1. Incidence, Predictors, and Outcome of Plaque Prolapse after Stent Implantation in Patients with Acute Myocardial Infarction: An Intravascular Ultrasound Analysis Young Joon Hong, MD, PhD; Myung Ho Jeong, MD, PhD, FACC, FAHA, FESC, FSCAI; Youngkeun Ahn, MD, PhD, FACC, FSCAI; Doo Sun Sim, MD; Jong Won Chung, MD; Jung Sun Cho, MD; Nam Sik Yoon, MD; Hyun Ju Yoon, MD; Jae Youn Moon, MD; Kye Hun Kim, MD, PhD; Hyung Wook Park, MD, PhD; Ju Han Kim, MD, PhD; Jeong Gwan Cho, MD, PhD, FACC; Jong Chun Park, MD, PhD; Jung Chaee Kang, MD, PhD The Heart Center of Chonnam National University Hospital, Chonnam National University Research Institute of Medical Sciences, Gwangju, Korea

2. ● Coronary angiography -- provides only simple, planar projections of three- dimensional coronary lumen anatomy. -- is limited to detect intrastent plaque prolapse (PP). ● Previous studies have shown that -- PP is not a rare phenomenon. -- PP has been detected frequently by intravascular ultrasound (IVUS). Background (I)

3. ● It has been known that several pre-intervention IVUS factors and aggressive stenting procedure have been associated with PP. ● Some studies have demonstrated that PP was associated with stent thrombosis. ● However, data on the characteristics of PP in patients with acute myocardial infarction (AMI) are lacking. Background (II)

4. Objectives ● to assess the incidence, predictors, and outcome of PP after stent implantation for infarct-related arteries in AMI patients.

5. ● a total of 310 patients with a first AMI - 125 ST segment elevation and 185 non-ST segment elevation MI - From January 9, 2001 to July 31, 2007 - who underwent pre-intervention IVUS within 24 hours from symptom onset - were stented successfully - had post-intervention IVUS imaging Patient Population (I)

6. Patient Population (II) ● Exclusion - prior MI, subacute or late stent thrombosis, restenosis after stenting, coronary artery bypass graft failure, patients studied with IVUS more than 24 hours after symptom onset, and patients in whom adequate IVUS images could not be obtained ● Identification of infarct-related arteries - electrocardiographic findings - left ventricular wall motion abnormalities on left ventricular angiogram or echocardiogram - coronary angiographic findings

7. Laboratory Analysis ● Venous blood samples were obtained within 24 hours after stenting. ● The blood samples were centrifuged, and serum was removed and stored at -70°C until the assay could be performed. ● Absolute creatine kinase-MB (CK-MB) levels were determined by radioimmunoassay (Dade Behring Inc., Miami, Florida). ● Cardiac-specific troponin I (cTnI) levels were measured by a paramagnetic particle, chemiluminescent immunoenzymatic assay (Beckman, Coulter Inc., Fullerton, California).

8. IVUS Imaging ● All IVUS examinations were performed before PCI after intracoronary administration of 200 µg nitroglycerin ● Commercially available IVUS system (Boston Scientific Corporation/SCIMed, Minneapolis, MN) ● IVUS catheter was advanced distal to the target lesion, and imaging was performed retrograde to the aorto-ostial junction at an automatic pullback speed of 0.5 mm/sec

9. IVUS Analysis (I) ● according to the American College of Cardiology Clinical Expert Consensus Document on Standards for Acqusition, Measurement and Reporting of Intravascular Ultrasound Studies ● using planimetry software (TapeMeasure, INDEC Systems Inc., Mountain View, CA) -- external elastic membrane (EEM) cross-sectional area (CSA) -- lumen CSA -- plaque plus media (P&M) CSA: EEM CSA minus lumen CSA -- plaque burden: P&M CSA divided by EEM CSA

10. Proximal Reference LesionSite Distal Reference EEM Lumen P+M Max P+M Thickness Min P+M Thickness Ca ++

11. IVUS Analysis (II) ● The lesion was the site with the smallest lumen CSA -- if there were multiple image slices with the same minimum lumen CSA  the image slice with the largest EEM and P&M was measured ● Plaque morphology -- Hypoechoic plaque: less bright compared with the reference adventitia -- Hyperechoic, noncalcified: as bright as or brighter than the reference adventitia without acoustic shadowing -- Calcified plaque: hyperechoic with shadowing : lesion contained >90° of circumferential calcium

12. IVUS Analysis (III) ● Coronary artery remodeling -- was assessed by comparing the lesion site to the reference EEM CSA ● Remodeling index (RI): the lesion site EEM CSA divided by the average of the proximal and distal reference EEM CSA -- Positive remodeling: RI >1.05 -- Intermediate remodeling: RI between 0.95 and 1.05 -- Negative remodeling: RI <0.95 ● Thrombus -- an intraluminal mass -- having a layered or lobulated appearance -- evidence of blood flow (microchannels) within the mass -- speckling or scintillation

13. IVUS Analysis (IV) ● A ruptured plaque -- contained a cavity that communicated with the lumen with an overlying residual fibrous cap fragment. -- a fragmented and loosely adherent plaque without a distinct cavity and without a fibrous cap fragment was not considered a plaque rupture. -- rupture sites separated by a length of artery containing smooth lumen contours without cavities were considered to represent different plaque ruptures. -- plaque cavity was measured and extrapolated to the ruptured capsule area.

14. Example of Plaque Rupture with Thrombus Thrombus Ruptured plaque cavity Thin fibrous cap

15. IVUS Analysis (V) ● At post-intervention -- minimum stent CSA -- Percent stent expansion: minimum stent CSA divided by mean reference lumen CSA -- PP was defined as tissue extrusion through the stent strut at post-intervention -- Volume of PP: subtracting lumen volume from stent volume

16. Baseline Characteristics (I) Plaque Prolapse (n=85) No Plaque Prolapse (n=225) p value Age (yrs)65±1365±111.0 Male gender, # (%)49 (58)130 (58)1.0 Clinical presentation, # (%) 0.081 Non-ST segment elevation MI44 (52)141 (63) ST segment elevation MI41 (48)84 (37) Diabetes mellitus, # (%)31 (37)80 (36)0.9 Hypertension, # (%)64 (75)154 (68)0.2 Smoking, # (%)30 (35)75 (33)0.7 Family history of coronary artery disease, # (%) 18 (21)34 (15)0.2 Previous percutaneous coronary intervention, # (%) 3 (10)9 (8)0.8 Thrombolytic therapy, # (%)11 (13)21 (9)0.4 Glycoprotein IIb/IIIa inhibitors, # (%)20 (24)44 (20)0.4 Use of distal protection devices, # (%)12 (14)12 (5)0.010

17. Baseline Characteristics (II) Plaque Prolapse (n=85) No Plaque Prolapse (n=225) p value Aspirin at admission, # (%)11 (13)21 (9)0.4 Statin at admission, # (%)10 (12)20 (9)0.4 Ejection fraction (%)46±1343±130.11 White blood cells (10 3 /mm 3 )8.9±3.19.2±3.60.6 Hemoglobin (g/dl)12.2±2.012.3±2.20.7 Platelet count (10 3 /mm 3 )220±90231±860.4 Creatinine clearance (ml/min)60±3166±350.15 Total cholesterol (mg/dl)181±47165±420.029 Triglyceride (mg/dl)132±67127±650.6 LDL cholesterol (mg/dl)110±43100±370.091 HDL cholesterol (mg/dl)45±1242±130.11

18. Coronary Angiographic Findings Plaque Prolapse (n=85) No Plaque Prolapse (n=225) p value Infarct-related artery, # (%)0.024 Left main0 (0)5 (2) LAD36 (42)131 (58) LCX14 (17)28 (12) RCA35 (41)61 (27) Lesion location, # (%)0.8 Ostium1 (1)3 (1) Proximal31 (37)90 (40) Middle46 (54)109 (48) Distal7 (8)23 (10) Multivessel disease, # (%)41 (48)112 (50)0.8 Thrombus, # (%)14 (16)22 (10)0.10 Calcium, # (%)7 (8)23 (10)0.6 TIMI flow grade 0, # (%)19 (22)30 (13)0.052

19. Procedural Results Plaque Prolapse (n=85) No Plaque Prolapse (n=225) p value Stent type, # (%)0.15 Sirolimus-eluting stent35 (41)103 (46) Paclitaxel-eluting stent19 (22)30 (13) Bare-metal stent31 (37)92 (41) No. of deployed stents, # (%)1.5±0.61.1±0.3<0.001 Stent diameter (mm)3.28±0.403.24±0.460.7 Stent length (mm)31±1321±8<0.001 Inflation pressure (mmHg)15.3±2.914.1±2.60.001 Reference diameter (mm)3.32±0.853.27±0.720.5 Pre-MLD (mm)0.63±0.320.68±0.510.18 Lesion length (mm)23±1215±80.001

20. Intravascular Ultrasound Findings Plaque Prolapse (n=85) No Plaque Prolapse (n=225) p value Reference EEM CSA (mm 2 )12.8±4.612.9±4.71.0 Lumen CSA (mm 2 )8.3±3.08.3±3.10.9 P&M CSA (mm 2 )4.6±2.64.5±2.61.0 Plaque burden (%)35±1134±110.7 Minimum lumen site EEM CSA (mm 2 )13.1±4.112.3±4.80.2 Lumen CSA (mm 2 )2.5±1.52.8±1.30.063 P&M CSA (mm 2 ) 10.6±4.29.4±4.30.040 Plaque burden (%)79.5±13.075.2±10.60.003 IVUS lesion length (mm)28±1218±8<0.001 Calcium arc (º)114±76195±81<0.001 Calcium length (mm) 3.6±2.75.5±3.70.008 Superficial calcium, # (%)51 (60)158 (70) 0.087 Minimum stent CSA (mm 2 )8.14±2.997.25±2.270.029 Stent expansion (%)98±2587±290.014

21. P=0.001 Plaque Rupture (%) P=0.089 Multiple Plaque Rupture

22. P=0.008 Plaque Cavity Area (mm 2 )

23. P=0.001 Thrombus (%)

24. P=0.044 Plaque Morphology

25. Remodeling Index P=0.017

26. Stent length (mm) ≤18>18, ≤28>28 (20/137) (23/89) (42/84) Plaque prolapse (%) p<0.001 Incidence of Plaque Prolapse according to the Stent Length

27. Plaque rupture (+) (43/112) (42/198) Plaque prolapse (%) p=0.001 Plaque rupture (-) Incidence of Plaque Prolapse according to the Presence/Absence of Plaque Rupture

28. Positive remodeling (41/113) (21/75) (23/122) Plaque prolapse (%) p=0.011 Intermediate remodeling Negative remodeling Incidence of Plaque Prolapse according to the Remodeling Pattern

29. Changes of Cardiac Enzymes at FU Plaque prolapse No plaque prolapse  CK-MB  cTnI

30. Plaque prolapse (+) Stent thrombosis (%) p=0.3 Plaque prolapse (-) 30-Day Stent Thrombosis Rate (2/85) (2/225)

31. Thrombus (OR=1.84, 95% CI 1.08-3.13, p=0.026) Multivariate Predictors of Post-PCI CK-MB Elevation Plaque rupture (OR=1.95, 95% CI 1.10-3.46, p=0.023) Plaque prolapse (OR=7.34, 95% CI 3.55-15.19, p<0.001)

32. Positive remodeling (OR=1.72; 95% CI 1.01-2.92, p=0.044) Multivariate Predictors of PP Stent length (OR=2.39; 95% CI 1.17-3.89, p=0.003) Plaque rupture (OR=1.96; 95% CI 1.14-3.37, p=0.015)

33. Conclusions The incidence of PP after stenting for infarct-related artery was 27%. Pre-intervention IVUS lesion characteristics – plaque rupture and positive remodeling – and longer stent length predict PP, and PP is associated with myonecrosis after stenting for infarct-related artery in patients with AMI.