Coronary intravascular lithotripsy/coronary lithotripsy

1. The Coronary Intravascular
Lithotripsy
SHOCKING THE CALCIUM

2. Introduction
• The amount of coronary artery calcification increases with
– age and
– the presence of cardiovascular risk factors and comorbidities.
• Up to 20% of percutaneous coronary intervention (PCI)
procedures are challenged by severe calcifications, and
coronary calcifications have been shown to be an
independent predictor of PCI failure and future adverse
cardiac events.
• Lesion calcification increases procedural complexity and time.
• More specifically, calcium localisation (superficial or deep),
distribution (focal, circumferential and longitudinal extension)
and thickness influence procedural success, stent delivery and
deployment.

3. • Coronary artery calcification (CAC) impacts on
interventional outcomes by
– impairing stent crossing,
– delaminating the drug-eluting polymer from the
stent, affecting drug delivery and elution kinetics,
– reducing stent expansion and apposition
• Similarly, calcified peripheral arterial disease
(PAD) adds to lesion complexity and is present
in 20% of revascularisation procedures.

4. • It has recently been described that a calcium
length greater than 5 mm, a thickness of greater
than 0.5 mm, and an arc greater than 180
degrees are associated with a higher risk of stent
underexpansion and are thus more likely to
benefit from plaque modification prior to stent
implantation.
• In concert with the progressive ageing of the
population, the frequency of severe coronary
calcification in patients undergoing PCI, currently
estimated to range between 18 and 26%, is likely
to grow.

5. • Several techniques to treat calcified lesions in native coronary
arteries are available
– high-pressure and super-high pressure non-compliant balloons,
– cutting/scoring balloons,
– atherectomy devices, both rotational and orbital, and
– excimer lasers.
• These devices
– rely on tissue compression and or tissue debulking, and
– have higher rates of procedural complications, such as dissections,
perforations and distal embolisation.
• Moreover, their success rate is reduced when deep, thick or
eccentric calcifications are present, and the induced tissue injury
might accelerate uncontrolled neointimal growth and restenosis.
• Balloon dilation, including by specialty balloons, may be of
insufficient force to lead to calcium fracture and vessel expansion.

6. • Rotational and orbital atherectomy may be biased by
the guidewire towards non-calcified segments of the
artery, resulting in ineffective ablation.
• Even when effective in facilitating stent delivery,
atherectomy may have a limited effect on deep
calcium, which restricts complete stent expansion and
vessel wall apposition.
• In addition, periprocedural PCI complications including
slow flow and periprocedural myocardial infarction
(MI) are still significantly higher with atherectomy than
traditional balloon-based therapies.

7. • The randomized controlled trials to compare
rotational atherectomy to standard therapy
before DES implantation, ROTAXUS (Rotational
Atherectomy Prior to Taxus Stent Treatment for
Complex Native Coronary Artery Disease) and
PREPARE-CALC (The Comparison of Strategies to
PREPARE Severely CALCified Coronary Lesions
Trial), failed to demonstrate a long-term clinical
benefit.
• So far, neither specialty balloons nor atherectomy
devices have been proved to be superior to high-
pressure non-compliant balloons in improving
clinical outcomes.

8. • Recently, an alternative way to disrupt calcium has
been developed that is based on the lithotripsy
concept used to treat kidney and ureteral stones.
• The Intravascular Lithotripsy (IVL) System (Shockwave
Medical) transforms electrical energy into mechanical
energy during low-pressure balloon inflation.
• The technology does not rely on direct vascular tissue
injury for plaque modification but on sonic waves,
which travel from the balloon-based catheter to the
surrounding tissue with the intention of safely and
selectively breaking both superficial and deep calcium
deposits with minimal soft tissue impairment, while
improving vessel compliance.

9. • In contrast to debulking techniques, the
calcium fragments resulting from the IVL
therapy remain in situ, reducing the likelihood
of distal embolisation.
• The safety and efficacy of the IVL with minimal
vessel injury was demonstrated in prospective
single-arm studies.

10. • IVL modifies calcific atherosclerotic lesions by
inducing calcium fracture before stent
deployment with the aim of facilitating drug-
eluting stent (DES) expansion and apposition.
• The second-generation coronary IVL catheter
(Shockwave Medical) is a single-use sterile
disposable catheter that contains multiple
lithotripsy emitters enclosed in an integrated
balloon.
The Coronary Intravascular Lithotripsy System

11. • The emitters create sonic pressure waves in the shape
of a sphere, creating a field effect on vascular calcium
circumferentially.
• These sonic pressure waves selectively disrupt and
fracture calcium in situ, altering vessel compliance,
while minimising injury and maintaining the integrity of
the fibro-elastic components of the vessel wall.
• Compared to contemporary non-compliant balloon
crossing profiles (0.033-0.035”), current coronary IVL
catheters have a modestly higher profile (0.043-
0.046”), similar to contemporary cutting balloons
(0.043”).

12. The System
• The Coronary IVL System
consists of
– a portable, rechargeable
generator,
– a connector cable with a
push button to allow
manually controlled delivery
of electric pulses, and
– a 6 Fr compatible, rapid-
exchange, semi-compliant
balloon catheter to be used
following standard
angioplasty practice over a
0.014" guidewire .

13. • The semi-compliant balloon integrates
– two radiopaque lithotripsy emitters 6 mm apart and
– two conventional markers at the proximal and distal edges of the
balloon.
• These emitters receive electrical pulses from the generator
vaporising the fluid (a standard mixture of 50% NaCl 0.9% and 50%
radiopaque contrast) within the balloon and creating a rapidly
expanding and collapsing bubble.
• This bubble can transmit unfocused circumferential pulsatile
mechanical energy into the vessel wall, in the form of sonic
pressure waves equivalent to approximately 50 atmospheres (atm).
• The balloons are available in diameters ranging from 2.5 mm to 4.0
mm with a standard length of 12 mm; their crossing profiles range
from 0.043" to 0.046"

15. Procedure
• The IVL catheter is connected via a connector cable to the
generator that is pre-programmed to deliver 10 pulses in
sequence at a frequency of 1 pulse/second for a maximum
of 80 pulses per catheter.
• The shockwave balloon must be sized accordingly to the
reference vessel diameter (ratio 1:1), placed in the target
calcified lesion and inflated up to 4 atm to ensure
apposition to the vessel wall; the lithotripsy emitters are
then activated to deliver the acoustic pulses by pushing the
button on the connector cable.
• If the IVL catheter is unable to pass into the lesion,
adjunctive therapies such as predilatation, buddy wire,
guide catheter extensions or atherectomy may be
performed.

16. • Once a cycle of 10 pulses has been delivered, the balloon
can be inflated up to 6 atm (nominal pressure) to increase
balloon compliance and to assess symmetrical expansion,
confirming calcium modification.
• Next, the balloon is deflated carefully to allow small air
bubbles to escape.
• The previous steps must be repeated for each intended IVL
cycle and at least two IVL cycles are recommended to treat
the target area.
• For the treatment of lesions longer than 12 mm, the
catheter needs to be repositioned and overlapping
treatment areas might occur.

17. • Due to the slightly higher profile of the shockwave catheter,
pre-dilatation with standard balloons might be necessary in
some cases to facilitate deliverability and positioning,
especially when lumen reduction is severe.
• Furthermore, although the system is labelled 6 Fr
compatible, it could be used with a 5 Fr guiding catheter
where the radial artery is small.
• The use of dilatation with non-compliant balloons after IVL,
although not mandatory, could be considered to expand
the lumen further.
• Moreover, aggressive plaque modification devices such as
cutting/ scoring balloons or atherectomy could be used as
adjuvant therapy in challenging lesions to improve results

18. • After coronary IVL is performed, intravascular
imaging may aid in the detection of the desired
calcium fracture within the target lesion.
• With IVUS, calcium fractures may be subtle,
identified as discrete separations across linear
luminal echogenicity.
• Due to its higher resolution, OCT is the technique
of choice to identify single or multiple partial or
full thickness calcium fractures.

21. Indications for the use of intravascular lithotripsy
• Coronary calcification noted on fluoroscopy or
noninvasive imaging (ie, computed tomography
coronary angiogram)
• Evidence of an undilatable lesion despite high-pressure
noncompliant balloon dilatation as lesion preparation
• Evidence of stent underexpansion, either
angiographically or on intravascular imaging
• Evidence of heavy calcification noted on intravascular
imaging, either optical coherence tomography or
intravascular ultrasonography

22. Advantages of IVL
• Compared with atherectomy or specialty balloons, IVL offers
several potential advantages.
1. Unlike atherectomy, IVL requires no specific training as the IVL
device is delivered similar to standard catheter-based PCI.
2. IVL therapy is balloon based, and, therefore, the risk of
atheromatous embolization may be lower than free debulking
devices. Accordingly, none of the patients in the Disrupt CAD I
& II, experienced slow-flow or no-reflow events, and the rate of
in-hospital MI was relatively low.
3. Plaque modification using IVL is not subject to guidewire bias;
instead, energy is distributed uniformly across the lithotripsy
emitter addressing calcium irrespective of its circumferential
location.

23. 4. Unlike traditional balloon technology, which is dependent on static
barometric pressure, IVL delivers circumferential ultrashort pulses
of high-intensity acoustic energy, which, by virtue of its
compressive and decompressive components, results in effective
circumferential modification of calcific atheroma.
5. In addition, whereas standard and specialty balloons are inflated
at high atmospheric pressure to modify calcium, IVL is typically
performed at low atmospheric pressure balloon inflation,
minimizing mechanical vascular trauma.
6. Side-branch protection using a guidewire may be easily performed
using IVL, without risk of wire entrapment or severing as may
occur with rotational or orbital atherectomy.
7. Lastly, in the DISRUPT CAD II study, IVL was highly effective,
achieving acute gain (1.67±0.49 mm) and residual stenosis
(7.8±7.1%) similar to that seen after DES of largely noncalcified
lesions.

24. Disadvantages of the IVL technology
• The intraballoon pulse-generating technology has
made the semicompliant balloon bulky and
difficult to deliver to the target lesion, which is
already troublesome in the setting of heavy
calcification. Therefore, supportive coronary
guidewires and guide extension catheters are
often used.
• May not be able to cross a lesion without the
need for atherectomy

25. Effects on Cardiac Rhythm
• Electric signals similar to pacing spikes on the
electrocardiogram (ECG) tracing during pulse-delivery have
been described.
• These so-called ‘shocktopics’ and asynchronous cardiac
pacing have been reported in up to 77.8% of the cases, with
a 16-fold increased risk in patients with a heart rate <65
BPM.
• Cardiac pacing has not been linked to any specific number
of IVL cycles or coronary artery anatomy, although its
frequency is higher when either the left anterior
descending artery or the right coronary artery are treated.

26. • The exact mechanism behind this phenomenon is still unclear.
• A potential explanation might be that the transformed
mechanical energy reaches and couples with the cardiac
conduction system producing ectopic atrial and or ventricular
captures.
• Although no relevant clinical events have been reported, it
warrants paying special attention to ECG and aortic pressure
waveforms changes during IVL administration; the resulting
VOO pacing mode is theoretically pro-arrhythmic (potential R
on T phenomenon) and, until further data become available,
pacemaker carriers should be assessed for inappropriate
device sensing during the IVL cycles and to ensure correct
pacing function post-procedure.
• Further investigation in the matter will be provided by the
substudies in the Disrupt CAD III trial.

27. CLINICAL OUTCOME AND SAFETY OF
CORONARY IVL

28. Disrupt CAD I
• A multicentre, prospective, single-arm study conducted
in seven centres in Europe and Australia, was the first
to assess the safety and efficacy of the Shockwave
Coronary IVL in 60 patients with severe (100%) calcified
lesions in native coronary arteries before drug-eluting
stent implantation.
• The balloon was successfully delivered in 59 patients
and stent implantation was successful in all cases, with
no major procedural complications, such as slow flow,
no reflow, distal embolisation or perforation reported.

29. • Device delivery was facilitated by pre-dilatation
with a small balloon in 37% of patients.
• Clinical success was 95%, defined as residual
diameter stenosis <50% without in-hospital major
cardiac adverse events (MACE; a composite of
death, MI and target vessel revascularisation) at
30 days.
• MACE at 6 months increased to 8.5% with three
non-Q wave MI events within the first 30 days
and two cardiac deaths.

30. • An optical coherence tomography sub-study in 31
patients in the Disrupt CAD I trial confirmed the effects
of IVL on the vessel wall.
• Calcium fractures were evident in 42.9% of the lesions
and multiple circumferential cracks in the same cross-
sectional area were witnessed in more than 25% of the
cases, with a higher incidence of fractures in heavier
calcified plaques.
• The presence of calcium ruptures allowed to increase
acute lumen gain (mean acute area gain = 2.1 mm2)
independently of the degree of calcification, enabling
successful stent implantation with uniform expansion.

31. • Coronary dissections (type B or greater) occurred in
four cases during angioplasty and were successfully
treated with stent implantation; no other procedural
complications were reported.
• This data provided the first results encouraging the use
of the Shockwave Coronary IVL for the treatment of
calcified lesions in the coronary vasculature.
• Following these findings, the device received European
CE mark approval in May 2017 for commercial use.

32. Safety and Effectiveness of Coronary
Intravascular Lithotripsy for Treatment of
Severely Calcified Coronary Stenoses
The Disrupt CAD II Study
• The Disrupt CAD II study was a prospective multicenter, single-
arm post-approval study to confirm the safety and effectiveness
of IVL for severe coronary artery calcification (CAC) lesions.
• Severe CAC was present in 94.2% of lesions.
• Successful delivery and use of the IVL catheter was achieved in
all patients.
• The post-IVL angiographic acute luminal gain was 0.83±0.47
mm, and residual stenosis was 32.7±10.4%, which further
decreased to 7.8±7.1% after drug-eluting stent implantation.

33. • The primary end point was in-hospital major
adverse cardiac events (cardiac death, myocardial
infarction, or target vessel revascularization) -
occurred in 5.8% of patients, consisting of 7 non–
Q-wave myocardial infarctions.
• There was no procedural abrupt closure, slow or
no reflow, or perforations.
• In 47 patients with post-percutaneous coronary
intervention optical coherence tomography,
calcium fracture was identified in 78.7% of
lesions with 3.4±2.6 fractures per lesion,
measuring 5.5±5.0 mm in length.

34. • The major findings of DISRUPT CAD II are as follows:
1. IVL was a feasible frontline tool for CAC plaque modification,
with the IVL catheter crossing the lesion and delivering therapy
in all cases;
2. IVL was highly effective, facilitating delivery of stents in all
cases and reducing stenosis in severely calcified coronary
arteries to a residual of <8% with an acute gain of 1.67 mm;
3. IVL was safe, with no reported type D to F dissections,
perforations, abrupt closure, or slow flow/no reflow and 5.8%
in-hospital and 7.6% 30-day rates of MACE in this high-risk
group; and
4. the IVL mechanism of action was shown to be intraplaque
calcium fracture, thereby modifying vascular compliance and
facilitating stent expansion.

35. Potential Uses

36. Acute Coronary Syndromes
• Calcified lesions in culprit vessels are common in patients
presenting with acute coronary syndromes (moderate
calcification is found 26.1% of these patients and severe
calcification in 5.9%).
• Their presence is a strong predictor of definite stent
thrombosis and target lesion revascularisation.
• The Disrupt CAD study included only patients with stable
and unstable angina. Although there is not enough
evidence to support the use of the IVL during primary PCI,
early experience has shown favourable results.
– Wong B, El-Jack S, Newcombe R, et al. Shockwave intravascular lithotripsy of
calcified coronary lesions in ST-elevation myocardial infarction: first-in-man
experience. J Invasive Cardiol 2019;31:E73–5. PMID: 31034437

37. Unprotected Left Main Calcified Stenosis
• PCI has become an option for the treatment of left
main (LM) disease, with a class IA recommendation for
patients with a SYNTAX score ≤22 and class IIA for a
SYNTAX score 23–32.
• Calcification increases procedural complexity and
therefore the risk of complications.
• The Coronary IVL System, with controlled pulses
delivered under low pressure, might potentially
improve plaque modification with a lower risk of vessel
closure, perforation or embolisation.

38. • In the presence of a calcified left main lesion,IVL
modifies coronary calcification, unlike noncompliant
balloon dilatation, restoring vessel compliance,
increasing stent expansion, and achieving better stent
artery apposition.
• Compared with atherectomy, IVL allows the
maintenance of additional coronary guidewires to
allow simultaneous access to the separate daughter
vessels, avoiding the risk of acute vessel closure
leading to periprocedural myocardial infarction.

39. Chronic Total Occlusions
• Moderate to severe calcification is frequently
found in chronic total occlusions, and debulking
devices are usually avoided because the
procedure is difficult and has a high risk of
complications; where standard balloons fail, the
Coronary IVL System might be useful in
facilitating lumen dilatation and communication
with the subintimal space.
– Azzalini L, Bellini B, Montorfano M, Carlino M. Intravascular
lithotripsy in chronic total occlusion percutaneous coronary
intervention. EuroIntervention. 2019. https://doi.org/10.4244/EIJ-
D-19-00175; PMID: 31012852; epub ahead of press.

40. Stent Underexpansion due to Underlying
Calcification
• Although the technique has been developed to treat
calcified lesions in native coronary arteries before
stenting, patients with severe stent underexpansion
because of heavy calcification are at a higher risk of
stent failure and future adverse events.
• Until now, undilatable lesions in previously stented
segments have been courageously approached with
debulking devices such as cutting balloons and
atherectomy, with unpredictable results and risks of
procedural complications and stent damage.

41. • Of note, the effectiveness of those techniques is
limited by the presence of metallic struts, and
deeper calcifications therefore remain
unaffected.
• Conversely, the circumferential sonic waves of the
Coronary IVL System, have the advantage of
extending beyond strut layers and fracture
deeper calcium deposits.
• Several case reports have supported the use of
the technology for optimising stent expansion
without complications.

42. • The efficacy of the system in segments with
multiple layers of stents has not been
demonstrated and its impact on stent
backbone/ polymer integrity and drug elution
is still unknown.
• Nonetheless, at present, there are no
alternative percutaneous options for patients
left with underexpanded stents due to heavy
calcification.

43. Challenging Lesions
• Some lesions might respond better to IVL
therapy than to other plaque modification
approaches.
• Reports have pointed out the usefulness of
the IVL therapy on creating calcium fractures
as assessed with intravascular ultrasound, and
achieving optimal stent expansion in
undilatable lesions that have been resistant to
specialty balloons and rotational atherectomy

44. • In contrast, some lesions might not be suitable for IVL
treatment or may remain resistant after the application of
all 80 pulses.
• Severe tortuosity or angulation, critical lumen reduction,
plaque indentation into the lumen and a very low vessel
expansion compliance (small vessels and multiple stent
layers present), could impact balloon deliverability and
positioning.
• Up to 46% of the lesions might also require dedicated
lesion pre-dilatation and/or post-dilatation with non-
compliant balloons or could benefit from adjuvant lesion
preparation with conventional devices such as specialty
balloons or atherectomy to either facilitate balloon delivery
or increase calcium compliance after lithotripsy therapy.

45. • While balloon rupture is uncommon, it can
cause vessel complications.
• Case reports have described sudden IVL
balloon burst during lithotripsy therapy with
important vessel dissection; however, it is fair
to highlight that either critical stenosis or
severe vessel tortuosity were present, which
suggests that, in some anatomies, the IVL
system might not be suitable or should be
used with caution.

46. • Furthermore, vessels with a diameter >4 mm
(maximum shockwave balloon size) or important
plaque eccentricity preclude appropriate IVL
balloon apposition to the vessel wall, and may
reduce the efficacy of the therapy.
• More data are needed on the specific efficacy of
IVL in concentric versus eccentric lesions.
• In the Disrupt CAD study, 22% of the patients had
eccentric plaques; nevertheless, overall device
success was 98%.

47. • Moreover, performing intracoronary imaging
where important coronary calcification is
suspected during the angiographic assessment
could help to accurately assess calcium
distribution, localisation and thickness.
• The use of intracoronary imaging before and after
lithotripsy therapy could not only assist the
appropriate selection of IVL balloon sizes but also
potentially help to identify IVL responders and
identify patients who might need adjuvant
therapy from other plaque-modification devices.

48. Calcific peripheral stenoses
• In patients with peripheral artery diseases, the presence of
calcifications is associated with higher critical limb
ischaemia, Rutherford class and risk of distal amputation.
• Percutaneous transluminal angioplasty (PTA) with
conventional balloons in severe peripheral artery
calcification has low efficacy because of suboptimal vessel
expansion, acute recoil and extensive vascular injury,
potentially causing long dissections requiring stent
implantation, or even vessel perforation.
• Drug-coated balloons (DCB) have been tested to overcome
the limitations of traditional angioplasty and stents, with
good acute results in terms of efficacy and safety and
durable vessel patency with low incidence of target lesion
revascularization.

49. Peripheral IVL may be used for the treatment of
moderate-severe calcific lesions in different sites with
a variety of indications
• Calcific stenoses often exist in the iliac and femoral arteries,
where large bore access may need to be inserted, such as
for transcatheter aortic valve implantation (TAVI),
transcatheter endovascular aneurysm repair and/or
mechanical circulatory support.
– The frequent co-existence of severe calcification and tortuosity
in patients with these conditions makes them suitable
candidates for IVL therapy.
– IVL will disrupt calcium and modify vessel compliance, allowing
the creation of a sufficiently large lumen to negotiate large bore
sheaths, facilitating device passage through calcific lesions.
Thus, IVL offers a new alternative to traditional high-pressure
dilatation or expandable/re-collapsible sheaths

50. • Calcific femoropopliteal lesions in patients with
symptomatic claudication or critical limb ischaemia.
– In this setting, IVL may overcome recoil and balloon
underexpansion, achieving sufficient lumen enlargement
to reduce the incidence of flow-limiting dissections, and
need for provisional stenting.
• Calcific small peripheral artery below the knee (BTK)
lesions in patients with symptomatic claudication or
critical ischaemia.
– IVL in BTK lesions obtained high procedural success and an
excellent safety profile as stand-alone treatment, unlike
traditional devices used in BTK arteries that are burdened
by a high rate of recoil and restenosis

51. • The IVL system components for use in the
peripheral circulation are the same as those
described for the coronary artery.
• Balloons designed for BTK and above the knee
peripheral arteries are
– longer (40 mm, 60 mm),
– have a higher crossing profile (0.045”-0.050”, 0.054”-
0.066”),
– have more emitters (five),
– have a longer duration of energy (20 seconds, 30
seconds) and a greater number of pulses per balloon
(160, 300).

52. Technical features of the intravascular lithotripsy system

53. Clinical outcome of peripheral
lithotripsy
• Disrupt PAD I/II are two multicentre single-arm
registries, conducted in 95 patients symptomatic
for intermittent claudication (Rutherford Class 2-
4) and ankle-brachial index (ABI) <0.90, with
angiographically calcific femoropopliteal lesions
with diameter stenoses ≥70% (average lesion
length 61.5 mm) and at least one patent run-off
vessel to the foot.
• Severe calcification using the PARC definition was
identified in 85.0% of subjects.

54. • Procedural success (<50% residual DS) was achieved in all
95 patients, with a mean acute gain of 3.0 mm (from
1.2±0.8 mm to 4.2±0.6 mm), and a reduction of percent
diameter stenosis from 76% to 23%.
• Furthermore, at one- and six-month follow-up there was no
TLR with vessel patency rates of 100% and 82%,
respectively.
• In the sixty patients followed up to 12 months, primary
patency was 54%, and clinically driven TLR 21%.
• These angiographic results paralleled a consistent
improvement in Rutherford classification (100% in Class 2-3
at index down to 9.5% Class 2 and 0% Class 3 at six months)
and ABI (0.7±0.2 to 1.0±0.3).

55. • In a Disrupt PAD II subgroup analysis, optimal balloon
sizing (1.1:1 balloon to reference vessel diameter) and
full coverage of lesion length were associated with 63%
patency and a reduction in the rate of clinically driven
TLR to 8.6% at 12 months.
• Peripheral IVL was safe, with major adverse events
(one type D dissection requiring stent implantation
which was from guidewire re-entry during a CTO
recanalisation) occurring in 1.5% of patients without
target limb emergency surgical revascularisation, major
amputation, thrombus or distal emboli requiring
treatment, vessel perforation or abrupt vessel closure.
• The rate of non-flow-limiting dissection was also low.

56. • Recent results from the Disrupt BTK study were
reported in 20 patients, Rutherford Class 3-5 (16
patients with critical limb ischaemia) with heavily
calcific infrapopliteal lesions (angiographic stenosis
72.6%, mean lesion length 52.2±35.8 mm).
• Procedural success was achieved in 95% of patients
with a residual percent stenosis of 26.2% and an acute
lumen gain of 1.5±0.5 mm.
• Two stents were implanted for residual stenosis but
none for flow-limiting arterial dissection (only one
grade B dissection reported), without major adverse
events.

57. Ongoing trials
• Disrupt PAD III is a prospective, randomised,
multicentre, study comparing IVL with DCB versus
PTA with DCB in 400 patients with
femoropopliteal lesions followed for 24 months.
• The study also includes a 1,000- patient all-comer
registry to assess real-world, acute performance
of IVL in the lower extremities, including iliac,
femoral, popliteal and infrapopliteal lesions.

58. DISRUPT CAD III
• A prospective, multicenter, single-arm, global
investigational device exemption (IDE) study
to evaluate the safety and effectiveness of the
Shockwave Coronary IVL System.
• The goal of this study is to generate the data
needed to obtain FDA approval for use of
coronary IVL in the United States

59. Future Prospects For Intervascular Lithotripsy
• The shockwave intravascular lithotripsy is an
innovative approach for treating severely calcified
lesions with PCI.
• Initial clinical experience using IVL, for lesion
preparation in real-world patients with severely
calcified lesions, has been promising and resulted
in excellent final angiographic and OCT results.
• Moreover, OCT imaging demonstrated that IVL
was effective in cracking the thick (more than 180
degree) calcium burden.

60. • IVL has the potential to be a permanent fixture in
cardiac catheterization laboratories throughout the
world, especially with an aging population who
progressive exhibit higher prevalence of calcified
lesions.
• Furthermore, its ease of use (delivering a balloon to
the lesion on any 0.014-inch guidewire), short learning
curve and less procedural complications could facilitate
rapid uptake.
• However, this is dependent on further studies
demonstrating outcomes in patients, including
comparisons with existing technologies.

61. LASERS IN CARDIOLOGY

62. Introduction
• When laser radiation interacts with tissue, there are
several potential results.
• The light can be absorbed and then reemitted at a
longer wavelength in the form of fluorescence.
Alternatively, the light can be absorbed and converted
to heat with a resultant rise in the tissue temperature.
• As this tissue heating continues, an ablation threshold
may be reached, at which point the tissue (and tissue
water) undergo vaporization.

63. • Alternatively, it is possible that light absorption
could result in direct bond breaking, resulting in
photochemical tissue ablation.
• All of these potential laser interactions with
tissue have been exploited to develop
cardiovascular applications of laser technology.
• Lasers have been used to induce fluorescence, to
heat biomaterials, and to ablate tissue in the
cardiovascular system.

64. • Laser technology has been evaluated for the
treatment of coronary artery disease,
ventricular and supraventricular arrhythmias,
hypertrophic cardiomyopathy, and congenital
heart disease.
• In most applications, laser radiation has been
used to ablate the abnormal and disease-
causing cardiovascular tissue.

65. • Currently lasers are approved by the United States
Food and Drug Administration for use in the arteries to
improve blood flow by:
– removal of plaque and thrombus (clots formed from
plaque rupture) from certain areas of the arteries (i.e.
Saphenous vein grafts, ostial lesions, long lesions, inside
stents) (Ben-Dor et al. , 2011); and
– to create channels between the epicardial and endocardial
surfaces to reduce angina (chest pain and discomfort
caused by lack of blood flow to the heart muscle).
• Additionally, researchers are studying how to use lasers
to better diagnose and treat arterial diseases,
particularly because currently there are no clinical
techniques to predict risk of plaque rupture.

66. • The major application, that has received FDA
approval in the United States, has been laser
angioplasty, or the use of laser radiation to
vaporize obstructing atherosclerotic plaque.
• Lasers have also been evaluated for ablation of
thrombus and for photoactivating drugs that may
inhibit restenosis following angioplasty.
• A more revolutionary approach to the treatment
of coronary artery disease has been the use of
laser radiation to vaporize multiple transmural
channels in the ventricular myocardium to
improve local perfusion.

67. • Laser ablative approaches have been used to ablate
ventricular foci responsible for arrhythmias and to
ablate supraventricular tachyarrhythmia pathways.
• Ablation of the abnormally thickened septum in
idiopathic hypertrophic subaortic stenosis (IHSS) has
also been performed using laser radiation.
• Laser-induced fluorescence spectroscopy has been
used to differentiate normal and atherosclerotic tissue,
as well as to assess myocardial metabolism based on
NADH fluorimetry.

68. LASER ANGIOPLASTY
• The ability of laser energy to vaporize
atherosclerotic plaque was first demonstrated in
1963 by McGuff and colleagues.
• The first intravascular recanalization using lasers
was reported by Choy who used argon laser
radiation for thrombolysis in animals.
• In 1983, Choy performed the first clinical
coronary laser angioplasty using an argon laser
and bare fiber intraoperatively.

69. • Concerns regarding laser thermal damage as witnessed
with laser thermal angioplasty resulted in the development
of pulsed laser angioplasty systems.
• Continuous wave laser radiation, such as that emitted by
the argon, Nd:YAG, or CO2 lasers, will vaporize tissue with
thermal damage to the adjacent tissue.
• In contrast, delivery of laser energy in the pulsed mode
eliminates gross and microscopic evidence of thermal
injury.
• Linsker reported the use of far ultraviolet (193 nm)
irradiation from excimer laser to vaporize atherosclerotic
lesions without apparent thermal damage in vitro.

70. • In 1988, Wollenek reported the first
percutaneous laser angioplasty performed
with an excimer laser coupled to a 1-mm
diameter single optical filter for recanalization
of a femoral artery occlusion.
• Also in 1988, Litvack et al. reported the first
percutaneous coronary angioplasty performed
with a pulsed excimer laser coupled to a
multifiber catheter

71. Excimer Laser Coronary Atherectomy
• Excimer lasers are pulsed gas lasers that use a
mixture of a rare gas and halogen as an active
medium to generate pulses of short wavelength,
high-energy ultraviolet (UV) light.
• The depth of laser penetration is directly related
to its wavelength, with UV laser (shorter
wavelength) having less depth of penetration,
less heat production and less unwanted tissue
damage.

72. • Excimer laser tissue ablation is mediated through three
distinct mechanisms: photochemical, photo-thermal
and photomechanical.
• UV laser light is absorbed by intra-vascular material
and breaks carbon–carbon bonds (photochemical).
• It elevates the temperature of intra-cellular water,
causing cellular rupture and generates a vapour bubble
at the catheter tip (photo-thermal).
• Expansion and implosion of these bubbles disrupts the
obstructive intra-vascular material (photomechanical).

73. • The threshold energy required for the
penetration of UV light into tissue and the
creation of a steam bubble is called ‘fluence’
(range:30–80 mJ/mm2).
• The number of pulses emitted during a 1–second
period is the ‘pulse repetition rate’.
• The duration of each pulse is termed a ‘pulse
width’, which is modified according to the nature
of the treated lesion for example fibro-calcific
lesions require higher fluence and repletion rate
for effective ablation.

74. Excimer Laser Equipment and General Technique
• The CVX-300 cardiovascular laser Excimer system
uses Xenon chloride (XeCl) as the active medium.
• The light emitted has a wavelength of 308 nm (in
the UVB spectrum) with a tissue penetration
depth between 30–0 μm.
• It is the only coronary laser-emitting device
currently approved by the US Food and Drug
Administration.

75. • It is essential that safety procedures should be
observed when performing laser atherectomy.
• Prior to activation, all persons in the catheter lab,
including the patient, must wear protective tinted
spectacles to minimise the risk of retinal exposure to
the UV light.
• All windows should be covered and doors locked.
• Even when the catheter is in vivo, all staff in the vicinity
should weareye protection in case the catheter housing
breaks, which could release UV light.

76. • ELCA catheters are advanced on a short monorail segment,
compatible with any standard 0.014-inch Q2 guidewire.
• This is a major advantage over alternative coronary atherectomy
techniques that require dedicated guidewires that are often more
difficult to deliver distally.
• Coronary catheters are available in four diameters (0.9, 1.4, 1.7, 2.0
mm and those most commonly used have a concentric array of
laser fibres at the tip.
• The laser fibres of eccentric laser catheters are focused toward one
hemisphere.
• These devices are primarily used for eccentric lesions or for
extensive debulking of in-stent restenosis (ISR).

77. • The larger diameter laser catheters (1.7, 2.0 mm) are
primarily used in straight sections of vessels with a diameter
>3.0 mm and require 7F and 8F guide catheters,
respectively.
• The 0.9- and 1.4-mm devices are used via a 6F guiding
system.
• Laser catheter size selection is primarily based on:
– (a) the severity of the lesion;
– (b) the reference vessel diameter and;
– (c) consistency of the target material.
• The 0.9-mm X80 catheter is used in non-crossable, non-
dilatable fibrocalcific lesions, due to its enhanced delivery
and ability to emit laser energy at high power (80 mJ/mm2)
at the highest repletion rate (80 Hz).

78. Saline Infusion Technique
• Both blood and iodinated contrast media contain non-
aqueous cellular macromolecules, such as proteins.
• These macromolecules absorb the majority of delivered
Excimer laser energy creating cavitating micro bubbles at
the site of energy delivery, increasing the likelihood of
traumatic dissection.
• By contrast, saline permits passage of light from the
catheter tip to the tissue without any interference so no
microbubbles are formed in this milieu.
• Therefore, a saline flush/infusion technique is used to
safely control energy delivery and minimise dissection risk.

79. • To clear blood from the catheter–tissue interface, a 1-l
bag of 0.9 % saline solution is connected to the
manifold via a three-way tap, and a clean 20-ml Luer-
Lok™ (Becton Dickinson) syringe replaces the contrast
syringe.
• Once the system has been purged of contrast,
confirmed by screening, 5 ml of saline solution should
be infused followed by continued injection – at a rate
of 1–2 ml/second – throughout laser activation.
• The guide catheter should be well intubated and
coaxial within the artery, ensuring saline delivery to the
catheter tip.

80. • For the standard coronary catheters activation
will automatically cease after 5 seconds with a
10-second rest period.
• An audible alarm sounds at the end of the rest
period to signal when to commence the next
laser train.
• The 0.9-mm X80 catheter permits 10 seconds
activation and 5 seconds rest, reflecting its use in
more complex lesions.

81. • The pulses of laser energy are delivered as the
catheter is slowly (0.5 mm/second) advanced
through the lesion, allowing adequate absorption
and ablation.
• If the catheter is advanced too rapidly the tissue
does not have time to absorb the light energy
and ablation will be sub-optimal.
• On completion of several anterograde trains,
retrograde lasing can be performed, particularly
in severe lesions when there is anterograde
resistance.

82. Contraindications and Avoiding Complications
• Other than unprotected left main disease (a relative
contraindication) there are no absolute coronary
contraindications for ELCA.
• ELCA complications are similar to those encountered
during routine PCI.
• Specific issues may arise from interruption of the saline
flush or contamination with contrast, which can generate
excessive heat and increase the risk of vascular
perforation.
• ELCA is not recommended when the operator is aware
that there is a long length of sub-intimal guidewire
positioning as may exist during hybrid PCI techniques for
chronic total occlusions (CTOs).

83. Clinical Indications for Excimer
Laser Coronary Atherectomy

84. Acute Coronary Syndromes & Myocardial
Infarction
• ELCA may be a beneficial given its potential for
effective thrombus removal, promotion of
fibrinolysis, platelet stunning effects and
concomitant plaque debulking.
• However, clinical data supporting the use of
ELCA in AMI remain limited.

85. • The largest study to date, the Cohort of Acute
Revascularization of Myocardial infarction with Excimer
Laser (CARMEL) multicentre registry, enrolled 151 AMI
patients, 65 % of whom had large thrombus burden in the
culprit artery.
• Following ELCA, Thrombolysis In Myocardial Infarction
(TIMI) flow grade was significantly increased (1.2 to 2.8),
with an associated reduction in angiographic stenosis (83 to
52 %).
• There was a low rate (8.6 %) of major adverse coronary
events (MACE).
• The maximal effect was observed in arteries with a large
angiographic thrombus burden.

86. • A single randomised trial, the Laser AMI study included
66 patients and sought to demonstrate safety and
feasibility.
• They used optimal lasing technique (saline flushing
with slow advancement [0.2–0.5 mm/second]) using
the CVX-300 Excimer laser system and treated the
majority of lesions with a laser-stent strategy (only two
patients required balloon angioplasty prior to stenting).
• Primary angiographic endpoints were myocardial blush
grade, TIMI flow and length-adjusted TIMI frame count.
The TIMI score increased from 0.2±0.4 at baseline to
2.65±0.5 post-laser to 2.9±0.3 post-stent (both p<0.01
versus baseline).

87. • Similarly, myocardial blush grade increased from
0.12±0.4 to 2.5±0.6 post-laser, and to 2.8±0.4
post-stent.
• No reflow was observed in 11 % of cases after
laser and a major dissection occurred in one case.
• There were no intraprocedural deaths and 95 %
event-free survival at 6 months with LV
remodelling occurring in 8 % patients.

88. Excimer Laser Coronary Atherectomy for Non-
crossable/Non-dilatable Lesions
• Balloon failure occurs when a lesion cannot be crossed with
a low-profile device, or when the balloon inadequately
expands with dilatation.
• This is a situation where ELCA may be applied, with a high
success rate in un-crossable or un-dilatable stenoses.
• However, in cases of significant calcification, the response is
less favourable (calcified 79 % versus non-calcified 96 %;
p<0.05).
• This is because the ablative effects of ELCA on calcium are
minimal and success relies on the ablation of more pliable
tissue within the calcific lesion, which will vary accordingly.

89. • In heavily calcified coronary lesions the default technique
for the majority of PCI operators remains rotational
atherectomy (RA), even among proficient ELCA users.
• RA requires delivery of a dedicated 0.009-inch guidewire
(Rotawire™) into the distal coronary vessel.
• This wire is less deliverable directly, and it may not be
possible either independently or through a micro-catheter.
• When this situation arises, ELCA can be used to modify the
lesion to create a channel through which a Rotawire™ can
subsequently be delivered distally (usually via a
microcatheter), to permit RA and case completion.

90. • This technique of combination of ELCA and RA was
termed as the RASER technique.
• This combined use of atherectomy devices is
particularly effective for non-crossable, non-dilatable
calcified stenosis frequently encountered in daily PCI
practice.
• The outcome is predictable and is associated with a
low complication rate in experienced hands.
– Fernandez JP, Hobson AR, McKenzie D, et al. Beyond the balloon: excimer
coronary laser atherectomy used alone or in combination with rotational
atherectomy in the treatment of chronic total occlusions, non-crossable and
nonexpansible coronary lesions. EuroIntervention 2013;9:243–50
– Fernandez JP, Hobson AR, McKenzie D, et al. Treatment of calcific coronary
stenosis with the use of excimer laser coronary atherectomy and rotational
atherectomy. Int Card 2010;2:801–06

91. Excimer Laser Coronary Atherectomy for
Chronic Total Occlusions
• The role of ELCA in the treatment of CTOs is for
resistant lesions: when equipment is unable to cross
the lesion or proximal cap despite attaining distal wire
position.
• It may also offer additional benefits as its ablative
effect is transmitted through the lesion architecture,
potentially weakening bonds between the constituent
components of the CTO.
• In addition, the antithrombotic and platelet-
suppressive effects of ELCA may reduce the risk of
thrombotic complications during disobilteration.

92. • A success rate of 86–90 % for ELCA in CTO cases
has been reported.
– Topaz O. Laser for total occlusion recanalization. In: Waksman R,
Saito S (editors). Chronic Total Occlusions: A Guide to Recalization.
Hoboken, NJ: Wiley-Blackwell, 2009
• From a technical perspective, saline is often not
used at the laser–lesion interface for CTO cases as
anterograde injections are usually avoided to
prevent extending areas of dissection.
• In addition, it is unlikely that saline would reach
the laser–tissue interface.

93. Excimer Laser Coronary Atherectomy in
Underexpanded Stents
• Stent under-expansion poses a significant risk for stent thrombosis.
• There are few PCI options available when this occurs. Maximal
balloon dilatation (both diameter and pressure) has often already
been undertaken, and RA risks metal fragment embolisation and
burr stalling.
• ELCA can modify the underlying resistant atheroma by delivering
energy to the abluminal stent surface without disrupting the stent
architecture.
• While having no impact on the calcification itself, ELCA modifies the
plaque behind the stent, which weakens the overall resistance, thus
enabling subsequent complete stent expansion.

94. • It has been found that delivering high power laser
energy (80 mJ/mm2/80 Hz), using the 0.9-mm
X80 catheter in the absence of saline, or with
contrast injection, amplifies the ablative effect.
• Within a stented environment ‘contrast-mileu’
lasing appears to be safe, facilitating high-
pressure balloon stent expansion.
– Egred M. A novel approach for under-expanded stent:excimer
laser in contrast medium. J Invasive Cardiol 2012;24:E161–E163.
PMID: 22865316
– Lam SC, Bertog S, Sievert H. Excimer laser in management of
underexpansion of a newly deployed coronary stent. Catheter
Cardiovasc Interv 2014;83:E64–8

95. • This technique has been evaluated in the
ELLEMENT registry of 28 patients.
• Procedural success was achieved in 96.4 %
(27/28) of cases, using an increase of either 1
cm2 on intravenous ultrasound (IVUS) or 10 %
using quantitative coronary angiography derived
minimal stent diameter as a definition.
• This confirmed efficacy, with a low associated
MACE rate.

96. In-stent Restenosis
• ELCA is a safe and effective technique in the
treatment of ISR.
• Excimer laser did not alter stainless-steel stent
endurance or liberate any significant material
when five types of stainless-steel stents were
subjected to 1,000 pulses of laser energy from a
2.0-mm eccentric Excimer laser catheter.
– Burris N, Lippincott RA, Elfe A, et al. Effects of 308 nanometer
excimer laser energy on 316 L stainless-steel stents: implications
for laser atherectomy of in-stent restenosis. J Invasive Cardiol
2000;12:555–9

97. • In a clinical study, the examination of 107 re-
stentoic lesions in 98 patients demonstrated
that lesions treated with ELCA compared with
balloon angioplasty alone, had a greater IVUS
cross-sectional area and luminal gain, with
more intimal hyperplasia ablation.
– Mehran R, Mintz GS, Satler LF, et al. Treatment of in-stent
restenosis with excimer laser coronary angioplasty:
mechanisms and results compared with PTCA alone.
Circulation 1997;96:2183–9. PMID: 9337188

98. • ELCA was found to be effective as an atherectomy device
for lumen enlargement and optimal lesion preparation.
• Even though ELCA for ISR of DES was used in significantly
more complex lesions, the long-term clinical outcomes
were favorable.
• This study had several potential limitations, such as the
absence of randomization to the treatment strategy, the
small number of intravascular imaging used, and the
retrospective nature of the study.

99. • The major findings were as follows:
– ELCA created more calcium fractures even if the calcium was thicker,
and this effect was more pronounced with contrast flush.
– ELCA resulted in larger final lumen dimensions and better stent
expansion compared with high-pressure balloon dilation alone.
– ELCA use to treat ISR due to peri-stent calcium-related stent
underexpansion was associated with better acute outcomes (larger
lumen and stent area).
– Lesions treated using ELCA had more fracture of peri-stent calcium
detected by OCT, especially using ELCA with contrast flush.

100. • This study compared the results of neointimal
modification before drug-coated balloon (DCB)
treatment with excimer laser coronary
atherectomy (ELCA) plus scoring balloon
predilation versus scoring balloon alone in
patients presenting with instent restenosis (ISR).

101. • The major findings of this study are
– Although there was significantly greater frequency of diffuse
restenosis and percent diameter stenosis (%DS) after
intervention in the ELCA group, comparable result was shown in
%DS, late lumen loss, and binary angiographic restenosis at
follow-up.
– On OCT analysis, a decreased tendency in the minimum lumen
area and a significant decrease in the minimum stent area were
observed in the ELCA group between 6-month follow-up and
after intervention
– The changes in the neointimal area were similar between the
groups, and target lesion revascularization showed comparable
rates at 1 year.
• Conclusions: Despite greater %DS after intervention, ELCA
before DCB had possible benefit for late angiographic and
clinical outcome

102. Saphenous Vein Grafts
• Occlusions in old saphenous vein grafts (SVGs) frequently
consist of degenerative diffuse plaques often containing
thrombus and prone to distal embolisation.
• Hence, distal protection devices (DPDs) are advocated
when attempting SVG-PCI, but their bulky nature may
prevent distal device delivery.
• ELCA is a safer alternative, allowing predictable debulking
during SVG-PCI.
• The low rate of distal embolisation duringELCA of
degenerative bypass grafts (1–5 %) may preclude the need
for routine DPD in the majority of cases.

103. • However, OCT images post-SVG ELCA make it is clear
that there remains friable fragments that could
embolise and cause no-reflow.
• Therefore, when using ELCA for SVGPCI, it is advisable
to stent on a DPD system to prevent no-reflow.
• Given advances in CTO success in recent years, SVG-PCI
is likely to be less frequently undertaken as operators
choose to treat the occluded native vessel.
• Nonetheless, if SVG-PCI is considered necessary, ELCA
remains a useful adjunctive therapeutic intervention.

104. • This study demonstrated that Excimer laser atherectomy of
diseased SVGs is feasible with results comparable to the 30-
day MACE in the control population from the SAFER trial.
• Whether the addition of laser to embolic protection
devices is of any clinical utility remains to be tested in
future studies

105. Bifurcations
• Generally PCI for coronary bifurcation lesions is best
treated with a main vessel (MV)-only stenting approach
with preservation of side branch (SB), rather than an
upstream two-stent strategy.
• However, in large vessels involving extensive side
branch disease it may be necessary to stent side branch
as well.
• ELCA could potentially be of value in these cases by
debulking the side branch lesion to permit more
predictable success with the MV-only approach.

106. Lesion Selection
• ELCA has been approved for seven lesion
types—
– long lesions,
– moderately calcified lesions,
– ISR before brachytherapy,
– saphenous vein graft lesions,
– ostial lesions,
– total occlusions,
– undilatable lesions

107. Complications of ELCA
• Periprocedural myocardial infarction due to abrupt closure,
coronary spasm
• Dissection-
– In one series, 5.5% of patients undergoing ELCA showed
evidence of significant dissection that impaired flow, resulted in
myocardial infarction, or required bypass surgery.
– Overall incidence of excimer laser induced dissections has been
reported to be 13-16% angiographically
• Vessel perforation has been reported to occur in 1-3% of
cases.
• Coronary artery aneurysm formation has been rarely
reported following excimer laser angioplasty.

108. Transmyocardial laser revascularization
• Transmyocardial laser revascularization (TMLR) is a
technique that uses laser ablation to create transmural
channels in the ischemic myocardium in order to
restore myocardial perfusion.
• It shows promise in patients who have angina that is
refractory to medical therapy and who are not
candidates for surgery or angioplasty.
• It has also been used as an adjunctive therapy with
minimally invasive coronary artery bypass graft surgery
to achieve more complete revascularization.

110. • Animal studies have shown that TMLR reduces
infarct size and preserves myocardial function
after an infarction.
• However, despite United States Food and Drug
Administration (FDA) approval of some of the
laser devices for treatment of intractable
angina, these techniques are in the early
stages of their development; while they offer
much promise, there is substantial risk
associated with their use.

111. Mechanism of effect
• The physiologic premise behind the application of TMLR is based
upon the work of early investigators who were seeking to emulate
reptilian circulation in the mammalian heart by creating direct
conduits for blood flow from the left ventricular cavity into the
myocardium.
• Development of the clinical high power CO2, holmium:yttrium-
aluminum garnet, and excimer laser systems led to FDA approval of
laser myocardial revascularization as a stand-alone therapy in
patients with intractable angina.
• This decision was based upon the demonstration of significant
reduction in anginal symptoms as assessed by angina class scale
and improvement in exercise capacity. However, there has been
little objective evidence of improvements in myocardial perfusion
as assessed by nuclear perfusion imaging.

112. • The mechanism of the observed clinical
benefit, ie, reduction in symptom intensity,
following TMLR remains uncertain. A number
of possibilities have been proposed to explain
these results
– Myocardial angiogenesis resulting from the
upregulation and release of vascular endothelial
growth factors and inflammatory mediators.
– Myocardial sympathetic denervation.
– Myocardial fibrosis that results in a tethering
action to improve myocardial function and
promote favorable remodeling

113. Clinical trials
• Several clinical trials have reported
encouraging results following TMLR in
patients with refractory angina who had
lesions not amenable to revascularization or
who were at high risk for revascularization

114. • Trial involved 192 patients with refractory angina and left ventricular
free-wall ischemia that was not amenable to direct coronary
revascularization.
• After a one-year follow-up, more patients undergoing TMLR
improved by at least two Canadian Cardiovascular Society (CCS)
classes (72 versus 13 percent for continued medical therapy) and
more had a significant improvement in quality of life.
• Myocardial perfusion, as assessed by thallium scanning, improved by
20 percent in the TMLR group compared to a 27 percent worsening
in the medical group.
• Overall survival at one year was the same in the two groups (85
versus 79 percent) but there was a marked reduction in
hospitalization for unstable angina with TMLR .

115. • This trial included 275 patients with refractory angina.
• At one year, more patients undergoing TMLR had an
improvement in angina (76 versus 32 percent with medical
therapy), a higher rate of survival free of cardiac events
that was primarily due to freedom from cardiac related
hospitalizations (61 versus 31 percent), and higher exercise
tolerance and quality-of-life scores.
• There was no difference in myocardial perfusion with
thallium imaging or in one-year survival (84 versus 89
percent).

116. • At five years, patients treated with TMLR continued to have
more frequent improvement in angina than those treated
medically (88 versus 44 percent improved by two or more
angina classes).
• The survival rate was also significantly higher for patients
initially assigned to TMLR; however, this difference
disappeared when patients crossing over were analyzed
separately.
• These benefits have not been confirmed in all trials.
• A limitation to these observations is that the surgical trials
were not blinded, thereby permitting a possible placebo
effect.

117. Complications
• Complications after TMLR are almost
exclusively cardiac-related and include
– myocardial infarction,
– left ventricular failure,
– atrial fibrillation, and
– ventricular arrhythmias.
• Risk factors for an adverse event include CCS
class IV status, unprotected left main stenosis,
and diabetes mellitus.

118. • The reported perioperative mortality has
ranged from 3 to 5 percent in most reports ,
but rates as high as 12 percent have been
described.
• The perioperative mortality may be related to
acute adverse effects of TMLR on the
myocardium that might lead to reduced
myocardial blood flow, regional ischemia, and
diastolic dysfunction, a result of an increase in
regional myocardial edema.

119. Combined TMLR and CABG
• This trial evaluated safety and efficacy of TMLR
combined with coronary artery bypass grafting in
patients with coronary disease not amenable to
complete revascularization with bypass surgery.
• The operative mortality was lower with the combined
approach (1.5 versus 7.6 percent for bypass surgery
alone) and the need for inotropic support or use of an
intra-aortic balloon pump was less after surgery.

120. • At thirty days, freedom from major adverse cardiac events
(death or myocardial infarction) was significantly greater
with TMLR (97 versus 91 percent), but this difference was
no longer significant at one year.
• There was also no significant difference in relief of angina
at one year.
• At five years, patients treated with TMLR had significantly
greater relief of angina by several measures.
• However, survival at this time was not significantly different
between the two groups.

121. PERCUTANEOUS TMLR
• In order to reduce the perioperative mortality associated
with surgical transmyocardial laser revascularization
(TMLR), percutaneous TMLR has been performed in the
catheterization laboratory using a holmium:yttrium-
aluminum garnet laser, which can channel energy through
flexible fibers, unlike the CO2 laser, creating channels in the
presence of blood.
• Preliminary phase I and open label phase II studies of
percutaneous TMLR found similar results to those seen
with the open chest CO2 TMLR studies: an improvement in
angina class and exercise capacity with minimal or no
change in nuclear perfusion scans.
– Catheter-based percutaneous myocardial laser revascularization in patients
with end-stage coronary artery disease.Lauer B, Junghans U, Stahl F, Kluge R,
Oesterle SN, Schuler G J Am Coll Cardiol. 1999;34(6):1663.

122. • The PACIFIC trial randomly assigned 221 patients with refractory
angina (Canadian Cardiovascular Society class III or IV) to
percutaneous TMLR or conventional medical therapy.
• At 12 months, those undergoing percutaneous TMLR had a greater
median increase in exercise tolerance (89 versus 12.5 seconds [14.4 versus
5.5 percent]) and the angina was more likely to be class II or lower (34
versus 13 percent of patients).
• There was no difference in survival or the combined end point of
death, myocardial infarction, or hospital admission between the
two groups.

123. • This trial is the only major blinded study of laser myocardial
revascularization.
• In this trial, 298 patients with refractory angina who were suboptimal
candidates for CABG or PCI were randomly assigned to low- or high-dose
laser channels or no laser channels, blinded as a sham procedure.
• There was no benefit of TMLR compared to continued medical therapy in
terms of patient survival, angina class, quality-of-life assessment, exercise
duration, or nuclear perfusion imaging.
• These findings raise doubt about previous positive studies, since they
underscore the powerful placebo effect in patients with end-stage cardiac
disease that can lead to physiologic benefits as well as improved
symptoms. The placebo effect can persist for 30 months or more

124. TMLR Combined with PCI
• The safety and efficacy of PCI, including angioplasty,
stenting, and/or atherectomy, combined with percutaneous
TMLR performed in the same myocardial territory served
by the treated vessel was addressed in a pilot study of 26
patients with class III/IV angina.
• Major periprocedural adverse events, due to subacute
vessel closure or tamponade, occurred in 11.5 percent.
• At six months, 19 percent of patients required repeat PCI
for restenosis, 12 percent had class III/IV angina, and the
mortality was 19 percent.
– First experience with hybrid percutaneous transmyocardial laser
revascularization and angioplasty in patients with lesions at high risk for
restenosis: Results of a phase I feasibility study. Stone GW, St Goar FG, Taussig
A, Power JA, Kosinski E, Shawl F Am Heart J. 2001;142(4):679

125. • In a meta-analysis, McGillion et al (2010) evaluated the
effectiveness of PMLR versus optimal medical therapy
for improving angina symptoms, health-related quality
of life (HRQL), and exercise performance; the impact
on all-cause mortality was also examined.
• A total of 7 trials (n = 1,213) were included. Primary
analyses showed that at 12-month follow-up, those
who had received PMLR had greater than or equal to 2
Canadian Cardiovascular Society class angina symptom
reductions, as well as improvements in aspects of
HRQL including angina frequency, disease perception,
and physical limitations.
• Percutaneous transmyocardial laser revascularization
had no significant impact on all-cause mortality.

126. • For secondary analyses, in which these
researchers considered data from 1 trial that
featured a higher-dose laser group, yielded no
significant overall impact of PMLR across
outcomes.
• The authors concluded that while PMLR may be
effective for improving angina symptoms and
related burden, further work is needed to clarify
appropriate dose and impact on disease-specific
mortality and adverse cardiac events.

127. Transmyocardial Laser Revascularization
Plus Cell Therapy
• Konstanty-Kalandyk (2018) noted that refractory angina has
limited effective therapeutic options and often contributes
to frequent hospitalizations, morbidity and impaired quality
of life (QOL).
• These researchers examined mid-term results of a
biointerventional therapy combining TMLR and intra-
myocardial injection of adipose derived stem cells (ADSC) in
patients with refractory angina not amenable to
percutaneous or surgical revascularization.
• This study included 15 patients with severe refractory
angina and anterior wall ischemia who were ineligible for
revascularization strategies.

128. • Adipose tissue was harvested and purified, giving
the stem cell concentrate.
• All patients underwent left anterior thoracotomy
and TMLR using a low-powered holmium:
yttrium-aluminum-garnet laser and intra-
myocardial injection of ADSC using a combined
delivery system.
• No deaths or major adverse cardiovascular or
cerebrovascular events were observed in the 6-
month follow-up.

129. • Mean ejection fraction increased from 35 % to 38 %, and mean
Canadian Cardiovascular Society Angina Score decreased from 3.2
to 1.4, with decreased necessity of nitrate usage; 73 % of patients
reported health improvement particularly regarding general health
and bodily pain.
• Improvement in endocardial movement, myocardial thickening and
stroke volume index (35.26 to 46.23 ml/m2) on cardiac MRI was
observed in 3 patients who had repeat CMR imaging after 6
months.
• The authors concluded that the findings of this study suggested that
interventional therapy combining TMLR with intra-myocardial
implantation of ADSC may reduce symptoms and improve QOL in
patients with refractory angina.
• Moreover, they stated that these early findings need further
validation in large, multi-center RCTs.

131. LASER PHOTOCHEMOTHERAPY
• An additional laser approach to the problem
of restenosis is the use of laser radiation to
photoactivate drugs capable of inhibiting
smooth muscle cell proliferation and intimal
hyperplasia.
• The drugs investigated for this purpose
include hematoporphyrins, phyocyanin,
phthalocyanine, and psoralen.

132. • Gregory demonstrated that UVA-activated
psoralen reduced intimal smooth muscle cell
proliferation assessed by bromodeoxyuridine
incorporation in a porcine angioplasty model.
• Although only preliminary in vitro and in vivo
animal data are available, the approach of
systemic (or local) administration and local
photoactivation of cytotoxic drugs is feasible
and offers a potential potent therapy for
restenosis and atherosclerosis.

133. ANTIARRHYTHMIC LASER THERAPY
• Laser ablation has been investigated for
several years as a means for treatment of
ventricular and supraventricular arrhythmias.
• Saksena evaluated the safety and efficacy of
intraoperative mapping-guided argon laser
ablation alone, or in conjunction with
standard surgical methods, in 20 consecutive
patients with refractory sustained ventricular
tachycardia or fibrillation.

134. • Thirty-eight VT morphologies were mapped and
ablated with laser irradiation alone (82%),
combined laser ablation and mechanical
resection (13%), or mechanical resection alone
(5%).
• Postoperative 30-daymortality was 5%, and only
one patient required postoperative
antiarrhythmic drug therapy.
• All survivors had suppression of inducible
sustained VT at discharge, and no episodes of
sudden death were reported at 1-year follow-up.

135. • Laser treatment has been proposed as an
alternative to surgical treatment of certain
supraventricular tachycardias (SVT).
• Bypass pathway ablation for Wolff-Parkinson-
White Syndrome, A-V node ablation for
atrioventricular nodal re-entry tachycardia, sinus
node ablation for automatic sinus tachycardia,
and ablation, partition andlor isolation
procedures for atrial reentrant tachycardia or
fibrillation, are all potential procedures that may
be performed more expeditiously and safely with
laser radiation

136. MYOCARDIAL ABLATION
• Laser radiation may be effectively used for the
ablation of myocardial tissue for the treatment of
various cardiovascular disorders.
• Isner demonstrated the feasibility of performing a
myotomy-myectomy for idiopathic hypertrophic
subaortic stenosis (IHSS) using laser radiation.
• The major advantage of this laser procedure is
the ability to perform percutaneously what
otherwise would require a thoracotomy and open
heart surgery.