1. IVUS-VH & Vulnerable Plaque Jang-Ho Bae, MD., PhD. Heart Center Konyang University Hospital Daejeon City, S. Korea Jang-Ho Bae, MD., PhD. Heart Center Konyang University Hospital Daejeon City, S. Korea

2. CAG 2004.9.2 CAG 2004.9.2 Case (48/M), STEMI (ant)

3. PCI 2004.9.2 Taxus Express 2, 3.0*24 mm, 10 atm

4. 6 months FU CAG (2005.3.21)

5. STEMI at 27 months (2006.12.14)

6. PCI 2006.12.14 Guide wireThrombectomy

7. Lumen volume 394.0 mm 3 Vessel volume 959.5 mm 3 Plaque Volume 565.5 mm 3 Segment length 33.9 mm Fibrous volume 257.1 mm 3 63% Fibro-fatty volume 50.8 mm 3 12% Dense-calcium volume 25.7 mm 3 5% Necrotic-core volume 77.8 mm 3 19%

8. ContentsContents 1. VP & TCFA 2. Fate of VP / intermediate lesion 3. Konyang experience with VP 1. VP & TCFA 2. Fate of VP / intermediate lesion 3. Konyang experience with VP

9. Underlying Pathologies of Culprit Coronary Lesions (thrombotic coronary death and ACS) Ruptured plaques (~70%) Stenotic (~20%) Nonstenotic (~50%) Nonruptured plaques (~30%) Erosion Calcified nodule Others/Unknown Naghavi M. et al. Circulation 2003;108:1772-8

10. Vulnerable Plaque Lesions are likely to rupture Lesions are likely to rupture Lesions composed of a lipid-rich core in the central portion of an eccentric plaque with a thin friable cap Lesions composed of a lipid-rich core in the central portion of an eccentric plaque with a thin friable cap Lesions are likely to rupture Lesions are likely to rupture Lesions composed of a lipid-rich core in the central portion of an eccentric plaque with a thin friable cap Lesions composed of a lipid-rich core in the central portion of an eccentric plaque with a thin friable cap Muller et al. Ann Epidemiol 1992 Libby et al. Circulation1995

11. Pathologic Definition of VP It can not be detectable in clinical practice Major criteria Active inflammation Active inflammation (monocyte/macrophage and sometimes T-cell infiltration) (monocyte/macrophage and sometimes T-cell infiltration) Thin cap with large lipid core Thin cap with large lipid core Endothelial denudation with superficial platelet aggregation Endothelial denudation with superficial platelet aggregation Fissured plaque Fissured plaque Stenosis > 90% Stenosis > 90% Minor criteria Superficial calcified nodule Superficial calcified nodule Glistening yellow Glistening yellow Intraplaque hemorrhage Intraplaque hemorrhage Endothelial dysfunction Endothelial dysfunction Outward (positive) remodeling Outward (positive) remodeling Naghavi et al. Circulation 2003;108:1664-72 The Center of Vulnerable Plaque Research

12. 70% of ACS culprit lesions 30% of ACS culprit lesions Naghavi et al. Circulation 2003;108:1664-72 Gossl M et al. Med Clin N Am 2007;91:573-601 “Vulnerable Plaque” = plaque not only prone to thrombosis/rupture but also at risk for rapid progression

13. Thin Cap Fibroatheroma (TCFA) Lipid Core Fibrous Cap Intimal Inflammation Most common type of VP Lesion at risk for rupture Lesion that most resembles the acute plaque rupture Area narrowing <75% (diameter stenosis <50%) in over 75% >10% area of the plaque  3mm 2 in 75% of case Length; 2-17mm (mean 8mm) <65 um Mean cap thickness+2SD of ruptured plaque Macrophage infiltration >25 cells/0.3mm diameter Virmani R et al. J Interven Cardiol 2003;16:267-72 Virmani R et al. JACC 2006;47:C13-8

14. Morphologic Variants of the TCFA Insignificant plaque burden Large eccentric necrotic core Large concentric necrotic core Healedrupture(s) Most common type Kolodgie FD et al. Curr Opin Cardiol 2001;16:285-92

15. New Methodologies to Detect VP 1.MRI 2.Coronary CT 3.Conventional gray-scale IVUS 4.Angiography 5.OCT 6.Thermography 7.VH-IVUS 8.NIR, …..

16. IVUS-RF Data Analysis ROI length  480um Lumen EEM ROI width=12  4 scan lines 64 samples along each line (240 lines/frame) 1 IVUS scan line Plaque Classification Tree Based on 8 spectral parameter 1.Maximum power 2.Corresponding frequency 3.Minimal power 4.Corresponding frequency 5.Slope 6.Y-intercept 7.Mid-band fit 8.Integrated backscatter

17. Tissue Characterization Media Fibrous Fibrofatty Dense calcium Necrotic core Densely packed collagen Significant lipid in collagen Calcium without necrosis Cholesterol cleft, foam cells, microcalcification

18. IVUS VH-IVUS Virmani VH Calcium = purple Examples in Tissue Characterization

19. IVUS VH-IVUS Virmani VH Calcium = purple Examples in Tissue Characterization

20. Predictive Accuracies of VH-IVUS FibrousFibrofattyCalcified Necrotic core 1 st version ex vivo 79.7%81.2%92.8%85.5% 2nd version in vivo (DCA) 87.1%87.1%96.5%88.3% Nasu K. J Am Coll Cardiol 2006;47:2405-12 Nair A. EuroInterv 2007;3:113-120 Histology vs. RF data in gray IVUS 2nd version ex vivo 93.5%94.1%95.8%96.7% Histology vs. VH-IVUS Nair A. Circulation 2002;106:2200-6

21. Gray scale IVUS vs. VH-IVUS

22. Lesion Classification Pathological intimal thickening Fibrocalcific lesion Fibrous cap atheroma Thin-cap fibroatheroma In at least 3 consecutive frames & PAV 40% Rodriguez-Granillo et al. Heart 2006;92:388-91

23. Cap thickness of TCFA  Axial resolution of IVUS-VH; 100- 150um  65um; based on autopsy and data of already ruptured plaque  Cap thickness <250um dramatically increases peak circumferential stress in the plaque  Axial resolution of IVUS-VH; 100- 150um  65um; based on autopsy and data of already ruptured plaque  Cap thickness <250um dramatically increases peak circumferential stress in the plaque Virmani R et al. J Interven Cardiol 2003;16:267-72 Schaar JA et al. Circulation 2003;108:2636-41

24. ContentsContents 1. Definition of VP 2. Fate of VP / intermediate lesion 3. Konyang experience with VP 1. Definition of VP 2. Fate of VP / intermediate lesion 3. Konyang experience with VP

25. Case (45/M), SA

26. 123 4 5 Distal Ref.Proximal Ref. EEM CSA = 17.6 Lumen CSA = 4.1 ~ 4.3 P+M CSA = 13.1 Max Lumen dia = 2.5 MLD = 2.3 Plaque burden = 74% EEM CSA = 17.8 Lumen CSA = 12.2 Max Lumen dia = 4.2 MLD = 3.7 P+M CSA = 5.6 Plaque burden = 0.32 EEM CSA = 14.4 Lumen CSA = 8.9 Max Lumen dia = 3.6 MLD = 3.1 P+M CSA = 5.5 Plaque burden = 0.38 04 mm10 mm19 mm 123 4 5

27. Lumen Volume 174.9mm 3 EEL Volume 361.3mm 3 Plaque Volume 186.4mm 3 Segment Length 19.7 mm Fibrous Volume 68.2 mm 3 59% Fibro-Fatty volume 6.2 mm 3 5% Dense Calcium Volume 11.7 mm 3 10% Necrotic Core Volume 28.9 mm 3 25%

28. Treatment in this patients ? EEM CSA = 17.6 Lumen CSA = 4.1 ~ 4.3 P+M CSA = 13.1 Max Lumen dia = 2.5 MLD = 2.3 Plaque burden = 74% TCFA Fibrous Volume 68.2 mm 3 59% Fibro-Fatty volume 6.2 mm 3 5% Dense Calcium Volume 11.7 mm 3 10% Necrotic Core Volume 28.9 mm 3 25%

29. Strategies in intermediate lesion IVUS IVUS FFR FFR IVUS IVUS FFR FFR

30. IVUS MLA < 4.0mm 2 357 intermediate lesion in 300 pts Clinical FU >1yr 357 intermediate lesion in 300 pts Clinical FU >1yr Abizaid AS, et al, Circulation 1999 Any event (%) Revascularization (%) 2.0-2.9N=17 3.0-3.9N=36 4.0-4.9N=55  5 N=193 2.0-2.9N=17 3.0-3.9N=36 4.0-4.9N=55 N=193

31. Deferral of PTCA Based on FFR Bech et al, Circulation 2001 325 patients referred for PTCA without documented ischemia If FFR >0.75, randomized to Defer (91) or Performance (90) groups If FFR >0.75, randomized to Defer (91) or Performance (90) groups If FFR <0.75, PTCA performed, Reference group (144) Patients free from angina (%)

32. FFR > 0.80 as a cut-off value Legalery et al, Eur Heat J 2005 Gray zone of FFR by European PCI guideline ; FFR 0.75 ~ 0.80

33. Natural History of Intermediate Lesion 10-yrs survival rate 10-yrs survival rate 90.1% vs. 85.8% (3342 pts with normal coronary vs. 2184 pts with noncritical stenosis (<70%) 90.1% vs. 85.8% (3342 pts with normal coronary vs. 2184 pts with noncritical stenosis (<70%) Noncritical stenosis; not significant independent determinant of survival Noncritical stenosis; not significant independent determinant of survival 10-yrs survival rate 10-yrs survival rate 90.1% vs. 85.8% (3342 pts with normal coronary vs. 2184 pts with noncritical stenosis (<70%) 90.1% vs. 85.8% (3342 pts with normal coronary vs. 2184 pts with noncritical stenosis (<70%) Noncritical stenosis; not significant independent determinant of survival Noncritical stenosis; not significant independent determinant of survival Crenshaw JH. et al. Am J Med Sci 1995

34. Evolution of Spontaneous Atherosclerotic Plaque Rupture With Medical Therapy In 14 Pts with 28 plaque ruptures, 22 months FU 50% healed without significant plaque modification No healing-prediction criterion could be found Rioufol G. et al. Circulation 2004;110:2875-80

35. Angioscopic F/U of 50 Ruptured Plaques (30 pts) in Non-culprit Lesions; 13±9 Mo FU Takano M et al, J Am Coll Cardiol 2005;45:652– 8 Overall healing; 30% Overall healing; 30% Remaining of thrombi in 35 (70%) Remaining of thrombi in 35 (70%) Thrombus color change from red (56%) at baseline to pinkish-white (83%) at follow-up Thrombus color change from red (56%) at baseline to pinkish-white (83%) at follow-up %DS at the healed plaque (12.3% to 22.7%, p<0.05) %DS at the healed plaque (12.3% to 22.7%, p<0.05) 1 pt need PCI 1 pt need PCI Pinkish-white thrombus on the yellow plaque Smooth white intima without thrombus DS=35% DS=43% Ruptured plaques in nonculprit lesions tend to heal slowly with a progression of angiographic stenosis

36. Plaque instability frequently occurs days or weeks before occlusive coronary thrombosis Composition of the retrieved material using suction catheter in 211 pts undergoing 1 PCI within 6 hrs after onset of symptom Only thrombus 54% Only plaque components 5% Both components 45% van der Wal AC, Koch KT et al, TCT 49 35 9 7 0 10 20 30 40 50 <1day 1-5 days >5days both % Fresh Lytic Organized Fresh & organized Acute coronary occlusion is often the final Stage in a series of successive thrombotic Events that occurred in the preceding days or weeks

37. ContentsContents 1. Definition of VP 2. Fate of VP / intermediate lesion 3. Konyang experience with VP 1. Definition of VP 2. Fate of VP / intermediate lesion 3. Konyang experience with VP

38. 1. To know clinical outcomes of intermediate lesion according to tissue type by VH-IVUS 2. To identify a lesion, which causes angina (needs PCI) in the future ObjectivesObjectives VH-IVUS for detection a VP

39. Study Design Patient population: 30%-70% stenosis by CAG 30%-70% stenosis by CAG Consecutive Consecutive Informed consent Informed consent Good quality of VH-IVUS Good quality of VH-IVUS Efficacy outcome measure: Time to occurrence of a major CV event: Time to occurrence of a major CV event: –Lesion progression requiring PCI –Cardiac death –AMI –Fatal or nonfatal stroke –Any events Jan 2007~Jun 2008 Patients enroll CAG & VH-IVUS 98 lesions in 94 pts 65 pts eligible CAG & VH-IVUS FU 48 lesions (72.7%) FU loss n=1 Clinical FU 64 pts (98.5%) 9 months Deathn=3 98 lesions in 94 pts 69 – 3 lesions eligible 8.7  2.9 months

40. Patients Demographics (n=94) Age, yrs Male, n (%) Hypertension, n (%) Diabetes, n (%) Smoking, n (%) Dyslipidemia, n (%) ACS, n (%) Prior MI, n (%) PCI, n (%) Hs-CRP, mg/dL 61.8  11.8 68 (72.3) 43 (45.7) 27 (28.7) 35 (37.2) 37 (39.4) 42 (44.7) 5 (5.3) 78 (83.0) 0.58  1.22

41. Angiographic Findings (n=98) Lesion location, n (%) LAD LCX RCA LM Diagonal Multi-vessel disease, n (%) MLD, mm Proximal ref. A diameter, mm Distal ref. A diameter, mm % diameter stenosis, % 53 (54.1) 20 (20.4) 15 (15.3) 8 (8.2) 2 (2.) 58 (59.2) 1.79  0.53 3.21  0.71 2.90  0.64 43.4  9.05 (30.0 ~ 66.2)

42. Gray Scale IVUS Findings (n=98) Minimal luminal area EEM area, mm 2 Luminal area, mm 2 P&M area, mm 2 Plaque burden, % Remodeling index Positive remodeling (>1.05), n (%) Luminal area <4.0mm 2, n (%) Volumetric analysis EEM volume, mm 3 Lumen volume, mm 3 P&M volume, mm 3 Lesion length, mm 15.2  5.8 5.4  2.1 9.9  4.2 63.4  9.3 0.96  0.13 23 (23.5) 31 (31.6) 215.2  128.1 97.5  54.2 116.3  80.5 13.9  7.2

43. IVUS-VH Findings at MLA (n=98) Fibrous area, mm 2 Fibrofatty area, mm 2 Dense calcified area, mm 2 Necrotic core area, mm 2 Fibrous area, % Fibrofatty area, % Dense calcified area, % Necrotic core area, % 3.95  2.29 0.92  1.17 0.53  0.52 1.17  0.96 60.2  14.1 12.1  9.7 9.1  8.6 18.7  11.5

44. TCFA by IVUS-VH In at least three consecutive frames; In at least three consecutive frames; 1) necrotic core > 10% without evident overlying fibrous tissue and 1) necrotic core > 10% without evident overlying fibrous tissue and 2) percent atheroma area > 40% 2) percent atheroma area > 40% Rodriguez-Granillo GA et al. JACC 2005;46:2038–42

45. TCFA Classification Less vulnerable Highest vulnerable NC > 20% > 50% Plaque burden Ca > 5% Remodeling index > 1.05 NC < 20% < 50% Plaque burden Proposed by Dr. Mintz G

46. IVUS-VH Findings at MLA (n=98) PIT (n=7,7.1%) Fibrocalcific A (n=17, 17.3%) Fibrous cap A (n=42, 42.9%) TCFA (n=28, 28.6%) Undetermined (n=4, 4.1%) TCFA, less vulnerable (n=13, 46.4%) TCFA, high vulnerable (n=15, 53.6%)

47. TCFA According to Diagnosis P=0.021 15 (27.3%) 13 (30.2%) (n=55)(n=43) P=NS TCFA, % Highest vulnerable TCFA, % (n=55)(n=43) 5 (53.6%) 10 (76.9%)

48. Medications (n=92 lesions) AspirinBeta-blockersACEIARBCCBStatinsOHAInsulin 98 (100) 61 (62.2) 46 (46.9) 15 (15.3) 25 (25.5) 73 (74.5) 20 (20.4) 2 (2.0)

49. 6 Mo Clinical outcomes (64/65 pts, 98.5%) Death* Myocardial infarction Stroke Requiring PCI 3 (4.7%) 0 (0) 7 (10.9%) 8 lesions in 7 pts *; Causes of death; CHF at 1 month, ICH at 4 months, SCD at 5 months

50. Case, 강 0 준, SCD at 5 Mo 2007-07-30

51. MLA Lumen Area 8.5 mm 2 EEL Area 28.2 mm 2 Plaque Area 19.7 mm 2 % Plaque Burden 70 % Fibrous Area 8.1 mm 2 54% Fibro-Fatty Area 5.3 mm 2 36% Dense Calcium Area 0.3 mm 2 2% Necrotic Core Area 1.2 mm 2 8% Fibrocalcific Atheroma

52. 2008-06-24 Case, (65/M), 염 0 철, SA LAD stenting 2007-09-18 Lumen Area 3.8 mm 2 % Plaque Burden 80 % Fibrous Area 5.1 mm 2 44% Fibro-Fatty Area 1.4 mm 2 12% Dense Calcium Area 2.1 mm 2 18% Necrotic Core Area 3.0 mm 2 26% TCFA QCA stenosis 35.4% MLD 2.10 QCA stenosis 50.4% MLD 1.59

53. Fibrous Area 2.7 mm 2 72% Fibro-Fatty Area 0.2 mm 2 5% Dense Calcium Area 0.2 mm 2 6% Necrotic Core Area 0.6 mm 2 17% Case, (71/M), 김 0 규, UA 2007-05-072008-01-22 QCA stenosis 56.0% MLD 1.10 QCA stenosis 50.0% MLD 1.00 Lumen Area 2.7 mm 2 EEL Area 8.7 mm 2 Plaque Area 6.0 mm 2 % Plaque Burden 69% Lumen Area 3.0 mm 2 EEL Area 6.8 mm 2 Plaque Area 3.7 mm 2 % Plaque Burden 55 % Fibrous Area 1.2 mm 2 73% Fibro-Fatty Area 0.2 mm 2 15% Dense Calcium Area 0.1 mm 2 3% Necrotic Core Area 0.1mm 2 8% Fibrous cap atheroma

54. Fibrous Area 5.5 mm 2 50% Fibro-Fatty Area 0.2 mm 2 2% Dense Calcium Area 0.2 mm 2 2% Necrotic Core Area 5.2 mm 2 47% Case, (46/M), 윤 0 선, SA QCA stenosis 35.64% MLD 2.80 IVUS MLA 8.60 mm 2 QCA stenosis 56.21% MLD 1.70 IVUS MLA 6.10 mm 2 Lumen Area 8.6 mm 2 EEL Area 24.2mm 2 Plaque Area 15.7mm 2 % Plaque Burden 65% Lumen Area 6.1 mm 2 EEL Area 21.7 mm 2 Plaque Area 15.6 mm 2 % Plaque Burden 72 % Fibrous Area 7.9 mm 2 70% Fibro-Fatty Area 1.4 mm 2 12% Dense Calcium Area 0.1 mm 2 1% Necrotic Core Area 2.0 mm 2 18% 2007-06-062008-02-14 TCFA

55. Fibrous Area 1.4 mm 2 70% Fibro-Fatty Area 0.1 mm 2 3% Dense Calcium Area 0.2 mm 2 10% Necrotic Core Area 0.3 mm 2 16% Case, (57/F), 김 0 순, SA LAD stenting 2007-05-172008-05-20 QCA stenosis 32.2% MLD 1.70 IVUS MLA 4.70 mm 2 QCA stenosis 78.4% MLD 0.90 IVUS MLA 3.20 mm 2 Lumen Area 4.7 mm 2 EEL Area 9.7 mm 2 Plaque Area 5.0 mm 2 % Plaque Burden 51 % Lumen Area 3.2 mm 2 EEL Area 10.3 mm 2 Plaque Area 7.2 mm 2 % Plaque Burden 69 % Fibrous Area 3.6 mm 2 77% Fibro-Fatty Area 0.6 mm 2 12% Dense Calcium Area 0.0 mm 2 0% Necrotic Core Area 0.5 mm 2 11% TCFA

56. Fibrous Area 1.8 mm 2 49% Fibro-Fatty Area 7.2 mm 2 30% Dense Calcium Area 0.6 mm 2 3% Necrotic Core Area 4.2 mm 2 18% Fibrous Area 10.5 mm 2 57% Fibro-Fatty Area 5.8 mm 2 32% Dense Calcium Area 0.7 mm 2 4% Necrotic Core Area 1.4 mm 2 8%2007-08-092008-05-30 Case, (74/M), 김 0 호, UA QCA stenosis 33.3% MLD 2.70 IVUS MLA 8.20 mm 2 QCA stenosis 70.1% MLD 1.13 IVUS MLA 5.10 mm 2 Lumen Area 8.2 mm 2 EEL Area 32.4 mm 2 Plaque Area 23.2 mm 2 % Plaque Burden 72% Lumen Area 5.1 mm 2 EEL Area 33.7 mm 2 Plaque Area 28.5 mm 2 % Plaque Burden 85 % Fibrocalcific Atheroma

57. 6 Mo Angiographic Follow Up (48/66 lesions, 72.7%) Baseline Ref. Diameter, mm Ref. Diameter, mm MLD MLD Follow up Ref. Diameter, mm Ref. Diameter, mm MLD MLD Late Loss, mm 3.03  0.61 1.84  0.59 2.87  0.54* 1.72  0.60 0.12  0.48 *;p=0.005 by paried t-test

58. Comparison between 2 groups CAG MLD MLD diameter stenosis, % diameter stenosis, % Gray scale IVUS MLA MLA Remodeling index Remodeling index Plaque area Plaque area Plaque burden Plaque burden Need PCI n=8 1.9  0.5 43.5  9.1 5.8  2.0 0.98  0.1 12.2  5.8 66.3  8.5 Stationaryn=40 1.8  0.6 43.2  8.9 5.5  2.5 0.95  0.1 9.6  4.2 63.1  7.0 P value nsnsnsnsnsns

59. Comparison between 2 groups VH-IVUS At MLA site Fibrous area Fibrous area Fibrofatty area Fibrofatty area Dense calcified area Dense calcified area Necrotic core area Necrotic core area Over the entire lesion Fibrous volume Fibrous volume Fibrofatty volume Fibrofatty volume Dense calcified volume Dense calcified volume Necrotic core volume Necrotic core volume Need PCI n=8 4.91  2.72 (61%) 1.48  1.84 (15%) 0.58  0.66 (9%) 1.58  1.71 (18%) 32.54  16.40 (63%) 8.51  9.41 (15%) 4.65  6.40 (7%) 8.08  7.04 (15%) Stationaryn=40 3.99  2.50 (63%) 0.75  0.85 (11%) 0.48  0.45 (9%) 1.04  0.81 (18%) 42.34  30.36 (62%) 8.35  9.04 (12%) 6.63  6.62 (9%) 10.78  8.39 (16%) P value ns0.077nsnsnsnsNsnsns

60. MLA vs. Lesion progression (need PCI) <4mm 2  4mm 2 Progression requiring PCI, % 6 (35.3%) 2 (6.5%) P=0.010  IVUS criteria is still important  But, 65% of intermediate lesion <4mm 2 does not rapidly progress

61. Lesion types vs. progression (need PCI) Progression requiring PCI, % 0 (0%) 2 (20%) 1 (5%) PIT; pathologic intimal thickening, FCA; fibrocalcific atheroma, CAPA; fibrous cap atheroma, TCFA; thin cap fibroatheroma Non-TCFA TCFA 3 (8.6%) P=0.014 (n=3) (n=10)(n=20)(n=13)(n=35)(n=13) 0 10 20 30 40 PITFCACAPATCFA 5 (38.5%) 0 10 20 30 40 5 (38.5%)

62. TCFA vulnerability vs. Lesion progression Lessvulnerable Highvulnerable Progression requiring PCI, % 2 (40.0%) 3 (37.5%) P=0.928  TCFA vulnerability was not helpful to identify a real VP, which showed a rapid progression requiring PCI  Different classification is needed (n=5)(n=8)

63. MLA < 4.0mm 2 & TCFA vs. Lesion progression (need PCI)  If MLA of intermediate lesion is less than 4.0mm 2 as well as TCFA, 67% will rapidly progress  It will be very helpful to see MLA as well as lesion type by VH-IVUS Variables; MLA < 4.0mm2 & TCFA 1 (4.2%) 3 (16.7%) P=0.001 0 10 20 30 40 50 60 70 nonesingledouble 4 (66.7%)

64. SummarySummary 1. 38.5% of TCFA in intermediate lesion needs an PCI in 6-9 months (vs. 35.3% of lesion <4.0mm 2 by IVUS) 2. It will be very helpful to decide a therapeutic decision, considering TCFA by VH-IVUS as well as MLA 3. PIT and fibrous cap atheroma in intermediate lesion have a favorable outcomes 1. 38.5% of TCFA in intermediate lesion needs an PCI in 6-9 months (vs. 35.3% of lesion <4.0mm 2 by IVUS) 2. It will be very helpful to decide a therapeutic decision, considering TCFA by VH-IVUS as well as MLA 3. PIT and fibrous cap atheroma in intermediate lesion have a favorable outcomes

65. To evaluate in vivo tissue characteristics of coronary plaque with rupture/ulceration (PRU) in culprit lesion To evaluate in vivo tissue characteristics of coronary plaque with rupture/ulceration (PRU) in culprit lesion ObjectivesObjectives Plaque Rupture & VH-IVUS

66. MethodsMethods Study Population 162 consecutive patients undergoing IVUS-VH examination before PCI or for lesion evaluation were studied prospectively Exclusion criteria Vessel tortuosity which precluded IVUS-VH examination History of PCI or CABG Refuse to study

67. DefinitionDefinition Plaque ulceration; a recess in the plaque beginning at the luminal-intimal border, typically without enlargement of the EEM compared with the ref. segment Plaque ulceration; a recess in the plaque beginning at the luminal-intimal border, typically without enlargement of the EEM compared with the ref. segment Plaque rupture; a plaque ulceration with a tear detected in a fibrous cap Plaque rupture; a plaque ulceration with a tear detected in a fibrous cap Plaque ulceration; a recess in the plaque beginning at the luminal-intimal border, typically without enlargement of the EEM compared with the ref. segment Plaque ulceration; a recess in the plaque beginning at the luminal-intimal border, typically without enlargement of the EEM compared with the ref. segment Plaque rupture; a plaque ulceration with a tear detected in a fibrous cap Plaque rupture; a plaque ulceration with a tear detected in a fibrous cap JACC 2001;37:1478-92. Plaque rupture or ulceration; a cavity in the vessel wall, with disruption of the intima, and flow observed within the plaque cavity. Plaque rupture or ulceration; a cavity in the vessel wall, with disruption of the intima, and flow observed within the plaque cavity. Intimal disruption; irregular intimal surface of ulcerated plaques and visible torn edges. Intimal disruption; irregular intimal surface of ulcerated plaques and visible torn edges. Blood flow in the vessel wall cavity; contrast injection may be used to prove and define the communication point. Blood flow in the vessel wall cavity; contrast injection may be used to prove and define the communication point.

68. Plaque Morphology Intact (n=94) Ulcer (n=43) Rupture (n=25)

69. Patients Demographics Number Male, n (%) Age, y Hypertension, n (%) Diabetes, n (%) Hyperlipidemia, n (%) Smoking, n (%) Cardiogenic shock, n (%) Peak TnI, ng/mL Prior MI, n (%) ACS, n (%) Ejection fraction, % Multivessel disease, n (%) LCX/RCALM LAD/LCX/RCA/Ramus/LM % PRU (-) 94 67 (71.3%) 60.6  10.0 61 (64.9%) 31 (33.0%) 15 (16.5%) 28 (29.8%) 0 (0%) 0.72  3.4 7 (7.4%) 19 (20.2%) 63.9  10.7 48 (51.1%) 52/19/16/1/6 (55.3/20.2/17.0/1.1/6.4) PRU (+) 68 52 (76.5%) 59.5  14.1 30 (44.1%) 15 (22.1%) 15 (22.7%) 34 (50.0%) 3 (4.4%) 13.7  10.1 5 (7.4%) 61 (89.7%) 57.4  10.9 34 (50.7%) 36/8/23/0/1 (53.0/11.8/33.8/0/1.5) P value 0.460 0.551 0.009 0.128 0.326 0.009 0.040 <0.000 0.982 <0.000 0.968 0.046

70. Patients Demographics Number Hs-CRP, mg/L Total cholesterol, mg/dL Triglyceride, mg/dL HDL-cholesterol, mg/dL LDL-cholesterol, mg/dL BUN, mg/dL Creatinine, mg/dL Uric acid, mg/dL PRU (-) 94 2.10  2.6 184  41 165  82 41.7  10.0 119  31 16.4  6.3 1.2  1.2 5.3  1.5 PRU (+) 68 3.70  3.6 184  46 149  104 45.5  12.5 120  35 17.7  9.9 1.1  0.6 5.7  1.6 P value 0.002 0.963 0.298 0.042 0.833 0.323 0.488 0.214

71. Lumen volume 204.2 mm 3 Vessel volume 425.5 mm 3 Plaque Volume 221.3 mm 3 Segment length 20.2 mm FI area 10.7 mm 2 71 % FF area 2.5 mm 2 16 % DC area 0.2 mm 2 1 % NC area 1.7 mm 2 11 % PR(+) STEMI, M/54, PR(+) PR(-) STEMI, M/56, PR(-) Lumen volume 106.0 mm 3 Vessel volume 263.5 mm 3 Plaque Volume 157.6 mm 3 Segment length 13.5 mm FV 39.0 mm 3 36 % FFV 8.7 mm 3 8 % DCV 25.7 mm 3 24 % NCV 35.2 mm 3 32 % FI area 5.2 mm 2 54 % FF area 1.2 mm 2 12 % DC area 0.7 mm 2 7 % NC area 2.6 mm 2 26 % FV 91.9 mm 3 65 % FFV 28.2 mm 3 20 % DCV 5.6 mm 3 4 % NCV 16.6 mm 3 12 % Plaque Rupture EEM CSA=25.1mm 2, RI=1.21 EEM CSA=18.7mm 2, RI=0.85

72. Plaque ulceration(+) STEMI, M/84, Plaque ulceration(+) PR(-) STEMI, M/56, PR(-) Lumen volume 106.0 mm 3 Vessel volume 263.5 mm 3 Plaque Volume 157.6 mm 3 Segment length 13.5 mm FV 39.0 mm 3 36 % FFV 8.7 mm 3 8 % DCV 25.7 mm 3 24 % NCV 35.2 mm 3 32 % EEM CSA=18.7mm 2, RI=0.85 FV 140.0 mm 3 67 % FFV 61.3 mm 3 29 % DCV 2.6 mm 3 1 % NCV 5.1 mm 3 2 % Lumen volume 172.1 mm 3 Vessel volume 477.9 mm 3 Plaque Volume 305.8 mm 3 Segment length 26.6 mm FI area 10.0 mm 2 58 % FF area 7.2 mm 2 42 % DC area 0.0 mm 2 0 % NC area 0.1 mm 2 1 % FI area 5.2 mm 2 54 % FF area 1.2 mm 2 12 % DC area 0.7 mm 2 7 % NC area 2.6 mm 2 26 % EEM CSA=25.4mm 2, RI=1.07 Plaque Ulcer

73. PR(+) SA, M/77, PR(+) PR(-) SA, F/63, PR(-) Lumen volume 188.3 mm 3 Vessel volume 471.4 mm 3 Plaque Volume 283.1 mm 3 Segment length 25.7 mm FV 111.5 mm 3 60 % FFV 3.1 mm 3 2 % DCV 30.0 mm 3 16 % NCV 42.2 mm 3 23 % FI area 7.5 mm 2 66 % FF area 0.2 mm 2 2 % DC area 0.6 mm 2 6 % NC area 3.0 mm 2 26 % Lumen volume 120.8 mm 3 Vessel volume 264.9 mm 3 Plaque Volume 144.1 mm 3 Segment length 15.9 mm FV 51.5 mm 3 59 % FFV 10.9 mm 3 13 % DCV 7.0 mm 3 8 % NCV 17.5 mm 3 20 % FI area 4.8 mm 2 58 % FF area 1.2 mm 2 15 % DC area 0.6 mm 2 7 % NC area 1.7 mm 2 20 % Plaque Rupture EEM CSA=18.5mm 2, RI=1.12 EEM CSA=17.0mm 2, RI=0.73

74. Volume, mm 3 or % P<0.000 P=0.001 P<0.000 P=0.025 P<0.000 P=0.005 P=0.022 P=0.001 Volumetric Analysis (n=162) PRU(-), n=94 PRU(+), n=68

75. Area, mm 2 Lesion Analysis (n=162) at MLA PRU(-), n=94 PRU(+), n=68 P<0.000 P=0.002 P=0.246 P=0.002 P<0.000 P=0.869 P<0.000 P=0.003

76. Independent Factor for Plaque Rupture/Ulceration Vessel volume Fibrous volume Fibrofatty volume Necrotic core volume Remodeling index Beta 1.107 1.022 0.522 0.684 0.168 P value 0.035 0.021 0.008 0.005 0.031 95% CI 0.000 ~ 0.005 0.001 ~ 0.016 0.003 ~ 0.021 0.005 ~ 0.028 0.046 ~ 0.915 This model includes IVUS-VH variables showing significance in univariate analysis as a variables

77. SummarySummary 1. Plaque rupture/ulceration is not associated with plaque composition at the MLD site, but those over the entire lesion length 2. Plaque rupture/ulceration is also associated with positive vascular remodeling 1. Plaque rupture/ulceration is not associated with plaque composition at the MLD site, but those over the entire lesion length 2. Plaque rupture/ulceration is also associated with positive vascular remodeling

78. ConclusionsConclusions  VH-IVUS has a great potential to identify a vulnerble plaque  Needs clinical correlation with VH-IVUS findings  VH-IVUS has a great potential to identify a vulnerble plaque  Needs clinical correlation with VH-IVUS findings

79. Thank you for your attention

80. Compositional Changes during FU (32/59, 54.2%) mm 3 P=0.040 Total Subjects In 5 Pts Underwent PCI P=NS In 27 Pts Not Underwent PCI P=0.050

81. 6 Mo Gray Scale IVUS FU (33/59, 55.9%) PCI Group N=5 No PCI Group N=28 P=0.008 P=0.228 Remodeling Index

82. 6 Mo Gray Scale Volumetric IVUS FU (33/59, 55.9%) PCI Group N=5 No PCI Group N=28 No significant changes in both groups

83. IVUS-VH Findings over entire lesion (n=98) Fibrous volume, mm 3 Fibrofatty volume, mm 3 Dense calcified volume, mm 3 Necrotic core volume, mm 3 Fibrous volume, % Fibrofatty volume, % Dense calcified volume, % Necrotic core volume, % 42.9  37.4 9.9  13.1 6.0  6.1 11.6  9.8 61.3  11.2 12.6  8.0 8.8  7.0 17.3  9.5

84. 6 Mo Gray Scale IVUS FU (33/59, 55.9%) PCI Group N=5 P=0.043 No PCI Group N=28 P=0.011 P=0.008 5.5 14.6 9.1 11.2 4.2 12.7 8.5 11.7 0 2 4 6 8 10 12 14 16 LAEEMAPALength BaseFU 15.4 9.8 15.1 5.6 15.3 9.1 14.7 0 2 4 6 8 10 12 14 16 18 LAEEMAPALength BaseFU

85. Late Loss, mm Ref D, mm MLD, mm P=0.004 P=0.016 P<0.001 6 Mo Angiographic Follow Up (35/59, 59.3%) PCI Group N=5 No PCI Group N=30