jeffrey j. popma, md klaus a. tiroch, md brigham and women’s hospital harvard medical school...
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Jeffrey J. Popma, MDKlaus A. Tiroch, MD
Brigham and Women’s HospitalHarvard Medical School
Boston, MA
CYPHER™ Stent Fracture:An Uncommon Complication
after “Ultra” Complex PCI
Within the past 12 months, I have had a financial Within the past 12 months, I have had a financial interest/arrangement or affiliation with the organization(s) listed interest/arrangement or affiliation with the organization(s) listed below.below.
Physician Name Company/Relationship
Jeffrey J. Popma, MD Research Grants: Cordis, Boston Scientific,
Medtronic, Abbott-Guidant, Biosensors,
Radiant, eV3
Medical Advisory Board: Cordis, Boston Scientific, Medtronic
Speaker’s Bureau: Sanofi, BMS, Boston Scientific, Pfizer
Conflict of Interest Statement
Case Reports: CYPHER™ Stent Fractures
Location # Pts
Halkin A., Leon M., Heart 2004;90:e45. U.S.A. 1
Takebayashi H., et al., Circulation. 2004;110:3430-34. U.S.A. 2
Lemos P., et al., Circulation 2003; 108:257-260. The Netherlands 4
Sianos G., et al., Catheterization and Cardiovascular Interventions 2004; 61:111–16.
The Netherlands 2
Wilczynska J., et al., International Journal of Cardiology 2006; Aug 11; E-pub ahead of print.
Poland 1
Min PK., et al., International Journal of Cardiology 2006; 106:404-06.
South Korea 1
Shite J., et al., EHJ 2006; 27:1389. Japan 1
Surmely, JF Circ J 2006; 70: 936 –938 Japan 1
Zaizen H., et al., International Journal of Cardiology 2006; Aug 22; E-pub ahead of print.
Japan 1
Definitions Used for Stent Fracture Classification Current Report Allie et al 1 Scheinert et al 2
Type 0 No strut fracture - -
Type I Single strut fracture or gap between struts greater than 2x normal
Single strut fracture only Minor – single strut facture
Type II Multiple strut fractures with V-form division of the stent
Multiple single stent fractures occurring at different sites
Moderate – facture >1 strut
Type III Complete transverse stent fracture without displacement of fractured fragments more than 1 mm during the cardiac cycle
Multiple single stent fractures resulting in complete transverse linear fracture but without stent displacement
Severe – complete separation of stent segments
Type IV Complete transverse stent fracture with abundant movement and displacement of fractured fragments of more than 1 mm during the cardiac cycle
Complete transverse linear type III fracture with stent displacement
-
1 Allie et al Endovascular Today 2004; July/August: 22-34 2 Scheinert et al J Am Coll Cardiol 2005; 45:312-315
349 Patients in the CYPHER arm with follow-up in SIRIUS- 40 Patients with not available CINE films- 2 patients neither of the follow-up CDs can be opened- 2 patients all CD missing305 patients analyzed with 497 follow-up angiograms
4 fractures identified (1.3%),- 3x Fracture Type 1 (0.98%) - 1x Fracture Type 2 (0.33%)
• All fractures occurred with multiple stents near the site of overlap, all vessels calcified including one chronic total occlusion.
• 1 ISR at that site with TLR (Type 1 Fracture – tissue growth)
BWH SIRUS Angiographic AnalysisDid We Miss Something Important?
Coronary Stents: CYPHER TAXUSPeripheral Stents:
Analysis population
125113 12101
CYPHER Angiograms Forwarded to Core Lab No Fracture By Available Paperwork No Stent Fracture Identified Bx Sonic
51 Cases291
226 Cases
39 Cases
Baseline Angiogram Available 28
* 45 stent fractures in 39 patients
Stent Fracture: Review of Adverse Event Reports MAUDE cases between August 2003-July 2006
Case 1: Diffuse LAD Disease
Case 1: Diffuse LAD Disease
2.5 mm x 23 mm; 2.5 mm x 33 mm; 3.0 x 18 mm CYPHER stents
Case 1: Diffuse LAD Disease
Final Angiographic Result
Case 1: Diffuse LAD Disease
3 Month Angiographic Follow-Up
Case 1: Diffuse LAD Disease
Stent Fracture with 3 mm of Stent Overlap
Type 4Stent Fractures
Case 1: Ostial RCA Stent Migration
2.5 mm x 13 mm Stent Overlap
Case 2: Ostial RCA Stent Migration
24 Month Follow-up Stent Fracture and Migration
Type 4Stent Fracture
Case 3: Late Aneursym Formation
2.5 mm x 23 mm CYPHER
Case 3: Late Aneursym Formation
3 Month Follow-up
Case 3: Late Aneursym Formation
4 Month Follow-up
Type 4Stent Fracture
Case 3: Late Aneursym Formation
BWH Angiographic AnalysisAdverse Event Reports (N=39)
13 mm4
(10.3%)4
(10.3%)
18 mm
23 mm
28 mm
33 mm
3(7.7%)
13(33.3%)
15 (38.4%)
Type 25 (12.9%)
Type 316
(41.0%)
Type 418
(46.1%)
Fracture Type Stent Length
Variable Stent fractureN = 28, (%)
SiriusN = 531, (%)
P Value
Location
LAD 12 (42.9) 234 (44.1) 0.94
LCx 4 (14.3) 134 (25.2) 0.27
RCA 12 (42.9) 160 (30.1) 0.23
Ostial Location 6 (21.4) 10 (1.9) <0.001
Lesion Length, mm 22.1±15.9 14.4±5.8 <0.001
0-9.9 mm 7 (25.0) 106 (20.0) 0.66
10-19.9 mm 9 (32.1) 342 (64.6) 0.001
20 or greater 12 (42.9) 82 (15.4) 0.002
Angulations ≥ 45 degrees 13 (46.4) 58 (10.9) < 0.001
Proximal Tortuousity 7 (25.0) 28 (5.3) 0.002
Calcification present 19 (67.9) 91 (17.1) <0.001
Total Occlusion 7 (25.0) 17 (3.2) <0.001
Stent Fracture: Baseline Angiographic FindingsStent Fracture: Baseline Angiographic Findings
Variable Stent fracture Sirius P Value
Baseline N = 28 N = 531
RVD, mm 2.66±0.50 2.79±0.45 0.14
MLD, mm 0. 56±0.39 0.97±0.40 <0.001
% Stenosis 77.8±15.3 65.1±12.6 <0.001
Final N = 28 N = 531
Within the Segment
Final MLD 2.06±0.48 2.38±0.42 <0.001
Final % Stenosis 24.6±11.1 16.1±9.7 <0.001
Within the Stent
Final MLD 2.33±0.49 2.67±0.40 <0.001
Final % Stenosis 14.8±8.9 5.4±8.2 <0.001
Stent Fracture: Baseline Angiographic FindingsStent Fracture: Baseline Angiographic Findings
Variable Stent fractureN = 28 (%)
SiriusN = 531 (%)
P Value
Number of Stents 1.5±0.7 1.4±0.7 0.46
Stent diameter 2.79±0.39 2.91±0.50 0.21
Maximal Balloon 2.97±0.55 3.3±0.5 <0.001
Total overlapping-stent length 35.1±16.5 21.5±6.7 <0.001
Stent-to-lesion length ratio 2.04±1.2 1.6±0.6 <0.001
Mean angle
Systole 64.8±27.6 NA NA
Diastole 32.5±23.1 NA NA
Systole-Diastole 32.3±15.2 NA NA
Post-stenting 20.4±16.6 NA NA
Max Angle After Stent 44.5±21.3 NA NA
Dissection 4 (14.3) 7 (1.3) 0.003
Perforation 2 (7.1) 0 (0.0) 0.005
Stent Fracture: Baseline Angiographic FindingsStent Fracture: Baseline Angiographic Findings
Variable Stent fracture Sirius
N = 38 (%) N = 350 (%) P Value
RVD, mm 2.72±0.48 2.79±0.42 0.33
Within the Segment
Follow-up MLD 1.41±0.69 2.15±0.61 <0.001
Late Lumen Loss 0.70±0.66 0.24±0.47 <0.001
Restenosis Rate 18 (47.4) 31 (8.9) < 0.001
Follow-up % Stenosis 48.6±23.0 23.6±16.4 <0.001
Within the Stent
Follow-up MLD 1.52±0.82 2.50±0.58 <0.001
Late Lumen Loss 0.96±0.71 0.17±0.44 <0.001
Follow-up % Stenosis 44.1±28.5 10.4±16.5 <0.001
Restenosis Rate 18 (47.4) 11 (3.2) <0.001
ISR Length, mm 6.55±5.96 9.1±5.8 0.01
Total occlusions 3 (7.9) 2 (0.6) 0.02
Aneurysm 5 (13.2) 2 (0.6) <0.001
Stent Fracture: Follow-up FindingsStent Fracture: Follow-up Findings
Stent Fracture: Follow-up FindingsStent Fracture: Follow-up Findings
N
In-Segment Follow-up
% DS
Occlusion Aneurysm TLR No ISR TLR
Classification <50% ≥ 50%
Type I 0 0 0 0 0 0 0
Type II 5 3 2 0 1 2 1
Type III 15 6 9 0 1 7 0
Type IV 18 12 6 3 3 11 4
Overall 38 20(52.6%)
18 (47.4%)
3(7.9%)
5 (13.2%)
20 (52.6%)
5(13.2%)
* One patient developed fracture with initial deployment
• CYPHER stent fractures are an uncommon cause of complications late after stent placement (SIRIUS no related complications)
• Compared with patients enrolled in the SIRIUS trial, patients with stent fractures have very diffuse and complex disease, including multiple stents, long lesions, total occlusions, and tortuosity
• Initial angiographic results are suboptimal compared with the SIRIUS trial, likely relating to vessel rigidity and diffuse disease
• TLR was performed in over 50% of cases – both with and without evidence of angiographic restenosis
• Newer designs may decrease the occurrence of stent fracture
CYPHERCYPHER™™ Stent Fracture: Summary Stent Fracture: Summary
Frequency of CYPHER stent fractures:Cordis World-wide Product Safety Database – 0.009%
MAUDE – 113 cases reported (August 2003 - July 2006)
Most reported by Cordis and not by health care practitioners
Risk factors for Stent fracture – “Ultra-complex lesions”: • RCA > LAD >> Circ• Very diffuse and complex disease• Long stented segments (long stents)• Multiple overlapping stents• Angulated vessel segments / tortuosity• Mobile vessels (flexion, extension, torsion)• Suboptimal initial angiographic results
• likely relating to vessel rigidity/calcification and diffuse disease
Stent Fracture: DiscussionStent Fracture: Discussion
• Restenosis and TLR rates depend on indication for follow-up angiography (routine or symptom-driven)– Reports clustered at sites who more routinely treat “ultra-complex” lesions
and obtain routine angiographic f/u:
– Visualization of CYPHER stent fractures more apparent than with other stent platforms due to its relative radio-opacity
– “Ultracomplex lesions” - Routine angiographic f/u:
– Binary angiographic restenosis 5-10%; TLR in half of these cases
– TLR performed with and without angiographic restenosis
“Ultracomplex lesions” with f/u only with symptoms:
– Binary angiographic restenosis 40 - 70%; TLR in half of lesions with restenosis
– TLR performed both with and without angiographic restenosis
Stent Fracture: DiscussionStent Fracture: Discussion
ProceduralOverexpansion
PlacementPost-dilation
Length/overlap
MaterialElongation
Yield strength Ultimate Tensile Strength
Endurance LimitGrain size
Processing
Stent Fatigue is Multifactorial
StentDesign
Dimensions
AnatomicalWhich vessel & where
Compliance Angulation
Dynamic motion# of cycles
• Dynamic loading in a vessel results in the following deformations:– Pulsatile (current fatigue test & FEA) – Bend (static bend modeling in FEA)– Twist– Stretch
• Above are likely a function of species, vessel (RCA, LAD, LCX) and location (proximal, distal)
Preclinical Testing: Dynamic Loading
Unusually high stent fracture rate in Korea relative to the rest of the world likely related to high proportion of routine angiographic f/u and frequent use of long stents
Rates (ppm) Korea Japan OUS US Worldwide
Cypher 1,650 258 210 41 86 (0.009%)
All BMS 199 0 7 7 8
†† Parts per millionParts per million* Adjusted for returns (From launch to 8/31/2006) *All rates are in PPM
CYPHER STENT FRACTURES:Complaint Databases (Cypher PPM† Levels)
Korea vs. Rest of World (ROW) Comparison -Fracture Rate by Stent Length
0102030405060708090
8mm 13mm 18mm 23mm 28mm 33mmStent Length
RO
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500
1000
1500
2000
2500
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3500
Ko
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CYPHER STENT FRACTURES:CYPHER STENT FRACTURES:Fracture Rate by Stent LengthFracture Rate by Stent Length
Study # of Patients Stent Length Follow-up ST TLR/TVR
RESEARCH 96 61.2 1 year 0 4.2
ARTS II 607 47.6 1 year 1.6 7.4
Colombo 66 80 1.1 years 1.5 15.2
Park Long 184 44.4 9 months 0 3.8
Park “FMJ” 347 71.9 17 months 0.3 4.1
Park RCT 250 40.8 9 months 0.5 2.5
Keriakes 337 32.3 1 year 0.3 4.7
Long Lesions with SES: SummaryNo Fractures Reported in Large Series
Degertekin M., et al., Am J Cardiol 2004;93:826–29; Serruys PW., et al., Eurointerv 2005; 2: 147-56; . Tsagalou E., et al., JACC 2005;45:1570-73; Kim YH., et al., CCI 2006; 67:181-87; Lee C., et al., AJC 2006;98:918-22; ACC 2006; Oral Presentation Kereiakes DJ., et al., JACC 2006;48(1):21-31. .