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188 PART IV Wires Technique
societies [23]. Nowadays, there is growing acceptance
that the utilization of the less invasive, percutaneous
revascularization is much preferred by patients and
cardiologists alike over the traditional management of
bypass surgery. Thus, the increased role of CTO-PCI
in contemporary management represents an important paradigm shift.
The rationale behind the movement toward an
increased utilization of percutaneous debulking
strategy along the management of CTO is supported
by introduction of detailed algorithms for precise
decision -making concerning optimal lesion crossing
and recanalization [24, 25]. The advancement of
interventional technology and enhanced debulking
techniques accompany this development [26, 27].
Consequently, have the success rate of CTO-PCI
steadily improved from around 60–70% [18] to reach
80–90% in properly selected patients who undergo
meticulous vessel and lesion preparations [7, 23, 28].
Thus, the marked benefits of successful PCI in these
lesions should be recognized to further advance this
strategy. Among the benefits are restoration of antegrade flow in a previously occluded artery, relief of
angina pectoris and ischemia, improved left ventricular
function, reduction of the need for target vessel revascularization, improved exercise capacity, decreased risk
of arrhythmias and a potential survival benefit when
compared with patients who failed CTO revascularization [1, 29]. Moreover, successful PCI is associated with
a lower risk of midterm major adverse coronary event
when compared to failed revascularization of CTO
(hazard ration(HR)):0.026,95% confidence interval(CI)
0.004-0.176,p=0.0002. Noteworthy, a J-CTO (Japanese
Chronic Total Occlusions) score of >3 is independently
associated with worse clinical outcomes (HR: 4.819,95%
CI: 1.463-15.870,p=0.0097) [30]. Several studies with a
follow up of up to 2 years have demonstrated that CTO
revascularization improves quality of life, reduces myocardial ischemia, and improves regional and global LV
function in select patients [31–33].
Principles of CTO-PCI
PCI in critical atherosclerotic lesions calls for experienced interventionalists capable of dealing with
specific management considerations. Among such
lesions are aorto-ostial disease, in-stent restenosis,
saphenous vein graft disease and CTOs. Achievement
of best acute procedural results, reduction of major
adverse coronary events, and optimal long-term outcomes depend on concrete tactical steps to be taken
prior to and along the planned CTO intervention.
Accordingly, in addition to patient preparation operators should also focus on other elements of the
planned revascularization. Recently, Olorunfemi and
Alfonso from the University of Miami, Florida,
emphasized the importance of the concepts of vessel
preparation and lesion preparation to the performance
of contemporary CTO-PCI [28]. Accordingly, vessel
preparation refers the series of steps taken by the operator to first assess the angiographic characteristics of
the target vessel and its tributaries, then modify the
targeted atherosclerotic lesion and its adjacent
vascular segment in readiness for the definitive
treatment of stent implantation. The goal of lesion
preparation is to ensure adequate procedural results
through proper stent sizing and expansion followed
by optimal struts apposition while preserving vessel
integrity including the segment proximal and distal to
the targeted lesion. Optimal vessel and lesion preparation necessitates adequate identification of high-risk
anatomical characteristics. These include the presence
of intimal, medial, and adventitial calcifications,
vessel tortuosity, identification of accompanying
thrombus, and the presence of associated bifurcation
or even trifurcation lesions. The third concept critical
to performance of contemporary CTO-PCI is “equip-
ment preparation.” It entails adequate experience with
various tools and technology and understanding of
the multi-facet mechanisms involved in debulking of
CTO lesions by various tools. Among these are recanalization, excision, abrasion, grinding, pulverization,
vaporization, dissolution, extraction, and aspiration
[34]. Altogether, the complexity of the target CTO
lesions, the demand from the devices and the technical
prowess of operators as well as the risk of potential
complications restricts the performance of CTO-PCI
to specialized and experienced interventional centers,
usually with available CABGS coverage.
Laser concepts and interactions
LASER, an acronym for Light Amplification by
Stimulated Emission of Radiation, is a remarkable
physics phenomenon originally theorized and published by Albert Einstein in 1917 [35]. Contemporary
medical laser devices contain a generator producing
intense electromagnetic energy. The laser energy consists of light photons bundled together to be transferred through optic fibers embedded in flexible
delivery catheters of various sizes. The aim of a laser
device is to create photo ablation of targeted biologic
tissues. Absorption of excimer laser energy within biotissue creates unique effects on the nonaqueous components of atherosclerotic plaques and accompanying
thrombi. Laser absorption in plaques is accompanied
mainly by photomechanical and photochemical
reactions and, to some extent, also a photothermal
reaction (Table 22.1). The culmination of absorption is
conversion of plaque material into gas vapor and
Table 22.1 Laser associated processes.
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Process Outcome
Photomechanical Formation of acoustic shock waves
Photochemical Dissociation of chemical bonds
Activation of chromophores
Conversion of chromophores into
photoproducts
Photothermal Denaturization of proteins
“Popcorn effect”
Charring
Vaporization and ablation
Hyperchromasia
Hyalinization of fibrillar collagens
Birefringence changes
Spindling of epithelial cells
CHAPTER 22 Laser Revascularization in Coronary CTO 189
induction of acoustic shock waves. The vaporization of
the plaque’s content and concomitant propagation of
acoustic resonance waves ultimately lead to debulking
and removal of the lased tissue [36] (Table 22.2). Early
experience with laser in CTO was obtained by utilization of the solid state, “cold” pulsed-wave, holmium:
YAG (Yttrium Aluminum Garnet), which operated at
2.09 micron in the mid-infrared optical spectrum
(Eclipse, Palo Alto, Cal). The device was had excellent
interaction with atherosclerotic plaques [37] and was
considered mechanically reliable and user friendly
tool, achieving considerable gains and associated with
low complications rate in debulking of complex lesions
[38, 39] including CTO. Figure 22.1 demonstrates the
application of this laser in a complex, long CTO occlusion. Noteworthy, the largest, long-term experience in
cardiovascular laser applications has been gained with
the pulsed-wave, “cold,” ultraviolet (308 nanometer
wavelength) excimer laser coronary angioplasty
Table 22.2
Laser induced effects.
Laser Effect
Shock waves Creation of pressure gradient
Gas bubble formation Expansion and implosion of atherosclerotic material
Inertially confined ablation Pre-ablation pressure generation
Heat Thermal damage to plaque and vessel
Thrombosis Thrombus formation
Thrombus absorption Dissolution of fibrin fibers
(ELCA) laser [40–42]. The CVX-300 excimer laser
system (Philips, Colorado Springs, CO, USA) is
approved in the USA and Europe for revascularization
of diseased native coronary arteries containing complex lesions including CTOs [43], old saphenous vein
grafts, diseased peripheral arterial vessels, and in electrophysiology as well for extraction and removal of
old/dysfunctional pacemaker and AICD (Automatic
Implanted Cardiac Defibrillator) leads. Similar to the
holmium: YAG laser [44]. the marked efficiency of this
device was demonstrated in successful debulking of
atherosclerotic lesions in the coronary vasculature of
heart transplant recipients [45]. These complex lesions
develop as a result of aggressive “allograft malignant
atherosclerotic vasculopathy” form of atherosclerosis
and are notoriously resistant to percutaneous revascularization, yet can yield to laser emission of various
wave-lengths. Noteworthy, this laser can be safely and
efficiently applied to CTO lesions in patients with
Free radical creation
“Mille feuille” phenomenon [acute vessel closure
from obstruction by expansion of multilevel
dissections]
Charring
Spasm
Collapse of the thrombus fiber scaffolding
Suppression of platelet aggregability
190 PART IV Wires Technique
depressed left ventricular ejection fraction and in
those with hemodynamic instability [25, 46, 47].
Interestingly, the versatility of excimer laser had been
demonstrated in critically ill infants with a “CTO”
caused by congenital pulmonic atresia, a condition
representing “non-coronary” total obstruction to flow.
The atresia, a thick membrane made of thick fibrotic
tissue, was impenetrable to guide wire, therefore it was
debulked and recanalized directly with a 0.9mm catheter, which in turn enabled insertion of a guidewire,
subsequent balloon dilatations, and restoration of
antegrade pulmonary artery flow and improved hemo-
Figure 22.1 An elderly man who presented with unstable angina pectoris with ischemia in the inferior-lateral leads.
a. The right coronary artery contains a long CTO with angiographic demonstration of intra-plaque vascular channels
b. A 1.2mm mid-infrared holmium: YAG catheter debulking the CTO.
c. Creation of a “pilot channel” initiated antegrade flow and enabled insertion of balloon for multiple dilatations.
d. Angiogram post balloon dilatations.
e. Final results without stenting. Restoration of TIMI 3 antegrade flow was associated with relief of angina and
resolution of ischemia.
CHAPTER 22 Laser Revascularization in Coronary CTO 191
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Figure 22.1 (Continued)
dynamics, thus successfully terminating a life threatening condition [48].
Figure 22.2 demonstrates the successful utilization
of excimer laser in a de-novo CTO lesion.
The merit of laser application in multiple types of
CTO lesions stems from its unique effect on each of
the major histopathologic components of these lesions
(Table 22.3). They include the atherosclerotic plaque,
organized thrombus, fibrosis, and calcifications. Of
note, both atherosclerotic plaque and its accompanying thrombus are amenable to the effects of the
excimer laser energy and, therefore, can be targeted
for debulking and removed with this technology. In
that regard, thrombus exhibits a specific anatomichistologic challenge within CTOs because layers of
underlying thrombus of varying age and consistency
are embedded within these lesions. Frequently, during
attempts to recanalize a CTO, the thrombus becomes
active and friable [49]. This process is accompanied by
enhanced platelet aggregation, formation of new
thrombus and discharge of vasoactive mediators. The
excimer laser induces unique effects on thrombi, with
its ability to produce mechanical impact on the fibrin
mesh within the clot leading to clot dissolution. A
beneficial laser-induced suppressive effect on platelet
aggregation has been demonstrated [50] with direct
correlation between the level of laser emission and the
inhibiting, suppressive impact on platelet aggregation.
This should be considered a clinically important
property of this device, especially when used for
patients who cannot receive 2b/3a receptor antagonists or in old saphenous vein grafts where convincing
evidence on the merit of these pharmacologic agents
is lacking [51]. Furthermore, a growing interest has
recently been shown in application of laser for recanalization of CTOs in the venous circulation, including
native, large occluded veins and old saphenous vein
grafts [52].
Laser technology and technique
Flexible laser catheters are supported and advanced
over standard or special 0.014-inch guidewires using
either an over-the-wire or rapid exchange method. The
lumen of over-the-wire catheters permits intracatheter exchange of guidewires as needed for penetration into the CTO. Structurally, laser catheters are
constructed by a flexible fiber-optic cable which contains high-purity silica fibers. A typical 2 mm COS
excimer laser catheter (Philips, Colorado Springs, CO)
has 240 fibers, each with a core diameter of 61 µm.
Figure 22.3 demonstrates 2 generations of the excimer
laser catheters. The optical fibers are arranged to
encircle the guidewire lumen and their distal tip is
rounded and polished. The ultraviolet laser light
emerges from individual fibers, penetrating approximately 40–50µm onto the target tissue. The energy
fluence levels range and can be gradually increased
from 25mJ/mm 2 at 40Hz to a level as high as 80mJ/
mm 2 at 80Hz, depending on catheter specifications
192 PART IV Wires Technique
Figure 22.2 Excimer laser debulking for CTO in a patient with long standing severe exertional angina pectoris.
a.The right coronary artery contains a proximal CTO.
b. Recanalization following excimer laser debulking with a 1.4mm [45mJ/25Hz] catheter. Antegrade flow restored.
c. Angiogram post balloon inflations.
d. Final angiogram post stenting.
and lesion requirements and as assessed by the operator assessment along the recanalization attempt [53].
The operator can use any shape of guiding catheter
deemed suitable to ensure adequate support for the
delivery of the guidewire and the laser catheter. The
guiding catheter shape and size should accommodate
the laser catheter in accordance with instructions for
use and the manufacturer recommendations. A selection of over-the-wire and rapid exchange excimer laser
catheters is available for coronary CTO intervention.
They vary in size from 0.7mm to 2.0mm with either
concentric or eccentric optical fiber arrays, depending
on the model [54]. Most concentric laser catheters
incorporate the “optimally spaced” fibers arrangement
(90 µm of space separating individual fibers) which
grants improved ablation area in comparison to the
older catheters (77 µm space between fibers). Laser
catheters permit advancement and exchange of guide-
Table 22.3 Clinical and angiographic laser effects.
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Positive effects:
Lesion morphology modification
Plaque vaporization and removal
Thrombolysis
Restoration of antegrade flow in the treated vessel
Cessation of ischemia
relief of angina
Stabilization of acute MI
Facilitation of stenting
Negative effects:
Spasm
Distal embolization
Dissection
Perforation
Q-T prolongation
CHAPTER 22 Laser Revascularization in Coronary CTO 193
Figure 22.3 Cross section of 2 types of excimer laser catheters.
wires into and across the CTO. These catheters are
readily advanced over the leading guidewire or
exchange with a different size. In most instances the
antegrade recanalization approach is preferred [20],
however, a small diameter catheter such as the 0.7mm
or the 0.9mm can be utilized for the purpose of retrograde CTO recanalization strategy. Adequate laser
induced recanalization through the obstructive CTO
leads to facilitation of adjunct balloon and stenting. A
constantly maintained, slow speed of the laser catheter
during CTO revascularization is of paramount importance. Careful advancement – preferably 0.2 mm/
second – 0.5 mm/second – is warranted to enable
maximal absorption within the plaque. The use of
saline flush during the laser activation is on one hand
required to reduce an enhancement effect of contrast
media enhancement on the magnitude of acoustic
shock waves, thereby controlling pressures within the
lased CTO. On the other hand, some interventionalists
maintain that the firm resistance of CTO indicates a
technical improvisation, calling for elimination of
saline “flush” injection. With this modification the
maximal effect of laser-induced acoustic shockwaves
should create enhanced debulking of the target lesion.
194 PART IV Wires Technique
The energy fluence levels range from 25mJ/mm2 at
2
pulse repetition of 40Hz to as high as 80mJ/mm
at
80Hz, and they can be increased gradually along the
debulking, depending on catheter specifications and
the operators’ assessment of the recanalization difficulty. The lasing “train” or “cycle” is 5 seconds on and 5
second off; however, with the 0.9mm catheter, operators can deliver energy for as long as 10 seconds.
Specifically, in coronary laser procedures the initial
catheter size should be chosen in accordance with the
morphology and tightness of the targeted lesion. From
mechanical and even safety perspectives, a small
catheter (such as the 0.9 mm) can be used initially.
However, recognizing that CTO contains a complete
occlusion, it can accommodate initiation of debulking
with a large catheter size. Laser debulking will create
what we have termed a pilot channel [as shown in
Figure 22.2]. Table 22.4 depicts the selection choice of
ELCA catheters for specific components of CTO.
During coronary (and peripheral arterial) CTO laser
interventions, adjunct pharmacotherapy including
thrombolytics, 2b/3a receptor antagonists, or direct
thrombin inhibitor can be administered combined
with the delivery of the laser energy. This concept of
enhanced or synergistic effect of laser energy on pharmacologic agents is termed power thrombolysis [55].
Activation of excimer laser requires simultaneous
injection of intracoronary saline flush. It reduces the
enhancement effect of contrast media on acoustic
shock waves, thereby decrease pressures within the
lased CTO. On the other hand, many interventionalists maintain that the firm resistance of CTO calls for
no saline injection, so a maximal effect of laserinduced acoustic phenomena will be gained to create
enhanced target lesion debulking [56].
Clinical applications of laser
The clinical candidates for laser coronary interventions are symptomatic patients who sustain acute or
chronic coronary thrombotic-ischemic syndromes
including acute myocardial infarction of the STEMI
(ST Elevation Myocardial Infarction) and non STEMI
types [41, 57, 58].
Acute and chronic ischemic-thrombotic peripheral
arterial disease is amenable to laser revascularization as
well [59]. Angiographically, patient candidates for
coronary laser revascularization frequently exhibit
complex atherosclerotic and thrombotic lesions considered nonideal or nonamenable for standard technologies, failed initial treatment with percutaneous
intervention, or deemed unfavorable for bypass surgery
[60]. As lasers continue to improve, this technology is
applied to ever more challenging, complex coronary
[and peripheral lesions alike] [61, 62]. Among the most
important indications for laser utilization in the
treatment of coronary [and peripheral] atherosclerotic
disease is recanalization of chronic total occlusions
(CTO) [11, 63]. Histologically, a CTO can represent a
de-novo total stenosis, critical post intervention restenosis or complete in-stent restenosis. The fundamental
merit the laser technology offers in CTO stems from its
unique interaction and effect on major histopathologic
components including atherosclerotic plaque, organized thrombus, fibrosis, and calcifications without
adverse impact on the vessel wall. Noteworthy, both
atherosclerotic plaque and its accompanying thrombus
are amenable to excimer laser energy and, therefore,
can be targeted for debulking with this technology. In
that regard, CTO’s thrombus exhibits a specific histologic-morphologic challenge for revascularization
because layers of underlying thrombus of varying age
and consistency are embedded within these lesions.
Frequently, during attempts to recanalize a CTO, the
thrombus becomes active and friable [49]. This process
is accompanied by enhanced platelet aggregation,
formation of new thrombus, and discharge of vasoactive mediators. The excimer laser induces unique
effects on thrombi, with its ability to produce
mechanical impact on the fibrin mesh within the clot
leading to clot dissolution. A beneficial Laser-induced
suppressive effect on platelet aggregation has been
demonstrated [50] with direct correlation between the
level of laser emission and the inhibiting, suppressive
Table 22.4 Optimal ELCA catheter size-correlation with CTO constituents.
CTO component Recommended laser catheter
Fibrosis 0.9mm-2.0mm [concentric]
Calcium 0.9mm X-80 [concentric]
Thrombus 0.9mm-1.7mm [concentric]
In-stent restenosis 0.9mm-2.0mm[concentric & eccentric]
Under-expanded stent in occlusion 1.4mm- 2.0mm [concentric]
Old saphenous vein graft occlusion 0.9mm -2.0mm [concentric or
eccentric]
CHAPTER 22 Laser Revascularization in Coronary CTO 195
(a)
(c)
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impact on platelet aggregation. This should be considered a clinically important property of this device, especially when used for patients with contraindication for
2b/3a receptor antagonists or in old saphenous vein
grafts, where convincing evidence on the merit of these
pharmacologic agents is lacking [51].
Laser debulking in coronary CTO –
clinical experience
The cumulative experience with strategies of CTO
revascularization highlights the usefulness of excimer
laser in several common yet technically challenging
CTO lesions and their associated clinical scenarios
[64]. These include the (guidewire) impenetrable
proximal cap [20]; inability to cross with a balloon
[65, 66]; lesion resistant to balloon dilatation “balloon
failure”; and lesion resistant to rotational atherectomy “rotablator failure” (as shown in Figure 22.4
which demonstrates the efficacy of excimer laser post
failure to recanalize a CTO by both balloon dilatation
and rotational atherectomy); resistant in-stent reste-
(b)
nosis (as shown in Figure22.5) and difficulty to track
other devices along the lesion. The laser is uniquely
capable of revascularization of CTO lesions laden
with fibrocalcific thrombotic layers [11] (described
in Table 22.5).
Ananthran and colleagues from the Katering
Hospital in the UK prospectively enrolled patients
undergoing CTO whereby the target lesion was successfully wired but balloon dilatation or microcatheter passage failed [67]. Their series included 27 acute
coronary syndrome patients (85% male) who underwent ELCA post the initial failure, whose mean age
+/− 11 years, and 33 % had systolic dysfunction.
was 69
All 27 procedures were successful and there were no
immediate in-hospital complications or MACE and 1
MACE occurred during 30 day follow up. The investigators concluded that ELCA supported CTO revascularization is a safe and efficient technique when the
target lesion is uncrossable by balloon or fails to conform to balloon dilatation. Similarly, Mohandes and
colleagues presented a series of 6 patients with CTO in
whom post successful wire crossing of the lesion
(d) (e) (f)
Figure 22.4 CTO of RCA: excimer laser performance post
balloon and rotational atherectomy failure. (a)
Rotablator failed to penetrate the lesion. Balloon
dilatation(b) failed as well (c). A 0.9mm X-80 laser
(d-arrow) was applied for debulking followed by a
1.4mm COS excimer laser that further expanded the
recanalization(e). After adjunct balloon dilatations and
stenting the target CTO and vessel were patent.
[Courtesy of Nelson Bernardo MD, FACC. MedStar
Washington Hospital Center, Washington, DC, USA]
196 PART IV Wires Technique
Figure 22.5 A patient with unstable angina secondary to
aggressive stent restenosis culminating in CTO of the LAD. a.
Occluded proximal LAD. b. 0.9mm Excimer laser performing
cross lesion debulking. c. Final angiogram with restoration of
TIMI 3 flow in the LAD without complications. d. Initial imaging
with OCT [Optical Coherence Tomography] of the in-stent
restenosis. e. OCT post laser debulking demonstrates marked
improvement of luminal diameter. Courtesy of Jan Pattanayak
MD, FACC and Scott Willis MD, FACC. Interventional Cardiology,
Mission Memorial Hospital, Asheville, NC.
CHAPTER 22 Laser Revascularization in Coronary CTO 197
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Figure 22.5 (Continued)
Table 22.5 CTO amenability to laser application.
Proximal cap impenetrable to guidewire
Balloon crossing failure
Lesion resistant to balloon dilatation “[balloon failure]”
Lesion resistant to rotational atherectomy “[rotablator failure”]
Resistant in-stent restenosis
Difficult tracking of other debulking devices
Occlusion containing severe fibrocalcific & thrombotic layers
Congenital heart defects exhibiting total vascular occlusion
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