2/20/2014

1

Take Heart Despite a Bad Heart:

Advances in Restoring Clogged

Coronaries without Bypass

Surgery

Garrett Wong, MD

February 22, 2014

Objectives

Review pathophysiology of coronary disease

Brief history of coronary interventions

Discuss new percutaneous options for

revascularization of complex lesions

Discuss advances in stent technology

Atherosclerosis Progression “CAT” Scan

CT Angiography Coronary Angiography – remains the Gold

standard

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2

Emergency Department Visits Annually in

the U.S.

95 MM visits1

8 MM for chest pain1

6.1 MM

Non-cardiac1

0.6 MM

for ST-

segment

Myocardial

Infarction2

1.0 MM

for Unstable

Angina2

0.4 MM

for Non-ST-

segment

Myocardial

Infarction2

1. Personal communication, W. Brian Gibler, MD, University of Cincinnati.

2. 2002 SMG Medicare Database.

ECG – Massive Anterior STEMI

Diagnostic Algorithm for Acute Coronary

Syndrome Management

Therapeutic goal: rapidly break apart fibrin

mesh to quickly restore blood flow

ST-segment elevation MI Non-ST Elevation ACS* Non-ST Elevation MI

+ Tn &/or + CK-MB

Consider fibrinolytic therapy, if indicated, or

primary percutaneous coronary intervention

(PCI)

Therapeutic goal: prevent progression to complete

occlusion of coronary artery and resultant MI or

death

Consider GP IIb-IIIa inhibitor + aspirin + heparin

before early diagnostic catheterization

&/or

Braunwald E, et al. 2002. http://www.acc.org/clinical/guidelines/unstable/unstable.pdf.

Acute Myocardial Infarction

Acute Coronary Syndrome with

Unfavorable Outcomes Clinical Manifestations of Arterial Thrombosis

UA/NSTEMI: Partially-occlusive thrombus

(primarily platelets)

Intra-plaque

thrombus

(platelet-dominated)

Plaque core

STEMI: Occlusive thrombus

(platelets, red blood cells, and fibrin)

Intra-plaque

thrombus

(platelet-dominated)

Plaque core

SUDDEN

DEATH White HD. Am J Cardiol 1997;80 (4A):2B-10B.

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Coronary Angiography – RCA thrombus History of Interventional Cardiology

1974 Andreas Gruentzig performs first

peripheral human balloon angioplasty

1976 Gruentzig presents results of animal

studies of coronary angioplasty at

American Heart Association

1977 First human coronary balloon

angioplasty performed intra-operatively

by Gruentzig, Myler and Hanna in SF

1977 Andreas Gruentzig performs first cath

lab PTCA on awake pt in Zurich

(Percutaneous Transluminal Coronary Angioplasty)

Interventional Cardiology - 1977

A new specialty is born

PTCA - Percutaneous Transluminal Coronary Angioplasty

– Plaque compression

– Stretching of medial wall

– Controlled injury

PTCA - 1977

Percutaneous Transluminal Coronary Angioplasty

– 50% Restenosis - A new disease

Elastic recoil

Vascular negative remodeling

Neointimal hyperplasia

– Abrupt and threatened closure

Coronary Stent - 1994

Palmaz-Schatz Coronary Stent

– Primary Stent implantation

Why are we stenting?

– Limitations of PTCA, atherectomy, laser

Restenosis, dissection, abrupt closure, suboptimal result

– Stenting - Scaffolding

Predictable, quick, angiographically seductive

Coronary Stenting

Restenosis reduced to 25%

Prevents elastic recoil

Prevents negative vascular remodeling

Increase intimal hyperplasia – In-stent restenosis

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Brachytherapy

In-Stent Restenosis – ISR

– Achilles heel of Percutaneous Coronary

Intervention

– Occurs by 6 - 12 months

– Recurs > 70% with standard therapy

Brachytherapy - Local radiation

– Gamma - Very penetrating - Iridium 192

– Beta - Limited penetration - Strontium 90

Drug Eluting Stents - 2003

Restenosis rate with Bare Metal Stents ~ 25%

Pathophysiology of restenosis defined

Drugs identified

– Inhibit smooth muscle cell migration

– Inhibit smooth muscle cell proliferation

– Inhibit extracellular matrix formation

Sirolimus - Rapamycin

Paclitaxel - Taxol

Polymer coating to bind drug, control release, vascular

biocompatible

Coronary Angiogram – Left Coronary Artery

Severe Ostial Left Main Disease

Question of PCI or CABG?

Typical PCI patient

– 1 or 2 vessel disease

Typical referral for CABG

– Severe Left Main disease

– Severe multivessel CAD

– Chronic total occlusions

– Severe LV dysfunction and diabetes

– Severe valvular disease

Two Very Different Procedures… Answer is not so clear anymore

Severe Left Main disease

– Syntax LM Subset

Severe multivessel CAD

– Syntax Trial

– EXCEL Trial

Chronic total occlusions

– New technologies and equipment

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SYNTAX Trial Design

Left Main Disease (isolated, +1, +2 or +3 vessels)

N=705

3 Vessel Disease (revasc all 3 vascular territories)

N=1095

De novo disease (n=1800)

Limited Exclusion Criteria

Previous interventions

Acute MI with CPK>2x

Concomitant cardiac surgery

Serruys PW et al. NEJM 2009;360:961-72

Primary endpoint = death/MI/stroke/repeat revasc at 1 year

P=0.12

31.0%

0 Cum

ula

tive E

vent

Rate

(%

)

25

50

Months Since Allocation

Before 1 year* 13.7% vs 15.8%

P=0.44

1-2 years* 7.5% vs 10.3%

P=0.22

2-3 years* 5.2% vs 5.7%

P=0.78

3-4 years* 6.4% vs 8.3%

P=0.35

36.9%

TAXUS (N=357) CABG (N=348)

SYNTAX: MACCE to 5 Years Left Main Subset

4-5 years* 5.9% vs 5.5%

P=0.82

0 12 60 24 36 48

Mohr FW et al. Lancet 2013;381:629–38

CABG PCI P value

Death 15.1% 7.9% 0.02

CVA 3.9% 1.4% 0.11

MI 3.8% 6.1% 0.33

Death, CVA or

MI 19.8% 14.8% 0.16

Revasc. 18.6% 22.6% 0.36

LM Disease

TAXUS (N=221)

CABG (N=196)

31.3%

32.1%

Months Since Allocation

Cum

ula

tive E

vent

Rate

(%

)

0 12 24

50

0

25

48 36 60

P=0.74

MACCE to 5 Years by SYNTAX Score Low to Intermediate Scores (0-32)

Serruys PW et al. Lancet 2013;381:629–38

TAXUS (N=135)

CABG (N=149)

CABG PCI P value

Death 14.1% 20.9% 0.11

CVA 4.9% 1.6% 0.13

MI 6.1% 11.7% 0.13

Death, CVA or

MI 22.1% 26.1% 0.40

Revasc. 11.6% 34.1% <0.001

LM Disease

Months

MA

CC

E (%

)

0 12 24

50

0

25

48 36 60

46.5%

29.7%

P=0.003

Serruys PW et al. Lancet 2013;381:629–38

MACCE to 5 Years by SYNTAX Score High Scores ≥33

SYNTAX Trial Patient Distribution

PCI LM

Legitimate

34%

Surgery

For LM Still

gold standard

66%

Results of the SYNTAX

Trial suggest that 1/3 of

all patients with Left

Main lesions are best

treated with PCI

Excellent alternative to

surgery…. at least up

to five years

Answer is not so clear anymore

Severe Left Main disease

– Syntax LM Subset

Severe multivessel CAD

– Syntax Trial

– EXCEL Trial

Chronic total occlusions

– New technologies and equipment

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CABG PCI P value

Death 9.3% 10.2% 0.81

CVA 3.9% 1.8% 0.24

MI 4.9% 8.8% 0.20

Death, CVA or

MI 14.8% 17.5% 0.56

Revasc. 14.6% 23.1% 0.04

Cumulative KM Event Rate ± 1.5 SE; log-rank P value

3-Vessel Disease

TAXUS (N=181)

CABG (N=171)

33.3%

26.8%

Months Since Allocation

Cum

ula

tive E

vent

Rate

(%

)

0 12 24

50

0

25

48 36 60

P=0.21

MACCE to 5 Years by SYNTAX Score Low Risk Scores (0-22)

R

Clinical follow-up: 1 mo, 6 mo and yearly through 5 years

EXCEL: Study Design

3600 pts with unprotected left main disease

SYNTAX score ≤32 Consensus agreement by heart team

Yes (N=2600)

No (N=1000)

Enrollment registry

PCI (Xience Prime) (N=1300)

CABG (N=1300)

@ 165 international sites

Answer is not so clear anymore

Severe Left Main disease

– Syntax LM Subset

Severe multivessel CAD

– Syntax Trial

– EXCEL Trial – Ongoing enrollment

Chronic total occlusions

– New techniques and equipment

CTO of the LAD

Chronic Total Occlusions

Recanalization of a CTO – The Final Frontier

Technically the most challenging coronary interventions

Difficult to Treat

– Time intensive

– Significant contrast load

– Significant radiation exposure

– Complications

– Previous success rate ~ 50%

– Success rates now 80 – 90%

Rationale for CTO Revascularization

Improvement of symptoms

– Improve coronary blood flow - O2 Supply

Reduction in ischemic burden

Enable completeness of revascularization

Improvement in LV function

Increase long-term survival

Improve electrical stability of myocardium - reduce

predisposition for arrhythmic event

Avoidance of surgical bypass procedures

Reduced medications

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Predictors of Success

Predictors of lower success

– Increasing age of lesion - chronicity

– Longer length of occlusion

– Non-tapered stump

– Origin of side branch at occlusion

– Bridging collaterals

1 Kinoshita I, JACC 1995;26:409

Guidewires

Polymer cover with Hydrocoat hydrophilic coating

Intermediate coils: Maintain .014" diameter for smooth device delivery

BMW

Intermediate section has both a hydrophilic coating and a polymer cover

BMW

Universal

Pilot/Whisper

Miraclebro 3

Tip feel and torque, 11 cm radiopacity, hydrophobic coating for tactile feel

Newer Specialty CTO Asahi Wires

Fielder XT

Fielder FC 11cm Spring Coil

3cm Radio-opaque Coil

0.014”

20cm Polymer Sleeve & SLIP COAT® PTFE Coating

Stainless Steel Core

16cm Radio-opaque spring coil

16cm Polymer Sleeve & SLIP COAT®

0.014” PTFE Coating

Stainless Steel Core

0.009”

SION

Guidewire Techniques – Support catheters

Crossing

– Balloon - OTW otherwise 1.5 mm Monorail

– Support - Finecross, Transit, Minnie, Quickcross

– Tornus

– Gopher

Eight (8) individual wires (0.007") stranded together to form the catheter

“Definition of insanity is doing the same thing over

and over again and expecting the same result.”

CTO – Newer Device Technology

Blunt Microdissection (Frontrunner - Cordis)

Radiofrequency (SafeCross - Kensey Nash)

Vibrational (Crosser - FlowCardia)

Dissection/Reentry (Cross Boss - Boston Sci)

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Frontrunner - Blunt microdissection

Adventitia

Fibro-calcific CTO

The CROSSER™ System High Frequency Mechanical Recanalization Technology

The Electronics

Generator provides high frequency current – 20 kHz

Transducer converts high frequency current vibrational energy

Excimer Laser Coronary Atherectomy

ELCA

Cross Boss CTO Catheter

Stingray

Balloon

Catheter

Bi-directional rotation of the torque device with the FAST SPIN Technique

1 mm atraumatic rounded tip

Intended to cross directly through the CTO or bypass the obstruction via a subintimal path

Stingray CTO Re-Entry System

Reentry Device

– Guidewire in false lumen beyond CTO

– Advance Flat balloon beyond CTO

– Self orients parallel to adventitia

– Deflect tip toward lumen

– Advance wire into distal lumen

CTO of the RCA

Contralateral injection of the L R collaterals

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CrossBoss Catheter Angioplasty and Stenting

Final Angiography Retrograde Technique

Collateral Channel

– Bypass graft

– Epicardial collateral

– Septal perforator

Technique

– Retrograde wire crossing

– Kissing wire technique

– CART technique Controlled Antegrade and

Retrograde subintimal Tracking

Collateral Pathways After RCA Occlusion

Microcatheter Balloon

Flexible tapered tip of ASAHI Corsair contributes excellent channel

tracking and also effectively works for super-selective tip injection

Corsair Catheter Collateral Crossing and Support Catheter

Hydrophilic Polymer Coating

60cm

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CTO of the RCA – Retrograde Approach CTO of the RCA - Retrograde

Identify an appropriate septal collateral

Septal channel wiring – In real time CTO of the RCA - Retrograde

CTO of the RCA - Retrograde Successive Balloon Angioplasty

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Multiple drug-eluting stents placed Final Angiography

Approaching CTO’s

63

Success not guaranteed

64

Improved techniques & technologies

65

UC Davis

More complex interventions

66

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Still no guarantees

67

Drug Eluting Stents for CTO

0

10

20

30

40

50

Average BMS

Research2004

Nakamura2005

Werner 2004

Serruys 2004

Colombo2005

Grube 2005

n = 340 n = 35

Cypher

n = 38

Taxus

n = 122

Cypher

n = 33

Cypher

n = 48

Taxus

n = 60

Cypher

Drug-Eluting Stents: 1st Generation

TA

XU

S

Polyolefin derivative Paclitaxel

Drug Polymer Stent

Cyph

er

PEVA + PBMA blend Sirolimus BX Velocity

Liberté Pre Post 1 Year

2 Years 4 Years 7 Years

Sirolimus-Eluting Stent: 7 year F/U

Target Lesion Revascularization at 5 Years TAXUS I, II-SR, IV & V

30%

12.3% (n=162)

21.0% (n=284)

5-Year HR [95% CI]:

0.53 [0.44, 0.65]

P<0.001

0%

0 1 2 3 4 5

20%

10%

TLR (

%)

BMS (n=1397)

TAXUS (n=1400)

Years Stone GW et al. JACC CV Int 2011;4:530–42

1st Gen Drug-Eluting Stents

The good, the bad, and the ugly!

7 years

40 mos

BMS DES

Incomplete

apposition

Late stent

thrombosis

Abn Vasomotion

*P<0.001 vs. control

Sirolimus

Control

* *

Delayed Healing!

Angioscopy

BMS

DES Late loss = 0

Eos

Giant cells

IVUS

Inflammation

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Definite/Probable ARC Stent Thrombosis to 5 Yrs (Per Patient)

(3/896) (23/893) (15/874) (11/850) (12/830)

Days Postprocedure

Acute ≤1d

Subacute 2-30d

Late 31-365d

Very Late

(10/803) (7/768)

366-

730d

731-

1095d

1096-

1460d

1461-

1825d

10.4%

(76/730)

Total 5 year

0.3

2.6

1.7 1.3 1.4 1.2 0.9

Serruys PW et al. TCT 2012

~4.6% in year 1 ~1.2%/year after year 1

European Society of Cardiology 2006

Drug-Eluting Stents: 2nd Generation

Drug Polymer

Xie

nce

V

VDF + HFP copolymer Everolimus Vision

O

O

O O HO

O

O

O O H O

O O

N O

H O

Stent

Pro

mu

s

Ele

men

t

VDF + HFP copolymer Everolimus Element (Ion)

O

O

O O HO

O

O

O O H O

O O

N O

H O

SPIRIT II, III, IV and COMPARE trials

MACE (Cardiac Death, MI, ID-TLR)

P<0.001

HR: 0.64 [0.54, 0.75] EES (n=4,247) PES (n=2,542)

4247 4086 3942 3291

2542 2363 2269 1944

Number at risk

XIENCE

TAXUS

11.1%

Card

iac D

eath

, M

I,

Isch

em

ic T

LR

(%

)

0

15

Time in Months

0 3 6 9 12 15 18 21 24

3820

2193

7.3%

10

5

7.6%

4.4%

Kereiakes DJ et al. EuroIntervention 2011:7:74-83

Pooled database analysis (n=6,789)

SPIRIT II, III, IV and COMPARE trials

Stent thrombosis (ARC definite/probable)

Kereiakes DJ et al. EuroIntervention 2011:7:74-83

Pooled database analysis (n=6,789)

4247 4177 4082 3479

2542 2463 2408 2110

Number at risk

XIENCE

TAXUS

2.3%

Ste

nt

thro

mb

osis

AR

C d

ef

or

pro

b (

%)

0

1

2

3

Time in Months

0 3 6 9 12 15 18 21 24

3998

2350

0.7%

p<0.001

HR: 0.30 [0.19, 0.47] EES (n=4,247) PES (n=2,542)

‘Caged’ (Stented) Vessel Etiology of DES events beyond 1 year

Delayed Healing Stent Thrombosis?

Benign NIH

In-Stent Restenosis

Late Acquired Malapposition Stent Thrombosis?

Neo-Atheroma

Stent Thrombosis?

* uncovered struts1

1. Virmani, R. CIT 2010

2/20/2014

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Potential of a Fully Bioresorbable Vascular

Scaffold

Benign NIH

In-Scaffold Restenosis Plaque Regression

Expansive Remodeling Late Lumen

Enlargement

Since struts disappear, issues related to very late persistent strut

malapposition and chronically uncovered struts become irrelevant

Rationale: Vessel scaffolding is only needed transiently

Bioresorbable Vascular Scaffolds (BVS)

Igaki-Tamai PLLA

Magnesium (eluting

paclitaxel) Biotronik Dreams

PLLA (w/PDLLA coat

eluting everolimus) Abbott Absorb

Reva ReSolve Iodinated tyrosine-

derivative (eluting

sirolimus)

Elixir DESolve PPLLA (eluting

myolimus)

Abbott Vascular Everolimus-Eluting Bioresorbable Vascular Scaffold Components

Bioresorbable

Coating

• Poly (D,L-

lactide) (PDLLA)

coating

• Naturally

resorbed, fully

metabolized

• Similar dose density and release rate to XIENCE V

Everolimus

• Poly (L-lactide) (PLLA)

• Naturally resorbed, fully metabolized

Bioresorbable

Scaffold

XIENCE V

Delivery System

• World-class deliverability

Polylactide Degradation & Lactate

Metabolism

CH3CH(OH)COO-

Lactate

CH3COCOO- + H+

Pyruvate

CH3COSCoA

Acetyl-CoA

Citrate

Isocitrate

Ketogluterate

Succinyl-CoA Succinate

Fumarate

Malate

Oxaloacetate

TCA (Krebs)

Cycle

H2O

CO2

ATP

Strut Remnant

C3H6O3 DIFFUSION

C3H6O3

Lactic Acid

CH3CH(OH)COO- + H+

Lactate

Intracellular

Mitochondrio

n

Lactate Shuttle1

Lactate serves as a

carbohydrate fuel source for

multiple metabolic pathways

Lactic Acid

1. Philp, A., et.al. J. Exp. Biol. 2005; 208: 4561-4575.

Krebs Citric Acid Cycle

Post-stenting 6-month 24-month

Complete strut

apposition

Late acquired incomplete

stent apposition with

tissue bridges between

fractured struts

Corrugated endolumen

Smooth endoluminal

lining

Struts largely

disappeared although

remnant just visible

(arrow)

ABSORB Trial (BVS cohort A): OCT Results

Serruys PW et al. Lancet 2009;373:897-910.

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Extensive Publications More than 120 Absorb Publications by CE Launch Overview of ABSORB Studies

Balloon angioplasty 1977

Bare metal stents 1990s

Drug-eluting stents 2000’s

FIRST SECOND THIRD FOURTH

Bioresorbable Drug- eluting stents 2006

Bioresorbable scaffolds

have been called

“The Fourth Revolution”

in PCI

Summary

• Significant advances have been made in the field of

Interventional Cardiology

• Previous bypass surgery patients are being successfully

treated with PCI and stenting

• Stent technologies are constantly evolving

• BVS technology is promising and may improve upon

some of the known drawbacks of metallic stents

• Ongoing studies and future studies will be necessary to

demonstrate their long-term efficacy and safety in a

broad range of patients

Thank You