1. Controversies in Myocardial Perfusion Imaging Thomas H. Hauser, MD, MMSc, FACC Director of Nuclear Cardiology Beth Israel Deaconess Medical Center Instructor in Medicine Harvard Medical School Boston, MA A major teaching hospital of Harvard Medical School

2. Harvard Medical School THH 10/05 Outline Women Diabetes Non-Cardiac Surgery Choice of Stress Imaging Modality

3. Harvard Medical School THH 10/05 Outline Women Diabetes Non-Cardiac Surgery Choice of Stress Imaging Modality

4. Harvard Medical School THH 10/05 Case 1 68 year old woman with a history of hypertension and dyslipidemia presents with a long history of exertional dyspnea. Her physical examination is normal. What test do you order? A.Resting echocardiogram B.ETT C.Nuclear imaging D.Cardiac catheterization

5. Harvard Medical School THH 10/05 Women and Cardiovascular Disease More than 500,000 women will die this year from CAD, stroke and other cardiovascular diseases –More women die from CVD than men CAD is the #1 killer of women –More than the next 7 causes of death combined AHA Statistics

6. Harvard Medical School THH 10/05 Women and Cardiovascular Disease AHA Statistics

7. Harvard Medical School THH 10/05 Women and Cardiovascular Disease CAD risk factors are the same for men and women Women are more likely to present with atypical symptoms or have silent events Physicians are less likely to consider a diagnosis of CAD in women Fossati et al, in Nuclear Cardiology, 2004

8. Harvard Medical School THH 10/05 Women: Inappropriate Triage Pope et al, N Engl J Med 2000;342:1163-70

9. Harvard Medical School THH 10/05 Women: Less Use of Diagnostic Tests Roger et al, JAMA. 2000;283:646-652

10. Harvard Medical School THH 10/05 Women: ETT Alone is Inadequate Nasir et al, Arch Intern Med. 2004;164:1610-1620 Specificity 80% Sensitivity 44%

11. Harvard Medical School THH 10/05 Women: Reasons for Poor Performance Peak HR and BP are lower Magnitude of STD is less Chest wall shape differs Vascular reactivity differs Prevalence of disease is lower

12. Harvard Medical School THH 10/05 Women: MPI Diagnosis Amanullah et al, JACC 1996;27:803

13. Harvard Medical School THH 10/05 Women: MPI Risk Stratification Berman et al, J Am Coll Cardiol 2003;41:1125– 33

14. Harvard Medical School THH 10/05 Case 1 68 year old woman with a history of hypertension and dyslipidemia presents with a long history of exertional dyspnea. Her physical examination is normal. What test do you order? A.Resting echocardiogram B.ETT C.Nuclear imaging D.Cardiac catheterization

15. Harvard Medical School THH 10/05 Case 1 68 year old woman with a history of hypertension and dyslipidemia presents with a long history of exertional dyspnea. Her physical examination is normal. What test do you order? A.Resting echocardiogram B.ETT C.Nuclear imaging D.Cardiac catheterization

16. Harvard Medical School THH 10/05 Case 1: Raw Data

17. Harvard Medical School THH 10/05 Case 1: Attenuation Map

18. Harvard Medical School THH 10/05 Case 1: Slices

19. Harvard Medical School THH 10/05 Case 1: Attenuation Correction

20. Harvard Medical School THH 10/05 Case 1: Gated Images

21. Harvard Medical School THH 10/05 Case 1: Quantitative Data

22. Harvard Medical School THH 10/05 Difficulties in Imaging Women Breast attenuation Small heart size

23. Harvard Medical School THH 10/05 Case 1 She exercised for 4.5 minutes of a modified Bruce protocol Peak HR of 119 (78% predicted maximal) Peak BP 230/92 Typical angina with stress Ischemic ECG changes

24. Harvard Medical School THH 10/05 Case 1 Her study is interpreted as abnormal. What do you do now? A.Begin a trial of medical therapy without further evaluation B.Refer for cardiac catheterization for definitive diagnosis and potential revascularization

25. Harvard Medical School THH 10/05 Women: Referral for Evaluation and Treatment Hachamovitch et al, JACC 1995:1457

26. Harvard Medical School THH 10/05 Women and Cardiovascular Disease CAD is highly prevalent among women Women can present with atypical symptoms ETT alone is controversial for evaluation of CAD Nuclear imaging may be preferable for the evaluation of women for both diagnosis of CAD and determination of prognosis Treatment of CAD is not gender-specific

27. Harvard Medical School THH 10/05 Outline Women Diabetes Non-Cardiac Surgery Choice of Stress Imaging Modality

28. Harvard Medical School THH 10/05 Case 2 A 58 year old man with type 2 diabetes visits his internist because he is worried about his CAD risk. He is taking a statin for dyslipidemia (last LDL 90). His BP is 130/80. The internist should: A.Start aspirin and an ACE-inhibitor B.Order an ETT C.Order an ETT with nuclear imaging D.Reassure him that he is at low risk

29. Harvard Medical School THH 10/05 Diabetes and Cardiovascular Disease Coronary artery disease is major complication of diabetes –Independent effect of diabetes –In patients with type 2 diabetes, obesity, hypertension and dyslipidemia also contribute The prevalence of CAD is estimated at up to 55% among patients with diabetes –More than 20% may have silent ischemia Delayed presentation ADA, Diabetes Care 1998;21:1551 Wackers et al, Diabetes Care. 2004 Aug;27(8):1954-61

30. Harvard Medical School THH 10/05 Evaluating CAD in Diabetics ADA, Diabetes Care 1998;21:1551

31. Harvard Medical School THH 10/05 Requirements for a Useful Screening Test Relatively high disease prevalence –CAD in 55% in diabetics Asymptomatic phase of the disease –Silent ischemia in 20% Available test that can detect the disease during the asymptomatic phase –Nuclear imaging Treatment that alters the natural history when preferentially applied during the asymptomatic phase –Lipid lowering, aspirin, ACE-inhibitor, β-blocker, revascularization

32. Harvard Medical School THH 10/05 Asymptomatic Diabetics ADA, Diabetes Care 1998;21:1551

33. Harvard Medical School THH 10/05 Diabetes and Cardiovascular Disease Haffner et al, N Engl J Med 1998;339:229-34

34. Harvard Medical School THH 10/05 Diabetes and Cardiovascular Disease Haffner et al, N Engl J Med 1998;339:229-34

35. Harvard Medical School THH 10/05 Diabetes = CAD “Some persons without established CHD will have an absolute, 10-year risk for developing major coronary events (myocardial infarction and coronary death) equal to that of persons with CHD, i.e., >20 percent per 10 years. Such persons can be said to have a CHD risk equivalent.” –Diabetes –Non-coronary atherosclerotic disease –Multiple risk factors NCEP-ATP III, Circulation, Dec 2002; 106: 3143

36. Harvard Medical School THH 10/05 Diabetes = CAD Patients with diabetes should be treated to the same lipid goals as those with CAD –Diabetes alone is high risk LDL goal of <100 (can consider a goal of <70) –The combination of diabetes and CAD is very high risk LDL goal of <70 NCEP-ATP III Update, Circulation, Jul 2004; 110: 227 - 239

37. Harvard Medical School THH 10/05 Diabetes = CAD Aspirin therapy –Age >40 Hypertension –Goal BP <130/80 –Treatment with two or more agents ACE-inhibitor Revascularization… –Mortality benefit proven only in those with 3VD ADA, Diabetes Care 2004;27(S1):S15

38. Harvard Medical School THH 10/05 Case 2 A 58 year old man with type 2 diabetes visits his internist because he is worried about his CAD risk. He is taking a statin for dyslipidemia (last LDL 90). His BP is 130/80. The internist should: A.Start aspirin and an ACE-inhibitor B.Order an ETT C.Order an ETT with nuclear imaging D.Reassure him that he is at low risk

39. Harvard Medical School THH 10/05 Case 2 A 58 year old man with type 2 diabetes visits his internist because he is worried about his CAD risk. He is taking a statin for dyslipidemia (last LDL 90). His BP is 130/80. The internist should: A.Start aspirin and an ACE-inhibitor B.Order an ETT C.Order an ETT with nuclear imaging D.Reassure him that he is at low risk

40. Harvard Medical School THH 10/05 Case 2 The patient’s internist, having recently read an editorial advocating screening MPI for patients with diabetes, refers him for ETT with nuclear imaging.

41. Harvard Medical School THH 10/05 Case 2

42. Harvard Medical School THH 10/05 Case 2 He exercised for 7 minutes of a Bruce protocol Peak HR of 140 (86% predicted maximal) Peak BP 178/80 No symptoms No ECG changes

43. Harvard Medical School THH 10/05 Case 2 The study is interpreted as normal. Based on this data, the patient is now: A.Low risk B.Intermediate risk C.High risk D.Very high risk

44. Harvard Medical School THH 10/05 Risk Stratification in Diabetics Giri et al, Circulation. 2002;105:32-40

45. Harvard Medical School THH 10/05 Risk Stratification in Diabetics Berman et al, J Am Coll Cardiol 2003;41:1125– 33

46. Harvard Medical School THH 10/05 Risk Stratification in Diabetics Berman et al, J Am Coll Cardiol 2003;41:1125– 33

47. Harvard Medical School THH 10/05 Case 2 The study is interpreted as normal. Based on this data, the patient is now: A.Low risk B.Intermediate risk C.High risk D.Very high risk

48. Harvard Medical School THH 10/05 Case 2 The study is interpreted as normal. Based on this data, the patient is now: A.Low risk B.Intermediate risk C.High risk D.Very high risk

49. Harvard Medical School THH 10/05 Diabetes and Cardiovascular Disease Coronary artery disease is common in diabetes and results in significant mortality and morbidity Diabetics without CAD have the same risk for adverse events as non-diabetics with CAD Screening diabetics for CAD is controversial The prognosis for diabetics with an abnormal MPI result is worse than for patients without diabetes A normal MPI result in diabetes does not imply low risk

50. Harvard Medical School THH 10/05 Outline Women Diabetes Non-Cardiac Surgery Choice of Stress Imaging Modality

51. Harvard Medical School THH 10/05 Case 3 A 64 year-old man with history of diabetes is referred to you for evaluation prior to elective repair of an abdominal aortic aneurysm. He feels well and plays golf every weekend without symptoms. He has had no prior cardiac evaluation. What do you recommend? A.No further testing needed B.Resting echocardiogram C.Nuclear imaging with dipyridamole stress D.Cardiac catheterization

52. Harvard Medical School THH 10/05 Peri-Operative Cardiac Complications 30 million patients undergo procedures that require general anesthesia each year. 10 million either have CAD or have a significant risk of CAD 1 million have cardiac complications –$20 billion Mangano et al, NEJM 1995;333:1750

53. Harvard Medical School THH 10/05 Operative Risk of Death or MI Ashton, C. M. et. al. Ann Intern Med 1993;118:504-510

54. Harvard Medical School THH 10/05 Determining Operative Risk Rapid determination of those that do not need testing Patient –Clinical risk predictors –Exercise tolerance Procedure –Procedural risk +/- Testing Eagle et al, 2002 AHA/ACC Guidelines

55. Harvard Medical School THH 10/05 No Testing Needed

56. Harvard Medical School THH 10/05 Patient: Clinical Risk Predictors Eagle et al, 2002 AHA/ACC Guidelines

57. Harvard Medical School THH 10/05 Major Clinical Predictors

58. Harvard Medical School THH 10/05 Patient: Clinical Risk Predictors

59. Harvard Medical School THH 10/05 Intermediate Clinical Predictors

60. Harvard Medical School THH 10/05 Patient: Exercise Tolerance Eagle et al, 2002 AHA/ACC Guidelines

61. Harvard Medical School THH 10/05 Intermediate Risk Predictors

62. Harvard Medical School THH 10/05 The Procedure Eagle et al, 2002 AHA/ACC Guidelines

63. Harvard Medical School THH 10/05 Minor Risk Predictors

64. Harvard Medical School THH 10/05 Intermediate Risk Predictors

65. Harvard Medical School THH 10/05 Risk Stratification with Nuclear Imaging Shaw et al. JACC 1996;27:787

66. Harvard Medical School THH 10/05 Case 3 A 64 year-old man with history of diabetes is referred to you for evaluation prior to elective repair of an abdominal aortic aneurysm. He feels well and plays golf every weekend without symptoms. He has had no prior cardiac evaluation. What do you recommend? A.No further testing needed B.Resting echocardiogram C.Nuclear imaging with dipyridamole stress D.Cardiac catheterization

67. Harvard Medical School THH 10/05 Case 3 A 64 year-old man with history of diabetes is referred to you for evaluation prior to elective repair of an abdominal aortic aneurysm. He feels well and plays golf every weekend without symptoms. He has had no prior cardiac evaluation. What do you recommend? A.No further testing needed B.Resting echocardiogram C.Nuclear imaging with dipyridamole stress D.Cardiac catheterization

68. Harvard Medical School THH 10/05 Case 3

69. Harvard Medical School THH 10/05 Case 3 He is referred for cardiac catheterization and found to have an 80% middle LAD stenosis. The interventionalist should: A.Do nothing B.Refer him for CABG C.Stent the lesion D.Perform PTCA

70. Harvard Medical School THH 10/05 Reducing Peri-Operative Risk Revascularization –CABG –PTCA –Stents Medical therapy –β-Blockers

71. Harvard Medical School THH 10/05 CABG Reduces Mortality Eagle et al, Circulation. 1997;96:1882-1887

72. Harvard Medical School THH 10/05 …Or Does It? McFalls et al. NEJM 351 (27): 2795

73. Harvard Medical School THH 10/05 … Or Does It?

74. Harvard Medical School THH 10/05 PTCA Reduces Adverse Events… Posner et al, Anesth Analg 1999;89:553–60

75. Harvard Medical School THH 10/05 PTCA Increases Events Within 30 Days Posner et al, Anesth Analg 1999;89:553–60

76. Harvard Medical School THH 10/05 Stents Increase Mortality 40 consecutive patients who underwent surgery within 6 weeks of PCI 8 deaths (20%) –Antiplatelet agents held in 7 11 episodes of major bleeding (28%)

77. Harvard Medical School THH 10/05 β-Blockers Reduce Mortality Mangano et al, NEJM 1996; 335:1713-1721, N = 192 with CAD or RF

78. Harvard Medical School THH 10/05 β-Blockers Reduce Mortality Poldermans et al. NEJM 341 (24): 1789

79. Harvard Medical School THH 10/05 β-Blockers Reduce Mortality Poldermans et al. NEJM 341 (24): 1789

80. Harvard Medical School THH 10/05 Unproven Benefit Statins ACE-inhibitors Nitrates Calcium channel blockers

81. Harvard Medical School THH 10/05 Case 3 He is referred for cardiac catheterization and found to have an 80% middle LAD stenosis. The interventionalist should: A.Do nothing B.Refer him for CABG C.Stent the lesion D.Perform PTCA

82. Harvard Medical School THH 10/05 Case 3 He is referred for cardiac catheterization and found to have an 80% middle LAD stenosis. The interventionalist should: A.Do nothing B.Refer him for CABG C.Stent the lesion D.Perform PTCA

83. Harvard Medical School THH 10/05 Non-Cardiac Surgery Patients with CAD or CAD risk factors frequently undergo non-cardiac surgery Most patients do not need further evaluation prior to their procedure Selected patients with risk factors and/or poor exercise tolerance may require risk stratification with nuclear imaging CABG and β-blockers reduce peri-operative mortality and morbidity PTCA and stents increase peri-operative mortality and morbidity

84. Harvard Medical School THH 10/05 Outline Women Diabetes Non-Cardiac Surgery Choice of Stress Imaging Modality

85. Harvard Medical School THH 10/05 Nuclear Imaging vs. Echocardiography The relative test performance between nuclear imaging and echocardiography is unknown –Nuclear imaging probably more sensitive –Echocardiography probably more specific Nuclear imaging is more expensive –Nuclear perfusion at rest and with stress, with gating $739 –Echo at rest and with stress, with doppler and color $358

86. Harvard Medical School THH 10/05 Echo is Better Kuntz, K. M. et. al. Ann Intern Med 1999;130:709-718

87. Harvard Medical School THH 10/05 Is Echo Better Kuntz, K. M. et. al. Ann Intern Med 1999;130:709-718

88. Harvard Medical School THH 10/05 Cost Effectiveness of Nuclear Imaging Hachamovitch et al. Circulation 2002;105:823

89. Harvard Medical School THH 10/05 Prevalence of CAD Kuntz, K. M. et. al. Ann Intern Med 1999;130:709-718

90. Harvard Medical School THH 10/05 Cost Effectiveness of Nuclear Imaging Hachamovitch et al. Circulation 2002;105:823

91. Harvard Medical School THH 10/05 Choice of Stress Imaging Modality Nuclear imaging is more expensive than echocardiography The increased expense of nuclear imaging is probably justified

92. Harvard Medical School THH 10/05 Summary Women –CAD is prevalent in women –Nuclear imaging may be preferable for the evaluation of women for both diagnosis of CAD and determination of prognosis Diabetes –Diabetes = high CAD risk –Screening for CAD with nuclear imaging is controversial Non-Cardiac Surgery –Nuclear imaging is a valuable tool for risk stratification –β-blockers reduce peri-operative mortality Choice of Stress Imaging Modality –No clear answer