HOW TO DEAL WITH

CALCIFIED CORONARY
ARTERY LESIONS
DR AWADHESH KR SHARMA
LPS INSTITUTE OF CARDIOLOGY
IN THE 18TH CENTURY, EDWARD JENNER AND CALEB HILLIER PARRY, TWO BRITISH PHYSICIANS,
INDEPENDENTLY NOTICED THAT CORONARY OSSIFICATION WAS OFTEN PRESENT IN PATIENTS DYING
OF ‘SYNCOPE ANGINOSA’.
CORONARY ANGIOGRAPHY OPENED THE POSSIBILITY OF EXPANDING THESE OBSERVATIONS TO LIVING
PATIENTS AND OFFERED REVASCULARISATION OPTIONS.
FOUR SPECIFIC CORONARY ANATOMIC FEATURES ARE COMMONLY CONSIDERED TO BE MARKERS OF
INTERVENTIONAL PROCEDURAL COMPLEXITY:
1) THE PRESENCE OF CALCIUM;
2) SEVERE TORTUOSITY;
3) HIGH THROMBUS CONTENT; AND
4) DIFFUSE ATHEROSCLEROTIC BURDEN WITH VARIABLE CALIBER AND AN ABSENCE OF A PLAQUE FREE
LANDING ZONES, TO FACILITATE SAFE STENT PLACEMENT.
Of these features, lesions with high calcium content (LHCC) are probably the most challenging and
most likely to impact adversely on both the acute and the long-term results of percutaneous coronary
intervention (PCI).

Obstructive calcium increases procedural complexity by interfering with lesion preparation and
balloon dilation, making delivery of balloons and stents difficult and by restricting final stent
expansion.

Rotational atherectomy (RA) has represented the predominant solution for LHCC, but recently new
technologies have become available to clinical practices.
 CLINICAL IMPLICATIONS OF
CORONARY CALCIFICATIONs
Coronary calcification is age and sex dependent, being more common in men older than 70 years of
age (>90% in men vs. 67% in women).
The incidence of coronary calcification varies on the used imaging modality, but when angiography
is used, it has been reported that moderate-severe calcification can be encountered in up to one-
third of coronary lesions.
Coronary calcification is commonly associated with larger plaque burden and a greater degree of
lesion complexity including involvement of coronary bifurcation or chronic total occlusion.
Bourantas et al. showed how patients with LHCC undergoing PCI are less likely to receive complete
revascularization (48% vs. 55.6%; p < 0.001) and more likely to die subsequently (10.8% vs. 4.4%; p <
0.001).

Notably, the association between LHCC and adverse clinical outcome is independent of clinical
presentation and the implanted stent categories.

In the pooled analysis of the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy)
and the HORIZON-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial
Infarction) trials, PCI performed on moderately/severely calcified coronary lesions in patients with
acute coronary syndrome was associated with a 62% higher risk of definite stent thrombosis and 44%
higher risk of ischemic target lesion failure.
Adverse clinical outcomes observed in patients treated with LHCC are partly related to comorbidity
but also to the increased technical complexity of PCI.
Typically, these lesions are challenging to cross with standard devices and are less likely to respond
to balloon dilatation.
Inevitably, inadequate preparation of any LHCC lesion before stenting increases the risk of stent
loss; stent underexpansion/fracture; and the rate of intraprocedural complications, such as no
reflow, coronary dissection, or perforation.
 IMAGING OF CALCIFIED CORONARY
LESIONS
LHCC is initially detected in emergency cardiac patients during coronary angiography.
Before injecting angiographic contrast, LHCC typically appears as linear areas of x-ray attenuation
(black areas) following the silhouette of the coronary artery, with a synchronous movement during
cardiac contraction and relaxation.
Severe coronary calcification is defined angiographically when, before contrast injection, both
sides of the arterial wall can be identified during cardiac motion.
During contrast injection, calcium content tends to appear as hazy areas with inhomogeneous
contrast staining and differentiation from thrombus is difficult using angiography alone.
The accuracy of coronary angiography to identify high calcium content is suboptimal, especially in
cases of in-stent restenosis.
A pivotal study by Mintz et al. showed that coronary angiography was able to identify calcium only
in 38% of cases and detection seemed to be dependent on the degree of the arch of calcification
(60% for moderate calcifications and 85% for severe calcifications).
Advanced intravascular imaging techniques enhance identification of LHCC, but also allow a
comprehensive assessment of calcium burden, distribution, and eccentricity.
These details inform and allow a tailored strategy for lesion preparation and can guide stent
optimization.
Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) are the 2 principal
intravascular imaging modalitieS.
Because calcium causes reflection of ultrasound, an LHCC typically appears on an IVUS image as a
hyperechogenic arch combined with deeper acoustic shadowinG.
In an initial postmortem study, IVUS reported a 90% sensitivity and 100% specificity for
identification of densecalcified plaque or of cluster of microcalcifications, with a lower accuracy for
identifying isolated microcalcifications (<50 mm, being below the IVUS spatial resolution of 100
mm).

These pathologic data are consistent with subsequent clinical data demonstrating the enhanced
sensitivity of IVUS in detecting coronary calcium compared with angiography (73% of cases vs. 38%;
p < 0.001).

Because of the higher penetration of ultrasound, IVUS detects abluminal calcified deposits within
the deeper layers (media or adventitia) of the vessel wall.

However, because of acoustic shadowing, IVUS allows only definition of the calcific arch, without
offering insights into thickness of the calcium.
Consequently, dedicated strategies for LHCC preparation have historically been based on
measurement of the calcific arch circumference detected on IVUS, with an arch >180 predicting
possible stent underexpansion.
Because of its higher spatial (axial and longitudinal) resolution, OCT has the potential to overcome
many of the limitations of IVUS by offering a more accurate definition and quantification of the
calcific plaque.
On OCT imaging, LHCC appears as areas of attenuation with clearly delineated luminal and abluminal
borders.
Notably, although calcium on IVUS has a characteristic and readily recognizable appearance, its
identification on OCT is challenging in nonhomogeneous plaque (fibro-lipidic-calcific) and if the
calcific deposit is nonsuperficial and deep, or underneath a lipidic or necrotic core.
Despite these limitations, OCT seems to be more accurate than IVUS in defining calcific burden,
because it provides additional measurable parameters on top of the degree of the calcific arch, such
as calcium area, calcium thickness, calcium length , and calcium 3-dimensional volume.

Each of these parameters have been showed to predict stent expansion and response to balloon
dilation.

OCT-based calcium scoring system, combining multiple OCT derived parameters of calcium
characterization, has been validated by Fujino et al.
This score combines calcific arch >180 DEGREE (2 points), calcific thickness >0.5 mm (1 point), and
calcific longitudinal length >5 mm (1 point).
A significantly higher risk of stent underexpansion has been observed in lesions with a score of 4.
intravascular imaging can also be used to assess the final stent result and OCT has better sensitivity
than IVUS in detecting stent malapposition and underexpansion and in evaluating the effects of
post-dilation.
TREATMENT OPTIONS
ABLATION TECHNIQUES
1. ROTATIONAL ATHERECTOMY
2. ORBITAL ATHERECTOMY
3. EXCIMER LASER
BALLOON BASED TECHNIQUES
1. CUTTING BALLOON
2. SCORING BALLOON
3. SUPER HIGH PRESSURE BALLOON
4. LITHOPLASTY BALLOON
The first group includes RA, orbital atherectomy (OA), and excimer laser; these techniques
theoretically “ablate” calcium promoting stent expansion.
Balloon-based techniques do not remove calcium but aim to increase plaque elasticity and allow
stent expansion by cracking the calcified component in 1 or multiple areas.
IVUS and OCT have shown that RA or OA act predominantly by modifying the plaque composition
with a selective action on the hard-calcified component, rather than by actually debulking the
target lesion.
These calcium cracks and dissection flaps are typical imaging findings and their presence is
associated with improved expansion of the stent.
 Much less frequently (<30%), true tissue ablation/removal is observed with residual evidence of
craters, tunnels, or gutters.
larger burrs and faster speeds are more likely to cause complications ranging from coronary
perforations, distal embolization, and PMI.
achieving plaque modification with small size ablative device is now the recommended approach.
 CALCIUM-ABLATION TECHNIQUES
ROTATIONAL ATHERECTOMY-
RA (Boston Scientific, Marlborough, Massachusetts) system is composed of a high-speed rotating
diamond-coated burr that acts as an abrasive rotatory surface against calcific plaque.
The elliptic-shaped metallic burr is available in different sizes (from 1.25 to 2.5 mm) and is mounted
over an advancer (RotaLink) drive-shaft connected to a motor that converts compressed gas into
rotational energy.
The rotaburr is advanced over a dedicated 0.009-inch wire (Rotawire) designed to maximize
flexibility and to minimize unfavorable wire bias.
The recently introduced RotaPro (Boston Scientific) represents an updated iteration and it makes
RA easier for a single-handed operator, by offering a better user-interface and controls integrated
on the advancer.
RA ablates preferentially the fibrocalcific plaque tissue according to the principle of differential
cutting, sparing the compliant elastic vessel tissue. The ablated tissue is pulverized in 5 to 10 mm
debris, which are released into the distal coronary microcirculation.
This is the likely mechanism underlying the potential for transient slow/no reflow following RA. The
rate of this possible complication following RA varies but it was quoted up to 24% in a recent
randomized clinical trial on 100 patients treated with RA.
Notably in this series, no difference in the incidence of slow flow was associated with the rotation
speed of the burr.
High-speed burr rotation is necessary to reduce the friction with the vessel wall while advancing
the device.
According to the principle of orthogonal displacement of friction, the burr-to-artery surface friction
is virtually removed at rotational speed >60,000 rpm, allowing unimpeded forward-and backward
movement of the burr through the diseased vessel.
The advised burr size/artery ratio is 0.5:0.6, and a safe range of burr revolution speed is considered
between 135,000 and 180,000 rpm.
Four factors influence significantly the result of RA: 1) calcium eccentricity; 2) luminal area; 3) burr
size; and 4) degree of guide wire bias.
An optimal scenario for RA in terms of predictable luminal gain is a lesion with concentric
circumferential calcium (cross-section >270 DEGREE of calcium) and a minimal lumen area smaller
than the burr size.
Complications of RA include burr lodging, coronary dissection, and perforation but their
occurrence can be usually minimized by optimal technique.
Avoiding extreme tortuosity, allowing for adequate time intervals between ablation runs, and
prevention of burr deceleration >5,000 rpm is recommended to minimize the risk of complications
during RA.
In many centers, RA may still represent the only available technique for LHCC that cannot be
crossed with a balloon, but clinical trials have failed to prove a consistent long-term benefit in
terms of restenosis and major adverse cardiac events.
The ROTAXUS trial compared PCI with RA þ DES (paclitaxel eluting) versus standard PCI with DES in
a randomized fashion in 240 patients with moderate-to-severe calcification.
RA was associated with increased acute lumen gain but also with larger in-stent late lumen loss at
9 months, with a neutral effect on restenosis. Moreover, no difference in clinical outcome was
observed after 2 years of follow-up.
the PREPARE-CALC trial randomized 200 patients with severely calcified coronary artery disease to
RA versus cutting/scoring balloon angioplasty.
RA was superior in terms of procedural success compared with the strategy with modified balloons
(98% vs. 81%; p ¼ 0.0001) and RA was not associated with excessive late lumen loss at 9 monthS.
However, the interpretation of these RA trials requires discussion because they were not designed
and powered for hard clinical endpoints and the definition of calcification severity has been based
on angiography and not intravascular imaging.
Across the studies, RA demonstrated a higher rate of acute procedural success, with lower rate of
stent loss.
Notably a 12% to 16% rate of crossover to RA in the control arm was consistently reported across
the comparative studies.
Notably in ROTAXUS, more than half of the lesions treated in both arms of the study had only a
moderate degree of calcifications and it is possible that the late lumen loss seen at 9 months in the
RA group in ROTAXUS could have been related to the use of first-generation DES.
No excessive lumen late loss was reported in the RA arm of the PREPARE CALC study, which used a
third-generation sirolimus eluting stent with resorbable polymer.
It is also possible to speculate that the 9 months follow-up interval could have been too short to
detect a significant impact of RA on the efficacy of the final stent result.
 ORBITAL ATHERECTOMY
OA is a newer treatment for LHCC and it consists of an eccentrically mounted diamond-coated 1.25-mm
crown, connected to a drive shaft and to a controller powered by a pneumatic console (CSI Diamond 360°
Coronary Orbital Atherectomy System, St. Paul, Minnesota).
Compared with the rotaburr, which only allows calcium ablation during forward advancement, the crown of
OA presents diamond chips both on front and back, allowing ablation during antegrade and retrograde
motion.
Compared with RA, this makes the entrapment or lodging of the OA crown much less unlikely.
 The crown is advanced over a dedicated (ViperWire Advance, St. Paul, Minnesota) a 0.014-inch wire, with
superior maneuverability compared with the 0.009-inch Rotawire.

 Using the controller, the operator can move the crown forward and backward and can regulate the speed of the
crown orbit (80,000 to 120,000 rpm).

 During both RA and OA, the procedure is performed with a continuous intracoronary infusion of a lubricant
solution.

 The mode of action of OA consists of fast elliptical rotation of the crown with progressive increase of the orbit
diameter as rotation speed increases.
Centrifugal force generated during rotation pushes and compresses the crown against the plaque
with a “sanding” action of the calcified component. In theory, OA might have a selective action on
the rigid calcified component, whereas healthy compliant tissue may flex away and be spared.
 During OA, the operator slides the crown forward and backward with a slow but continuous movement (in
contrast to the slow pecking motion during RA) with the possibility to slow down further in those segments
requiring more ablation.

 Notably, by increasing its orbit as rotational speed increases, OA allows ablation of calcium using the same
device (1.25-mm crown) in vessels up to 3.5-mm diameter.
 The ORBIT I study demonstrated safety and feasibility of OA within a cohort of 50 patients, reporting a
device success (defined a residual stenosis <50% after OA) in 98% of cases and procedural success (defined
as residual stenosis <20% after stenting) in 94% of cases. In this study, no cases of slow/no reflow following
OA were documented, but 6 dissections were documented with no clinical sequelae (12%).

 The ORBIT II study (prospective, single arm, nonrandomized) further confirmed the preliminary results of
the ORBIT I in a larger cohort of patients (443 patients in 49 U.S. centers) demonstrating device success of
98.6% and procedural success of 91.4%, with 2.3% rate of severe coronary dissections (types C, D, E, and F
according to National Heart, Lung, and Blood Institute classification) .
Currently, the ECLIPSE study will randomize 2,000 patients with calcified lesions to OA and conventional
balloon angioplasty with coprimary outcome measures of acute minimum stent area measured by OCT and
target vessel failure defined as combination of cardiac death, target vessel-related myocardial infarction, or
ischemia-driven target vessel revascularization .

 Compared with RA, OA might be associated with a more profound plaque/vessel modification producing
longer and deeper cuts.

 The occurrence of true “ablation” of calcium component on OCT has been reported more frequently in
patients treated with OA but it is uncertain whether this increased plaque modification by OA is associated
with better stent results and clinical outcomes.
EXCIMER LASER
 Excimer laser is a technique introduced more than 2 decades ago as an
alternative to balloon angioplasty and based on the principle of photo ablation
of atherosclerotic plaque.
 Laser produces ablation of atherosclerotic material via 3 main mechanisms: 1)
photochemical (by breaking the molecular bonds); 2) photothermal; and 3)
photomechanical.
 Photomechanical ablation occurs when laser acts on a liquid medium (saline,
contrast dye, blood) with consequent release of expanding and exploding
bubbles that press over the plaque.
 This effect is magnified particularly when the laser acts directly on blood or contrast medium.
 Consequently, to reduce the risk of coronary dissection, laser ablation is typically performed
during continuous intracoronary injection of saline.
 The current excimer laser system (CVX-300 ELCA System, Spectranetics Inc., Colorado Springs,
Colorado) is based on a XeCl laser and generates energy (also referred as fluence) up to 80
mJ/mm2, with a laser catheter consisting of fibers arranged concentrically or eccentrically
around the guidewire.
Catheters dimensions can range from 0.9 mm (5-F compatible) to 1.4 mm and 1.7 mm (7-F
compatible) and 2.0 mm (8-F compatible), and these measurements correspond to the actual
diameter of the intraplaque tunnel achieved with a single passage of the laser catheter.
 The selection of the appropriate size is based on a catheter/vessel diameter ratio of 0.5:0.6.
 The clinical use of coronary laser is limited, but treatment of uncrossable and undilatable lesions
remains a major indication with a reported procedural success of 93%.
 Many uncrossable lesions have a high calcium content. Unfortunately, increasing
proportions of calcification seem to reduce the efficacy of laser, because Mintz et
al.have reported that enlargement of cross-section area via laser atheroablation
(reduction of plaque-media burden) and vessel expansion (enlargement of external
elastic lamina) was effective without significant modification on the calcified arch.
 Consequently, the laser is rarely used as the first line strategy for LHCC, but it is the only
option when either the microcatheter will not cross or a Rotawire/Viper wire cannot be
deployed.
 The feasibility and efficacy of combining laser to facilitate RA has been described and referred as the RASER
technique.

 Laser does seem to have a role in calcific undilatable in-stent restenosis, especially when instent restenosis
is a direct consequence of an initially underexpanded stent.

 A recent OCT study showed superiority of laser over high pressure balloon dilation in treating undilatable
in-stent restenosis and confirmed the action of laser in cracking calcium behind stent struts especially when
flushing with contrast dye rather than saline.
 BALLOON BASED TECHNIQUES
CUTTING AND SCORING BALLOON
 The cutting balloon (FlexTome, Boston Scientific) consists of a noncompliant balloon with a set of 3
microblades mounted longitudinally on the surface with the aim to create incisions within atherosclerotic
plaque during balloon inflation.

 The device is 6-F compatible and balloon diameter sizing for lesion preparation should be in 1:1 ratio with
vessel diameter.

In terms of lesion preparation, cutting balloon offers the benefit of a more controlled lesion predilation with
less adjacent vessel wall trauma and less risk of dissection.
 The presence of cutting elements on the surface of the balloon allows effective
dilation with a lower inflation pressure.
 However, the GLOBAL trial failed to show a superiority of cutting balloon for type A/B
lesions compared with standard balloons and the adoption of cutting balloons has
been limited to more complex coronary scenarios, particularly in-stent restenosis and
LHCC .
 An IVUS substudy of the REDUCE trial confirmed that cutting balloon was associated
with larger final cross-section areas in both calcific and noncalcific lesions, but the
difference in plaque-media area was significant only in noncalcific lesions.
 Crossability and trackability are important limitations of cutting-balloons in LHCC. Similar clinical outcomes
have been reported between RA-assisted PCI and cutting balloon–assisted PCI for LHCC, but in many
centers this technology is being used less frequently.

 The issue of cutting balloon tracking may be improved by a new generation of low-profile semicompliant
balloons with a scoring element on the surface (AngioSculpt, Biotronik, Berlin Germany; Scoreflex
OrbusNeich, Hong Kong, China; NSA Alpha BBraun, Melsungen, Germany).

 During inflation, the radial force is mainly exerted on the scoring element and this is transmitted to the
vessel wall causing incisions in the atherosclerotic plaque.
 The presence of the nitinol element ensures anchoring of the balloon with a lower risk of “melon-seeding”
and/or balloon-slippage effects and a lower risk of dissection and perforation.

 These scoring balloons were not intended specifically for LHCC but preliminary experience has
demonstrated feasibility in moderate calcification.
 SUPER HIGH-PRESSURE BALLOON

 This technology consists of a rapid-exchange noncompliant balloon (OPN Sys Medical,

Frauenfeld, Switzerland) with a twin-layer structure allowing inflation pressure up to 35
to 40 atm without bursting of the balloon.
 This unique property offers application for undilatable lesions and undilatable
underexpanded stents when other options have failed.
 Even though super highpressure balloon can be used both before and after stent
implantation, most evidence confirms safety and efficacy during stent post-dilation. We
regard super high-pressure balloons for LHCC preparation before stenting as a “last
resort.
 LITHOPLASTY BALLOON
 Lithoplasty is the latest technology available for the treatment of LHCC.

 Lithoplasty consists of pulsatile mechanical energy delivered via miniaturized

emitters placed along the length of a semicompliant rapid-exchange balloon
(Shockwave Coronary Rx Lithoplasty System, Shockwave Medical, Santa Clara,
California).
 The balloon is inflated at a pressure of 4 atm initially and then impulses of
mechanical energy are delivered to the LHCC at a frequency of 1 Hz.
 This energy interacts with the atherosclerotic plaque, causing vibration that
cracks and fractures calcific components in the superficial and deeper layers.
 This preferential effect on deep calcium is a major benefit of lithoplasty
compared with other ablation techniques.
 Being a balloon-based technique, it is user-friendly with a short learning curve
and this, combined with early evidence of efficacy, suggests it will become a
standard approach for many LHCC.
 Ali et al. have demonstrated, using OCT in 31 patients, that lithoplasty can fracture calcified arch
in43% of cases with multiple fractures produced in >25% of cases.
 Notably, the efficacy of the technique is proportional with the calcium burden, with a higher rate
of calcium fractures (77%) in cases with higher degree of coronary calcifications.
 No serious safety issues or technique complications (coronary perforations, major dissections,
slow/no reflow) have been reported in the studies.

 DISRUPT CAD I-IV TRIALS HAVE SHOWN THAT Intravascular lithotripsy safely and effectively
facilitates stent delivery and optimizes stent expansion in patients with severely calcified coronary
lesions.
 The potential for electrical interference by coronary lithoplasty has been described with a phase
of ventricular pacing in VOO mode during lithoplasty balloon activity. It is hypothesized this could
result in a proarrhythmic R on T pacing and this may mandate caution in using lithoplasty in
patients with pacemakers.
 The transformational impact of lithoplasty has been augmented in reports showing its efficacy
also in dealing with underexpanded stents, when all other technology had failed.
 Uncrossable lesions remain the main limitation of this technique and it has been proposed that
the combination of lithoplasty balloon with RA might achieve superior lesion preparation.
 Use of intravascular imaging for detecting inadequate LHCC modification post RA and guiding additional
balloon lithoplasty has also been suggested.
 CONCLUSIONS

 The presence of large calcific burden in coronary lesions adds an extra level of clinical and technical
complexity to PCI. The panorama for the percutaneous management of LHCC has evolved over the past 5
years.

 Even though the diffusion of novel techniques for treatment of LHCC is not homogeneous (with OA having
U.S. Food and Drug Administration but not CE-mark approval and lithoplasty balloon having CE-mark but
not Food and Drug Administration approval) it is becoming more evident that the combination of
intravascular imaging and novel therapeutic techniques is revolutionizing the treatment of LHCC.
 Intravascular imaging, and OCT in particular, can provide details about the degree of calcification, the
location, and the distribution of the calcified burden, with special reference to eccentricity versus
concentricity, luminal versus deep location, thickness, and longitudinal extension.

 Information derived from intravascular imaging will allow the operator to select the most appropriate
technology to prepare LHCC.

 When the degree of calcification is moderate the operator could achieve lesion preparation with balloon-
based techniques and increasingly with the lithoplasty balloon.

 Conversely, higher degree of calcification may still require a more aggressive lesion preparation with
ablation techniques, such as RA or OA.
 Because of its ease of use, shorter learning curve, and unique action on both superficial and deep calcium,
lithoplasty balloon seems to be a transformational technology.

 Although confirmatory data are still required, in our opinion this technology will change the landscape of
LHCC treatment and revolutionize the way it is treated in the future.
Thanks