Further lipid pool Further lipid pool Clinically silent Clinically silentIntermediate From 3rd decade From 3rd decade Further lipid pool Further lipid pool Clinically silent Clinically silent Atheroma From 4th decade From 4th decade More lipid pool More lipid pool Clinically silent or overt Clinically silent or overtAtheroma From 4th decade From 4th decade More lipid pool More lipid pool Clinically silent or overt Clinically silent or overt Fibroatheroma Lipid core Lipid core Fibrotic layer Fibrotic layer Smooth muscle cells Smooth muscle cells Clinically silent or overt Clinically silent or overtFibroatheroma Lipid core Lipid core Fibrotic layer Fibrotic layer Smooth muscle cells Smooth muscle cells Clinically silent or overt Clinically silent or overt K. Eagle

7. AHA C LASSIFICATION Foam cell LipidLipid Fibrous cap TYPE VI Erosion or disruption of fibrous cap Erosion or disruption of fibrous cap FibrinnetworkFibrinnetwork CoronarythrombusCoronarythrombus PlateletattachmentPlateletattachment Plaque hemorrhage ComplicatedPlaqueComplicatedPlaque Surface defect Surface clot Hemorrhage in plaque Luminalthrombus From 4th decade Clinically overt Surface defect Surface clot Hemorrhage in plaque Luminalthrombus From 4th decade Clinically overt K. Eagle

8. C LINICAL P RESENTATION / D EFINITIONS Classic Angina: Transient discomfort or pain sensation occuring in the precordium, provoked by stress (physical or mental) and relieved by rest or nitroglycerin. Atypical Angina: Transient discomfort or pain that is lacking one or more of the criteria of classic angina. Angina Equivalent: Sensation of dyspnea, fatigue, or weakness as a manifestation of cardiac ischemia. Classic Angina: Transient discomfort or pain sensation occuring in the precordium, provoked by stress (physical or mental) and relieved by rest or nitroglycerin. Atypical Angina: Transient discomfort or pain that is lacking one or more of the criteria of classic angina. Angina Equivalent: Sensation of dyspnea, fatigue, or weakness as a manifestation of cardiac ischemia. A. D EFINITIONS

9. C LINICAL P RESENTATION / D EFINITIONS 1. Provoked by physical or mental stress 2. Associated with ST-segment depression 3. Lasts < 15 minutes 4. Exercise testing usually provokes chest pain and produces ST-segment depression 5. Medical treatment with beta blockers, nitrates, or calcium channel blockers improves symptoms 1. Provoked by physical or mental stress 2. Associated with ST-segment depression 3. Lasts < 15 minutes 4. Exercise testing usually provokes chest pain and produces ST-segment depression 5. Medical treatment with beta blockers, nitrates, or calcium channel blockers improves symptoms B. C HARACTERISTICS

10. Classic Dissection Makita S, et al. Am J Cardiol 2000;86:242-44. Changes in CRP levels in patients with classic dissection. Black arrows, CRP re-elevation (on the second peak) in patients with progression of thrombosis in false lumen. White arrow, CRP re-elevation (on the second peak) without definite aortic event. Black squares, 2 patients who underwent surgical intimal fenestration for organ malperfusion on the day of surgery.

11. Chronic CAD Lilly LS. Pathophysiology of Heart Disease 2007:152. Normal Endothelial Cell Patent lumen Normal endothelial function Platelet aggregation inhibited

12. Chronic CAD Stable Angina Plaque Lumen narrowed by plaque Inappropriate vasoconstriction Lilly LS. Pathophysiology of Heart Disease 2007:152.

13. Chronic CAD Unstable Angina Platelets Plaque rupture Platelet aggregation Thrombus formation Unopposed vasoconstriction Thrombus Lilly LS. Pathophysiology of Heart Disease 2007:152.

14. Chronic CAD Variant Angina No overt plaques Intense vasospasm Lilly LS. Pathophysiology of Heart Disease 2007:152.

15. G RADING O F A NGINA P ECTORIS B Y T HE C ANADIAN C ARDIOVASCULAR S OCIETY C LASSIFICATION S YSTEM Class I: Ordinary physical activity does not cause angina, such as walking, climbing stairs. Class II: Slight limitation of ordinary activity. Angina occurs on walking or climbing stairs rapidly, walking uphill, walking or climbing stairs after a meal, or in cold, or in wind, or under emotional stress, or only during the few hours after awakening. Angina occurs on walking more than two blocks on the level and climbing more than one flight of ordinary stairs at a normal pace and in normal conditions. Class I: Ordinary physical activity does not cause angina, such as walking, climbing stairs. Class II: Slight limitation of ordinary activity. Angina occurs on walking or climbing stairs rapidly, walking uphill, walking or climbing stairs after a meal, or in cold, or in wind, or under emotional stress, or only during the few hours after awakening. Angina occurs on walking more than two blocks on the level and climbing more than one flight of ordinary stairs at a normal pace and in normal conditions. Source: JACC 1999; 33: 2092-197

16. G RADING O F A NGINA P ECTORIS B Y T HE C ANADIAN C ARDIOVASCULAR S OCIETY C LASSIFICATION S YSTEM Class III: Marked limitations of ordinary physical activity. Angina occurs on walking one to two blocks on the level and climbing one flight of stairs in normal conditions and at a normal pace. Class IV: Inability to carry on any physical activity without discomfort-anginal symptoms may be present at rest. Class III: Marked limitations of ordinary physical activity. Angina occurs on walking one to two blocks on the level and climbing one flight of stairs in normal conditions and at a normal pace. Class IV: Inability to carry on any physical activity without discomfort-anginal symptoms may be present at rest. Source: JACC 1999; 33: 2092-197

17. P ATHOPHYSIOLOGY C ORONARY B LOOD F LOW Vascular tone Vascular tone Coronary perfusion pressure Coronary perfusion pressure Collaterals Collaterals Duration of diastole Duration of diastole C ORONARY B LOOD F LOW Vascular tone Vascular tone Coronary perfusion pressure Coronary perfusion pressure Collaterals Collaterals Duration of diastole Duration of diastole D ETERMINATES O F M YOCARDIAL O XYGEN S UPPLY A ND D EMAND D ETERMINATES O F M YOCARDIAL O XYGEN S UPPLY A ND D EMAND M YOCARDIAL O 2 C ONSUMPTION Wall tension Wall tension Contractility Contractility Heart rate Heart rate Preload Preload Afterload Afterload M YOCARDIAL O 2 C ONSUMPTION Wall tension Wall tension Contractility Contractility Heart rate Heart rate Preload Preload Afterload Afterload

18. C OLLATERAL F LOW Source Undetermined

19. C OLLATERAL F LOW Lilly. Pathophysiology of Heart Disease, 4th Ed. Lippincott Williams, 2007. Page 9

20. C OLLATERAL F LOW Lilly. Pathophysiology of Heart Disease, 4th Ed. Lippincott Williams, 2007. Page 9

21. External arterial compression during systole External arterial compression during systole Intrinsic autoregulation Intrinsic autoregulation - Metabolic factors Reduced oxygen vasodilation Reduced ATP adenosine vasodilation - Endothelial factors EDRF - NO vasodilation Prostacyclin vasodilation Endothelin-1 vasoconstriction - Neural factors  adrenergic receptors vasoconstriction  adrenergic receptors vasodilation External arterial compression during systole External arterial compression during systole Intrinsic autoregulation Intrinsic autoregulation - Metabolic factors Reduced oxygen vasodilation Reduced ATP adenosine vasodilation - Endothelial factors EDRF - NO vasodilation Prostacyclin vasodilation Endothelin-1 vasoconstriction - Neural factors  adrenergic receptors vasoconstriction  adrenergic receptors vasodilation V ASCULAR T ONE

22. C ORONARY P ERFUSION P RESSURE Approximated by diastolic blood pressure (DBP) Marked reductions in DBP lead to hypoperfusion… eg. hypotension, severe aortic valve regurgitation Approximated by diastolic blood pressure (DBP) Marked reductions in DBP lead to hypoperfusion… eg. hypotension, severe aortic valve regurgitation

23. D IASTOLE Flow to coronaries in systole reduced by: – external compression of arteries – local venturi effect in ascending aorta Heart rate compromises diastolic filling time Flow to coronaries in systole reduced by: – external compression of arteries – local venturi effect in ascending aorta Heart rate compromises diastolic filling time

24. H EART R ATE # of contractions requires more ATP generation…. this requires more oxygen C ONTRACTILITY Force of contraction requires more ATP…. increases O 2 consumption

25. P ATHOPHYSIOLOGY OF C HRONIC I SCHEMIC S YNDROMES Fixed vessel narrowing Endothelial cell dysfunction Non-Coronary factors Fixed vessel narrowing Endothelial cell dysfunction Non-Coronary factors

26. F IXED V ESSEL S TENOSIS MaximalCoronaryFlowMaximalCoronaryFlow5x5x4x4x 3x3x 2x2x 1x1x 25%25%50%50%75%75%100%100% Maximum Coronary Flow Flow Resting Coronary Flow Flow Source Undetermined

27. E NDOTHELIAL C ELL D YSFUNCTION Normal response to stress: vasodilation….increased blood flow/shear stress sympathetic activation EDRF - NO Normal vessel: EDRF - NO outweighs  - constriction from catecholamines Diseased vessel: vasoconstrictive response overcomes inadequate EDRF - NO release….”sensitized” to vasoconstrictive platelet products Normal response to stress: vasodilation….increased blood flow/shear stress sympathetic activation EDRF - NO Normal vessel: EDRF - NO outweighs  - constriction from catecholamines Diseased vessel: vasoconstrictive response overcomes inadequate EDRF - NO release….”sensitized” to vasoconstrictive platelet products

28. N ON- C ORONARY F ACTORS Anemia Hypoxia Decreased perfusion pressure…hypotension, aortic regurgitation Anemia Hypoxia Decreased perfusion pressure…hypotension, aortic regurgitation Increased Oxygen Demand Aortic stenosis Severe HCM Thyrotoxicosis Aortic stenosis Severe HCM Thyrotoxicosis Inadequate Oxygen Supply

29. D IAGNOSIS History Physical exam Electrocardiogram Exercise ECG test Exercise test with imaging Pharmacological stress test Coronary angiography History Physical exam Electrocardiogram Exercise ECG test Exercise test with imaging Pharmacological stress test Coronary angiography

30. H ISTORY: “A NGINA ” Tightness Constriction Not pleuritic Radiation - jaws, arms Heaviness Not “stabbing” Dull, not sharp Association: SOB, sweat Tightness Constriction Not pleuritic Radiation - jaws, arms Heaviness Not “stabbing” Dull, not sharp Association: SOB, sweat Steady, lasts minutes More than a few seconds Not usually > 10-15 min. Steady, lasts minutes More than a few seconds Not usually > 10-15 min. Duration Exertion, emotion Cold air Large meal Exertion, emotion Cold air Large meal Provocation Nitroglycerine - sec. to min. Rest Nitroglycerine - sec. to min. Rest Relief Quality

31. P HYSICAL E XAM BP HR Diaphoresis BP HR Diaphoresis Transient mitral valve regurgitation (rare) Pulmonary rales (rare) Transient mitral valve regurgitation (rare) Pulmonary rales (rare) During ischemia Not during ischemia Usually no abnormal findings Occasional associated issues: – aortic stenosis – HCM – aortic regurgitation - diastolic murmur Usually no abnormal findings Occasional associated issues: – aortic stenosis – HCM – aortic regurgitation - diastolic murmur } } systolic murmur

32. E LECTROCARDIOGRAM Usually shows change during an episode Typically transient ST-segment depression or T-wave flattening/inversion Rarely transient ST-segment elevation Usually shows change during an episode Typically transient ST-segment depression or T-wave flattening/inversion Rarely transient ST-segment elevation

33. Source Undetermined

34. E XERCISE ECG S TRESS T EST Treadmill or bicycle exercise Constant monitoring of: 12 lead ECG heart rate BP (periodically) Treadmill or bicycle exercise Constant monitoring of: 12 lead ECG heart rate BP (periodically) Graded increase in exercise until: angina occurs with ECG changes… or marked ischemia on ECG… or target heart rate is reached… or patient can no longer continue Graded increase in exercise until: angina occurs with ECG changes… or marked ischemia on ECG… or target heart rate is reached… or patient can no longer continue

35. S TRESS T EST S IGNS: “S EVERE ” CAD SX/ECG change occurs in 1st 3-6 min. of exercise or persists > 5 min. after Magnitude of ST depression > 2mm Systolic BP falls during exercise High grade arrythmia - eg. Sustained ventricular tachycardia - occurs Cardiopulmonary limitations preclude exercise beyond 2-3 min. SX/ECG change occurs in 1st 3-6 min. of exercise or persists > 5 min. after Magnitude of ST depression > 2mm Systolic BP falls during exercise High grade arrythmia - eg. Sustained ventricular tachycardia - occurs Cardiopulmonary limitations preclude exercise beyond 2-3 min.

36. E XERCISE T EST W ITH I MAGING Nuclear tracer injected at peak exercise image the heart Myocardium perfused by narrowed artery “takes” up less tracer than that served by normal coronaries Compare relative myocardial uptake at rest to that with exercise… Exercise “cold” spots that look normal at rest… viable heart muscle served by stenotic arteries Exercise cold spots that are also present at rest: dead heart muscle or very severe flow Nuclear tracer injected at peak exercise image the heart Myocardium perfused by narrowed artery “takes” up less tracer than that served by normal coronaries Compare relative myocardial uptake at rest to that with exercise… Exercise “cold” spots that look normal at rest… viable heart muscle served by stenotic arteries Exercise cold spots that are also present at rest: dead heart muscle or very severe flow Myocardial Perfusion Scintigraphy

37. E XERCISE T EST W ITH I MAGING Image LV wall motion at rest Image immediately p maximum stress Ischemic myocardium shows: – reduced systolic wall thickening – reduced systolic wall motion… hypokinesia/akinesia Image LV wall motion at rest Image immediately p maximum stress Ischemic myocardium shows: – reduced systolic wall thickening – reduced systolic wall motion… hypokinesia/akinesia Echocardiographic wall motion

38. P HARMACOLOGIC S TRESS T EST: C HOICES Vasodilator Myocardial perfusion image Narrowed vessels have vasodilatory response c/w normal Before/after images “relative” tracer uptake Vasodilator Myocardial perfusion image Narrowed vessels have vasodilatory response c/w normal Before/after images “relative” tracer uptake Adenosine - Thallium or Sestamibi: Catecholamine stress mimics exercise Image for ischemia by ECG and wall motion analysis Catecholamine stress mimics exercise Image for ischemia by ECG and wall motion analysis Dobutamine Echocardiography

39. C ORONARY A NGIOGRAPHY Direct injection of radiopaque dye into coronary arteries Carries higher risk c/w noninvasive testing Most reliable method to obtain anatomical data When to do: – to establish Dx when uncertainty exists – to identify advanced CAD for potential revascularization with PCI or CABG Direct injection of radiopaque dye into coronary arteries Carries higher risk c/w noninvasive testing Most reliable method to obtain anatomical data When to do: – to establish Dx when uncertainty exists – to identify advanced CAD for potential revascularization with PCI or CABG

40. Source Undetermined

41. T REATMENT S TRATEGIES Prevent progression of atherosclerosis Prevent conversion of stable to unstable lesions Relieve symptoms to improve quality of life Prolong life Prevent progression of atherosclerosis Prevent conversion of stable to unstable lesions Relieve symptoms to improve quality of life Prolong life

42. P REVENT P ROGRESSION OF A THEROSCLEROSIS Identify / treat hyperlipidemia Identify / treat hypertension Identify / treat diabetes mellitus Identify / treat smoking Counteract obesity, sedentary lifestyle, depression, and other habits (e.g. cocaine) Identify / treat hyperlipidemia Identify / treat hypertension Identify / treat diabetes mellitus Identify / treat smoking Counteract obesity, sedentary lifestyle, depression, and other habits (e.g. cocaine)

43. P REVENT D ESTABILIZATION OF P LAQUES Reduce shear stress –  -blocker – regular exercise Reduce shear stress –  -blocker – regular exercise Reduce thrombogenicity of blood – aspirin, clopidogrel Reduce thrombogenicity of blood – aspirin, clopidogrel Reduce vasoreactivity of vessels –  blocker, nitrate, calcium blockers – no smoking – control lipids (statins) Reduce vasoreactivity of vessels –  blocker, nitrate, calcium blockers – no smoking – control lipids (statins)

44. R ELIEVE S YMPTOMS OF A NGINA  -blockers O 2 demand - Contractility O 2 Delivery - Slow HR O 2 demand - Contractility O 2 Delivery - Slow HR Drug Class Mechanism Side Effects Long acting nitrates Long acting nitrates Ca ++ blockers Fatigue/Depression Excess HR Bronchospasm Impotence Fatigue/Depression Excess HR Bronchospasm Impotence O 2 Demand - Preload O 2 Supply - Coronary Perfusion - Constriction O 2 Demand - Preload O 2 Supply - Coronary Perfusion - Constriction Headache Hypotension Reflex HR Headache Hypotension Reflex HR Headache Flushing Edema Headache Flushing Edema Preload Wall stress HR (D,V) Perfusion/ Constriction Preload Wall stress HR (D,V) Perfusion/ Constriction

45. A NTIANGINAL T HERAPY Sublingual NTG0.3-0.6 mg<5 min<30 min Aerosol NTG0.4 mg<5 mg<30 min NTG ointment (2%)0.5-2.0 in<60 min6 h Transdermal NTG5-15 mg30-60 min8-14 h Oral isosorbide5-30 mg15-30 min3-6 h Oral isosorbide (SR)40 mg30-60 min6-10 h Oral tetranitrate10 mg30 min6-12 h Sublingual NTG0.3-0.6 mg<5 min<30 min Aerosol NTG0.4 mg<5 mg<30 min NTG ointment (2%)0.5-2.0 in<60 min6 h Transdermal NTG5-15 mg30-60 min8-14 h Oral isosorbide5-30 mg15-30 min3-6 h Oral isosorbide (SR)40 mg30-60 min6-10 h Oral tetranitrate10 mg30 min6-12 h D OSAGE A CTION D URATION M EDICATION A. N ITRATES

46. A NTIANGINAL T HERAPY Diltiazem30-90 mg tid-qid15 min30 minRenal/Hepatic Yes Nifedipine10-30 mg tid-qid<20 min1-2 hHepatic Yes Verapamil80-120 mg tid-qid2 h3-4 hHepatic Yes Amlodipine2.5-10 mg qd-bid<3 h7-8 hHepatic No Isradipine2.5-5.0 mg qd-bid2 h6-8 hHepatic No Nicardipine20-30 mg tid<20 min1 hHepatic No Felodipine2.5-10 mg qd2 h2.5-5 hHepatic No Diltiazem30-90 mg tid-qid15 min30 minRenal/Hepatic Yes Nifedipine10-30 mg tid-qid<20 min1-2 hHepatic Yes Verapamil80-120 mg tid-qid2 h3-4 hHepatic Yes Amlodipine2.5-10 mg qd-bid<3 h7-8 hHepatic No Isradipine2.5-5.0 mg qd-bid2 h6-8 hHepatic No Nicardipine20-30 mg tid<20 min1 hHepatic No Felodipine2.5-10 mg qd2 h2.5-5 hHepatic No D OSAGE O NSET LA F ORM M EDICATION B. C ALCIUM C HANNEL B LOCKERS P EAK E LIMINATION

47. A NTIANGINAL T HERAPY Atenolol25-100 mg qdLowNoRenal No Metoprolol25-100 mg bidModNo Hepatic Yes Propranonol10-40 mg qidHighNoHepatic Yes Pindolol5-10 mg bidModYesRenal No Labetalol100-200 mg bidLowNoHepatic No Acebutolol200-400 mg bid-tidLowNoHepatic Yes Timolol10-30 mg bidModNoRenal/Hepatic No Atenolol25-100 mg qdLowNoRenal No Metoprolol25-100 mg bidModNo Hepatic Yes Propranonol10-40 mg qidHighNoHepatic Yes Pindolol5-10 mg bidModYesRenal No Labetalol100-200 mg bidLowNoHepatic No Acebutolol200-400 mg bid-tidLowNoHepatic Yes Timolol10-30 mg bidModNoRenal/Hepatic No D OSAGE L IPOPHILICITY LA F ORM M EDICATION C. B ETA B LOCKERS ISAISA E LIMINATION

48. Catheter based opening of fixed artery obstruction - main use is angina not / controlled with medical Rx. Multiple types of devices - Balloon- Laser - Stent- Cutting catheter - Rotoblator- Drug Eluting Stent Relieves angina caused by stenoses of > 50-60%… esp. when more severe Does not prevent acute MI in stable angina… issue is restenosis in 15-40% of pts. Catheter based opening of fixed artery obstruction - main use is angina not / controlled with medical Rx. Multiple types of devices - Balloon- Laser - Stent- Cutting catheter - Rotoblator- Drug Eluting Stent Relieves angina caused by stenoses of > 50-60%… esp. when more severe Does not prevent acute MI in stable angina… issue is restenosis in 15-40% of pts. P ERCUTANEOUS C ORONARY I NTERVENTION

49. Chronic CAD “Coronary Stent” by NIH, Wikimedia CommonsWikimedia Commons

50. Chronic CAD Schematic representation of stent placement removed Original image available from Lilly L, et al. Pathophysiology of Heart Disease 2007;164.

51. Chronic CAD Original image available from Lilly L, et al. Pathophysiology of Heart Disease 2007;164. Schematic representation of stent placement removed

52. Surgically bypass arteries with advanced fixed obstruction Involves up front risk of death, stroke, sternal infection, post-op debility Relieves angina reliably Prolongs life in select anatomic subsets Disease can return in bypass grafts… arterial grafts preferred… left internal mammary artery to LAD Surgically bypass arteries with advanced fixed obstruction Involves up front risk of death, stroke, sternal infection, post-op debility Relieves angina reliably Prolongs life in select anatomic subsets Disease can return in bypass grafts… arterial grafts preferred… left internal mammary artery to LAD C ORONARY A RTERY B YPASS S URGERY

53. Relative Advantages of Coronary Revascularization Procedures Chronic CAD Percutaneous Coronary Interventions (PCI) Less invasive than CABG Shorter hospital stay and easier recuperation than CABG Superior to pharmacological therapy for relief of angina Coronary Artery Bypass Graft Surgery (CABG) More effective for long-term relief of angina than PCI or pharmacologic therapy Most complete survival in patients with: –> 50% left main stenosis –3-vessel CAD, especially if LV contractile function is impaired –2-vessel disease with tight (>75%) LAD stenosis, especially if LV contractile function is impaired –Diabetes and multivessel disease CAD, coronary artery disease; LV, left ventricle; LAD, left anterior descending coronary artery; MI, myocardial infarction. Lilly L, et al. Pathophysiology of Heart Disease 2007;166.

54. Improves symptoms: -  -blocker- Ca ++ blockers - PCI - Nitrates- Statins- CABG Prevents acute ischemic syndromes: - ASA- Lipid lowering agents -  -blocker- Stop smoking- ? ACE inhibitors Prolongs life - CABG in: - Lipid lowering drugs Improves symptoms: -  -blocker- Ca ++ blockers - PCI - Nitrates- Statins- CABG Prevents acute ischemic syndromes: - ASA- Lipid lowering agents -  -blocker- Stop smoking- ? ACE inhibitors Prolongs life - CABG in: - Lipid lowering drugs C HRONIC S TABLE A NGINA: T HERAPEUTIC B ENEFITS Left main stenosis signif. 3 vessel disease 2 vessel with prox. LAD Left main stenosis signif. 3 vessel disease 2 vessel with prox. LAD Especially if LV function LV function and/or and/or (+) stress test Especially if LV function LV function and/or and/or (+) stress test

55. Lilly. Pathophysiology of Heart Disease, 4th Ed. Lippincott Williams, 2007. Page 165

56. P ROGNOSIS M AJOR P REDICTORS : Advanced age LV dysfunction Extent of CADAnnual mortality 1 vessel< 4% 2 vessel7 - 10% 3 vessel10 - 12% Left main15 - 25% M AJOR P REDICTORS : Advanced age LV dysfunction Extent of CADAnnual mortality 1 vessel< 4% 2 vessel7 - 10% 3 vessel10 - 12% Left main15 - 25%

57. C ORONARY A RTERY D ISEASE P ROGNOSTIC I NDEX 1 - vessel disease, 75%93 >1 - vessel disease, 50% to 74%93 1 - vessel disease, > 95%91 2 - vessel disease88 2 - vessel disease, both > 95%86 1 - vessel disease, > 95% proximal LAD83 2 - vessel disease, > 95% LAD83 2 - vessel disease, > 95% LAD79 3 - vessel disease79 3 - vessel disease, > 95% in at least 173 3 - vessel disease, 75% proximal LAD67 3 - vessel disease, > 95% proximal LAD59 1 - vessel disease, 75%93 >1 - vessel disease, 50% to 74%93 1 - vessel disease, > 95%91 2 - vessel disease88 2 - vessel disease, both > 95%86 1 - vessel disease, > 95% proximal LAD83 2 - vessel disease, > 95% LAD83 2 - vessel disease, > 95% LAD79 3 - vessel disease79 3 - vessel disease, > 95% in at least 173 3 - vessel disease, 75% proximal LAD67 3 - vessel disease, > 95% proximal LAD59 5 - Y EAR S URVIVAL R ATE (%) E XTENT O F CAD Reference: JACC 1999; 33: 2092-197

58. C HRONIC S TABLE A NGINA Development Clinical definitions Myocardial oxygen supply and demand Pathophysiology Diagnosis Treatment strategies Prognosis Development Clinical definitions Myocardial oxygen supply and demand Pathophysiology Diagnosis Treatment strategies Prognosis

59. Additional Source Information for more information see: http://open.umich.edu/wiki/CitationPolicy Slide 5: K. Eagle Slide 6: K. Eagle Slide 7: K. Eagle Slide 10: Makita S, et al. Am J Cardiol 2000;86:242-44. Slide 11; Lilly LS. Pathophysiology of Heart Disease 2007:152. Slide 12: Lilly LS. Pathophysiology of Heart Disease 2007:152. Slide 13: Lilly LS. Pathophysiology of Heart Disease 2007:152. Slide 14: Lilly LS. Pathophysiology of Heart Disease 2007:152. Slide 15: Source: JACC 1999; 33: 2092-197 Slide 16: Source: JACC 1999; 33: 2092-197 Slide 18: Source Undetermined Slide 19: Lilly. Pathophysiology of Heart Disease, 4th Ed. Lippincott Williams, 2007. Page 9 Slide 20: Lilly. Pathophysiology of Heart Disease, 4th Ed. Lippincott Williams, 2007. Page 9 Slide 26: Source Undetermined Slide 33: Source Undetermined Slide 40: Source Undetermined Slide 49: “Coronary Stent” by NIH, Wikimedia Commons, http://commons.wikimedia.org/wiki/File:PTCA_stent_NIH.gifhttp://commons.wikimedia.org/wiki/File:PTCA_stent_NIH.gif Slide 50: Original image available from Lilly L, et al. Pathophysiology of Heart Disease 2007;164. Slide 51: Original image available from Lilly L, et al. Pathophysiology of Heart Disease 2007;164. Slide 53: Lilly L, et al. Pathophysiology of Heart Disease 2007;166. Slide 55: Lilly. Pathophysiology of Heart Disease, 4th Ed. Lippincott Williams, 2007. Page 165 Slide 57: Reference: JACC 1999; 33: 2092-197