Stent restenosis

1. Restenosis of DES
A New Classification System Based on Disease
Mechanism to
Guide Treatment and State-of-the-Art Review
Dr. Sumit Shanker

2. Definition
• ISR has classically been defined as a luminal narrowing with
>50% diameter stenosis of a stented coronary segment or within
5 mm of a stent edge

3. INCIDENCE OF DES-ISR
• DESs demonstrated superiority to BMSs, which has led to the near
elimination of BMSs from routine clinical practice
• Second-generation DESs have improved on prior technology with a
modification of stent design, alloy composition (including strut thickness),
polymer, and drug that is eluted.
• Incidence of ISR rates ranging from 5% to 10%

4. PATHOGENESIS OF DES-ISR
• Many of the traditional mechanisms for the pathogenesis of BMS-ISR,
including biological, mechanical, and technical factors, also apply to DES-
ISR
• While DESs minimize neointima proliferation compared with BMSs,
hypersensitivity to the polymer and the drug, local inflammation, and delayed
healing are the main contributors of neointima formation

5. • In BMS-ISR, the neointimal tissue is composed of vascular smooth muscle cells and
extracellular matrix in a diffuse pattern
• The peak presentation incidence of this phenomenon occurs ≈6 months after
implantation
• By contrast, the coating on DESs inhibits and causes delayed intimal proliferation,
which can remain present for many years.
• Furthermore, DESs are associated with a more focal pattern, often involving the
stent edges, compared with the diffuse pattern characteristic of BMS-ISR.

6. • While BMS-ISR is associated with predominantly homogenous high-signal
tissue echogenicity, DES-ISR is more commonly associated with a layered
pattern with heterogeneous tissue composition.
• Early ISR,
• Characterized by homogenous neointimal hyperplasia, and neoatherosclerosis with thin-
cap fibroatheroma and
• Late ISR
• Lipid-rich neointima

7. • Neoatherosclerosis can occur years after stent placement and is
characterized by accumulation of lipid foamy macrophages within
the neointima, with or without necrotic core formation, and
calcification
• The late stent failure that is associated with DESs may be due, in
part, to the higher prevalence of neoatherosclerosis and diffuse
in-stent thin-cap neoatheroma with DESs

9. ROLE OF INTRACORONARY
IMAGING
• Intracoronary imaging can differentiate between a mechanical
mechanism and a biological cause.
• Mechanical causes of ISR can be related to stent underexpansion,
undersizing, or stent fracture.
• Inadequate lesion preparation in de novo coronary artery
calcification can predispose to stent underexpansion and can
prove difficult to treat

10. • In cases of stent underexpansion or undersizing, identifying the tissue composition
can guide optimal device selection
• Soft tissue is more likely to respond to treatment with high-pressure balloon
inflation, whereas calcified lesions may require adjunctive therapy, including excimer
laser coronary atherectomy, rotational atherectomy, or intravascular lithotripsy.
• Well-expanded stents with exuberant neointimal hyperplasia may be best treated
with cutting balloons followed by drug coated balloons (DCBs), an additional DES
based on an alternative drug, or vascular brachytherapy (VBT).

11. • Intracoronary imaging can uniquely delineate the number of stent
layers at the lesion site, as well as assess the expansion of each
layer of stents
• In cases of multiple layers of ISR, VBT offers a treatment option,
as further layers of stent should be avoided

13. • Stent fracture as a causality of ISR is best evaluated by intracoronary
imaging and is characterized by the absence of stent struts at the site
of fracture
• The true incidence of stent fracture is often underappreciated but has
been reported to range from 1% to 8%
• Local mechanical irritation of the vessel from fractured stent struts
coupled with decreased local drug availability secondary to distortion
of the stent architecture and polymer coating may increase the risk of
restenosis

15. • Fractional flow reserve has been validated for the evaluation of ISR, with a
favourable prognosis when revascularization is deferred with a cutoff of
≥0.80

16. WAKSMAN CLASSIFICATION FOR
DES-ISR

17. TREATMENT OF ISR
• Medical Management
• Attempts to manage ISR using medical therapy failed to significantly
reduce the recurrence rate

18. Balloon Angioplasty
• Plain balloon angioplasty historically represents the initial intervention performed
for both BMS-ISR and DES-ISR
• The procedure, however, was associated with edge-related complications and high
recurrence of ISR (>50%).
• High-pressure balloon angioplasty can be used for stent underexpansion
• Short, noncompliant balloons may be more useful and may prevent longitudinal
barotraumas; however, effort should be made to avoid edge-related complications
and slippage of the balloon outside the stent (watermelon seeding phenomenon)

19. Cutting and Scoring Balloon
• Scoring balloons were introduced to minimize barotraumas to the
vessel wall and slippage of a conventional balloon when inflated
over fibrotic scar tissue
• Cutting balloons use multiple blades that anchor the device in the
lesion, avoiding the watermelon seeding effect, with the
theoretical advantage of cutting the neointimal tissue.

21. Ablative Therapy: Atherectomy and Laser
• Both rotational atherectomy and excimer laser coronary atherectomy act by
debulking the lesion
• Rotational atherectomy may be beneficial in selected cases with calcified
neoatherosclerosis or underexpanded stents that are resistant to highpressure
balloons.
• Excimer laser coronary atherectomy produces monochromatic light energy,
which generates heat and shock waves to disrupt and modify plaque.

22. Drug-Coated Balloons
• DCBs offer the advantage of avoiding the implantation of an additional
metallic layer when treating ISR and are recommended by European Society
of Cardiology guidelines as a treatment option (Class I, Level of Evidence:
A)
• DCBs use lipophilic drugs, such as paclitaxel, to inhibit neointimal
proliferation

23. Repeat DES
• Adverse events were significantly higher in patients treated with DCBs who
had >2 stent layers, whereas minimal differences were noted in events
between those with 1 or 2 layers of prior stent.
• This supports our practice to avoid a third layer of stents in favour of
alternative modalities
• No clear evidence guides which type of DES should be used to treat ISR of
a DES

24. Vascular Brachytherapy
• Brachytherapy inhibits neointimal formation within the stent by delivering localized
radioactive Strontium-90 β-radiation via a hydraulic mechanism with the Beta-Cath
Device
• Adjunctive debulking with excimer laser coronary atherectomy before VBT may
improve clinical outcomes
• VBT is primarily used for refractory ISR, and its use should be considered when
multiple layers of stent are present.
• Treatment with VBT can be repeated when necessary, with a 12-month interval
between applications

25. Bioresorbable Scaffolds
• The use of bioresorbable scaffolds for ISR is based on the hypothesis that
bioresorbable vascular scaffold would gradually disappear after providing a
stronger dilatation than DCBs as an alternative to DESs for the treatment of
ISR.

27. CONCLUSIONS
• ISR remains a challenging clinical problem with DESs. ISR remains difficult
to treat, and optimizing stent implantation at the time of stent deployment
with imaging-guided techniques is perhaps the best strategy to minimize ISR
• Lesions with ISR should universally undergo intracoronary imaging
assessment to determine the cause