Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3592_Библиотеки_им_академика_М_И_Перельмана
.pdf
Vascular and Intravascular Imaging Trends, Analysis, and Challenges, Volume 1
https://t.me/medicina_free
Everolimus-eluting stent (EES): OCT evaluation 8 months after EES
implantation showed that most struts were covered with uniform and thin
neointima. The frequency of low-intensity neointima was very low, suggesting
a good vessel healing pattern [39]. These findings are in concordance with the
good clinical outcome data associated with this stent platform, showing a
reduction of stent thrombosis compared to first-generation stents [40, 41].
Toledano et al reported OCT follow-up (at least one year) of 66 DESs: 21
EESs, 23 SESs and 22 PESs. The average tissue coverage thickness of the
struts per stent was greater in EESs than in SESs and PESs, while the
percentage of uncovered and malapposed struts was much lower in EESs,
with no significant differences between SESs and PESs [42].
Zotarolimus-eluting stent (ZES): OCT imaging studies revealed a higher
mean neointimal thickness and a lower prevalence of uncovered struts as well
as malapposed struts in ZESs than in SESs [43]. The OCTAMI trial (optical
coherence tomography in acute myocardial infarction) found no differences
in 6 month follow-up strut coverage and a similar vessel response to ZESs,
when compared to identical BMSs, implanted during primary percutaneous
coronary intervention (PCI) in STEMI patients [44].
• Drug-eluting balloons (DEBs).
OCT has been established as the reference technique to evaluate stent
performance regarding neointimal coverage in vivo. Therefore, randomized
OCT studies are the cornerstone for the evaluation of newer stents or
alternative techniques. A recent ‘hybrid’ approach tries to combine the
advantages of BMSs in terms of strut coverage while reducing the ISR
rate, using a BMS and DEB simultaneously, and studies have focused on
OCT follow-up to determine its safety.
The OCTOPUS trial compared strut coverage and neointimal proliferation
of a therapy using a BMS postdilated with a paclitaxel DEB to everolimus
DESs at 6 month follow-up using OCT, showing comparable results for the
percentage of uncovered struts, but more neointimal proliferation in the
BMS + DEB group (although there was no difference in the rate of ISR)
[45]. Other ongoing studies are also comparing the use of BMSs alone or
associated with DEBs in terms of OCT findings at follow-up [46]. OCT studies
are thus a valuable tool as a first step in evaluating in vivo stent performance,
but these data must be supported by clinical outcomes.
• Biodegradable polymers.
Recently published long-term follow-up studies combining data from three
large randomized trials showed a reduction in the incidence of LST with
biodegradable polymer DESs compared to durable polymer SESs [47–49].
It has been hypothesized that the lower rates of late adverse events
associated with biodegradable polymer stents are related to improved
vascular healing as assessed by intravascular imaging. An OCT substudy of
the LEADERS trial reported that a biodegradable polymer biolimus-eluting
stent (BES) showed superior stent strut coverage at 9 months, despite an
overall comparable degree of neointimal suppression compared to a durable
1-6
Vascular and Intravascular Imaging Trends, Analysis, and Challenges, Volume 1
https://t.me/medicina_free
polymer SES [50]. However, further data showed that subsequent improvement of SES coverage between 9–24 months resulted in similar strut coverage
for the BES and SES at 24 months [51]. On the other hand, the OCTDESI
pilot trial compared biodegradable polymer PESs with durable polymer PESs
and found no difference in the proportion of uncovered struts at 6 months
[52]. Also, a novel rapid-breakdown biodegradable polymer SES compared to
a durable polymer EES showed a similar degree of early stent strut coverage
as assessed by OCT at 4 months, although coverage patterns were more
homogeneous for the biodegradable polymer SES [24].
1.2.1.3 Clinical applications
It has already been stated that OCT assessment of strut coverage is widely used for
the evaluation of newer stents and techniques. In the same way, OCT evaluation of
this re-endothelialization process may help to define the optimal duration of dual
antiplatelet therapy after stent implantation, both to define general strategies and to
individualize treatment.
1.2.1.4 Limitations
Current OCT resolution is insufficient to detect thicknesses <20 μm, which prevents
accurate distinction between the absence of endothelialization and the presence of a
very thin layer of 3–5 endothelial cells.
The vascular healing process involves the participation of the coagulation system
and many types of cells in different phases, all of them covering the stent struts.
Optical coherence tomography is unable to distinguish between fibrin, giant cells,
granulomatous reaction and degree of endothelialization [16]. There are promising
findings with optical density analysis that claim to be able to distinguish between
neointima and fibrin/thrombus, but further investigation is warranted to confirm
them [20].
As previously remarked, there is no clinically validated cut-off value for the
percentage of uncovered struts associated with stent thrombosis, and there is a need
for a homogeneous definition in order to compare different clinical studies.
1.2.2 Restenosis
ISR is defined as a luminal renarrowing after stent deployment. Binary angiographic
restenosis is defined as ⩾ 50% luminal narrowing at follow-up angiography (see
figure 1.2). Complete evaluation must include both an assessment of luminal
narrowing and the patient’s clinical context [53]. In case of an intermediate lesion,
the use of fractional flow reserve or intracoronary imaging can guide the clinical
decision.
OCT allows both quantitative and qualitative analysis of ISR (table 1.1).
Neointima is defined as the tissue layer between the inner border of stent struts
and the luminal border. Therefore, quantification of neointimal tissue is the key to
differentiate between the normal process of re-endothelialization and ISR. OCT
1-7
Vascular and Intravascular Imaging Trends, Analysis, and Challenges, Volume 1
https://t.me/medicina_free
Figure 1.2. Example of ISR measurements.
Table 1.1. OCT assessment of ISR.
Quantitative assessment Qualitative assessment
Stent area measurements Structural characteristics
• Stent cross-sectional area
• Minimum and maximum stent diameter
• Luminal area
• Intimal hyperplasia area
• Percentage of intimal hyperplasia
Strut measurements Intensity
• Mean strut coverage thickness • Hyperintense
Length measurements Luminal border
Volume measurements Microvessels; intraluminal material
• Homogeneous
• Heterogeneous
• Layered
• Hypointense
• Regular
• Irregular
allows the accurate measurement of stent cross-sectional area (CSA), minimum and
maximum stent diameter, intimal hyperplasia (IH) area (calculated as stent area
minus luminal area), and percentage of intimal hyperplasia (IH area divided by stent
area) [ 23].
However, considering ISR as a mere problem of diameters and areas is an
oversimplification. ISR is a complex process that is not completely understood,
which may reflect different underlying mechanisms (or different stages of the same
mechanism). Experimental and clinical studies have identified excessive neointimal
1-8
Vascular and Intravascular Imaging Trends, Analysis, and Challenges, Volume 1
https://t.me/medicina_free
hyperplasia as the leading cause of stent restenosis, at least in BMSs [3, 54]. This
intimal hyperplasia reaches a peak between 6 and 12 months after BMS deployment,
and it was considered to be followed by a quiescent period with no further growth of
this layer [3]. Clinical and histological evidence of very late restenosis of BMSs
(occasionally observed beyond 4 years), showing late neointimal progression and
neoatherosclerosis development, has now turned the paradigm of ISR into an
evolving process [5–7, 55]. In DESs, it may be an even more complex process,
initially inhibited by antiproliferative drugs, involving different mechanisms and
progression.
OCT qualitative studies have provided evidence regarding the nature and
evolution of ISR. Its high-resolution images have shown variation in structure,
backscatter and composition of the hyperplastic tissue that could not be identified
using IVUS. Gonzalo et al described three OCT patterns (see figure 1.3) of ISR in a
sample of 148 cases (both BMS and DES from first and second generation) [56]:
• Homogeneous neointima: uniform signal-rich band without focal variation or
attenuation.
• Heterogeneous neointima: Focally changing optical properties and various
backscattering patterns.
• Layered neointima: layers with different optical properties.
Other differential characteristics between restenotic tissue include: high or low
backscattering, the presence of microvessels, luminal shape and the presence of
intraluminal material [56].
The observation of ISR with different optical properties suggests that it may have
different compositions. It has been argued that non-homogeneous patterns may
represent an artifact related to the progressive attenuation of the light, but there is no
difference in the maximal tissue coverage thickness between the different patterns
and sometimes there is a clearly visible border between layers, which support that
these images are related to the presence of a different tissue [56]. Pathological studies
have shown that restenosis in DESs can consist of heterogeneous components,
including proteoglycan-rich tissue, organized thrombus, atheroma, inflammation
and fibrinoids, and also the density and orientation of smooth muscle cells vary
within restenotic tissue [57, 58]. It can be hypothesized that OCT patterns may
translate these tissue differences, although current data regarding correlation of
histopathology and OCT appearance is scarce and remains poorly understood [23].
Anecdotal reports have related heterogeneous tissue to the presence of fibrinoids or
proteoglycans [59, 60]. Nakano et al demonstrated OCT signal (peak intensity and
attenuation rate) differences over time in neointima after ⩽6 months and >1 year,
thus signal analysis of OCT may also be useful to unveil the components or
processes of neointimal growth and ISR [19]. Recently, Itoh et al used the
normalized standard deviation of OCT signal intensity to assess homogeneity in
ISR tissue, finding that high values were a useful predictor for non-homogeneous
images, and in some histological samples taken from these patients chronic
infl
ammation and fibrin thrombi were observed [61].
1-9
Vascular and Intravascular Imaging Trends, Analysis, and Challenges, Volume 1
https://t.me/medicina_free
Figure 1.3. Examples of three different restenotic patterns. (A) Homogeneous, showing uniform optical
properties. (B) Layered, with two concentric separate areas of different signal intensity. (C) Heterogeneous,
several focal changes in optical intensity.
The assessment of ISR patterns by OCT showed low inter- and intra-observer
variability. However, low reproducibility has been reported for the evaluation of
other parameters such as tissue backscatter, which highlights the need for objective
methods for the analysis of image properties to improve the accuracy [56, 62].
Moreover, there are still some limitations of OCT imaging that should be taken into
account, such as the relatively low-penetration power of the light source, the
influence of catheter position in the tissue backscatter and other possible artifacts.
Further analyses have tried to correlate OCT ISR features and clinical and
angiographic characteristics. Heterogeneous neointima is more frequently present in
focal restenosis (rather than diffuse) and at minimum lumen area [56, 62]. The time
from stent implantation also seems to influence OCT appearance, the layered
1-10
Vascular and Intravascular Imaging Trends, Analysis, and Challenges, Volume 1
https://t.me/medicina_free
pattern being more frequent in stents implanted ⩽12 months before the OCT
examination, while the heterogeneous pattern has been found in a higher proportion
in very late ISR (>5 years) [56, 62]. The homogeneous pattern is more common in
the early stages. Yamaguchi et al found, in a group of 25 patients with late ISR, that
the heterogeneous pattern was more prevalent in patients with late ISR who had
more abrupt neointimal growth in serial OCT evaluation, while the homogeneous
pattern was associated with a more gradual decrease of luminal area [63].
Acute coronary syndrome is associated with irregular luminal shape, the presence
of intraluminal material, or more asymmetric ISR [56]. Both findings suggest that it
translates to an active process with potential clinical implications. Following this
line of thought, Kim et al studied the correlation between in-stent neointimal tissue
patterns and major cardiovascular events (MACEs) at follow-up, excluding patients
with significant restenosis and definite OCT evidence of neoatherosclerosis. They
found that age and initial clinical presentation of acute coronary syndrome were the
main independent predictors of heterogeneous neointima, and this pattern was
independently associated with MACEs at follow-up [64]. There is also initial
observational data suggesting that ISR patterns may have a distinct response to
the different treatment modalities (i.e. plain balloon angioplasty, paclitaxel-coated
balloon dilatation or DES implantation) [65].
Most of these data are preliminary and need to be confirmed, but they constitute a
promising line of investigation where OCT may play a major role.
1.2.3 Neoatherosclerosis
Neoatherosclerosis refers to an atherosclerotic change in neointimal tissue, which is
histologically defined as clusters of lipid-laden foamy macrophages within the
neointima with or without necrotic core formation [66] (see figure 1.4). In recent
years, growing evidence has suggested that neointima is subject to atherosclerotic
changes similar to native vessels that may lead to late clinical events. The paradigm
that considers neointimal development a quiescent process after the first year of
BMS implantation has been widely disproved by clinical, angiographic and
histopathological data. Histological studies have found that in the first 2–3 years
after stenting, endothelial coverage is formed by smooth muscle and collagen rich
neointima, but also chronic inflammation elements can be found (macrophages,
T cells and giant cell infiltration); after that (more than 3–4 years) smooth muscle
cells are sparse, with abundant collagen toward the lumen and evidence of
neoatherosclerosis, namely foamy macrophages around stent struts, with an
increasing incidence over time [66, 67]. These neoatherosclerotic changes have
been related to very late BMS thrombosis both in autopsy findings and thrombectomy specimen analysis [68, 69].
Moreover, DESs, which were designed to avoid excessive neointimal growth,
have proved to also be affected by this neoatherosclerotic process. Clinical and
histologic studies of DESs have demonstrated evidence of continuous neointimal
growth during long-term follow-up, which is designated as the ‘late catch-up’
phenomenon [70
, 71]. Furthermore, pathological studies suggest that this
1-11
Vascular and Intravascular Imaging Trends, Analysis, and Challenges, Volume 1
https://t.me/medicina_free
Figure 1.4. OCT findings suggestive of neoatherosclerosis. (A) ISR showing a hypointense area similar to
lipidic plaque (asterisk), and linear images with high intensity (arrow) compatible with cholesterol crystals.
(B) Heterogeneous restenosis with microcalcifications (arrow). (C) Thin-cap fibroatheroma inside a stent
composed of a predominant lipidic component (asterisk), and a thin fibrous cap (solid arrow), with an area of
rupture (dashed arrow). (D) Microvessels (arrow).
atherosclerotic change occurs more quickly in DESs than in BMSs [66]. This
phenomenon is poorly understood, and it has been speculated to be related to the
incomplete maturation of the regenerated endothelium [72].
OCT is recognized as a valuable tool for atherosclerotic plaque quantitative and
qualitative evaluation, and some of the plaque characteristics can be identified and
quantified with good correlation with pathological findings [23, 73]. Therefore, OCT
imaging is a unique tool to determine the presence of these atherosclerotic features
within the intrastent lumen and to analyze the evolution and clinical implications of
neoatherosclerosis in vivo.
Atherosclerotic findings that can be visualized inside the stent neointima include:
• Calcific intima: well-delineated, signal-poor region with sharp borders.
• Lipidic intima: signal-poor region with diffuse borders [74].
• Macrophage infiltration: increased signal intensity accompanied by heteroge-
neous back shadows [75].
• Cholesterol crystals: bright spikes inside a lipidic plaque.
• Thin-cap fi broatheroma (TCFA): fibrous cap thickness at the thinnest part
⩽65 μm and an angle of lipidic tissue ⩾180°.
• Neointimal rupture: break in the fibrous cap that connected the lumen with
the underlying lipid pool.
1-12
Vascular and Intravascular Imaging Trends, Analysis, and Challenges, Volume 1
https://t.me/medicina_free
• Microvessel: evidence of neovascularization; a small vesicular or tubular dark
or hypointense structure with a diameter ⩽200 μm. In-stent microvasculature
is divided into two categories: intraintimal, located within the most superficial
50% of the neointimal thickness, and persistent, within the deepest 50% [7].
Several studies have used OCT to evaluate the presence of neoatherosclerosis and
assess its temporal development and clinical implications. Habara et al found a high
incidence (90.7%) of possible neoatherosclerotic change [35] in restenotic lesions 5
years after BMS implantation, while it was scarce (17.9%) in 1 year ISR. Neointimal
disruption, which has an analogous morphology to ruptured fibroatheroma in a
native coronary artery, occurred more frequently in ⩾5 year lesions (18.6%) than in
1 year lesions (0%) [6]. Similarly, Takano et al demonstrated that neointima
exhibited a homogeneous OCT appearance, and there was a lack of lipid-laden
intima in the early phase (6 months). Conversely, lipid-laden intima, intimal
disruption and luminal thrombus formation were more frequently observed in the
late phase (5 years) when compared to the early phase. Furthermore, although
microvasculature was present in both stages, the appearance of intraintimal neovascularization was more prevalent in the late phase and in segments with lipidladen intima, suggesting that the expansion of neovascularization from persistent to
intraintima may contribute to neoatherosclerotic progression [7].
OCT analysis in 50 patients with DES-ISR (median follow-up period 32.2
months) demonstrated a high incidence of TCFA-containing neointima (52%), instent neointimal rupture (58%) and intraluminal thrombi. The presence of TCFA
was significantly higher in ISR >20 months post-implantation. Interestingly,
patients presenting with unstable (versus stable) angina showed a thinner fibrous
cap and an increasing number of unstable OCT findings, including TCFA-containing neointima, neointima rupture and thrombus, suggesting a clinical implication for
these neoatherosclerotic findings [76]. Current data show that first-generation DESs
have a constant rate of VLST (0.26%–0.4%/yr), with little evidence of a plateau up
to 5 years [77], and neoatherosclerosis may be a relevant cause that warrants further
investigation.
The progression of neoatherosclerosis in the same patient was evaluated by Kim
et al with serial OCT imaging at 9 months and 2 years after DES implantation. On
qualitative evaluation of neointimal morphology, lipid-laden neointima (27.6%
versus 14.5%, p = 0.009) and thin-cap neoatheroma (13.2% versus 3.9%, p = 0.07)
were more frequently detected at the 2 year follow-up compared to at 9 months. In
matched cross-sectional evaluation, the change of neointimal morphology from a
homogeneous to heterogeneous or lipid-laden pattern was observed in 23 (30.3%) of
76 lesions [78].
Neoatherosclerosis has been described in both BMSs and DESs, but they seem to
present a different temporal pattern as supported by histological data [66]. OCT has
provided further evidence on this aspect. Yonetsu et al demonstrated a greater
incidence of lipid-laden intima inside DESs than in BMSs at ⩽4 years postimplantation, although no significant difference was observed afterward, suggesting
an earlier onset of neoatherosclerosis in DESs [79]. There was more
1-13
Vascular and Intravascular Imaging Trends, Analysis, and Challenges, Volume 1
https://t.me/medicina_free
neovascularization in BMSs than in DESs in the early phase, showing again a
different response and vascular healing that may influence the development of
neoatherosclerosis [79].
The presence of atherosclerotic features in the neointima can also be objectively
quantified by measurements of the attenuation, backscatter, intensity and normalized standard deviation (NSD) of the OCT signal, showing a good correlation with
visual assessment [79]. However, there is a lack of consensus regarding cut-off values
and further investigation is needed to standardize this quantitative assessment.
Evidence regarding underlying mechanisms and risk factors of neoatherosclerosis
is scarce. OCT evaluation of 179 stents with significant neointimal growth
(⩾100 μm) found that for a stent age ⩾48 months, all subtypes of drug-eluting
stent, current smoking, chronic kidney disease and angiotensin-converting enzyme
inhibitors/angiotensin II receptor blockade use were independent predictors for
neoatherosclerosis [80]. However, these observational data provide a low level of
evidence, and the mechanism of neoatherosclerotic change needs to be investigated
in the future, as well as possible therapeutic strategies to avoid its development.
1.2.4 Incomplete stent apposition (malapposition)
1.2.4.1 Definition and quantification
Apposition is defined as contact of the stent struts with the vessel wall. A strut is
considered to be malapposed (see figure 1.5) if it is separated abluminally from the
luminal contour of the vessel [23]. Evaluation of apposition requires an adequate
visualization of both elements, which can only be achieved with intracoronary
imaging techniques. OCT is the most precise and sensitive technique to evaluate
apposition due to his high spatial resolution and imaging quality. With OCT,
Figure 1.5. Example of measurement of incomplete stent apposition.
1-14
Vascular and Intravascular Imaging Trends, Analysis, and Challenges, Volume 1
https://t.me/medicina_free
metallic stent struts appear as highly reflective surfaces and cast shadows on the
vessel wall behind and we can only visualize the adluminal reflection of the strut
(while the optical shadow hides the body of the strut and its abluminal side), thus the
contact between the strut and the vessel wall cannot be directly assessed by OCT.
Apposition must be indirectly assessed by measuring the distance between the
adluminal border of the stent and the vessel wall and then subtracting the strut
thickness (strut and polymer thickness in DESs). To enhance accuracy, the measurement line should be as perpendicular to the strut and vessel wall as possible [81].
The use of two kinds of correction factors for apposition assessment is recommended. The first one consists of adding an empirical margin between 10–20 μmto
take into account the OCT axial resolution. The second approach tries to correct the
intense signal generated by the reflection of light against the metallic struts (so-called
strut blooming). The true edge of the strut lies somewhere in the middle of that
blooming. The correction for blooming consists of measuring its thickness in a
random sample of study struts and then adding to the analysis of apposition a
correction factor equal to half of the blooming thickness. The use of one or another
correction is more of a theoretical methodological issue than a relevant practical
matter [82, 83]. To obtain a global estimation of ISA, a thorough cross-sectional
analysis is required (at least at 1 mm intervals, choosing the best images with clearly
identifiable vessel wall and struts within two frames distal or proximal) and for a
certain cross section (or the global stent assessment) measurements can refer to the
distance of ISA (maximum, median, average), ISA volume, or percentage of
malapposed struts [81, 84].
When analyzing bioresorbable intracoronary devices, the abluminal side of the
strut and its contact with or detachment from the vessel wall can be directly
evaluated by OCT [85].
Considering apposition, the following classification may be applied [81]:
• Malapposition (or ISA): defined as a strut–vessel distance greater than the
corrected strut–polymer thickness.
• Protruding: a strut–vessel distance more than half of the corrected strut–
polymer thickness.
• Embedded: a strut–vessel distance less than half of the corrected strut–
polymer thickness.
Both protruding and embedded struts are well-apposed. This discrimination
might be of interest because of the flow disruption and potential increased
thrombogenicity caused by protruding struts. However, recent data suggest that
protruding struts and struts malapposed with moderate detachment (ISA distance
<100 μm) pose minimal disturbance to blood flow compared to floating struts [86].
Moreover, to the best of current knowledge, there is no evidence of a clinical impact
related to protruding struts, and the criterion for optimal stent deployment is to
avoid ISA [82].
The evaluation of apposition is not possible in the strut’s ‘jailed
and they may be considered as an independent category. There is evidence that
’ side branches,
1-15
Соседние файлы в папке Библиотека им академика М.И. Перельмана