OCT Stent Thrombosis and Neoatherosclerosis Gary S Mintz

OCT, Stent Thrombosis, and Neoatherosclerosis Gary S. Mintz, MD Cardiovascular Research Foundation New York, NY

Gary S. Mintz, MD Grant Support: Boston Scientific Corporation, Volcano Therapeutics, Inc. Honoraria: Boston Scientific Corporation, Volcano Therapeutics, Inc. , St. Jude Medical, Inc. , Pfizer, Inc.

Stent

OCT and IVUS in DES with Late/Very Late ST Median time to presentation 615 days (394, 1186) VLST Controls* 18 36 Cross-sections with uncovered struts (%) 33. 3 (0, 43. 7) 9 (0, 7. 8) 0. 003 Cross-sections with >30% uncovered struts (%) 21. 6 (0, 43. 7) 0 (0, 6. 9) 0. 002 Malapposed struts per patient (%) 5. 9± 6. 3 1. 8± 1. 5 0. 001 Minimum stent CSA (mm 2) 5. 7± 1. 4 5. 9± 1. 4 1. 0 Mean EEM CSA (mm 2) 19. 4± 5. 8 15. 1± 4. 6 0. 003 1. 24 (1. 06, 1. 43) 0. 99 (0. 90, 1. 11) <0. 001 4. 1± 2. 3 1. 2± 1. 5 0. 001 Stents “Remodeling index” (lesion/reference EEM CSA) Malapposition area (mm 2) Thrombus aspiration demonstrated neutrophils and eosinophils in the majority of cases. P *matched for: stent type and IVUS reference EEM and lumen CSA and stent diameter (Guagliumi et al, JACC Cardiovasc Intervent 2012; 5: 12 -20)

Stent thrombosis 4 years after Cypher stents

OCT findings in 18 patients with very late DES thrombosis • 4 had ruptured neointima without uncovered or malapposed stent struts. • Among 14 patients with no neointimal rupture. . . • uncovered struts were seen in 9 patients • malapposed struts were seen in 7 patients • lipid-laden neointima was seen in 4 patients. Ko et al. Int J Cardiovasc Imaging 2012; 28: 715 -23

OCT findings in 33 patients (27 DES, 6 BMS) with VLST • VLST was associated with in-stent neointimal rupture in 23 (70%); all but one had thrombi near the site of the ruptured neointima. • Stent malapposition was observed in 14 (42%), but. . . • • only 9 (64%) had thrombi at the malapposed segments 6 (18%) also had neointimal rupture. • Stent fracture was detected in 3 DES-treated lesions, all with concomitant neointimal rupture. • Lesions with neointimal rupture presented with a higher frequency of STEMI vs non-STEMI (65% vs. 20%, p=0. 040) Kang et al. JACC Cardiovasc Imaging 2012; 5: 1267 -8

Limitations of OCT • Cannot penetrate red thrombus • Flow must be re-established before imaging • Stent measurements are not the same as with IVUS and will require independent assessment to determine OCTderived predictors of early ST • The simple decision whether to perform thrombectomy and then OCT. . . or OCT and then thrombectomy will affect the findings • If thrombectomy is performed before OCT, neoatherosclerosis is underreported (~10%) compared to OCT without thrombectory (~70%, Kang et al, JACC Cardiovasc Imaging, in press). . . perhaps because the neoatherosclerosis elements are removed (Yamaji et al, Circ Cardiovasc Interv, 2012; 5: 47 -54)

Population Stent duration Thrombectomy Guagliumi et al. Ko et al. Kang et al. 18 DES-LST (15 VLST) 18 DES-VLST 27 DES-VLST 21 mo 41± 18 mo 74 mo (13– 40 mo) (46– 90 mo) Before OCT After OCT Thrombi Aspirated White 94% Red 79% Rupture 17% 22% 63% Malapposition 78% 39% 52%

OCT and BMS Neoatherosclerosis - I # Lipid laden intimal Intimal disruption Thrombus Intraintimal neovasacularization <6 months 20 0 0 5% >5 years 21 67% 38% 52% 0% 62% Takano et al. J Am Coll Cardiol 2009; 55: 26 -33

OCT and BMS Neoatherosclerosis - II (60 stents in 39 patients 6. 5± 1. 3 yrs after implantation) • Lipid-rich neointima was found in 20 stents (33. 3%) in 16 patients (41%) with an average fibrous cap thickness of 56. 7± 5. 8µ. • 6 patients had plaque disruption • 6 patients had mural thrombus Hou et al. Heart. 2010; 96: 1187 -90.

OCT and In-stent Neoatherosclerosis after BMS - III <1 year >5 years 39 43 Homogeneous neointima* 94. 2± 11. 5% 39. 5± 28. 5% <0. 0001 Heterogeneous neointima* 5. 8± 11. 5% 60. 5%± 28. 5% <0. 0001 Peri-stent 6. 8± 8. 6% 25. 6± 18. 6% <0. 0001 Neointima 0 13. 1± 12. 8% <0. 0001 0 18. 6% 0. 006 Intraluminal material 2. 6% 20. 9% 0. 02 With shadowing 0 16. 2% 0. 01 2. 6% 4. 7% 1. 0 # P-value Microvessels* Disrupted neointima Without shadowing *of sections throughout the stent Habara et al. Circ Cardiovasc Interv 2011; 4: 232 -8

OCT & In-stent Neoatherosclerosis after BMS - IV (n=22, Median F/U time = 11 years) Kang et al. JACC Cardiovasc Imaging 2012; 5: 1267 -8

OCT & In-stent Neoatherosclerosis after DES (n=50, median follow-up of 32 months) • 52% lesions had at least one in-stent TCFA-like neointima • 58% had at least one in-stent neointimal rupture. • Patients presenting with unstable angina showed ¡ ¡ Thinner fibrous cap (55μ vs. 100μ, p=0. 006) Higher incidence of TCFA-like neointima (75% vs. 37%, p=0. 008) Higher incidence of neointimal rupture (75% vs. 47%, p=0. 044) Higher incidence of thrombi (80% vs. 43%, p=0. 010) and red thrombi (30% vs. 3%, p=0. 012) 100% Survival free of TCFA-like neointima, neointimal rupture, or red thrombus 0 0 24 Kang et al. Circulation 2011; 123: 2954 -2963 48 72 96

Incidence & time course of neoatherosclerosis in BMS and DES from the MGH OCT Registry %LRP P<0. 01 P<0. 05 P<0. 01 Yonetsu et al. Am J Cardiol 2012; 110: 933– 9 P=NS P<0. 05

Microvessel TCFA-like neointima Neointimal rupture Calcium Red thrombus Mixed thrombus White thrombus Kang et al. Circulation 2011; 123: 2954 -63

Yonetsu et al. Am J Cardiol 2012; 110: 933– 9

Predictors for Neoatherosclerosis Retrospective MGH OCT Registry Adjusted OR p SES 3. 86 0. 007 PES 24. 17 <0. 001 ZES 7. 18 0. 013 EES 6. 46 0. 007 Age >65 years 1. 84 0. 121 Stent age >48 months 10. 45 <0. 001 Current smoking 7. 03 <0. 001 Chronic renal disease 3. 69 0. 035 ACE-I / ARB use 0. 39 0. 028 Risk vs BMS Yonetu et al. Circ Cardiovasc Imaging 2012; 5: 660 -6

Serial OCT in 76 DES-treated lesions Thrombus Lipidic neointima TCFA Neovascularization 9 mos 10. 5% 14. 5% 3. 9% 44. 7% 2 yrs 9. 2% 27. 6% 13. 2% 73. 7% 1. 0 0. 0009 0. 07 <0. 001 P-value Percentage of uncovered struts significantly decreased from 4. 4% at 9 mos to 2. 3% at 2 yrs (p<0. 001). Completely covered lesions were more frequently observed at 2 yrs (44. 7% vs. 59. 2%, p= 0. 07), but approximately one-half of the stented lesions were still not completely covered at 2 yrs. Kim et al. JACC Cardiovasc Imaging 2012; 5: 1147 -55

Using NIRS, lipid was detected within stented vessels in 58 of 65 patients. LCBI/4 mm measured 173± 191. NIRS identified lipid that was not detected by OCT in 18 (28%) stented vessels of which 3 (18%) had evidence of thin-cap neointima. Ali et al, unpublished

Causes of Stent failure Bare Metal Stents Stent Thrombosis <30 d Mechanical complications incl. underexpansion >1 y x Drug-eluting Stents Restenosis <5 y >5 y x Intimal hyperplasia Stent Thrombosis <30 d - 1 y x x >18 m x x x Late malapposition or aneurysm x x x Delayed healing x Uncovered stent struts/fibrin deposition x Vessel wall inflammation <18 m x x Neoatherosclerosis Stent fracture >1 y Restenosis x x x

Neoatherosclerosis (atherosclerosis developing within the neointima of a stent) is one of the causes of stent failure. . . • Occurs earlier in DES (≈18 -24 months) than in BMS (≈4 -5 years) • Occurs with greater frequency in all types of DES than in BMS although most of the data comes from first generation DES • Can present as either late ISR or VLST and may be responsible for the majority of very late (beyond 1 year) DES thrombosis and/or restenosis • Presentation and treatment are associated with greater clinical instability ¡ ¡ ¡ ACS vs stable angina (or sxs vs no sxs) in patients with ISR STEMI vs non-STEMI in patients with stent thrombosis Post-procedural myonecrosis in patients treated for ISR • Is best diagnosed using OCT Takano et al. J Am Coll Cardiol 2009; 55: 26 -33 Nakazawa et al. J Am Coll Cardiol Img 2009; 2: 625 -8 Lee et al. J Am Coll Cardiol. 2010; 55: 1936 -42 Hou et al. Heart. 2010; 96: 1187 -90 Kang et al. Circulation 2011; 123: 2954 -2963 Habara et al. Circ Cardiovasc Interv 2011; 4: 232 -8 Park et al. J Am Coll Cardiol 2012; 59: 2051 -7 Yonetsu et al. Am Heart J 2012; 110: 933 -9 Yonetsu et al. Circ Cardiovasc Imaging 2012; 5: 660 -6 Habara et l. Eur Heart J Cardiovasc Imaging. 2012 Sep 3