fighting restenosis: tips and tricks · 2019. 11. 1. · treating des restenosis • use longer...

Fighting Restenosis:Fighting Restenosis:Tips and TricksTips and Tricks

SCRIPPS CLINIC

Paul S. Teirstein

Chief of Cardiology

Director, Interventional Cardiology

Scripps Clinic

Disclosure Statement of Financial InterestDisclosure Statement of Financial Interest

Within the past 12 months, I or my spouse/partner have had a financialinterest/arrangement or affiliation with the organization(s) listed below.

Affiliation/Financial Relationship Company

Grant/Research Support Boston, Abbott, Medtronic, Edwards

Consulting Fees/Honoraria Boston, Abbott, Medtronic, Edwards

President (unpaid) NBPAS

SCRIPPS CLINIC

Treating DES Restenosis

• Get over feeling guiltyIt’s not your fault, it’s the technology’s faultPatients are very grateful, even the Platinum Frequent Flyers

• Be prepared to WORK. The greater acute gain you get the less chance offuture restenosis or at least a longer time interval for recurrence

• Dealing with ISR takes time and energy. The lesions are often very

SCRIPPS CLINIC

• Dealing with ISR takes time and energy. The lesions are often veryrecalcitrant with non-expandable scarring around the stent.

• Use ultra-high balloon pressures. Test your balloons on the back table. MostNC balloons now rupture closer to 30 atm. Its hard to get adequate results atjust 20 atm

• Use IVUS to adequately size high pressure balloons.• Longer inflations (>3min) seem to really help achieve the desired gorgeous

angiographic appearance


• Use longer balloons so they don’t slip as much

• Consider Wolverine, AngioSculpt and Chocolate balloons taken tohigh pressures. BUT, these specialty balloons can be very difficult todeliver

• If you do not get full balloon expansion, move quickly to laser. Most

SCRIPPS CLINIC

• If you do not get full balloon expansion, move quickly to laser. Mostoften I use the 0.09” laser set at 80/80 with contrast injections. If yousee cavitation (bubbles) that is a good sign, BUT, beware, you can getno-reflow from the cavitation. If you see bubbles, limit laser runs toonly 2-3 and keep an eye on flow

• Try to avoid Rotablation of unexpanded stents. The burr can get stuckand then it’s a nightmare.

• Shockwave (lithotripsy) may be a real help for the non-dilatable stent


• Oral therapies for restenosis have been disappointing. Oral rapamycin isavailable but high toxicity, high cost, and marginal efficacy

• Peripheral drug eluting balloons are available but the smallest diameter is4.0mm x 40mm long. Can be used for some RCA ISR lesions and SVG ISRlesions. Use 3 parallel stiff 0.014” guidewires. Obtain special consent!

• Coronary drug eluting balloon (DEB) for ISR trials will begin shortly

SCRIPPS CLINIC

• Coronary drug eluting balloon (DEB) for ISR trials will begin shortly• Restenting is always an option but we worry about more than two layers of

stent, especially in smaller (<3.0) vessels• Data does not support changing DES brands, but it seems logical to try

something different.• Newer Osiro stent has thinner struts in the 3.0mm and below iterations.

Might be a good choice if a 3rd or 4th layer is needed.• Brachytherapy use is on the increase. Scripps does >100 brachy cases per

year.

Undilatable CalcificCoronary StenosisCausing StentUnderexpansion andLate Stent ThrombosisA Complex ScenarioSuccessfully ManagedWithIntravascular LithotripsyCarlos Salazar, JavierEscaned, GabrielaTirado and NievesTirado and NievesGonzalo

JACC: CardiovascularInterventionsAugust2019DOI: 10.1016/j.jcin.2019.02.010

Platinum Card Frequent Flyer:Platinum Card Frequent Flyer:TwentyTwenty--one Cines from One Patientone Cines from One Patient

The CardiovascularResearch FoundationThe CardiovascularResearch Foundation

Lenox Hill Heart and VascularInstitute of New York

Lenox Hill Heart and VascularInstitute of New York

SCRIPPS CLINIC

Intracoronary Brachytherapy forMulti-Drug Resistant In-Stent

Restenosis

Paul Teirstein M.D.Paul Teirstein M.D.

Chief of Cardiology

Scripps Clinic

Disclosure Statement of Financial Interest

• Grant/Research Support

• Consulting Fees/Honoraria

• Medtonic

• Abbott

• Boston Sci

Within the past 12 months, I or my spouse/partner have had a financialinterest/arrangement or affiliation with the organization(s) listed below.

Affiliation/Financial Relationship Company

• Boston Sci

Background

In-stent restenosis (ISR), althoughinfrequent with current generation drug-eluting stents (DES), is a major limitation ofthe long-term efficacy of percutaneousthe long-term efficacy of percutaneouscoronary intervention (PCI).

Treatment Options

Medical Management Balloon angioplasty Scoring balloon Cutting balloon Another DES used for DES ISR (off label) Another DES used for DES ISR (off label) Laser or rotational atherectomy (off-label) Drug eluting balloon Bypass surgery Brachytherapy (off-label)

Rational for Study

DES reduces ISR

Brachytherapy is effective treatment for bare metalstent (BMS) ISRstent (BMS) ISR

No approved percutaneous treatment for DES ISR

Hypothesis – SCRIPPS V

To determine the safety and efficacy ofcoronary brachytherapy for the treatment ofrecurrent ISR within DES

Single center, observational, non-placebo trial

Approved by Scripps IRB

Inclusion Criteria At least 18 years old and eligible for PCI

Target lesion with recurrent restenosis (>50%)previously treated with 2 or more layers of differentDES

Signs and/or symptoms of ischemia attributable totarget lesion or stenosis > 50%

Target lesion in native artery or bypass graft

Able to understand and sign informed consent

Exclusion Criteria Confirmed pregnancy

Allergies to dual anti-platelet therapy of anyanticoagulation required during procedure

Life expectancy < 1yr Life expectancy < 1yr

Unsuccessful coronary revascularization (residualstenosis >30%)

Angiographic evidence of thrombus

Previous brachytherapy to target artery

Primary endpoints

At 30 days and 8 months

All-cause death

Myocardial infarction

Target vessel revascularization (TVR)

Secondary endpoints @ 2 years

Enrollment

May 2006 – September 2013

65 patients enrolled65 patients enrolled

100% follow-up at 8 months +/- 2 weeks

98.5% follow-up at 2 years

Baseline Characteristics

Hypertension 60 (92%)

Hyperlipidemia 65 (100%)

Diabetes 33 (50%)

Non-insulin dependent diabetes 21 (32%)

Insulin-dependent diabetes 12 (18%)

Chronic kidney disease 13 (20%)

COPD 4 (6%)

Previous CABG 29 (45%)

Tobacco use history 35 (54%)

Family history CAD 29 (45%)

Peripheral artery disease 8 (12%)

Heart failure 5 (8%)COPD – chronic obstructive pulmonary diseaseCABG – coronary artery bypass graftingCAD – coronary artery disease

Medications

Aspirin 64 (98%)

Clopidogrel 53 (82%)

Prasugrel 12 (18%)

ACEI 31 (48%)

ARB 14 (22%)ARB 14 (22%)

Beta blocker 49 (75%)

Calcium channel blocker 23 (35%)

Nitrates 24 (37%)

Ranolazine 14 (22%)

Statin 50 (77%)

ACIE – Angiotension converting enzyme inhibitorARB – Angiotension receptor blocker

Stentology

Layers of stent*

1 0

2 43 (66%)

3 9 (14%)

4 3 (5%)

Unknown 10 (15%)

Number of previous procedures = lost in translation

Stentology

Prior Type of Drug Eluting Stent

Cypher + Taxus and/or secondgeneration DES

51 (77%)generation DES

Second generation DES only 5 (8%)

Unknown 10 (15%)

Interventional Tools

Restenosis Location

19%

39%21%

Ramus 2%LIMA-LAD 5%SVG 14%

Intracoronary Radiation

FDA approved Novoste™ Beta-Cath™ system

Strontium/yttrium-90 beta radiation

Median dose 23 Gy Median dose 23 Gy

Radius dose of 2mm

Median time 4 min 26 sec

Treatment length 40-60 mm

Follow Up

Telephone contact with patient at 30 days and 8months and 2 years Review symptoms, medications, allergies, any adverse

events, repeat procedures

If unable to reach patient, questionnaire is sent bycertified mail

Ultimately, 100% follow up at 8 mos +/-2 weeks,98.5% follow up at 2 years

Obtain all records of medical events during the followup

Results

N = 6530

days8 months

Target vessel revascularization 0 15 (23%)

Non-Target Vessel2 (3%) 7 (11%)

Non-Target VesselRevascularization

2 (3%) 7 (11%)

Any Revascularization 2 (3%) 22 (34%)

TVR CABG 0 3 (5%)

Stent Thrombosis 0 0

Myocardial infarction 0 5 (8%)

Death 0 0

Results

N = 658 months

N = 652 yearsN = 64

Target vessel revascularization 15 (23%) 22 (34%)

Non-Target Vessel7 (11%) 9 (14%)

Non-Target VesselRevascularization

7 (11%) 9 (14%)

Any Revascularization 22 (34%) 32 (50%)

TVR CABG 3 (5%) 4 (6%)

Stent Thrombosis 0 0

Myocardial infarction 5 (8%) 5 (8%)

Death 0 3* (5%)

*Cardiac death = 1

• 186 Patients undergoing VBT for recurrent DES-ISR were enrolled

Negi et al. J Am Coll Cardiol Int. 2016;9(12): 1259-1265

• 186 Patients undergoing VBT for recurrent DES-ISR were enrolledfrom a percutaneous coronary intervention registry.

• Clinical, procedural, VBT, and outcome data were collected forDES-ISR treated with radiation.

• Follow-up was obtained by phone call and clinic visits.

Baseline Characteristic N=186

Age (years) 65±11

Male (%) 62

Body Mass Index (kg/m2) 30.1±6.2

Hypertension (%) 95

Smoking (%) 62

Baseline Characteristics

Smoking (%) 62

Diabetes (%) 46.5

Dyslipidemia (%) 94

Previous CABG (%) 55

Presentation with unstable angina (%) 30

STEMI (%) 3


ISR Details

Angiographic and Lesion-Specific Characteristics

Number of previous ISR episodes

• 1-2 (%) 4

• 3-4 (%) 63

• >4 (%) 25

• Unknown (%) 8


• Unknown (%) 8

Pattern of restenosis

Focal (%) 73

Diffuse (%) 23

Proliferative (%) 4

30 days 6-months 1-year 2-years 3-years

TLR 1 (0.5%) 6 (3.3%) 22 (12.1%) 31 (17.2%) 30 (19.4%)

Surgical TLR 0 0 0 3 (1.6%) 5 (2.8%)

Outcomes at 30 days, 6 months, 1, 2,and 3 years

TVR 3 (1.6%) 13 (7.1%) 35 (19.1%) 54 (30%) 55 (30.5%)

Surgical TVR 0 0 0 3 (1.6%) 5 (2.8%)

MI 0 1 (0.5%) 3 (1.5%) 10 (5.6%) 11 (6.7%)

LST 0 0 1 (0.5%) 1 (0.5%) 1 (0.5%)

Death 1 (0.5%) 7 (3.8%) 10 (5.4%) 18 (9.8%) 23 (13.2%)

LST, late stent thrombosis; MI, myocardial infarction; TLR, target lesion revascularization; TVR, target vessel revascularization


Kaplan-Meier Estimates of Target Lesionand Vessel Failure

TLR TLF


Washington Hospital Center

57% of Multiple (recurrent) ISR grouptreated with brachytherapy vs 17% ofthe group presenting with first episodethe group presenting with first episodeof ISR (p<0.01).

Washington Hospital Center

~15% MACE

Conclusions Multi-drug resistant ISR is infrequent but the absolute

# of patients with DES ISR is growing.

Intracoronary brachytherapy is a safe treatment forrecurrent DES ISR

TVR rates following brachytherapy for multi-drugresistant ISR are favorable at 8 months (23%) andacceptable at 2 years (34%) in this challenging patientgroup.

While brachytherapy reduces and slows thetimeframe of ISR following DES, restenosis is noteliminated.

PT1

PT1 Paul Teirstein, 9/14/2018

Coronary Brachytherapy Caveats

• Call for radiation oncologist when passing guidewire• Work hard to get a great result. Use cutting, scoring, laser,

and very high balloon pressures (ie 28-30 atm).• Use longer inflation times: 3-4 minutes, if tolerated• All brachy trials were done immediately after PCI of

significant ISR. We don’t have data on PCI, followed by

SCRIPPS CLINIC

significant ISR. We don’t have data on PCI, followed bybrachytherapy a week or month later.

• In the initial SCRIPPS trial, 1/3 of patients had a new BMSat the time of brachytherapy and no thrombosis signalobserved. In the larger RCTs, new stent during brachyprocedure was associated with a 7% early stentthrombosis rate.

• All data comes from trials using 1 year of DAPT. Shorter islikely okay but has not been studied.

fighting restenosis: tips and tricks · 2019. 11. 1. · treating des restenosis • use longer...

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