1. TAXUS Perseus Core Data Elements: Qualitative and Quantitative Angiography
Jeffrey J. Popma, MD
Alexandra Almonacid, MD
Brigham and Women’s Hospital
St. Elizabeth Medical Center
Tufts University School of Medicine
Boston, MA
Angiographic Core Laboratory

2. Core Lab Lessons: Beyond Late Lumen Loss
After 15 years, substantial observer variabilities are still found with qualitative angiographic interpretations  independent Core Laboratory analyses have become standard for FDA DES studies
Discrepancies noted with Clinical Site Observations:
Baseline % diameter stenosis (e.g., NASCET Carotid)
Lesion Length and Reference Vessel Diameter
Final Angiographic Result
Binary restenosis (? 50-70% threshold for revascularization)
“Oculostenotic reflex”

3. Core Lab Lessons: Beyond Late Lumen Loss
Our initial focus with QCA was to determine the late term lumen dimensions, and relate them to the early angiographic results and late clinical events
Balloon angioplasty – less acute gain; less late loss
DCA – more acute gain; more lumen loss; better net gain
Continuous measures replaced binary criteria
Loss index (LL/AG) provided relative benefit --> drugs failed
With stents, LL was attributable to intimal hyperplasia.
Acute gains and late loss was similar (essentially) for all bare metal stents
? Possible exception related to strut thickness
Late loss replaced loss index as a surrogate

4. Beyond Late Lumen Loss
Clinical indices were further refined to determine those events that directly related to failure of the stent
TLR replaced “any” revascularization and TVF (in some studies)
Early (< 30 d) stent thrombosis was not included in the criteria for “restenosis” or calculations for late lumen loss but was placed in the early clinical failure category alone
To lower sample sizes, “surrogate” markers were sought to identify was to lower sample sizes required for device approval
In-Lesion (Segment) late lumen loss became the preferred endpoint for many device trials

5. (all stents used to treat the target lesion)
QCA methodology
in-segment
in-stent
(all stents used to treat the target lesion)
5 mm
stented segment
5 mm
proximal
edge
distal
edge

6. BMS Restenosis was Near Gaussian allowing expression with mean±SD
Example: 3.0 mm Bare Metal Stent
Mean late loss = 1.0 ± 0.5 mm
Pts. with angio restenosis
Angio Restenosis is any late loss over 1.5 mm (50% DS)
Pts. with
clinical restenosis
Clinical TLR correlates with late loss over 2.1 (70% DS)
1.0
Mean late loss
Pts. w/o restenosis
0.8
0.6
Distribution Density
0.4
0.2
0.0
-0.50
-0.25
0.00
0.25
0.50
0.75
1.00
1.25
1.50
1.75
2.00
2.25
2.50
Late loss (mm)
Donald Baim, Summer in Seattle, 2006.

7. DES Have Different Late Loss Distributions
Mean late loss = 0.2 mm
Clinical restenosis
What % of patients are above that line?
0.4 mm
0.6 mm
1.0 mm (BMS)
Mauri et al. Circulation. 2005;111:3435

8. Angiographic predictors of TLR
TAXUS-IV
Follow-up % Diameter Stenosis is a Better Predictor
ROC Analysis combining all patients
1.0
Late Loss
AUC = 0.918
MLD
AUC = 0.940
Sensitivity
0.5
Diameter Stenosis
AUC = 0.944
0.0
0.0
0.5
1.0
1 - Specificity

9. Surrogate Angiographic Endpoints
LL and % DS vs. TLR - A curvilinear relationship
11 RCTs with Cypher, Taxus, Endeavor, and BMS (5381 pts)
All patients RVD <2.5mm RVD mm RVD > 3.0mm
All patients
Probability of TLR
Probability of TLR
In-stent late loss
In-segment %DS
Pocock S et al ACC 2006

10. Sidebranch Compromise With Overlapping Stents TAXUS V Multiple Stent Analysis
Blinded core lab analysis of all multiple stent patients
Main Vessel Analysis:
Main vessel No Reflow, TIMI flow, Dissection, Distal Embolization, Abrupt Closure
Side Branch Analysis (for branches >1 mm):
Branch occlusion (total occlusion)
Branch narrowing (Δ≥70%  100%)
Branch TIMI flow

11. TAXUS V: SB Analysis With Multiple Stents
Control n=184 pts
TAXUS n=188 pts
P value
Total Sidebranches (n)
268
289
% pts with Sidebranch
87.5
89.1
0.74
# Branches (per pt.)
1.60±1.01
1.66±0.99
0.55
Sidebranch RVD (mm)
1.40±0.36
1.42±0.37
0.45
Multiple Stent Report – EM – , Exhibit 6

12. Side Branch Analysis in Multiple Stenting
Sidebranch Occlusion
Side Branch Narrowing (Δ ≥ 70%  100%)
TIMI Flow Reduction

13. Impact of the Overlap Region (per side branch)
Control
TAXUS
Any Sidebranch
Occlusion
Any Sidebranch
Narrowing
Any TIMI Flow
Reduction
p=0.74
p=0.23
p=1.00
p=0.10
p=0.025
37/203
34/207
8/48
15/55
56/203
58/207
21/48
24/55
51/203
68/207
12/48
26/55
Non-overlap
region
Overlap
Non-overlap
region
Overlap
Non-overlap
region
Overlap

14. 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:
* Type 5 implies
spiral fracture of stent

15. Stent Fracture with 3 mm of Stent Overlap
Stent Fractures
Type 4
Stent Fractures
Stent Fracture with 3 mm of Stent Overlap

16. * Preliminary Analysis
Incidence of TAXUS-Express Stent Fracture
Detailed angiographic review of TAXUS IV and VI
Core Lab remains blinded due to ongoing adjudication
Taxus IV: 7 Fractures TAXUS VI: 3 Factures
- Type 1 N=3 - Type N=1
- Type 2 N= Type 2 N=1
- Type 3 N=1 - Type 3 N=1
- Type 4 N=2
- Of the 10 fractures, 5 cases had overlapping stents (all overlaps were longer thatn 3 mm). In 4 of 5 cases, the stent fracture was within 5 mm of the overlap
* Preliminary Analysis

17. Incidence of TAXUS Stent Fracture
In patients assigned to angiographic FU
0.85%
0.81%
0.71%
N=819
N=420
N=1239
Taxus IV
Taxus VI
Overall

18. TAXUS-Express Type I Fractures
Taxus IV
24.9mm Stented Segment
Overlap >3mm

19. Fundamental “Pitfalls” for the Seasoned Professional Interventionalist
Forget the angiographic inclusion and exclusion criteria, the patient really needs the Taxus Perseus stent
“I don’t really see a stenosis, but it must be tight behind that diagonal branch” or “Who needs two views, it looks pretty tight in this one”
I’m sure the Core Lab can measure that tip of the injection catheter
Who needs documentation, I’ll remember all the views I took when the patient comes back for at follow-up
I can’t believe that this lesion isn’t causing symptoms, I going to fix it anyway

20. Pitfalls in QCA
Make certain that all patients meet the angiographic inclusion and exclusion criteria with respect to lesion length, vessel size, and lesion complexity
A “Friendly Feedback” sheet will give you a 20 point score for the film quality
Dr. Almonacid and I will provide “personal” feedback if we disagree with the patient being enrolled in the study. Remember, we’re colleagues and friends, but

21. Pitfalls in QCA
An accurate calibration source (the injection catheter filled with contrast) is the only way that we can identify the absolute changes in the MLD, edges, and within the stent between the final and the follow-up
We need to see the very distal, nontapered portion of the catheter and document the size of the catheters on the Technician’s
Nitroglycerin with the final stent placement and at FU is essential to control vasomotor tone for the calculations of late lumen loss

22. Please Use the Worksheet
Pitfalls in QCA
“Who needs the documentation, I will remember the views I took when the patient comes back for follow-up”
Please Use the Worksheet

23. Pitfalls in QCA
At the time of follow-up angiography, you see and intermediate stenosis (50-60%) and say
“I can’t believe that this lesion isn’t causing symptoms, I going to fix it anyway”

24. Summary
Core QCA data elements should include conventional morphologic and quantitative angiographic parameters in order to classify “tested” and “untested” therapies
- Newer analysis methods are needed for bifurcations
Late lumen loss is a reason index (% diameter stenosis may be better) for the late angiographic outcome but its ability to predict TLR (and MACE) may be limited in DES v. DES studies
Core QCA elements should add sidebranch patency (for overlapping stents), stent fracture, aneurysms, and stent thrombosis to assess long-term safety

25. Slides posted on http://www.clinicaltrialresults.org

26. Technologist Worksheet or detailed catheterization report with sequential angiographic views
Dicom3 Compatible CDs or 35 mm film
Please don’t forget the nitroglycerin
Follow Image Acquisition Guidelines
Match 2 Pre, Final, and Follow-up
Document everything on cine, particularly in the radiation studies
Near 100% angiographic follow-up is essential
Simple
QCA
Requests