The document discusses definitions and etiology of in-stent restenosis as well as treatments for it. It defines angiographic, IVUS/OCT, and pathological definitions of restenosis. It also discusses the causes of in-stent restenosis including mechanical factors like underexpansion and biological factors like neointimal hyperplasia. The document then summarizes various treatment strategies for in-stent restenosis such as plain balloon angioplasty, atherectomy, brachytherapy, repeat stenting, and drug-coated balloons. It provides details on studies comparing the effectiveness of these different treatment methods.

3.  Binary Angiographic Restenosis:
Re-narrowing of more than 50 % of the vessel diameter as determined by coronary
angiography.
 IVUS/OCT Definition of Restenosis:
Re-narrowing of more than 75% of reference vessel area on cross section.
 PATHOLOGICAL Definition of Restenosis:
Pathological vessel re-narrowing of more than 75% of vessel area in cross section.
 CLINICAL Restenosis:
clinical restenosis is sometimes used to refer to restenosis of the treated lesion accompanied by
requirement for re-treatment, for example, due to symptoms or signs of ischemia.

4.  DES caused a reduction of 35 – 70 % in stent restenosis observed with
BMS.
 With DES rate of stent restenosis reported to be between 3 to 20 percent,
depending on:
› DES Type
› Duration of follow-up
› Complexity of the lesions
 For first-generation DES (sirolimus or paclitaxel DES), the rate of
restenosis is between 13 and 16 percent at five years.
 In a pooled analysis of multiple studies comparing everolimus-eluting with
zotarolimus-eluting stents, the rates of TVR at up to five years of follow-up
were 6.3 and 5.0 percent, respectively.

6. Etiology
Of
ISR
Mechanical
Causes
Biological
Causes

7.  Under Expantion
 Stent Fracture
 Residual plaque/Plaque protrusion
 Edge dissection
 Intramural hematoma
 Elastic recoil of vessel wall
 Constrictive vascular remodeling

8.  Neo-Intimal Hyperplasia
 Neo-Atherosclerosis

9. Features of DES Vs BMS Restenosis
Characteristic DES BMS
Imaging Features
Angiographic appearance Focal more common Diffuse more common
Time course of late luminal loss Out to 5 years Maximum by 6 – 8 months
OCT tissue characteristic Layered/Heterogenous
Homogenous high signal band
typical
Histopathological Features
Smooth Muscle Hypocellular Rich
Proteoglycal High Moderate
Peri-sturt fibrin/Inflamation Frequent Occasional
Time to edothelize Upto 48 mo. 3 – 6 mo.
Thrombus occasional occasional
Neoatherosclerosis Frequent, Accelerated Late , slow

11. Focal: 10mm or less
Diffuse: >10mm
Importantly the pattern of restenosis at
presentation is a predictor of subsequent
outcome after re-intervention. In the
original study target lesion
revascularization rates were 19%, 35%,
50%, and 83% in groups I-IV, respectively
(p < 0.001).

14.  Majority of ISR present with progressive
worsening angina.
 Majority of BMS-ISR present within 3 – 6
months of stent implantation.
 Majority of DES-ISR present around 6 – 12
months.
 3 – 20 % of ISR present as acute MI.

15.  Routine angiographic assessment for restenosis is not
recommended due to
› Increase morbidity and mortality.
› Asymptomatic pts. With non-functional angiographic
restenosis have a benign course.
› So called occulo-stenotic reflex leads to increase
revascularization rates with no clear benefit.
 Non-invasive assessment of restenosis (Symptoms/Non
invasive testing) seems an appropriate approach.

19.  Earliest approach.
 Addresse two causes of stent restenosis
 Neointimal hyperplasia (Reduses tissue volume)
 Stent underexpansion(Dilates stent)
 Baloon to vessel ratio is 1.1 : 1.0.
 Balloon length is targeted to treat restenotic segment only.
 Inflated at restenosis site @ Nominal pressure.
 Under expansion is manifested as dog boning.
 If dog boning, switch to non compliant baloon that facilitates high pressures
upto 25 atm.
 Dilation resistant lesions: High prsessure balloons with inflation pressure upto
40 atm. High perforation risk.

20.  Watermalon seeding
› Proximal or distal displacement of ballon from targeted segment.
 Geographic Miss
› Inadvertant trauma to non targeted segment due to baloon slip.
 Solution:
› Stepwise ballon inflation
› Sequential angioplasty starting with smaller balloon size.
› Use od buddy wire.
› Anti-slip cutting or scoring balloons.
 Stand alone angioplasty is not TOC because
› Residual stenosis after procedure is high.
› Significant early lumen loss after 30-60 mins.
› Superior other techniques.

21.  Atherectomy devices treat ISR by removing
rather than compressing tissue.
 Two categories
› Remove and retrieve (Directional atherectomy)
› Disrupt and displace (Rotational/Laser atherectomy)

22.  Plaque debulking using a metal burr studded with diamonds.
 Rotated at a speed of 150000 to 200000 rpm.
 Plaque pulverization produces micro particles of size 20 to 50 um that
can pass microcirculation.
 Roster Trial: (Rotational atherectomy vs. balloon angioplasty)
› No evidence of increased acute luminal gain.
› Improved rates of repeated revascularization.
 ARTIST Trial: (Rotational Atherectomy + Balloon angioplasty vs.
Balloon angioplasty)
› Higher rates of repeat revascularization.

23.  XeCl based excimer laser ablation using ultra violet
spectrum wavelengths.
 A randomized multicenter trial showed increased acute
luminal gain and improved revascularization rates.
 Longterm results are similar to rotational atherectomy in a
registry analysis using IVUS for comparison.
 This technique is also fallen out of use due to superior
techniques.

24.  Plaque is removed from vessel by a cutting device mounted on a directional
balloon catheter.
 Upon inflation plaque is incised into the windowed balloon housing and
removed with catheter.
 Tissue is avaiable for histological analysis.
 Small-scale registries showed encouraging results and a comparison against
rotational atherectomy suggested more potent and a lower incidence of
subsequent target lesion revascularization with directional atherectomy.
However, as with other debulking techniques, compelling randomized trial data
against standard therapy were not realized and the deviceis no longer in
widespread use, at least in the coronary arena.

25.  Cutting balloons are comprised of standard balloon catheters
mounted with lateral metallic blades known as athertomes.
 Scoring balloons have a broadly similar mechanistic basis to cutting
balloons. The main difference is that low profile nitinol wires (on the
order of 125 μm) in spiral formation are mounted on the surface of
the balloon catheter instead of blades.
 As a result the deliverability and flexibility of the catheters are
increased, at the expense of a lesser degree of plaque incision.

26.  There are two main advantages to their use:
› The incision of the blades into the stenotic plaque may favor
subsequent extrusion.
› The interaction of the blades with the plaque anchors the balloon in
the plaque and prevents “watermelon-seeding”; this in turn might
reduce problems related to geographic miss.
 ISAR-DESIRE 4:
› In patients presenting with DES restenosis neointimal modification with
scoring balloon significantly improves the angiographic antirestenotic
efficacy of paclitaxel-coated balloon angioplasty.

27.  An initial large registry of patients treated with ISR from Lenox Hill, New
York, compared outcomes of matched patients according to treatment with
cutting balloon, rotational atherectomy, stenting, or plain angioplasty.
Results suggested a clear edge for cutting balloon angioplasty in terms of
angiographic and clinical outcomes at follow-up.
 RESCUT randomized trial:
› Although cutting balloons showed less procedural balloon slippage, no advantage in terms
of the primary endpoint of binary angiographic restenosis at 7-month angiographic follow-up
was seen.

28.  Intra-coronary radiation therapy.
 The therapy is applied at the time of mechenical treatment
of stenosed stent.
 Radioactive material usually in the form of seeds is applied
to the stenosed segment in a specialized catheter and is
left to dwell there for 3-5 min and 30-45 minutes.
 Beta or Gamma radiation both are effective.

29.  Two main drawbacks
 Specialized laboratory equipments with difficult
treatment protocols.
 Impaired vascular healing after treatment.
 Two important multicenter trials SIRS & TAXUS
V ISR showed superiority of DES treatment
over brachytherapy.

30.  Used to treat ISR in past.
 Disadvantage.
› Additional stent layer resulting Onion skin layering/ Luminal
crowding.
› Chronic inflammation due to stent results in luminal hyperplasia
offsetting acute initial gain in case of stent restenosis.
 RIBS Trial (Balloon Angioplasty Vs. BMS)
› Acute initial gain was offset by late lumen loss.

31.  ISAR DESIRE TRIAL: (SES/PES vs Baloon angioplasty)
› Both DES outperformed balloon angioplasty in primary
angiographic end point.
› Similar results were observed for repeat TLR.
 RIBS II: (SES Vs. Balloon Angioplasty)
› SES outperformed balloon angioplasty in both angiographic and
clinical end point at 9 months.
 SISR & TAXUS V ISR showed DES superiority over brachytherapy.

32.  DES Angioplasty already has a 35 – 70 % reduction in ISR
compared with BMS implantation.
 There are two major factors recognized in DES restenosis.
› Drug Hyporesponsivness.
› In-stent neoatherosclerosis.
 Stent fracture/Underexpansion results in impaired drug delivery to
underlying endothelium resulting in ISR.
 DES ISR can be treated with same DES or Switch DES.

33.  Study from Milan: No differences in patients treated
with same DES versus switch strategy.
 RIBS-III registry: showed better angiographic
outcomes and lower rates of clinical events in patients
with switch DES versus no-switch strategy.
 Only randomized trial to examine this issue was ISAR-
DESIRE 2: no difference(DES vs. switch DES) in late
lumen loss at 6-8 months.

34.  DCB catheters are comprised of standard angioplasty
balloons and a matrix coating that is applied to the surface
of balloon.
 The Balloon coating is typically comprised of two
elements:
› A lipophilic active drug (paclitaxel).
› Spacer or excipient (increases the solubility of the drug and
facilitates transfer from the balloon to the vessel wall).

35.  The lesion must first be dilated with a standard or
noncompliant balloon in order to extrude and compress
neointima and correct stent under expansion if present.
 Only after achieving satisfactory initial results should DCB
angioplasty be done.
 single 30- to 60-second balloon inflation.
 Transfer of paclitaxel to the vessel wall results in effective
suppression of neointimal hyperplasia.

36.  PACCOCATH-ISR: Reduced late loss at 6 months
compared to balloon angioplasty alone. 5 Yrs. Results
confirmed durability of efficacy.
 PEPCAD-II: Late loss at 6 month was less with deb versus
DES angioplasty.
 RIBS-IV: Acute luminal gain was more with DES but
clinical events and restenosis at 1 year was not different
from DEB strategy.

37.  PEPCAD DES: DEB is superior to plain angioplasty.
 ISAR DESIRE III:
› DCB was comparable to repeat stenting with PES at 6-8
months.
› DCB & PES were superior to plain balloon angioplasty.
 It seems reasonable to conclude that by obviating the
need for repeat stent implantation, DCB angioplasty
may be the preferred treatment option for this
indication.