Angioscopic and Virtual Histology Intravascular Ultrasound Characteristics of

Angioscopic and Virtual Histology Intravascular Ultrasound Characteristics of Culprit Lesion Morphology Underlying Coronary Artery Thrombosis Akiko Maehara, MD Cardiovascular Research Foundation Columbia University Medical Center New York, NY

Akiko Maehara, MD § Contracted Research/Grant Support: § Boston Scientific Corporation § Honoraria: § Volcano Therapeutics, Inc.

Plaque Morphology of AMI/SCD w/Thrombi Plaque Rupture 60%(f) – 80%(m) th Plaque Erosion 20%(m) - 40%(f) Calcified Nodule 2% - 7% th th

VH-IVUS Classification Thin-cap FA Thick-cap FA More than 10% Confluent Necrotic PIT Fibrous Fibrocalcific More than NO more than 10% 15% 10% Confluent confluent Fibrofatty Necrotic Core

Erosion IVUS Angioscopy OCT Kubo T, et al JACC 2007

Comparison between Ruptured thrombosis vs. Erosive thrombosis - Pathology. Erosion (n=50) Rupture (n=65) p-value Age (yrs) 43 9 52 10 <0. 0001 Male 74% 89% 0. 03 Vessel Area (mm 2) 9. 5 5. 2 13. 7 6. 0 <0. 0001 Plaque Burden (%) 77. 1 13. 8 71. 3 14. 9 0. 02 Necrotic Core (%) 18. 3 24. 4 38. 3 23. 4 <0. 0001 52% 46% 0. 53 Occlusive Thrombus (%) Kramer M et al, JACC Img 2009; 54

Clinical Background No Plaque Rupture (n=19) Plaque Rupture (n=18) p-value Age 60 12 57 11 0. 29 Men 12 (63%) 18 (100%) Women 7 (37%) 0 (0%) Myocardial Infarction 74% 56% Unstable Angina 33% 16% Current Smoking 42% 39% >0. 99 Hyperlipidemia 90% 72% 0. 35 Diabetes Mellitus 42% 24% 0. 41 Multiple lesion per pt 21% 6% 0. 16 0. 004 Clinical Syndrome 0. 65 Risk Factors Sanidas et al. AJC, 2010

Comparison between Ruptured thrombosis vs. Erosive thrombosis No Plaque Rupture (n=23) Plaque Rupture (n=17) p-value 73. 9% 64. 7% 0. 53 Lumen Area (mm 2) 3. 5 1. 4 3. 1 0. 6 0. 34 Vessel Area (mm 2) 16. 0 4. 4 20. 3 5. 5 0. 09 Plaque Burden (%) 78. 2 5. 5 83. 6 4. 7 0. 002 Necrotic Core (%) 23. 1 11. 9 19. 1 10. 1 0. 26 Lumen Area (mm 2) 4. 8 2. 0 5. 4 1. 7 0. 40 Vessel Area (mm 2) 16. 0 4. 3 18. 6 5. 3 0. 11 Plaque Burden (%) 70. 3 8. 0 70. 3 7. 9 0. 97 Necrotic Core (%) 34. 3 12. 9 28. 7 9. 1 0. 13 TCFA MLA site Maximum NC site Sanidas et al. AJC, 2010

Small rupture NC fissure thrombus Big rupture thrombus Sanidas E @ CRF

WHC AMI IVUS Acute MI 2002 -2005 N=1400, 67% NSTEMI N=189 (14%) N=739 (53%) N=472 (33%) Age 80 Age<65 Age: 65 -79 NSTEMI 71% 29% 63% 37% 30 (71%) 12 (29%) 23 (44%) 29 (56%) Hassani et al. JACC 2006: 47; 2413 -9 IVUS

Clinical Background Age, yrs Male Known Coronary Artery Disease Peripheral Vascular Disease Renal failure Creatinine (mg/dl) White blood cell, 109/l LDL, mg/dl HDL, mg/dl Age>80 85. 3 3. 5 52% 38% Age<65 p-value 54. 6 7. 6 <0. 001 60% 0. 8 11% 0. 004 24% 4% 38% 13% 1. 4 1. 0 1. 1 7. 8 2. 9 9. 7 3. 8 98 29 112 46 40. 8 12. 3 40. 4 11 Hassani et al. JACC 2006: 47; 2413 -9 0. 007 0. 008 0. 02 0. 008 0. 14

Angiography Multiple Vessel Disease LAD/LCX/RCA Prox/Mid/Distal Age>80 79% 52/7/41% 31/62/7% Thrombus Calcification RVD, mm MLD, mm Percent Stenosis, % Lesion Length, mm 1 (2%) 59% 2. 9 0. 8 1. 1 0. 4 59 15 14. 7 6. 8 Age<65 p-value 40% <0. 001 44/17/52% 0. 33 33/52/15% 0. 41 10 (20%) 8% 3. 0 0. 8 1. 0 0. 6 68 18 10. 6 4. 3 Hassani et al. JACC 2006: 47; 2413 -9 0. 007 <0. 001 0. 78 0. 13 0. 01 0. 001

IVUS Thrombus Calcified Plaque Calcified Length, mm Age>80 1 (2%) 57% 5. 5 2. 9 Age<65 7 (14%) 10% 3. 5 2. 8 Lesion Max Calcified Arc, Prox Ref Calcified Arc, Distal Ref Calcified Arc, MLA, mm 2 Remodeling Index, mm 2 199 91 90 50 68 30 2. 6 1. 2 0. 85 0. 2 115 71 <0. 0001 65 23 0. 2 49 18 0. 4 2. 8 1. 8 0. 5 1. 03 0. 2 0. 0004 Hassani et al. JACC 2006: 47; 2413 -9 p-value 0. 04 0. 009 0. 006

Small rupture NC fissure thrombus Big rupture thrombus Sanidas E @ CRF

Subclinical plaque rupture increase plaque burden. Plaque Burden (%) # of prior ruptures at healed rupture site # of prior ruptures at acute rupture site Burke et al. Circulation 2001; 103: 934 -40

Difference of TCFA Morphology According to the quartile of QCA DS 3115 Non-Culprit Lesions Multiple NC Single NC QCA Diameter Stenosis

Plaque Burden in AMI - Histology- Author n Plaque Burden(％) Necrotic Core (%) Occluded Thrombus Erosion 50 71. 3 13. 8 18. 3 24. 4 30 (46%) Rupture 65 77. 1 14. 9 38. 3 24. 4 26 (52%) Kramer et al. JACC 55, 2010; 122 -32

Plaque Burden and MLA in AMI by IVUS Author n Kotani 78 Tanaka 100 Hong 122 Plaque Burden (％) Culprit/Non. Culprit=86. 6/73. 8 No-reflow /Reflow=89/85 85. 8 Kotani et al. Circulation, 2003; 107: 2889, Tanaka Circulation, 2002; 105: 2148, Hong et al. Circulation 2004; 110: 928 MLA(mm 2) 2. 0/3. 4 2. 2/2. 3 2. 2

Age & Gender Difference - Plaque Burden†p=0. 007 (n=990) †p=0. 06 Mean P&M CSA (mm 2) †p=0. 06 p. ANOVA Men=0. 79 Women=0. 002 ‡p<0. 001 ‡p=0. 016 ‡p<0. 001 <58 58 -68 Men >68 *p=0. 0009 *p=0. 0057 Women Mean Plaque Burden (%) *p=0. 52 p. ANOVA Men=0. 0015 Women=0. 18 ‡p=0. 047 Qian J, Am J Cardiol, 2009 103: 1344 -8. <58 ‡p=0. 10 58 -68 Age (years) ‡p=0. 0083 >68

Age & Gender Difference - VH *p=0. 01 *p<0. 001 DC *p=0. 001 *p=0. 061 NC *p=0. 061 †p=0. 016 †p<0. 001 †p=0. 001 *p=0. 38 † p=0. 14 †p=0. 004 Mean NC (%) Mean DC (%) † p=0. 746 ‡p=0. 80 <58 ‡p=0. 015 ‡p=0. 02 58 -68 >68 Age (years) Fibrous ‡p=0. 99 ‡p=0. 022 >68 58 -68 Age (years) FF *p<0. 001 † p=0. 135 †p=0. 004 *p=0. 18 † p=0. 085 Mean FF (%) Mean FT (%) *p=0. 014 ‡p=0. 018 <58 ‡p=0. 42 ‡p=0. 087 ‡p=0. 037 <58 58 -68 >68 Age (years) Qian J, Am J Cardiol, 2009 103: 1344 -8. ‡p=0. 59 <58 ‡p<0. 001 58 -68 Age (years) Men Women ‡p=0. 029 >68

Big Rupture +Thrombus Man>Woman Small Rupture (or Erosion) Woman>Man +Thrombus Thrombotic Event Classical Erosive Thrombosis Woman>Man Younger (Before menopause) Plaque burden 70% Rupture/ Healed Rupture/ 95% Healed Stetenosis Old (80 yo~) Woman=Man