1. R4 하 상 진

2. Introduction Circulation. 2007 May 1;115(17):2344-51.

3. Stent thrombosis risk factors 1. Procedural related 2. Patient & lesion related 3. Antiplatelet therapy 4. Thrombogenicity of the Stent 5. Impaired Reendothelialization MECHANISMS OF STENT THROMBOSIS 1. Persistent slow coronary blood flow (local or arterial) as occurs with dissection or hypoperfusion 2. Prior to reendothelialization, exposure of the blood to prothrombotic subendothelial constituents, such as tissue factor, or to the stent itself. 3. Failure to suppress platelet adhesion / aggregation at a time of prothrombotic risk, as occurs with premature cessation of antiplatelet therapy or drug resistance

4. Late stent thrombosis between BMS and DES

5. High incidence of stent thrombosis in AMI with large thrombus burden at 2 years ( cumulative rate, 8.2% ) J Am Coll Cardiol. 2007;50:573–583. ACS is an independent risk factor for LST with 4 years F/U. Eur Heart J. 2007;28(suppl):509. Figure 3. Mechanisms of late stent thrombosis in ostial and bifurcation stenting J Am Coll Cardiol. 2006;48:193–202.

6. Additional risk factors for LST 1. Penetration of necrotic core 2. Malapposition 3. Excessive stent length 4. Bifurcation lesions Thrombus, along with an underlying necrotic core, is a frequent finding in culprit plaques in patients dying with AMI.  thrombus affect drug distribution !!! Circulation. 2005;111:1619 –1626. The impact of underlying lesion characteristics on arterial healing and perhaps long-term outcomes in patients receiving DES for this indication ???

7. purposes Using our autopsy database of patients dying after Cypher or Taxus DES implantation, we compared the vascular pathological responses to DES implantation in patients receiving DES for AMI with that of patients receiving them for stable angina.

8. Methods Patient Selection  CVPath DES autopsy registry of 138 cases (collected from 2002 to September 2007) 1. AMI patient group : 25 patients presenting with AMI treated with DES and had an underlying necrotic core with a ruptured thin fibrous cap as the culprit lesion 2. Stable angina group : 46 patients had fibroatheroma (defined as necrotic core with a thick fibrous cap >100 μm) as an underlying plaque in the DES-treated segment.  20 patients excluded from analysis for the following reasons: bifurcation treated with 2 stents (n=6), evidence of local hypersensitivity reaction (n=1), chronic total occlusion of the stented segment (n=3), unknown stent duration (n=5), recipient of a heart transplant (n=1), or ineligibility for morphometry because of artifacts or overlapping with a stent of a different duration (n=4).

9. Pathological Assessment and Morphological Analysis Definitions 1. Acute thrombus : platelet-rich thrombus that occupied 30% of the cross-sectional area of the lumen 2. Restenosis : >75% cross-sectional area narrowing by neointimal formation. 3. Cause of death : stent related, non–stent-related cardiac, and noncardiac 4. Stent-related cardiac death : presence of a luminal thrombus with or without distal embolization 5. Non–stent-related cardiac death : patent DES without evidence of thrombus or restenosis in association with ≥ 1 nonstented major coronary arteries with severe cross-sectional area narrowing (>75%) or the presence of congestive heart failure and/or valvular heart disease.

10. Histologic sections for evaluating culprit sites (CSs) 1. CSs in patients with AMI :stented segments with presence of a necrotic core and a ruptured fibrous cap 2. CSs in patients with stable angina : sections with the largest underlying necrotic core and overlying thick fibrous cap (>100 μm).

11. Morphometric and histological analysis 1. Plaque area = external elastic lamina area – stent area 2. Fibrous cap thickness measurement : at thinnest portion of the fibroatheroma and at remnant site of ruptured plaque 3. Necrotic core arc 4. Total stent length 5. Neointimal thickness above stent strut : mean thickness between luminal surface of strut and vessel lumen 6. Fibrin deposition struts number 7. Inflammation ( > 10 inflammatory cells around strut ) struts number

12. Results

16. Fig 2. Histologic sections

17. Figure 3. Histological sections of the stented artery from a 65- year-old man who died suddenly 9 months after Taxus stent implantation for AMI.

18. Figure 4. Correlation between fibrous cap thickness and percent uncovered struts.

19. Discussion 1. Culprit lesions from patients presenting with AMI respond differently to DES implantation than CSs from patients with stable angina and result in significantly delayed healing (compared with stable lesions or even NCSs within the same lesion). 2. Patients receiving DES for this indication may be at increased risk for LST as a result of excessively delayed healing at the CSs.

20. Plaque Morphology Influences Local Healing Characteristics After DES Placement  In late stent thrombosis, the CSs of patients presenting with AMI 1. less neointimal growth and greater inflammation, fibrin deposition, and uncovered struts. 2. showed greater delayed arterial healing with evidence of persistent fibrin deposition and incomplete stent strut coverage  the underlying plaque morphology is the most reasonable explanation for our findings of delayed healing at the CS of ruptured plaque  Thrombus modulates arterial drug distribution in DES.

21. BMS and LST  underlying mechanisms of LST in BMS : Bifurcation stenting, radiation therapy, plaque disruption in an adjoining nonstented artery, restenosis, and lipid core prolapse after stenting.  The median time to thrombosis in BMS : 70 days  In a recent clinical retrospective study of LST after BMS implantation in 4503 patients, the cumulative incidence of stent thrombosis was 0.5% at 30 days, 0.8% at 1 year, and 2.0% at 10 years.

22. Clinical Implication  Delayed arterial healing in DES 1. Safety of DES in short term follow up 2. Prolonged antiplatelet therapy  Higher frequency of stent thrombosis with AMI patients than when patients receive DES for “stable” indications.

23. Data form patients receiving DES vs BMS for AMI  Massachusetts Registry evaluating 8000 patients with AMI treated with DES or BMS at 2 year follow up. : DES patients demonstrated a 2.7% reduction in risk-adjusted mortality Eur Heart J. 2007;28:2706 –2713.  Retrospective study of the effectiveness of DES for STEMI and demonstrated a 2-year angiographic rate of stent thrombosis of 3.2% that increased to 8.2% in those with large thrombus burden. J Am Coll Cardiol. 2007;50:573–583.  Registry of DES versus BMS for STEMI showing a significantly higher rate of death between 180 and 730 days after stent placement for DES versus BMS (hazard ratio, 6.7; P0.002), whereas there was no increased risk in patients treated for non-AMI. European Society of CardiologyCongress; September 1–5, 2007; Vienna, Austria.

24. Conclusions Vessel healing at the culprit site in AMI patients treated with DES is substantially delayed compared with the culprit site in patients receiving DES for stable angina, emphasizing the importance of underlying plaque morphology in the arterial response to DES. Our data suggest an increased risk of thrombotic complications in patients treated with DES for AMI.