Vasomotor Response to Nitroglycerine Over 5 Years Follow-Up After Everolimus-Eluting Bioresorbable Scaffold Implantation

JACC: CARDIOVASCULAR INTERVENTIONS

VOL. 10, NO. 8, 2017

ª 2017 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER

ISSN 1936-8798/$36.00 http://dx.doi.org/10.1016/j.jcin.2016.12.020

Vasomotor Response to Nitroglycerine Over 5 Years Follow-Up After Everolimus-Eluting Bioresorbable Scaffold Implantation Dariusz Dudek, MD, PHD,a Łukasz Rzeszutko, MD, PHD,b Yoshinobu Onuma, MD, PHD,c Yohei Sotomi, MD,d Rafał Depukat,b Susan Veldhof, RN,e Divine Ediebah, MS,e Peter Staehr, MD,f Wojciech Zasada, MD, PHD,g Krzysztof P. Malinowski, MS,h Grzegorz L. Kaluza, MD, PHD,i Patrick W. Serruys, MD, PHDj

ABSTRACT OBJECTIVES This study investigated the vasomotor response to nitroglycerine (NTG) up to 5 years after ABSORB implantation. BACKGROUND There are no data regarding long-term vasomotor response after everolimus-eluting bioresorbable vascular scaffold ABSORB implantation. METHODS We performed quantitative coronary angiography of the scaffolded and proximal and distal adjacent segments of patients from ABSORB Cohort B study before and after 200 mg of intracoronary NTG at 2, 3, and 5 years of follow-up. The mean changes of maximal and mean lumen diameters in the scaffolded and adjacent segments were calculated. RESULTS The mean in-scaffold lumen diameter change in response to NTG showed a trend to increase over time with absolute values of 0.03
0.09 mm, 0.05
0.12 mm, and 0.07
0.08 mm at 2, 3, and 5 years, respectively (p ¼ 0.40). The maximal in-scaffold lumen diameter change significantly increased with values of 0.03
0.14 mm, 0.06
0.16 mm, and 0.11
0.1 mm at 2, 3, and 5 years, respectively (p ¼ 0.03). The normalized mean lumen diameter change after NTG in the scaffold relative to the adjacent segments was 51.9
54.8% at 5 years of follow-up (p ¼ 0.60). CONCLUSIONS Although there was a numerical increase of the vasomotor response to NTG after ABSORB implantation measured by quantitative coronary angiography with mean lumen diameter, the change was not statistically significant. However, the maximal lumen diameter changes increased over time from 2 to 5 years and attained statistical significance. The vasomotor response to NTG after ABSORB implantation moderately trended to increase, which is consistent with the progressive degradation and bioresorption of the scaffold, but the degree of vasomotor response remained lower in comparison with adjacent segments. (J Am Coll Cardiol Intv 2017;10:786–95) © 2017 by the American College of Cardiology Foundation.

From the aJagiellonian University Institute of Cardiology, Krakow, Poland; bUniversity Hospital, Krakow, Poland; cThoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands; dAcademic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; eAbbott Vascular, Diegem, Belgium; fAbbott Vascular, Santa Clara, California; gKrakow Cardiovascular Research Institute, Krakow, Poland; hJagiellonian University Medical College, Krakow, Poland; iCardiovascular Research Foundation, Orangeburg, New York; and the jInternational Center for Circulatory Health, National Heart and Lung Institute, Imperial College, London, United Kingdom. Drs. Dudek, Rzeszutko, and Depukat have received Investigator grants during the progress of the study from Abbott Vascular. Drs. Onuma and Serruys are members of the Abbott Vascular Advisory Board. Drs. Ediebah, Staehr, and Veldhof are full-time employees of Abbott Vascular. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Dudek and Rzeszutko contributed equally to this work and are joint first authors. Manuscript received February 29, 2016; revised manuscript received November 16, 2016, accepted December 16, 2016.

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JACC: CARDIOVASCULAR INTERVENTIONS VOL. 10, NO. 8, 2017 APRIL 24, 2017:786–95

A

t the 1-year follow-up of patients in the

Everolimus-Eluting Coronary Stent System in

ABBREVIATIONS

ABSORB Cohort B2, tests with different

the Treatment of Patients with de Novo

AND ACRONYMS

stimuli

methergine)

Native Coronary Artery Lesions) is a multi-

showed the return of vasomotion function (1). After

center, single-arm, unblinded trial evaluating

endothelial-dependent stimulation with acetylcho-

the safety and feasibility of the ABSORB bio-

line, a vasodilatory response was observed in 30%

resorbable vascular scaffold 3.0  18 mm in

of patients, suggesting recovery of normal endothe-

the treatment of patients with up to 2 de novo

lial function (1). The recovery of vasomotion was

coronary lesions with diameter of 3.0 mm and

correlated with signs of bioresorption as a reduction

length of <14 mm in native coronary arteries. A total

of hyperechogenicity assessed with intravascular

(acetylcholine

or

of 101 patients enrolled in the trial were randomly

IVUS = intravascular ultrasound

NTG = nitroglycerine QCA = quantitative coronary angiography

ultrasound (IVUS) examination (2). At the 2-year

assigned to group B1 (n ¼ 45) with invasive follow-up

follow-up among a small analyzable group of pa-

at 6 and 24 months or group B2 (n ¼ 56) with control

tients from Cohort A (using ABSORB 1.0), the

imaging procedures at 12 and 36 months. All patients

response to nitroglycerine (NTG) and acetylcholine

were requested, according to a protocol amendment,

was even greater than at 1 year as seen in Cohort

to undergo invasive imaging follow-up at 5 years.

B2 and almost 50% of patients showed recovery of

The ABSORB study was sponsored by Abbott

endothelial function (1). Although these observa-

Vascular. The study protocol was approved by the ethics

tions were made in separate cohorts of patients

committee at the participating institutions and the pa-

who had different versions of the device implanted,

tients gave written informed consent before inclusion.

it was confirmed that, during the resorption process,

ANGIOGRAPHIC ASSESSMENT AND VASOMOTION

the mechanical integrity of the scaffold is lost as ex-

TEST WITH NTG. Oral nitrates,

pected. The vessel, freed from a constraining scaf-

cium channel blockers were to be stopped at least 12 h

fold,

seemed

to

respond

again

to

b-blockers, and cal-

vasomotor

before the coronary angiography and vasomotion test

stimulation. However, most recently the ABSORB-II

procedure. Vasomotion response in group B1 and B2

study did not meet its co-primary endpoint of supe-

patients was tested at 2, 3, and 5 years by injecting

rior vasomotor reactivity of the ABSORB scaffold in

200 m g intracoronary NTG. In the present paper, to

comparison to the Xience V stent after 3 years (3),

assess endothelial independent vasomotory reaction without the potential influence of other vasoactive

SEE PAGE 796

In ABSORB II at 3 years, ABSORB demonstrated vasomotion consistent with previous evidence, such as ABSORB Cohort B. The reason for not showing superiority over Xience in ABSORB II was that XIENCE unexpectedly showed some movement contrary to historical data with older generation metallic stents. Angiography may not be the most appropriate methodology for assessing differences in vasomotion. The revised platform of the scaffold (ABSORB bioresorbable vascular scaffold Rev.1.1) has a prolonged bioresorption process with a loss of structural scaffold integrity between 6 and 12 months and complete resorption at approximately 3 years (4). The aim of the current study was to examine the vasomotility up to 5 years after implantation of the Conformité

Européenne

marked

and

commercially

available ABSORB bioresorbable vascular scaffold (ABSORB bioresorbable vascular scaffold Rev.1.1) in Cohort

B

as

measured

by

the

endothelial-

independent, NTG-induced vasomotion (5).

METHODS

stimulation, the angiographic results of the tests performed only with NTG at 2, 3, and 5 years of follow-up are presented. Quantitative coronary angiography (QCA) analysis of the scaffolded segment (determined as the length between the radiopaque platinum markers at both ends of the ABSORB bioresorbable vascular scaffold) as well as 5-mm adjacent to the proximal and distal segments was performed. The same matching projections were used for the 2-, 3-, and 5-year vasomotion analysis. The absolute (mm) difference of maximal and mean lumen diameter before and after the administration of NTG was measured in the scaffold as well as in the adjacent reference segments. A normalized change in mean lumen diameter (in percent) of the scaffolded segment relative to the reference segments was calculated as: % normalized mean lumen diameter change ¼

in scaffold Mean LD change ðprox mean LD change þ distal Mean LDÞO 2  100%

The QCA analyses with the CAAS II software (Pie Medical, Maastricht, the Netherlands), were per-

STUDY POPULATION. The ABSORB Cohort B trial

formed by an independent Core Laboratory (Cardial-

(A

ysis, Rotterdam, the Netherlands).

Clinical

787

Long-Term Vasomotion After ABSORB Implantation

Evaluation

of

the

Bioresorbable

Dudek et al.

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Long-Term Vasomotion After ABSORB Implantation

T A B L E 1 Mean Lumen Diameter Change and Normalized Mean Lumen Diameter

Percent Change in Response to NTG in Patients After ABSORB Implantation

33 at the 2-year and 47 at the 3-year follow-up were included. The reasons for exclusion from the analysis were: no 2- nor 3-year angiogram available

Proximal Ref. Segment (mm)

Cohort B Data*

In-Scaffold (mm)

Distal Ref. Segment (mm)

(15 patients) and a vasomotion test was not analyzable due to lack of proper paired angiogram before

Mean lumen diameter change (mean
SD) Cohort B1 at 2 yrs

0.17
0.28

0.03
0.09

0.13
0.22

and after administration of NTG (6 patients). For the

Cohort B2 at 3 yrs

0.09
0.19

0.05
0.12

0.16
0.17

5-year follow-up, angiographic data from 53 patients

Cohort B at 5 yrs

0.10
0.17

0.07
0.08

0.16
0.18

were collected according to a protocol amendment.

0.02
0.11

0.03
0.19

Of the 53 serial patients, 2 patients did not have

Difference (3 yrs – 2 yrs)

0.08
0.23

p Values

0.17

Difference (5 yrs – 3 yrs)

0.01
0.18

p Values

0.79

Difference (5 yrs – 2 yrs)

0.07
0.22

p Values

0.20

0.41 0.02
0.10 0.40 0.04
0.09 0.07

0.53 0.005
0.18 0.89 0.02
0.19 0.60

vasomotion measurements, so n ¼ 51 (L ¼ 52) serial patients have vasomotion data. Intracoronary ultrasound gray scale images of previously scaffolded segments were collected from 51 patients at the 5year follow-up and analyzed in relation to the type

Normalized mean lumen diameter percent change (mean
SE) Cohort B1 at 2 yrs

–

41.62
18.66%

–

Cohort B2 at 3 yrs

–

56.68
24.10%

–

The absolute average change of the mean lumen

Cohort B at 5 yrs

–

51.88
54.83%

–

diameter after NTG in the in-scaffold segment showed

Difference (3 yrs – 2 yrs) p Value

15.05
31.49% 0.62

Difference (5 yrs – 3 yrs) p Value Difference (5 yrs – 2 yrs) p Value

4.80
63.50%

of reaction to NTG.

a trend to increase from 0.03
0.09 mm at 2 years to 0.05
0.12 mm at 3 years up to 0.07
0.08 mm at

0.93

5 years. (p ¼ 0.4) (Table 1, Figure 1A). The maximal

10.25
67.39%

lumen diameter change after NTG increased signifi-

0.86

*At 2 yrs (n ¼ 33), 3 yrs (n ¼ 47), and 5 yrs (n ¼ 51).

cantly over time from 0.03
0.14 mm at 2 years, 0.06
0.16 mm at 3 years and 0.11
0.1 mm at 5 years (p ¼ 0.04) (Table 2, Figure 1B). At the distal adjacent segment, a response to NTG

INTRACORONARY ULTRASOUND IMAGING. Previously

was unchanged over time with mean lumen diameter

scaffolded vessels at the 5-year follow-up were

change of 0.13
0.22 mm at 2 years, 0.16
0.17 mm at

examined with IVUS catheters (EagleEye, Volcano

3 years, and 0.16
0.18 mm at 5 years of follow-up

Corporation, Rancho Cordova, California) with a

(p ¼ 0.53 for 2-year vs. 3-year follow-up and p ¼ 0.6

pullback speed of 0.5 mm/s. The region of interest

for 2-year vs. 5-year follow-up). Similarly, at the

beginning 5 mm distal to and extending 5 mm prox-

proximal edge the mean lumen diameter change did

imal to the treated segment was examined. The

not change significantly throughout 5 years, although

scaffold length, mean and minimum vessel and

it was numerically smaller at 3 years than at the

lumen area and volume, and mean plaque area and

2-year follow-up (0.09
0.19 vs. 0.17
0.28; p ¼ 0.17)

plaque volume were measured with a computer-

and remained unchanged at 5 years (0.10
0.17;

based contour detection program.

p ¼ 0.79; 3 years vs. 5 years).

STATISTICAL ANALYSIS. The continuous variables are

presented as mean
SD unless otherwise specified. For dichotomous variables percentages were calculated. For comparisons, the t test was used as appropriate. Pairwise comparisons between measurements time point were performed by a Wilcoxon signed rank test. Overall comparison of serial measurements was assessed by applying semiparametric mixed effect models. A p value of <0.05 was considered significant. Due to no planned formal hypothesis for assessing the success of the study, there was no statistical adjustment applied. All p values are provided for hypothesis generation only and should therefore be interpreted cautiously.

RESULTS

The

magnitude

of

the

vasomotor

response

in-scaffolded segment in comparison with nonscaffolded adjacent segments expressed as normalized mean lumen diameter change (in percent) was 41.6
18.7% at 2 years and slightly increased to 56.7
24.1% at 3 years, then remained at the level of 51.9
54.8% at 5 years (p ¼ 0.6) (Table 1, Figure 2). In the Figure 3, the relative (%) changes of the mean lumen diameter after intracoronary NTG injection in the scaffolded and adjacent segments at different time points are shown. Figure 4 shows paired analysis of relative (%) changes of mean lumen diameter after NTG. In some patients, paradoxical vasoconstriction (relative change of mean lumen diameter

after

NTG

below

0)

was

observed.

The percentage of scaffolded segments with paraOf a total of 101 patients enrolled in the ABSORB

doxical vasoconstriction was 36.4% and 31.9% at

Cohort B1 and B2 study, analyzable angiograms of

2 and 3 years, respectively, and decreased to

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Long-Term Vasomotion After ABSORB Implantation

F I G U R E 1 LD Change Over Time

(A) Progression of mean lumen diameter (LD) change after nitroglycerin injection over time. Plot with CIs. (B) Progression of maximal LD change after nitroglycerin injection over time. Plot with CIs. CI ¼ confidence interval.

15.4% at 5 years (Figure 3). Imaging follow-up at 5

Nevertheless, the degree of vasomotor response in

years showed that there was no difference between

the scaffolded segment was lower in comparison to

patients

adjacent segments.

with

vasoconstriction

or

vasodilation

regarding lumen dimensions in QCA; however, pa-

After metallic stent implantation, vasomotion at the

tients with vasoconstriction had larger vessels when

stented segment is obviously absent (6–8). For the first

measured by IVUS gray scale. Plaque areas and plaque

time, the recurrence of vasomotility in a “stented”

volumes were similar in both groups (Table 3).

segment was shown and trended to improve in our patient cohort over time as reported previously (1,2).

DISCUSSION

The ability of the artery to respond to vasodilator stimuli may be an important index of physiological

The most important finding of the present analysis

recovery, although the extent of correlation of this

is that the mean lumen diameter change after

finding to exercise- and/or stress-induced vasodilation

intracoronary NTG injection increased numerically up

remains undetermined.

to 5 years after scaffold implantation but did not

Generally, the degree of vasomotor response of the

attain statistical significance. However, the maximal

adjacent segments to NTG is smaller in our study than

lumen diameter changes after NTG progressively

in previous reports evaluating the vasoreactivity and

increased statistically significantly between 2, 3, and

endothelial function after metallic stent implanta-

5 years of follow-up consistent with the progressive

tion. In a paper by Shin et al. (6), the reactivity of

degradation

adjacent segments was tested with an injection of

and

bioresorption

of

the

scaffold.

T A B L E 2 Overall Comparison of Mean and Maximal Lumen Diameter Change (p Value From Semiparametric Mixed Effects Models)

2 yrs (n ¼ 33) (L ¼ 33)

3 yrs (n ¼ 47) (L ¼ 48)

5 yrs (n ¼ 51) (L ¼ 52)

Difference 2 yrs vs. 3 yrs

Difference 2 yrs vs. 5 yrs

Difference 3 yrs vs. 5 yrs

Overall p Value

Mean luminal diameter change (mm) in scaffold

0.03
0.09 (33)

0.05
0.12 (47)

0.07
0.08 (52)

NA

0.04
0.09 (19)

0.02
0.10 (28)

0.25

Maximal luminal diameter change (mm) in scaffold

0.03
0.14 (33)

0.06
0.16 (48)

0.11
0.10 (52)

NA

0.08
0.19 (19)

0.04
0.16 (28)

0.03

L ¼ total number of scaffolded lesions.

789

790

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Long-Term Vasomotion After ABSORB Implantation

introduced. This current version allowed better early

F I G U R E 2 Response to NTG

dimensional and clinical outcomes at 6 months by improved radial strength and was designed to also have slightly longer bioresorption time (12). Between 6 months and 1 year, the scaffold stops constraining the vessel, which should facilitate the return of vasomotion and late lumen gain (3). Indeed, after 1 year significant changes in lumen diameter at the scaffolded segments were observed after injection of methergine or acetylcholine (13). In the current study, we were not able to demonstrate universal increase of

vasomotor

response

following

endothelial-

independent stimulation with NTG from the second to the fifth year of clinical observation (Figure 5 shows an example of serial QCA measurements before and after NTG, 3 and 5 years after the index procedure). The mixed results of our study as well as the recent failure of the ABSORB-II study to meet its primary endpoint of superior vasomotor reactivity raises The response to nitroglycerin of the scaffolded segments in comparison with

important

nonscaffolded adjacent segments expressed as changes of normalized mean

assessment of vasomotion response. In ABSORB II

lumen diameter (LD) percent change over time. Plot with standard errors.

at

3

questions

years,

about

ABSORB

the

future

demonstrated

of

the

vasomotion

consistent with previous evidence such as ABSORB Cohort B. The reason for not showing superiority over 2 mg of nitrates and the percent diameter change

Xience in ABSORB II was that Xience unexpectedly

varied from 16.6
3.5% to 20.7
5.0%, whereas in

showed some movement contrary to historical data

our study the same parameter at 5 years of follow-up

using older generation metallic stents. It might be

varied from 4.1
6.42% to 7.69
8.60%. However,

hypothesized that the myogenic components of the

only mild vasodilation was also shown in other

wall structure at 3 years in response to nitrate billows

studies. Hofma et al. (9) reported vasodilation of

between the tether points of the metallic stent ring

reference segments of about 7
7% 6 months after

structures that are separated by 1,600 m m. Although

bare-metal stent(s) implantation or 15
11% after SES

this billowing might not be visible individually on

stent implantation. Sabate et al. (10) observed 7% to

angiography due to its limited imaging resolution

9% vasodilation of reference segments at 6 months

(200 m m), it may effect changes in boundary by

after balloon angioplasty combined with or without

the detection algorithm that results in a statistical

intracoronary radiation. The reasons for the incon-

difference

sistent results could be different methodology of

investigations

testing with different nitrates (isosorbide dinitrate or

modalities such as IVUS and optical coherence to-

NTG), different dosages given (0.1 to 0.3 mg of NTG or

mography and an angiographic metal strut-to-strut

1 to 3 mg of isosorbide dinitrate), shorter washout

diameter performed before and after nitrate admin-

time after interruption of vasoactive drugs before

istration could potentially help to elucidate this

follow-up angiogram (12 to 48 h) and different seg-

unexpected finding (14).

between with

the

populations.

Further

other

intravascular

imaging

ments taken into evaluation. In the evaluation by

The loss of structural integrity and the absorption

Shin et al. (6), the most vasoactive segments 5 to

process of ABSORB as a precondition for the return of

20 mm from the stented area were chosen for QCA

vasomotion can be evaluated with IVUS by assessing

analysis, whereas in our study only 5-mm adjacent

the reduction of echogenicity of the scaffold structures over time as resorption progresses (2,15). Over

segments were analyzed. In the ABSORB Cohort A first-in-man study, the

time, the polymeric struts become less hyper-

recovery of vasomotion in scaffolded segments was

echogenic. The comparison of data from the 6-month

shown for the first time 2 years after an ABSORB

follow-up from Cohort A using the first generation

scaffold implantation (11). However, due to the sub-

of the scaffold, with serial examinations at 6 and

optimal radial strength and recoil at 6 months, some

24 months of follow-up from Cohort B using the

refinements of the polymer were made and the

device with revised platform, confirmed the intended

revised,

longer bioresorption time of the newer platform.

current

version

of

the

ABSORB

was

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Long-Term Vasomotion After ABSORB Implantation

F I G U R E 3 LD Change After Nitroglycerin

Relative percentage change of mean lumen diameter (LD) after intracoronary nitroglycerin (Nit) administration in different time points. The (A) 2-year, (B) 3-year, (C) 5-year follow-up changes. Below the graphs, tables presenting percent and number of patients showing vasodilation or vasoconstriction after intracoronary nitroglycerin administration.

At 2 years, the percent change of hyperechogenicity

pre-existing struts are replaced ultimately by con-

from baseline was 13.8% and twice as high as the

nective tissue with smooth muscle cells (18). The

minimal level for the first generation of the scaffold

clinically observed progression of the maximal

(6.9%; p for trend <0.01) (12,13,15). At 3-year follow

lumen diameter change after NTG (Figure 2) over the

up of Cohort B patients the hyperechogenicity

course of 5 years after ABSORB implantation, along

continued to decrease to 10.4%. This confirmed that

with the documented resorption process in preclini-

the degradation and resorption process, although

cal studies, may suggest a continued restoration of

slightly

vasomotion as there is cellularization of this provi-

prolonged,

was

still

ongoing

and

was

accompanied by an increase in the vasodilatory ca-

sional matrix.

pacity of the vessel wall reported concomitantly (16).

The reasons remain unclear for some paradoxical

Preclinical studies conducted in porcine coronary

vasoconstriction in scaffolded segment as well as

arteries demonstrate that the polymer is no longer

proximal and distal reference segments following

detectable after 3 years and the struts have been

NTG administration seen in some patients in Cohort

replaced by provisional matrix (17). This provisional

B1 at 2 years, and also in some patients from Cohort

matrix

B2 at 3 years after ABSORB implantation (4,16).

follows

a

timely

maturation

such

that

791

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Long-Term Vasomotion After ABSORB Implantation

F I G U R E 4 Relative Percentage Changes of LD After NTG

Paired measurements of relative percentage changes of mean lumen diameter (LD) after nitroglycerin between 2 and 5 years (A) and 3 and 5 years of follow-up (B). Table contains averaged values, ranges and difference of relative (%) change of the mean lumen diameter after nitroglycerin in paired measurements.

T A B L E 3 5-Year QCA and IVUS Measurements of Previously Scaffolded Segments in

Patients With Vasodilation and Vasoconstriction After NTG Administration

A decrease of average mean blood pressure by 13.6
6.4% observed in Cohort B1 at 2 years after NTG administration with a suspected subsequent barore-

In-Scaffold Vasoconstrictors (N ¼ 8) (L ¼ 8)

In-Scaffold Vasodilators (N ¼ 43) (L ¼ 44)

p Value*

24.32
7.65 (8)

20.21
2.68 (41)

0.15

Vessel volume (mm3)

368.82
122.22 (8)

275.43
69.74 (41)

0.03

Lumen volume (mm3)

202.20
75.78 (8)

132.27
35.91 (41)

0.0049

166.62
57.77 (8)

143.67
42.99 (41)

0.30

assessment after full recovery of the blood pressure

ceptor reflex and adrenergic stimulation resulting in

IVUS Scaffold length (mm)

3

Plaque volume (mm )

increase of sympathetic tone was hypothesized as a potential

mechanism

for

the

vasoconstriction

(4,19,20). Therefore, for the vasomotion assessment in Cohort B2 at 3 years, optimal pre-hydration

Average vessel area (mm )

15.71
5.02 (8)

13.71
3.40 (41)

0.35

after NTG injection was recommended. Despite this

Average lumen area (mm2)

8.53
2.7 (8)

6.55
1.61 (41)

0.02

measure, however, similar paradoxical vasoconstric-

Minimum lumen area (mm2)

5.62
1.83 (8)

4.72
1.32 (41)

0.17

tion was still observed in the 3-year vasomotion

Average plaque area (mm2)

7.18
2.78 (8)

7.13
2.21 (41)

0.98

analysis. However, at the 5-year follow-up, the

32.54
12.61 (8)

27.93
9.44 (40)

0.36

number of patients presenting some degree of vaso-

Reference vessel diameter (mm)

2.76
0.48 (8)

2.59
0.30 (44)

0.29

In-scaffold minimal lumen diameter (mm)

2.17
0.36 (8)

2.11
0.31 (44)

0.47

21.00
6.64 (8)

18.69
7.19 (44)

0.39

2

Lumen area stenosis (%) QCA

Percent diameter stenosis (%)

constriction in scaffolded segments decreased to 15.4%. Another potential reason for the paradoxical

Values are mean
SD (n). *Wilcoxon’s rank sum test. N ¼ total number of patients; L ¼ total number of scaffolded lesions; n ¼ number of valid lesion analyses.

response could be the underlying disease as observed during exercise (21). Paradoxical vasoconstriction of stenotic lesions during exercise was hypothesized to result from an imbalance between insufficient nitric

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Long-Term Vasomotion After ABSORB Implantation

F I G U R E 5 Case Example

Case example of the serial changes of vasomotion at the 3- and 5-year follow-ups. The stenosis at mid-left anterior descending artery (A) was successfully treated with ABSORB bioresorbable vascular scaffold (BVS) (3.0  18 mm), resulting in the mean lumen diameter (LD) of 2.49 mm post-procedure (B). At the 3-year follow-up (C, D), vasodilation was observed after the injection of nitroglycerin (þ0.13 mm), which was more pronounced at 5-year follow-up (þ0.17 mm) (E, F). %DS ¼ % diameter stenosis; MLD ¼ minimum lumen diameter; NTG ¼ nitroglycerin; PCI ¼ percutaneous coronary intervention; RVD ¼ reference vessel diameter.

oxide release from dysfunctional endothelium and

evaluated at different time points rather than a serial

adrenergic stimulation, but the vasoconstrictive effect

analysis of consecutive patients. Additionally, phar-

used to be reversed by nitrates administration (22).

macological vasodilation is just one aspect of vaso-

Although we found on IVUS gray scale imaging that

motion; the study does not provide information on

patients with vasoconstriction had larger vessels than

recovery of endothelial function. The angiographic

patients with vasodilation at the 5-year follow-up,

analyses were limited only to in-scaffold and 5-mm-

we observed no differences in plaque vessel areas

long adjacent segments. The evaluation of the

and volumes. As such, the paradoxical vasoconstric-

response to NTG in longer and more distant seg-

tion found in selected patients cannot be attributed

ments or even contralateral vessels would bring

simply to a greater disease burden. However, even

probably more adequate information for compari-

with similar plaque burden, differences may still exist

sons with scaffolded segments.

in the functional response of the arterial wall to

Last, the sample size is small and could result in

different stimuli between individual segments and

inherent high data variability with the methodology

patients.

used, specifically the resolution of angiography and the consequent accuracy of QCA. It was previously

STUDY LIMITATIONS. The present study remains a

shown that repetitive measurements of lumen di-

combination of data from 2 cohorts of patients

mensions

have

interobserver

and

intraobserver

793

794

Dudek et al.

JACC: CARDIOVASCULAR INTERVENTIONS VOL. 10, NO. 8, 2017 APRIL 24, 2017:786–95

Long-Term Vasomotion After ABSORB Implantation

variability of 0.11 mm and 0.10 mm, respectively (23).

administration could potentially help to elucidate

In our study, only the averaged maximal lumen

this unexpected finding.

diameter change after NTG administration at 5 years exceeded this threshold. Thus, the observed small

ADDRESS

changes of the mean lumen diameter in response to

Dudek, Jagiellonian University Institute of Cardiology,

FOR

CORRESPONDENCE:

stimulation with NTG may have been below the range

Kopernika 17th Strasse, Krakow 31-501, Poland. E-mail:

of detection of the QCA methodology.

[email protected].

Dr. Dariusz

PERSPECTIVES

CONCLUSIONS Although there was a numerical increase of the

WHAT IS KNOWN? The appearance of vasomotility

vasomotor response to NTG from 1 to 5 years after

up to 2 years after ABSORB implantation was previ-

ABSORB implantation measured by QCA with the

ously shown.

mean lumen diameter, the change was not statistimaximal lumen

WHAT IS NEW? We have not found improvement in

diameter changes increased over time from 1 to 5

response to NTG using mean lumen diameter change

years and attained statistical significance. Further-

by QCA. Only the maximal lumen diameter change

more, in the most recent insight from the ABSORB II

increased significantly. This suggests a trend toward

trial at 3 years, ABSORB demonstrated vasomotion

vasomotor recovery in 5-year follow-up, which is

consistent with previous evidence such as ABSORB

consistent with the progressive degradation and bio-

Cohort B. The reason for not showing superiority over

resorption of the scaffold; however, the degree of

Xience in ABSORB II was that Xience unexpectedly

response to NTG remained lower than in adjacent

showed some movement contrary to historical data

segments.

cally significant. However, the

using older generation metallic investigations

with

other

stents. Further

intravascular

imaging

modalities such as IVUS and optical coherence tomography and an angiographic metal strut-to-strut diameter

performed

before

and

after

WHAT IS NEXT? Different stimulation agents and/or different methodology should be applied in further studies to verify these findings.

nitrate

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KEY WORDS ABSORB, bioresorbable scaffold, vasomotion

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