1. Virtual Histology:From Theory to Vulnerable Plaque Detection Shaoliang Chen MD Nanjing First Hospital Nanjing Cardiovascular Hospital

3. Acute coronary syndrome (ACS) commonly results from rupture of thin-cap fibroatheroma (TCFA), and occasionally results from erosion or calcified nodules. Pathological features of TCFA are the presence of thin fibrous cap (<65μm) and a large lipid core. Bruke AP et al. N Eng J Med.1997;336:1276-1282 Falk E, et al. Circulation. 1995; 92: 657-671 Virmani R, et al. Arterioscler Thromb Vasc Biol. 2000; 20: 1262

4. IVUS – Listening through walls Lumen Lipid Vessel US signal Backscattered signal or RF data Backscattered

5. From Conventional IVUS imaging to Radiofrequency Signal Processing Conventional IVUS images are derived from the envelope of the RadioFrequency signal recorded by the US transducer Conventional IVUS images are derived from the envelope of the RadioFrequency signal recorded by the US transducer More information can be derived from the processing of the raw RF signal itself for: More information can be derived from the processing of the raw RF signal itself for:  tissue characterization  evaluation of mechanical properties  assessment of flow 0.511.522.533.544.55 -150 -100 -50 0 50 100 150 blood wall catheter

6. Virtual histology IVUS (VH-IVUS) uses amplitude and frequency of echoes Especially, Necrotic Core component is known to related to plaque vulnerability. VH- IVUS differentiates coronary plaque into 4 types Frequency Amplitude

7. “Conventional” IVUS Assessment of Patients Presenting with ACS

8. Echolucent Plaque=Vulnerable Plaque?

9. Echolucent Plaque and VH

10. Echolucent Plaque and VH(n=53) VH Phenotype of Echolucent Lesion Echolucent Zone Adjacend of Echolucent Zone Yang AHA 2008

11. Plaque Classification 1. “ Adaptive Intimal Thickening ” Plaque comprised of nearly all fibrous tissue (<5% of fibrofatty, calcification and/or NC plaque). 2. Pathological Intimal Thickening” – Mainly mixture of fibrous, fibrofatty (>5%), and necrotic core and some calcified tissue <5%.

12. Plaque Classification “Fibro-Atheroma” – Fibrotic cap and significant Necrotic Core (confluent NC >5% of total plaque volume) in fibrotic and/or fibrofatty tissue It will very likely be that the most important goal is to differentiate the FibroAtheroma plaque types from the other three plaque types during assessments of high risk lesions for rupture.

13. Definition of thin-cap fibroatheroma (TCFA) by VH-IVUS In at least 3 consecutive frames, (1)Percent Necrotic Core area to plaque area> 10% without evident overlying fibrous component (2)Percent plaque area to vessel area > 40% Rodriguez-Granillo et al. J Am Coll Cardiol,2005; 46:2038-42

14. Not only volume of NC, but also extent of NC contact with lumen are important. Measurement of angle of NC contact with lumen (NCCL) was performed by a MATLABTM at Thoraxcenter, Erasmus MC, by Dr. Garcia-Garcia HM. Overall NC 31.1% Blue area; major NCCL, 28.3% purple plus blue area Total NCCL, 30.5% Red line; angle of the major NCCL, 9° White and red line; angle of the total NCCL, 35° Sawada T, Shite J et al Eur Heart J 2008; 29:1136-46

15. By necrotic core angle contact with lumen, VH-IVUS may estimate thin fibrous cap. However, IVUS can not visualize surface fibrous cap due to limited resolution >100μm.

16. Thin-Cap FibroAtheroma (TCFA) Courtesy of Renu Virmani

17. VH is entirely dependent on drawing accurate borders

18. Is VH-TCFA really vulnerable?

19. Recent MI Culprit lesion Distal Prox

20. Acute Plaque Rupture 79 years old male Unstable, DM (type II), hypertension, lipid disorder, prior MI VH IVUS; TCFA with three layers

21. 52-yo Male with Abn Nuc Scan (DB)

22. Pre-intervention Post-intervention (Peak CK-MB release measured 21.2 ng/ml)

23. Global VH-IVUS Registry

24. Serial VH Evaluation

25. Case Examples Baseline TCFA PIT Follow-up ThCFAFibroticTCFA

26. Changes of plaque morphology TCFA n=20 ThCFA n=93 PIT n=62 65% 10% 25% 90% 3%1% 6% 71% 10% Fibrotic/fibrocalcific plaques did not change. Kubo T, JACC in press

27. Changes at MLA site Plaque Area Lumen Area

28. Serial VH in Patients After Stenting: DES vs BMS Kubo ACC2008

29. Serial VH of DES BaselineFollow-up Stented segment Reference segment

30. Serial VH of BMS Baseline Follow-up Stented segment Reference segment

31. Abutting Necrotic Core to the Lumen * p<0.05 Kubo ACC2008

32. The PROSPECT Trial 700 pts with ACS UA (with ECGΔ) or NSTEMI or STEMI >24 o 1-2 vessel CAD undergoing PCI at up to 40 sites in U.S., Europe PCI of culprit lesion(s) Successful and uncomplicated Metabolic S. Waist circum Fast lipids Fast glu HgbA1C Fast insulin Creatinine Biomarkers Hs CRP IL-6 sCD40L MPO TNFα MMP9 Lp-PLA2 others Formally enrolled PI: Gregg W. Stone Sponsor: Abbott Vascular; Partner: Volcano

33. 3-vessel imaging post PCI Culprit artery, followed by non-culprit arteries

35. PROSPECT Methodology IVUS/VH Core Lab Analysis Lesions are classified into 5 main sub-types based on VH composition

36. PROSPECT: Acute MI

39. MLA: 6.1 mm 2

40. PROSPECT: Baseline Features N = 697

41. PROSPECT: Imaging Summary Length of coronary arteries analyzed

42. PROSPECT: Imaging Summary Non culprit angio and IVUS lesions (LM, P/MLAD, PLCX and P/M/DRCA only)

43. PROSPECT: Imaging Summary Non culprit angio and IVUS lesions (LM, P/MLAD, PLCX and P/M/DRCA only)

44. PROSPECT: Imaging Summary Per pt incidence of IVUS lesions with MLA <4.0 mm 2

45. PROSPECT: Imaging Summary Presence of ≥1 VH lesion subtypes (2765 lesions in 614 pts)

46. PROSPECT: Imaging Summary Per patient incidence of VH-TCFAs

47. Longitudinal sections from 50 autopsy pts 10.9 meters examined from 148 coronary arteries 44% of pts had ≥1 TCFA (range 0 - 6) Mean 0.46 TCFAs/pt (0.55 vs. 0.38 in pts dying of CV ds. vs. other) - 1.21/pt in hearts with ruptured plaques - Cheruvu PK et al. JACC 2007;50:940–9