Electronic supplement
Methods
Study device
The Absorb BVS consists of a polymer backbone of Poly-L lactide (PLLA) coated
with a thin layer of a 1:1 mixture of Poly-D, L-lactide (PDLLA) polymer, and the
anti-proliferative drug everolimus to form an amorphous drug eluting coating matrix
containing 100 micrograms of everolimus/cm2 of scaffold. The details of the device
have been previously described (1,2). The scaffold design has in-phase zigzag hoops
linked by bridges that allow a uniform strut distribution and provide uniform vessel
wall support and drug transfer.
Study Procedure
Target lesions were scaffolded after mandatory pre-dilatation. Post-dilatation with a
balloon shorter than the implanted scaffold could be performed at the operator’s
discretion (if an optimal angiographic result was not obtained immediately after
scaffold deployment). Additional stenting with a Xience V drug-eluting metallic stent
for edge dissection or insufficient coverage of the lesion occurred in 3 out of the 101
patients. Treatment with aspirin was started at least 6 hours prior to the index
procedure (3). A loading dose of 300 mg of clopidogrel was administered before the
procedure, followed by 75 mg daily for a minimum of 6 months.
3-Dimensional OCT
To visualize more comprehensively in three dimensions, connections and
disconnections of the struts inside the global structure of the scaffold, 3-D OCT
analysis was used (2,4). First, image sequences were generated from the OCT image
files. Every single strut was detected in each OCT cross section. After segmentation
of scaffold struts, three-dimensional images were reconstructed using a volume
rendering software (OSIRIX, version 3.8.1). X and Y axis pixel resolution were
calculated in each image sequence using the image software (Image J), while the slice
interval was set as 0.2 mm, according to the pullback speed of 2.0 mm/s and the frame
rate of 100 frame/second.
To display the changes in spatial distribution of the struts along the scaffold
from post-procedure to late follow-up, the ‘spread-out-vessel chart’ was used as
described previously (5). Briefly, these graphics were obtained by correlating the
longitudinal distance from the distal edge of the scaffold to the strut (abscissa) with
the angle where the struts were located in the circular cross section with respect to the
center of gravity of the vessel (ordinates). In each cross-section (axial resolution of
200 microns), the circumferential length of each individual strut was depicted in an
angular fashion. The resultant graphic represented the scaffolded vessel, as if it had
been cut longitudinally along the reference angle and spread out on a flat surface.
IVUS greyscale analysis
Treated vessels post-procedure and at follow-up were examined with phased array
intravascular ultrasound catheters (EagleEye™; Volcano Corporation, Rancho
Cordova, CA) using a pullback speed of 0.5 mm per second (6). The presence of
scaffold disruption was assessed using the same criteria used in OCT analysis.
1
Definitions
The composite ischemia-driven major adverse cardiac event (ID-MACE) was cardiac
death, any myocardial infarction and ischemia driven TLR for a QCA diameter
stenosis (DS) of ≥50% with either symptoms or ischemia, or DS ≥70% at the time of
scheduled or unscheduled angiography. For non-Q MI, elevation of CK levels ≥2
times the upper limit of normal with elevated CK-MB was required, a definition
dating from the design time in 2008 (7). All events were adjudicated by an
independent clinical event committee and all imaging procedures (QCA, IVUS
Grayscale, IVUS-VH, echogenicity and OCT) were analyzed by an independent core
lab (Cardialysis B.V., Rotterdam, the Netherlands).
2
Table e1. Baseline characteristics
p values
Total
Cohort B1
Cohort B2
51 patients
30 patients
21 patients
52 lesions
30 lesions
22 lesions
Age (mean ± SD, years)
62 ± 10
64 ± 10
59 ± 9
0.1
Male gender (n (%))
37(73)
22(76)
15(68)
0.75
Current Smokers (n (%))
12(24)
5(17)
7(32)
0.32
4(8)
3(10)
1(5)
0.63
Hypertension Requiring Medication
(n (%))
30(59)
16(55)
14(64)
0.58
Hyperlipidemia Requiring
Medication (n (%))
38(75)
26(90)
12(55)
0.01
Prior target vessel Intervention (n
(%))
11(22)
8(28)
3(14)
0.31
Prior myocardial infarction (n (%))
15(29)
12(41)
3(14)
0.06
Left Anterior Descending (n(%))
27(53)
13(45)
14(64)
0.26
Left Circumflex (n(%))
9(18)
7(24)
2(9)
0.27
Right Coronary Artery (n(%))
16(31)
10(35)
6(27)
0.76
A (n(%))
0
0
0
-
B1 (n(%))
28(57)
15 (52)
13 (65)
0.39
B2 (n(%))
20(41)
13(45)
7(35)
0.56
C (n(%))
1(2)
1(3)
0
1
Mean Reference Vessel Diameter
(mm)
2.61 ± 0.33
2.63 ± 0.37
2.57 ± 0.27
0.52
Minimum Luminal Diameter (mm)
1.08 ± 0.27
1.06 ± 0.29
1.12 ± 0.25
0.43
B1 vs. B2
Diabetes (n (%))
Target Vessel
AHA / ACC Lesion Classification
3
58 ± 11
59 ± 11
56 ± 10
0.34
Lesion Length (mm)
10.1 ± 3.6
10.7 ± 4.0
9.2 ± 2.7
0.15
Maximum diameter of balloon at
scaffolding or post-dilatation
3.03 ± 0.24
3.08 ± 0.23
2.96 ± 0.24
0.1
Mean diameter of balloon at
scaffolding or post-dilatation
2.55 ± 0.27
2.78 ± 0.21
2.69 ± 0.22
0.14
29 (57)
15(52)
14(64)
0.57
Diameter Stenosis (%)
Post dilatation (n(%))
4
Table e2. Patient and lesion characteristics in patients with or without late discontinuities
Cases with late
discontinuities
21 patients
21 lesions
Cases without late
discontinuities
28 patients
29 lesions
63.7 ± 11.2
15 (71.4)
5 (23.8)
2 (9.5)
60.7 ± 0.16
21 (72.4)
6 (20.7)
1 (3.4)
0.29
1
1
0.57
Hypertension Requiring Medication (n (%))
11 (52.4)
19 (65.5)
0.39
Hyperlipidemia Requiring Medication (n (%))
13 (61.9)
4 (19.0)
8 (38.1)
24 (82.8)
7 (24.1)
6 (20.7)
0.12
0.74
0.3
9 (42.9)
4 (19.0)
8 (38.1)
17 (58.6)
5 (17.2)
7 (24.1)
0.39
1
0.36
0
10 (50)
9 (45.0)
1 (5.0)
2 (10.0)
0
17 (60.7)
11 (39.3)
0 (0)
7 (25.0)
0.56
0.77
0.42
0.27
2.59 ± 0.37
1.21 ± 0.30
53.4 ± 10.2
10.0 ± 3.86
0.05 ± 0.05
2.62 ± 0.31
1.00 ± 0.22
61.2 ± 10.2
10.2 ± 3.49
0.04 ± 0.04
0.77
0.01
0.01
0.91
0.33
14 (66.7)
14 (48.3)
0.25
2.83 ± 0.36
2.87 ± 0.27
0.69
2.56 ± 0.30
2.56 ± 0.24
0.99
0.18 ± 0.18
0.18 ± 0.16
0.96
Age (mean ± SD, years)
Male gender (n (%))
Current Smokers (n (%))
Diabetes (n (%))
Prior coronary Intervention (n (%))
Prior myocardial infarction (n (%))
Target Vessel
Left Anterior Descending (n(%))
Left Circumflex (n(%))
Right Coronary Artery (n(%))
AHA / ACC Lesion Classification
A (n(%))
B1 (n(%))
B2 (n(%))
C (n(%))
Calcification (n(%))
Preprocedure
Reference Vessel Diameter (mm)
Minimum Luminal Diameter (mm)
Diameter Stenosis (%)
Lesion Length (mm)
Curvature before scaffolding (cm-1)
Post dilatation (n(%))
Maximum diameter of balloon after scaffolding or
post-dilatation (mm)
Mean diameter of balloon after scaffolding or
post-dilatation (mm)
Absolute recoil (mm)
P values
5
Figure e1. Flow chart of patient with OCT at baselines and follow-up
BL= baseline, 6M = 6 months, 24M = 24 months, 36M = 36 months, OCT = optical
coherence tomography
6
Figure e2
Each series of framed illustrations (yellow, green and orange) represents the
observation at different time points (post-procedure, at 6 months and at 2 years).
An Absorb BVS 3.0 mm scaffold was implanted with good conformability in an
angulated stenosed segment of a RCA (A: pre-procedural angiography, B: post
procedural angiography, white arrows indicate the extremities of scaffolded segment).
On OCT (C-F), the scaffold was well expanded with full apposition of struts.
At 6 months, the repeat angiography showed a good persistent result (G). IVUS did
not show any abnormality (H), however, OCT (I-L) showed a malapposed proximal
metallic marker (J, white arrow) as well as overhung struts (K, white arrows). Panels
M and N shows 3-D reconstruction of OCT images at 6 months. White arrow
indicates the proximal marker and malapposed overhung struts, which are connected
proximally and distally to the vessel wall.
At 24 months (2Y), angiography (Q) and IVUS (R) showed patency of the scaffolded
segment. The malapposed proximal marker (white arrow in T) and overhung strut
(white arrow in V) still remained on OCT (S-V). Although these covered struts
seemed to be malapposed and overhung on 2-dimension (V), they were attached to
the vessel wall on 3-dimension (white arrows in O and P).
7
Figure e3
Each series of framed illustrations (light blue, yellow and light green) represents the
observation at different time points (post-procedure, at 1 year and at 2 years). The
figure shows a case with non-ischemia driven TLR. An Absorb BVS 3.0 mm scaffold
was implanted in the mid LAD lesion (post procedural angiography: G, white arrows
indicate the scaffolded segment). Immediately after the procedure, OCT demonstrated
a good expansion of the scaffold without any malapposition (B and C). Planned
angiography at 1 year showed late lumen enlargement with, on OCT (E and F),
malapposed and stacked struts (late discontinuity). The patient remained
asymptomatic but the investigator, concerned by the malapposed struts observed at
one year, performed a non-protocol mandated angiography at 2 years. Two-year
angiography demonstrated a patent scaffolded segment with further angiographic
lumen enlargement (G). OCT (H, I and J) and IVUS (K and L) showed malapposed
struts in the scaffolded segment. Despite the absence of documented ischemia, an
additional metallic stent in the previously scaffolded segment was implanted followed
by post dilatation with a larger balloon.
8
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