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Vascular and Intravascular Imaging Trends, Analysis, and Challenges, Volume 1
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challenging, and proper lesion preparation, optimal scaffold optimization, and the
early detection and correction of peri-procedural complications are pivotal for
achieving favorable results. Optical coherence tomography (OCT) is a catheterbased imaging system that uses near-infrared light to produce high resolution crosssectional images of the coronary arteries. It is a state-of-the-art technique, which can
precisely measure the vessel lumen and assess scaffold apposition, coverage and the
appearance of struts over time. OCT plays an important role in decision making for
the best treatment strategy, through accurate plaque characterization, selection of
proper landing sites, and avoidance of scaffold malapposition and underexpansion.
This chapter aims to review current bioresorbable technology and provide insight
into the potential advantages of using OCT for BRS optimization, through a series
of real-world clinical cases.
2.1 Introduction
BRSs are considered to be cutting-edge technology and have generated great interest
among interventional cardiologists worldwide. Since the introduction of drugeluting stents (DESs) which release, locally and predictably, anti-proliferative
agents, the risk of restenosis and therefore repeat revascularization has been reduced
significantly when compared to bare metal stents (BMSs) [1, 2]. It is well known that
stents can improve immediate outcomes by sealing any possible intimal tissue flaps,
preventing acute vessel closure and optimizing final vessel caliber [3]. DESs, by
blocking negative remodeling and limiting neointimal hyperplasia, potentially allow
physiological arterial healing. However, early generation sirolimus and paclitaxeleluting stents have been associated with delayed arterial healing, incomplete
endothelization of stent struts, premature neoatherosclerosis [4] and very-late stent
thrombosis (ST) [5]. Neoatherosclerosis is a term usually used to characterize the
growth of an atherosclerotic plaque inside an implanted coronary stent. The process
includes three important stages: macrophage infiltration, detectable atherosclerotic
plaque development and necrotic core plaque formation [6]. New generation DESs
emerged as a possible solution to prevent delayed re-endothelization and include
devices with several features, such as thinner struts, more biocompatible polymers
and different anti-proliferative agents, such as zotarolimus and everolimus [7]. A
wide range of DESs is now available and they may lower thrombotic risk as they are
less prone to hypersensitivity reactions and cause less arterial injury. On the other
hand, the permanent caging of the coronary vessel may be associated with
suppressed wall motility, altered vasodilation properties, chronic inflammation
and very-late ST. Although a fully bioresorbable device has been investigated for
over 20 years, the development of a scaffold with sufficient and durable radial
strength, without exaggerated thick struts, which allows controlled delivery of an
anti-proliferative agent and that can degrade progressively without generating an
overwhelming inflammatory response, has been rather challenging.
Importantly, BRSs are associated with potential advantages over standard
metallic stents. These include the restoration of vasomotion after the disappearance
of struts, late luminal gain, reduction of ST, restoration of functional endothelium,
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improved lesion imaging with computed tomography, facilitation for grafting the
stented segment, and freedom from side-branch obstruction from scaffold struts,
struts overhanging on ostial lesions or restenosis induced by stent fracture [8, 9].
This chapter overviews BRS technology and discusses the advantages of performing intracoronary imaging with OCT in real-world clinical practice.
2.2 Historical background and the search for the ideal bioresorbable
scaffold
Interventional cardiology has undergone several breakthroughs in the past 40 years,
since Andreas Gruentzig, using a manufactured expandable balloon, performed the
first coronary angioplasty in an awake patient in 1977, and changed the future of
cardiovascular medicine [10]. This technique, now referred to as plain old balloon
angioplasty (POBA), although providing an immediate reasonable angiographic
result, was associated with compromised outcomes, mainly as a result of acute vessel
closure due to coronary dissection, restenosis due to elastic recoil, or accelerated
neointimal proliferation. In 1986, Jacques Puel and Ulrich Sigwart implanted the
first coronary Wallstent
device composed of a cobalt-based stainless steel alloy [11]. In 1987 Julio Palmaz, an
Argentinian interventional vascular radiologist, and Richard Schatz, an American
cardiologist, implanted the first coronary Palmaz–Schatz stent
NJ, USA), a self-expanding, stainless steel device [12]. This newer technology
provided a solution for the early complications surrounding POBA by sealing any
dissection flaps and preventing vessel recoil. Restenosis rates were reduced but still
remained unacceptably high, with many patients needing repeated revascularizations after BMS index implantation [13]. During the late 1980s and early 1990s, a
large number of interventional tools were developed, including rotational atherectomy devices, intravascular ultrasound and improvements in stent design. In 1997,
over one million angioplasties had been performed worldwide, positioning this
technique as one of the most commonly performed medical interventions. DESs
were specifically developed to address the problems encountered with BMSs, namely
restenosis and ST. The first DES to be launched was the Cypher
Corporation, Warren, NJ, USA) in 2003, a sirolimus-eluting, expandable, stainless
steel device, which was shortly followed by the Taxus
Corp., Natick, MA, USA) in 2004, a paclitaxel-eluting, expandable, stainless steel
device. Over the following years, several stents followed, with differences focusing
on the employed anti-proliferative agent and the design of the stent itself—the type
of metal, strut thickness, mechanical properties and polymer specificities.
After POBA, BMSs and DESs, bioresorbable devices are considered the fourth
landmark in the history of interventional cardiology. The search for an optimal
absorbable device started over two decades ago, but the initial developed scaffolds
failed to reach the market as they were associated with marked inflammatory
responses, leading to neointimal hyperplasia and/or thrombus formation [14]. The
major reason for the delay in expanding this technology was the inability to develop
an ideal polymer, which could limit inflammation and restenosis and, at the same
®
(Boston Scientific, Natick, MA, USA), a self-expanding
®
(Cordis, Warren,
®
stent (Cordis
®
stent (Boston Scientific
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time, fully reabsorb, leaving the vessel completely healed over time. The most
frequently used polymer in BRSs is poly-
L-lactic acid (PLLA), which is a semi-
crystalline polymer—regions with high concentration of polymer with a crystalline
structure interconnected by amorphous chains binding the crystallites—since an
amorphous polymer is more susceptible to hydration than a crystalline one. It is a
biodegradable and thermoplastic polyester that undergoes self-catalyzed hydrolytic
degradation to lactic acid, with the final products being carbon dioxide and water
[15]. The reabsorption process includes several stages that can overlap: hydration of
the polymer (absorption of water from the surrounding tissue), depolymerization by
hydrolysis, loss of mass (fragmentation into segments of low-weight polymer and
reduction of radial strength), assimilation/dissolution of the monomer (phagocytosis
of small particles) and, finally, changing of the soluble monomer (
L-lactate) into
pyruvate, which subsequently enters the Krebs cycle and is converted into carbon
dioxide and water. The final products are excreted through the kidneys and lungs,
leading to a complete absorption of the device. Semi-crystalline polymers are used
predominantly for mechanical support, while amorphous polymers allow for a more
uniform drug delivery and structure loss at a predicted time. The duration of the
degradation process depends on the crystallization of the polymer and varies
between 2 and 4 years [16]. More recently, a metallic scaffold with a backbone
made of absorbable magnesium alloy, sirolimus-eluting and with an open cell
design, has also been used in clinical practice. The device resorption process has two
stages: first, ions and water from the surrounding tissues reach the metallic backbone, creating magnesium hydroxide and beginning corrosion. In the second stage,
magnesium phosphate is slowly converted into an amorphous calcium phosphate,
cracks appear in the core and the material is resorbed and, within a 12 month period,
95% of the magnesium is resorbed [17].
2.3 Bioresorbable scaffolds: current clinical evidence
Absorbable devices are more accurately called scaffolds, due to their transient vessel
support and absence of a permanent metallic implant. Several PLLA-based/
polymeric absorbable scaffolds have been clinically evaluated for the treatment of
coronary artery disease. These include the Absorb
Clara, CA, USA), the DESolve
system (Elixir Medical Corporation, Sunnyvale, CA, USA) and a tyrosine-derived
polycarbonate polymer stent (Reva Medical, San Diego, CA, USA).
The Igaki-Tamai
first BRS implanted in humans. It was constructed with PLLA, being both selfexpandable and balloon expandable; its zigzag helical coil pattern resulted in less
vessel trauma at implantation and also reduced thrombus formation or intimal
hyperplasia. Its strut thickness was larger (0.17 mm) and the vessel coverage by
struts was greater than for standard metallic stents. Self-expansion was achieved
by the use of heated contrast (up to 70°) and expansion was further optimized by
inflation of the delivery balloon up to 14 atm. Continued self-expansion of the stent
at 37° in the 20–30 min following deployment would optimize the final result.
®
®
myolimus-eluting bioresorbable coronary scaffold
®
(Igaki Medical Planning Company, Kyoto, Japan) was the
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The first-in-humans study was reported in 2000 by Tamai et al [18], comprising 15
patients (25 scaffolds implanted) and revealed no safety concerns. Major adverse
cardiovascular events (MACEs), including scaffold thrombosis (ScT), were reported
at 6 months follow-up and the neointimal growth was comparable to that of BMSs
(0.48 mm). A second study, which randomized 50 patients, had promising outcomes,
with intravascular ultrasound (IVUS) demonstrating complete absence of stent
struts at 3 years. The MACE-free survival was 82% at 4 years and freedom from
cardiac death and MACE at 10 years were 98% and 47%, respectively [19, 20].
Despite the favorable results, the failure of the scaffold to reach the clinical arena
was primarily related to the need for high temperatures to induce self-expansion,
which is cumbersome to accomplish in routine daily practice, and is associated with
concerns related to the potential induction of arterial wall necrosis, which may lead
to excessive intimal hyperplasia, increased platelet adhesion and, subsequently, ScT
[21]. The device is now used in Europe for peripheral intervention and has no drug
elution.
2.3.1 The Absorb
The Absorb
®
scaffold
®
(figure 2.1) was the first everolimus-eluting BRS and is the best
documented so far. It consists of four components: a bioabsorbable PLLA scaffold
based on a proven MULTI-LINK BMS pattern, a poly-
DL-lactide (PDLLA)
coating that contains and controls the release of the anti-proliferative drug everolimus, and the XIENCE V (Abbott Vascular, Santa Clara, CA, USA) delivery
system. Both PLLA and PDLLA are fully resorbable with complete absorption
expected at 24–36 months, with minimal inflammatory response [22]. The firstgeneration device (BVS 1.0) was tested in the ABSORB Cohort A, a single-arm,
prospective, open-label study which enrolled 30 patients with a single, de novo,
Figure 2.1. The Absorb everolimus-eluting bioresorbable scaffold. Reprinted with permission from Abbott
Vascular.
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coronary artery lesion [23–25]. At 5 years of follow-up, the ischemia driven MACE
incidence was 3.4% and ScT was not reported. Interestingly, between 6 months and 2
years, an enlargement of the vessel lumen was detected by intravascular imaging
(IVUS and OCT), although with no change in the angiographic late loss. Vessel
motility tests were performed at 2 years and physiological response to vasoactive
stimuli was present, suggesting the return of the vessel’s vasomotion in the
scaffolding area. A second-generation Absorb (BVS 1.1) was tested in the Absorb
Cohort B, as a single-arm, multicenter trial that included 101 patients with a
maximum of two de novo coronary artery lesions, with a maximum diameter of 3
mm and a length up to 14 mm [26, 27]. The studied population was further divided in
two groups: the first 45 patients were randomized to a 6 and 24 months follow-up
with invasive imaging (quantitative coronary angiography (QCA), IVUS and OCT)
(cohort B1) and the remaining 56 patients were randomized to the same tests at 12
and 36 months (cohort B2). At 2 years, nine clinical events were reported, including
six ischemia driven (ID) target lesion revascularizations (TLRs). At the 2 year
follow-up, a similar neointimal growth was observed between small and large vessels
and only one patient in each group had detectable incomplete stent apposition. In
cohort B2, the late lumen loss and neointimal growth were slightly larger than in B1
at 6 months, but similar to other studies at the same time point. Furthermore, the
authors reported that the scaffolded segments clearly responded to vasomotion
stimuli. Three intravascular imaging techniques (OCT, IVUS gray-scale and IVUSvirtual histology) were used for monitoring the resorption activity and documented
several stages of the ongoing process. The Absorb EXTEND, a prospective, openlabel clinical study, assessed the safety and performance of the Absorb BRS in a
larger and more diverse population, with increased lesion complexity [28]. A report
concerning the 12 month follow-up of the first 512 patients was disclosed in 2015 and
revealed an ID-MACE and ID-target vessel failure of 4.3% and 4.9%, respectively.
Four cases of ScT were recorded, two subacute and the other two occurring as late
ScT. A comparison between the Absorb EXTEND and the SPIRIT trial (XIENCE
®
V
EES) in the treatment of de novo native coronary lesions, regarding the incidence
and clinical sequelae of small side-branch occlusion (SBO)—1209 branches of 435
patients in the Absorb EXTEND versus 682 side branches in 237 patients in the
SPIRIT—revealed that the BRS was associated with a higher incidence of SBO
when compared to EES, and that patients with SBO had an increased incidence of
in-hospital myocardial infarction (MI) (6.5% in SBO group versus 0.5% in non-SBO,
p < 0.01). A post hoc analysis showed that the BRS was associated with SBO only in
vessels with a reference vessel diameter ⩽0.5 mm [29].
The ABSORB II [30–33] is a single-blind, prospective, multicenter randomized
clinical trial (RCT) that compared the Absorb
®
with the Xience®metallic stent,
admitting treatment of de novo coronary lesions in different major epicardial vessels,
with pre-determined diameters: (i) a maximum lumen diameter between 2.25–3.8 mm
(QCA) and (ii) a maximum lesion length of ⩽48 mm. Primary endpoints were the
evaluation of vasomotion through the assessment of both mean and minimum
lumen diameters at 3 years. In a cohort of 501 patients, acute lumen gain was lower
in the BRS group. However, the 1 year rates of angina were lower in the BRS arm,
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whereas performance during maximum exercise was similar in both groups.
The 2 year analysis of the clinical results showed there were no statistically
significant differences between the two devices regarding the composite clinical
endpoints: ‘patient-oriented composite endpoint’ (PoCE), ‘device-oriented composite endpoint’ (DoCE), target lesion failure (TLF) or MACE. Although the absolute
rate of definite or probable ScT was higher in the Absorb
®
group, it was not
statistically significant (1.5% versus 0%, p = 0.174). Furthermore, at 3 years the
clinical endpoints were not different between the groups. Nonetheless, the DoCE
was significantly higher in the Absorb arm, driven by target vessel MI (6.0% versus
1.0%, p = 0.011), although 52% of the cases were peri-procedural. Eight definite ScT
and one late probable ScT were documented after BRS implantation, against none in
the XIENCE group (p = 0.033). Potential mechanisms leading to early versus late ScT
include protruding or malapposed struts (early ScT) and incomplete lesion coverage,
malapposition, strut discontinuity and underexpansion (late and very-late ScT).
Although BRSs may have several advantages over DESs—maintaining normal
vessel function, allowing for a future percutaneous or surgical revascularization if
necessary, elimination of potential triggers for late ScT, such as chronic inflammatory response and delayed endothelization—the resorbable scaffold experience and
outcomes in routine clinical practice were largely unknown. GHOST-EU [34]isa
retrospective, non-randomized, multicenter registry comprising 1189 patients with
coronary artery lesions suitable for stenting, undergoing single or multivessel PCI
with the Absorb device. The inclusion criteria encircled a great number of patients,
with complex clinical scenarios (myocardial infarction, chronic kidney disease,
depressed left ventricle function) and complex coronary disease (ostial lesions,
bifurcations, chronic total occlusions, left main disease). TLF had a cumulative
incidence of 2.2% at 30 days and 4.4% at six months, and diabetes was the only
predictor of TLF, with a 2.4 fold increase. The cumulative incidence of ScT was
higher than expected, 1.5% at 30 days and 2.1% at 6 months, with 70% of the cases
occurring subacutely. ScT is known to be a multifactorial event, associated with
different causal mechanisms, according to the timing of its occurrence. Early events
are usually due to procedural issues—dissection, device malapposition and underexpansion—and late events are usually related to the device’s inner characteristics
and vessel response. The Absorb scaffold is a thick-strutted platform, and has been
described as having 1.5 fold more thrombogenicity than thin-strutted metallic stents
[35]. Nonetheless, it is still unknown if any deleterious struts-induced event may
outweigh the late benefits, after scaffold biodegradation and vessel healing. The
authors concluded that early and midterm outcomes in this cohort of patients with
unselected clinical characteristics and lesions were acceptable and comparable to
second-generation DESs, with ScT comparable to the first-generation DESs.
ABSORB China [36], ABSORB III [ 37], ABSORB Japan [38], AIDA [39],
EVERBIO II [40] and TROFI II [41] are randomized trials which showed more
adverse events, mainly attributable to excessive ScT, in the BRS group when
compared to the XIENCE stent. In ABSORB II, the rates of recurrent angina
were less frequent in the Absorb arm. ABSORB IV [42] is a prospective RCT,
designed to be an extension of ABSORB III, with TLF as the predesignated primary
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endpoint and angina as the major secondary outcome. The results showed
non-inferiority between the scaffold and the metallic DES group regarding TLF,
and also similar rates of angina at 1 year.
A significant number of trials and studies regarding the use of BRSs in different
clinical settings have been published, potentially expanding the indications and
advantages of absorbable scaffolds in specific clinical scenarios: (i) in acute coronary
syndromes (POLAR-ACS [43], BVS-EXAMINATION [44] and PRAGUE-19 [45])
BRSs were reported as a safe and feasible device, with a high rate of procedural
success; (ii) in chronic total occlusions (CTOs) (CTO-Absorb Pilot Study [46] and
Goktekin et al [47]), CTO recanalization with a BRS had excellent feasibility and
safety, with adequate lesion preparation being fundamental to device success;
(iii) and ostial lesions (GHOST-EU registry), where BRSs, with suboptimal
technique implantation, were an independent predictor of clinical events.
The excessive ScT seen for resorbable scaffolds in recent clinical trials, particuarly
in the ABSORB III, led to Absorb being pulled off the market in September 2017.
The poor device results may be accounted for by the thicker struts, the limited ability
to over-expand, poor outcomes in smaller vessels and the need for precise sizing and
optimal implantation techniques.
2.3.2 Metallic magnesium BRSs
The first magnesium-based metallic scaffold to be implanted in humans was AMS-
®
1
(Biotronik AG, Bülach, Switzerland), a balloon expandable device with a strut
thickness of 165 μm, which was evaluated in the PROGRESS-AMS trial [48].
Magnesium was the chosen metal as it is one of the major intracellular cations in the
body. It is an important cofactor not only for numerous enzymes, transporters and
nucleic acids, but also for several functions such asneuromuscular activity [49]. In
the former trial, immediate angiographic results were similar to those of other
metallic stents but the radial support was lost in the short term, due to an almost
complete degradation of the scaffold only after 4 months, resulting in early
neointimal growth and negative remodeling. Additionally, the device had no antiproliferative drug and, hence, high rates of late loss and TLR. Yet, no myocardial
infarction, ScT or death occurred. These findings suggested that the scaffold lacked
sufficient mechanical strength or support. A few years later, an improved drugeluting version emerged, DREAMS 1G
®
(magnesium-based, paclitaxel-eluting),
which was evaluated in the prospective, multicenter, first-in-man trial Biosolve I.
The scaffold was associated with good safety and efficacy at 12 months (7% of TLR)
[50] and no cardiac death or ScT. The newer DREAMS 2G
®
is an absorbable
scaffold made of a refined magnesium alloy backbone and contains a PLLA-based
polymer coated with sirolimus with an absorption period of 12 months.
BIOSOLVE-II, a prospective, multicenter, non-randomized trial, revealed low rates
of TLR/TLF and no ScT at 6 months follow-up [51]. BIOSOLVE-III was designed
to confirm the positive outcomes of the modified metallic scaffold, now being called
Magmaris
®
—sirolimus-eluting, 150 μm strut thickness and width, higher acute
radial strength, resorption rate of 95% at 12 months [52]. Although BIOSOLVE-III
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included more patients with type B2/C lesions and more severe calcification, late
lumen loss was nearly identical to BIOSOLVE-II, and TLR was 3.3% at 1 year in
comparison to 6.6% for Absorb, 5.2% for EES and 5.7% for DESolve [53], with no
ScT observed. Overall, safety device improvement may be due to the shorter
resorption rate of the magnesium scaffold in contrast to the polymeric ones, in
which the resorption occurs at 3 years. BIOSOLVE-IV, a prospective multicenter
registry, reported a 12 month TLF rate of 4.2% and one case of ScT due to double
antiplatelet therapy interruption, corroborating the excellent safety pro fi le reported
in the previous clinical trials [54].
2.3.3 Other resorbable scaffolds
DESolve
®
(Elixir Medical, Sunnyvale, CA, USA) is a PLLA-based scaffold coated
with the anti-proliferative drug myolimus, with more than 85% of the drug being
released in 4 weeks. Features include the potential to maintain adequate mechanical
support with bioabsorption at about 1 year, a wide safety margin for postdilation
without strut fracture and the ability to self-correct to the vessel wall in cases of
minor malapposition. It was evaluated in the prospective, multicenter DESolve
First-in-Man Trial which included 15 patients [55]. At 6 months, imaging studies
with OCT and IVUS revealed a late lumen loss of 0.19 ± 0.19 mm with no evidence
of scaffold recoil or late malapposition. At 12 months there were no reports of ScT
or MACEs directly attributable to the device, and assessment with computed
tomography showed excellent vessel patency. Currently, the second-generation
DESolve CX, with thinner struts (120 μm) is being evaluated in clinical trials.
The REVA
®
stent (Reva Medical, CA, USA) is made of a tyrosine-derived
polycarbonate polymer that is both resorbable and radiopaque, after being chemically modified to incorporate iodine molecules. It metabolizes to aminoacids,
ethanol and carbon dioxide, with tyrosine entering the Krebs cycle. Its degradation
time can reach 2 years, depending on the molecular weight of the polymer [56]. The
REVA has a distinctive feature, a ‘slide-and-lock’ mechanism, conceived to prevent
deformation and weakening of the polymer during stent deployment; the locking
system, aside from preventing the stent from going back during deployment,
provides additional support in a later stage, during vessel remodeling. RESORB,
a first-in-human multicenter study which included 30 patients, began its enrollment
in 2007. At 6 months follow-up there was no significant elastic recoil or neointimal
hyperplasia. However, TLR was unacceptable with a rate of 66.7%, probably due to
focal mechanical failures and the absence of an anti-proliferative substance. The
scaffold was redesigned and evaluated in ReZolve
®
—a more robust polymer, a
spiral slide-and-lock mechanism and a coating of sirolimus, with 95% of the drug
being eluted at 90 days. In the RESTORE Pilot Study, the technical success rate was
only 85% due to the high crossing profile and sheathed delivery system. Twelvemonth results showed an excellent acute lumen gain, the occurrence of two cases of
TLR and one cardiac death [57]. ReZolve2
®
is a second-generation sirolimuseluting scaffold and was designed to overcome ReZolve’s failures. It has a lower
profile, a sheathless delivery system and a 30% increase in radial strength. In 2014,
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REVA transitioned to a new platform, Fantom®, which is sirolimus-eluting and was
designed to have an even lower crossing profile, higher visibility, a large expansion
range with a high safety margin against strut fracture, increased radial strength and
complete reabsorption within 3 years, with potential full restoration of natural
vasomotion. Results from the second-generation Fantom BRS, a scaffold with
thinner struts (125 μm), enhanced radial strength and minimal recoil, were presented
at PCR 2018. Fantom II showed a low MACE and very-late ScT rates (5% and
0.4%, respectively), and no evidence of chronic scaffold recoil [58]. The Fantom
clinical trial program is still ongoing.
2.4 The clinical utility of optical coherence tomography in the
optimization of bioresorbable scaffolds
In the past 15 years OCT has become an important technology in the evaluation of
coronary artery structure, overcoming the limited spatial resolution and drawbacks
in the assessment of vulnerable plaques of IVUS. It is a catheter-based imaging
system that uses near-infrared light to produce cross-sectional images of the inner
vascular wall, with a resolution of 10–20 μm, which is approximately ten-fold higher
than that of IVUS, with the caveat of limited depth penetration [59]. It is unable to
penetrate red blood cells, so it has to be performed in a blood-free environment,
through the injection of a contrast medium, allowing operators to visualize long
coronary segments in a matter of seconds. As a result of this exceptional high
resolution, deep plaque analysis and more accurate detection of PCI-associated
complications is now possible, leading to more favorable clinical outcomes [60], and
turning OCT into one of the most useful techniques to assess lumen geometry and
guide coronary intervention. In addition to identifying the thickness of the tissue
layers that separate the superficial plaque from the lumen, and being capable of
accurate plaque characterization—a sensitivity of 96% and a specificity of 97% in
detecting calcified nodules [61]—it provides a clear evaluation of the interface
between the lumen of the vessel and the stent, allowing for clear detection of
malapposition, underexpansion, edge dissection or tissue protrusion. BRSs have
important differences when compared to standard metallic stents, which can be
depicted by a thorough OCT analysis. For metallic stents, struts are clearly visible
and neointimal growth can be measured at any time—the area between the struts
and the lumen contour. For BRSs, at an early stage, struts are still visible and
neointimal proliferation can still be assessed, with degradation progressing steadily.
However, in the long term, as the resorption process subsides with vascular repair,
and the polymer is progressively replaced by a provisional matrix of proteoglycan,
scaffold struts are no longer visible and distinguishing between the strut area and
underlying plaque becomes a challenge. Even though OCT is not capable of
differentiating PLLA from proteoglycan, which is one of the first structural changes
to occur in vascular repair [62], it is able to precisely measure the lumen and scaffold
and assess scaffold apposition, coverage and the appearance of polymeric struts over
time. Thus OCT has been one of the favorite techniques for studying BRSs. Serruys
et al have assessed dynamic vessel changes in the entire population of the Absorb
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Cohort B trial using several imaging modalities (QCA, IVUS, radio-frequency
backscattering (IVUS-VH) and OCT) at different time points [63]. The overall OCT
analysis showed that, after an initial decrease in minimal and mean lumen area,
values stabilized. Increase in neointima between one and three years was compensated by a simultaneous enlargement in minimum and mean scaffold area (in cohort
B2 the mean scaffold area increase was 0.88 ± 1.72 mm
formation of 0.93 ± 0.94 mm
2
). The number of struts counted in all-frame analysis
2
, p < 0.001, with neointimal
steadily increased from baseline to 1 and 3 years, a finding interpreted as the
dismantling of the scaffold, and 98% of the struts showed coverage, with the mean
black core area unchanged up to 3 years. In the discussion, the authors refer to the
fact that some preclinical investigation showed that changes in strut appearance in
OCT correspond to the appearance of connective tissue which will subsequently
shrink and ultimately disappear. As this last process is associated with wall thinning,
this change may have an impact on lumen enlargement. In contrast to IVUS, OCT
was able to detect the endoluminal interface of the vessel wall behind the polymeric
struts with near perfect delineation of the neointimal tissue surrounding them. IVUS
mainly detected the lumen boundaries determined by strut brightness. This difference has some impact in the follow-up: no change in mean lumen area with OCT
versus an increase with IVUS. Allahwala et al aimed to determine if OCT, after
successful angiographic BRS implantation, influenced decision making with regard
to the need for postdilation, in a small population of patients with predominant type
A lesions [64]. The authors observed that 28% of patients with optimal angiographic
results required further BRS optimization following OCT, a similar finding to the
ABSORB trial, and hypothesized that this number could increase if more complex
lesions had been included. Bourantas et al evaluated the implications of the Absorb
BRS on the morphology of superficial plaques and included 46 patients with BRS
versus 20 patients with BMSs who underwent OCT at baseline and follow-up [65].
The study revealed that plaques in native coronary segments maintained the same
morphology, in contrast to treated segments in which neointimal formation covered
calcific spots and turned thin-capped fibroatheromas into thick-capped ones. Also,
there was a significantly higher reduction in lumen dimensions in BMSs than in
BVSs. In Absorb BRSs, neointimal tissue continued to develop after short-term
follow-up and did not compromise luminal dimensions, as the scaffold was shown to
expand. Finally, the distribution of neointimal tissue over thin-capped fibroatheromas and calcific plaques in both BMSs and BRSs revealed a similar pattern. These
findings are discrepant when compared to other studies, maybe due to the use of
different imaging modalities to measure neointimal thickness, as well as the
implantation of two different types of stents in the BMS group.
Nakatani et al published a consensus amongst multiple core labs and expert
researchers of OCT, and proposed a new standardized and comparative method for
quantitative analysis on OCT, that specifically applies to the Absorb BRS and, in
general, for metallic stents [66]. These authors focused their attention on the
following parameters: tracing of both the luminal and abluminal stent/scaffold
contours, measurement of the endoluminal and abluminal incomplete stent apposition (ISA) area—in metallic stents is the area between the endoluminal leading
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