Michael Knizhnik — Endovascular treatment for patients with critical limb ischemia: yesterday,...

Michael Knizhnik

Belinson Hospital, Rabin MC, Petah-Tiqva, Israel

"

Almaty 4 July 2014

66% of PAD patients may have stable symptoms. Up to 5% will eventually

require amputation.

However, cardiovascular mortality in patients with PAD is sharply increased

with a significantly higher overall death rate. JVIR 2013

A diagnosis of PAD is critical evidence of more atherothrombotic, with

high risksof subsequent CVS events and death. Cardiovasc Dis.2005

• Within 3 months of presentation:

– death in 9%

– MI in 1%

– stroke in 1%

– amputation in 12%

– persistent CLI in 18%

• 1-year mortality: 21.0%

• 2-year mortality: 31.6%

interventional radiologist

vascular surgeon

orthopaedist

podiatr cardiologist

endocrinologist

?

plastic surgeon

Recommendation 24. Optimal treatment for patients with critical limb ischemia (CLI)

Revascularization is the optimal treatment for patients with CLI

Which kind of revascularization?

F3.2 Endovascular treatment of infrapopliteal occlusive disease Endovascular procedures below the popliteal artery are usually indicated for limb salvage and there are no data comparing endovascular procedures to bypass surgery for intermittent claudication in this region. Angioplasty of a short anterior or posterior tibial artery stenosis may be performed in conjunction with popliteal or femoral angioplasty. Use of this technique is usually not indicated in patients with intermittent claudication. There is increasing evidence to support a recommendation for angioplasty in patients with CLI and infrapopliteal artery occlusion where in-line flow to the foot can be re-established and where there is medical co-morbidity. In the case of infrapopliteal angioplasty, technical success may approach 90% with resultant clinical success of approximately 70% in some series of patients with CLI. Salvage rates are reported as being slightly higher.

Röntgen 1895 X-ray imaging Heuser 1919 Venography in man Moniz 1927 Arteriography Forssmann 1929 basilic vein cath. to the heart* Dos Santos 1929 tranlumbar aortography Farinas 1941 transfemoral aortography Seldinger 1951 arterial access Fogarty 1963 embolectomy catheter Dotter 1964 arterial dilation w rigid catheters Gruntzig 1974 balloon angioplasty Palmaz 1985 balloon expandable stent Parodi 1991 stent graft

S.Seldinger

1953 a method of percutaneous insertion of a catheter into a blood vessel or space.

A needle is used to puncture the structure and a guide wire is threaded through the needle; when the needle is withdrawn, a catheter is threaded over the wire; the wire is then withdrawn, leaving the catheter in place.

Ch. Dotter M. Judkins

Described angioplasty in 1964, jugular veinthrough the liver biopsyalso developed

http://en.wikipedia.org/wiki/Jugular_vein

http://en.wikipedia.org/wiki/Liver_biopsy

A. Gruentzig

1974 - Peripheral angioplasty

1984 the original nitinol stent, which was the first in the world implanted into vessels,

biliary tracts, the esophagus, and other hollow organs.

I.Rabkin

Foot arteries anatomy & angiosomes

•IN NORMAL SUBJECTS, FOOT CIRCULATION IS ANASTOMOTIC

LOTS OF ARTERIAL-ARTERIAL BRANCHES = COLLATERALS

In Diabetic Patients Collaterals Formation is Reduced or Absent

Circulation, 1999;99:2239-2242; Cardiovasc Res. 2001 Feb 16;49(3):554-60; Circulation, 2004;2343-2348

IN DIABETIC SUBJECTS, FOOT CIRCULATION BECOMES

BECAUSE OF LACK OF COLLATERALS FUNCTIONALLY TERMINAL

THIS IS THE REASON WHY WE NEED TO IMPROVE THE

FLOW TO THE WOUNDED AREA MOST DIRECT

THE SAME REASON WHY WE NEED TO LOOK AT THE WOUND,STUDY THE VASCULAR ANATOMICAL

SITUATION, IDENTIFY THE RELATED ARTERY AND TREAT IT WHEN POSSIBLE

Angiosome: Anterior Tibial

Angiosome: Peroneal Calcanear Branch

Angiosome: Posterior Tibial

M. Manzi, MD

Contralateral femoral (retrograde)

Ipsilateral femoral (antegrade)

Ipsilateral popliteal (retrograde)

Pedal

HEALING VARIABLES

•Number of vasc. levels involved

•Plantar arch patency

•Amount of tissue destruction

•Presence of infection

•Need of debridement or skin graft

•Available conduit for bypass

•Comorbidity

•Nutritional status

• Complete vessel treatment

- pressure wire

• Restenosis less of an issue

• Clinical follow-up and team

approach more important

- wound clinic

01-2014 JB5799

In high risk patients, choosing Visipaque can help optimise

outcomes and minimise costs6,12

Visipaque reduces the likelihood of cardiac and renal

complications in high risk patients6-10

Visipaque helps minimise discomfort for patients undergoing

intra-arterial procedures11

In patients at high risk of contrast-related adverse events,

choice of contrast agent is critical1-4

Visipaque is the only X-ray contrast agent for intravascular use

with an osmolality similar to blood at all iodine concentrations5

01-2014 JB5799

In patients at high risk of contrast-related adverse events, choice of contrast agent is critical.

01-2014 JB5799

An increasing number of patients are at high risk of contrast-related adverse events

Increased

risk of13 Cardio-renal

syndrome15-17

Increased

risk of14

e.g. with diabetes, renal

impairment, proteinuria,

hypertension, gout, recent

nephrotoxic treatment1,2

CM volume and

osmolality should

be limited2

Risk factors for CM-related adverse events1,2,13-17

Ageing

patients

CVD

CKD

Intra-

arterial

procedures

Other

vulnerable

adult patients

Paediatric

patients

There are many interacting risk factors for CM-related adverse events, including age, CKD, CVD and interventional cardiology procedures1,2,13-17

– As the population ages, the number of patients at high risk of CM-related adverse

events increases

CKD: chronic kidney disease

CM: contrast media

CVD: cardiovascular disease

01-2014 JB5799

Patients with multiple risk factors are more likely to experience adverse events such as contrast-induced acute kidney injury18

CKD is the most significant risk factor for CI-AKI, which is the 3rd most common cause of hospital-acquired acute renal failure19

Formal risk scoring in the cardiac angiography setting shows that the presence

of multiple risk factors increases the likelihood of CI-AKI further18

* SCr >1.5 mg/dl score =4 or eGFR score =2 (40–60 ml/min/1.73 m2), 4 (20–40 ml/min/1.73 m2), or 6 (<20 ml/min/1.73 m2) † SBP <80 mmHg ** NYHA class III/IV± pulmonary oedema †† baseline haematocrit <39% for men and <36% for women

CI-AKI risk increases as the number of risk factors increases

(n=8,357)18

Renal impairment* 2–6

Hypotension† 5

Intra-aortic balloon pump 5

Congestive heart failure** 5

Age >75 years 4

Anaemia†† 3

Diabetes mellitus 3

CM volume 1 per 100

ml3

Risk factors Score

≤5

6-10

11-15

≥16

7.5%

14.0%

26.1%

57.3%

Total score Risk level Incidence of CI-

AKI

Low

Moderate

Hig

h

Very

high

Adapted from Mehran 200418


CM: contrast media

CI-AKI: contrast-induced acute kidney injury

eGFR: estimated glomerular filtration rate

NYHA: New York Heart Association

SBP: systolic blood pressure SCr: serum creatinine

01-2014 JB5799

In patients undergoing interventional procedures, contrast-induced

acute kidney injury increases the risk of further cardiovascular

events20,21

Cardio-renal syndrome can be exacerbated by CI-AKI, which increases the risk of death, CV events

and associated hospital stays in patients undergoing percutaneous coronary intervention20-25


CM: contrast media

CV: cardiovascular MACE: major adverse cardiac events

PCI: percutaneous coronary intervention

% p

atie

nts

16

12

8

4

0

13.8%

Outcome: Mortality In-hospital MACE In-hospital stroke Vascular complications

Adapted from Iakovou 200220

Card

iovascula

r events

No CI-AKI

CI-AKI

p<0.0001

5.3%

p=0.001

7.9% 2.9% 4.7% 1.4%

p=0.0008

4.7% 0.9%

p=0.0003

CI-AKI increases the risk of CV events in patients receiving CM for PCI (n=8,268)20

01-2014 JB5799

Even transient contrast-induced acute kidney injury results in increased hospitalisation, morbidity and mortality for cardiovascular events

Both transient and persistent CI-AKI are prognostically significant for hospitalisation, morbidity and mortality during extended follow-up26,27

Physicians may disregard mild or transient increases in SCr after CM procedures, even though they lead to worse short- and long-term outcomes26

* CI-AKI defined as a >25% increase or >0.5 mg/dl (>44.2 mmol/l) increase in SCr within two days of intravascular administration

of iodinated CM when no other major kidney insult was identified

CI-AKI* increases the risk of hospital admission for CV events

(incuding myocardial infarction, heart failure, stroke and target

vessel revascularisation) dialysis and death26

Cum

ula

tive e

vent

rate

for

com

posite e

ndpoin

t

0 12

24

36

0.6

0.4

0.2

0.0

Follow-up (months)

Persistent CI-AKI

Transient CI-AKI

No CI-AKI

p=0.021

p=0.035

Hospital adm

issio

n, dia

lysis

and d

eath

Adapted from Wi 201126


CM: contrast media

CV: cardiovascular

SCr: serum creatinine

01-2014 JB5799

Patients at higher risk of contrast-induced acute kidney injury are more likely to incur the considerable long-term costs associated with it

When adjusted by risk level, the average cost of managing CI-AKI per PCI performed is higher in high risk patients, since they are more likely to develop it28

– The largest cost driver is the increased length of stay associated with the

initial hospitalisation28

*Risk levels taken from the risk scoring system developed by Mehran et al (2004)18

Average 1-year cost per CI-AKI event28

Average 1-year cost per PCI procedure28

12,000

8,000

4,000

0

Cost $

Cost $

Patient CI-AKI risk level*

CI-AKI event Lo

w

Hig

h

Very

high

Moderat

e

Dialysis

MACE

In-hospital

Adapted from Subramanian 200728


MACE: major adverse cardiac events

PCI: percutaneous coronary intervention

9,000

6,000

3,000

0

01-2014 JB5799

Choice of contrast agent is critical to minimise the

likelihood of contrast-related events in high risk patients1-4

Hyperosmolality has long been recognised by international guidelines as one of the key determinants of CM-related adverse events, particularly in high risk patients1-4

ACR: American College of Radiology



CM: contrast media

CV: cardiovascular

KDIGO: Kidney Disease Improving Global Outcomes


Increased

risk of6

Increased

risk of2,3

Increased

risk of29

CV

effects

and

MACE

Patient

discomfort

Hyperosmolality as a factor in CM-related adverse events1-3,6

CI-AKI

The KDIGO Clinical Practice Guideline states that

wherever possible isosmolar agents should be used

in people with CKD at high risk for CI-AKI4

ACR guidelines suggest that for intra-arterial injections, isosmolar CM are associated with the least amount

of discomfort2 2013

2013

ACR guidelines state attention should be paid to limiting osmolality in patients with CV disease2

2013 Hyper-

osmolality

01-2014 JB5799

Visipaque is the only X-ray contrast agent for

intravascular use with an osmolality similar to

blood at all iodine concentrations5

Visipaque reduces the likelihood of contrast-related

cardiac and renal complications in high risk patients6-10

Visipaque helps minimise discomfort for patients

undergoing intra-arterial procedures11

01-2014 JB5799

Examining the rate of contrast-induced acute kidney injury with Visipaque compared with low osmolar agents in high risk patients

A recent comprehensive meta-analysis investigated the incidence of CI-AKI in comparative studies of isosmolar Visipaque and LOCM6

A broad range of publications were considered6

The baseline SCr across all included studies was ≥1.6 mg/dl and average

GFR was ≤50 ml/min/1.73 m2, indicating that patients had, on average, moderately impaired renal function6


GFR: glomerular filtration rate

LOCM: low osmolar contrast media

SCr: serum creatinine

-Strict inclusion criteria were applied6 - studies needed to be randomised, prospective,

head-to-head comparisons of Visipaque and a LOCM

- they needed to have CI-AKI as a primary and/or

secondary endpoint

- they needed to be of high methodological quality

(with a Jadad score ≥2)

25 were included

in the meta-analysis

145 potential articles

were identified

01-2014 JB5799

Visipaque is associated with a lower risk of contrast-induced acute kidney injury than low osmolar agents in high risk patients6

Intra-arterial use of isosmolar Visipaque significantly reduced the risk of CI-AKI* compared to LOCM† in the interventional cardiology setting (RR=0.46; CI: 0.27–0.79; p=0.004)6

*CI-AKI defined as SCr increase of ≥0.5 mg/dl from baseline measured up to 3 days after contrast media exposure †Pool of LOCM (iohexol, iomeprol, iopamidol, iopromide, ioversol and ioxaglate)

CI-AKI risk is lower with intra-arterial Visipaque than with LOCM (n=4,769)6

0.01 0.1 10 1

Study

100

Aspelin (NEPHRIC) 03

Hill 94

Sinha 04

Wessely 09

Hardiek 08

Laskey 09

Solomon (CARE) 07

Juergens 09

Li 08

Nie 08

Han 10

Hernández 08

Rudnick (VALOR) 08

Jo (RECOVER) 06

Mehran (ICON) 09

Favours Visipaque Favours LOCM

Adapted from McCullough 20116

CI: confidence interval



RR: relative risk

01-2014 JB5799

Visipaque has minimal cardiovascular effects, which is critical when managing patients at risk of contrast-related adverse events

Fluid shift as CM flows through coronary arteries may lead to adverse CV effects, resulting in heightened cardiac risk31

Potential CV effects of CM Benefits of Visipaque

Changes in electrophysiological parameters

(e.g. QT-interval, QRS vector difference)32-35

Less impact on electrophysiological parameters than

ioxaglate and iohexol32-35

Haemodynamic changes can induce

myocardial ischaemia during coronary

procedures35,36

Minimal change in left ventricular systolic pressure

(compared to a significant fall with iopromide)35

Minimal changes in haemodynamic parameters

(left ventricular end diastolic pressure, aortic pressure)

compared with iohexol36

Reduced contractility and lowered cardiac

output, resulting in the heart beating faster

in order to compensate35

Lower impact on heart rate variability than

iopromide, ioxaglate or iomeprol in clinical trials35,37-39

Electrical

activity

Mechanical

performance

Heart rate

variability

CM: contrast media

CV: cardiovascular

01-2014 JB5799

Visipaque is associated with fewer major adverse cardiac events than low osmolar agents in the interventional cardiology setting8-10

Visipaque was associated with fewer MACE than LOCM in the interventional cardiology setting8-10

Several large prospective clinical trials have shown that Visipaque is associated with significantly fewer MACE (such as cardiac death, stroke and coronary artery bypass graft) than LOCM8-10

*In-hospital included cardiac death, emergency recatheterisation for ischaemia, repeat revascularisation, CABG, subacute thrombosis,

stroke/TIA, non-fatal MI, abrupt closure of target vessel, systemic arterial thromboembolic event, and unplanned coronary artery bypass

surgery

% p

atie

nts

MACE criteria*

p<0.025

In-hospital8 (n=1,276)

In-hospital9

(n=856)

≤30 days post-discharge10 (n=208)

p=0.003

p=0.027

iopamidol ioxaglate iopromide Visipaqu

e

Visipaqu

e

Visipaqu

e

1.9% 5.4% 4.8% 8.8% 9.5% 9.0%

12

10

8

6

4

2

0

Majo

r advers

e c

ard

iac e

vents

Adapted from Harrison 20048, Davidson 20009 and Nie 200810

CABG: coronary artery bypass graft



MI: myocardial infarction

TIA: transient ischaemic attack

01-2014 JB5799

In high risk patients, choosing Visipaque can help

optimise outcomes and minimise costs6,12

01-2014 JB5799

In high risk patients, choosing Visipaque can help optimise

outcomes and minimise costs6,12

Visipaque reduces the likelihood of cardiac and renal

complications in high risk patients6-10

Visipaque helps minimise discomfort for patients undergoing

intra-arterial procedures11

In patients at high risk of contrast-related adverse events,

choice of contrast agent is critical1-4

Visipaque is the only X-ray contrast agent for intravascular use

with an osmolality similar to blood at all iodine concentrations5

• Major amputation was required more often in those with fewer patent arteries (P < 0.001).

When is a technically successful peripheral angioplasty effective in preventing above-the-ankle amputation

in diabetic patients with critical limb ischaemia?

Faglia E et all. Diabetic Medicine 2007; 24: 823-829

Crural patent arteries after PTA

N. patients no requiring amputation (n=398)

N. patients requiring amputation (n=22)

3

2

1

0

67

143

179

9

0

0

7 (4%)

15 (62%)

• 159 TMA/153 patients

• 159 limbs revascularized: bypass (15.2%) and by endovascular procedure (84.8%).

• Predictive factors for healing: - number of vessels open at ankle level (OR: 7.42)

Effect of revascularization on transmetatarsal amputation healing in diabetic ischemic foot

Dalla Paola et al. VII meeting of the DFSG, 2008

N. open vessels Time of healing (days)

0 160.0 ± 155.6

1 125.9 ± 113.7

2 95.0 ± 79.5

3 88.6 ± 108.5 By-pass =78+/-52 days

p=0,0

4

p=0.03

n.s.s.

“In diabetic ischaemic foot TMA outcome is influenced to kind of revascularization. Every vessel open at ankle level reduces about of 31 days the time of healing. Data from this study indicate that efforts should be done during revascularization to open the most number of vessels to reduce time of healing.”

BTK PTA…Yesterday

For limb salvage only;

At least one direct vessel to the foot (ankle level);

For wounds healing too;

For deambulation salvage;

Two or three vessels to the foot (inflow);

Foot vessels revascularization (outflow).

BTK PTA… TODAY

≠ Treating angiographic images

= Treating patients’ complaints

Restoring outflow

1 artery straight-line flow to foot

= PRIMARY GOAL OF ANY TREATMENT

EXC : Diabetics poor collateralisation

PRE POST

Single spot lesions A rare example

Pre-op Post-op

Occlusion all 3 BTK vessels

Which vessel to treat?

Pre-op Post-op Pre-op (distal)

Occlusion at distal popliteal: which vessel to treat?

Pre-op Post-op Pre-op Post-op

Length dependent strategy decision Short lesion

Focal PTA technique

+ Balloon expandable stents

+ Nitinol stents

Intermediate lesion Nitinol stents

Long lesion Long low pressure balloons

with or without additional focal stenting

Lesion passage

Stiff 0.014 – 0.018” hydrophilic wire

Extra support with 4-5F multipurpose glide cath

Tandem lesion on ATA

Pre Post

Pre-op Post-op

Distal lesion

Stabilizer+

Cordis 0.014”

Ultrasoft SV

BSCI 2x30

Ultrasoft SV (BSCI) – short occlusion distal ATA

After suboptimal PTA Flow-limiting dissection

Residual stenosis

Coronary stents

Dedicated BTK stents Bare

Passive coating

Active coating

Bioabsorbable

Pro-kinetic Explorer (Biotronik)

PRE POST PRE POST

Cypher (Cordis) – Distal P3-segment high grade stenosis

3.0/28

Cypher stent

Pre-op

Cypher (Cordis) – proximal lesion

Pre-op

3.5/33

Cypher

stent

Guidewire

passage

and PTA

Post-op

PTA

Cypher (Cordis) – Occlusion TFT

Pre-op

Post-op

2x Cypher stent

Magic Explorer (Biotronik) – Bifurcation lesion

Pre Post

Disadvantages Crushability

Limited flexibility

Stent damage

Disturbed flow dynamics

Dedicated design for small vessels Do not place a large vessel stent in smaller diameters!

Metal overload

Impaired flow dynamics

4x40 Astron Pulsar

Dilation popliteal lesion

Passeo baloon

3x80

Courtesy of O. D’Archambeau – J Hendriks

Dilatation ATA lesion

baloon3x20

Resulting in dissection


Stenting

4x80


Post dilation

3x80



PRE POST

Knee straight

POST

Knee bend

FINAL FLOW

Low pressure balloons L 8-17 cm

Ø 2.5-3.5mm

Improve outcome with spot stenting Achieving dynamic flow

into foot is goal

Dilation Pre-op Post-op

Passeo-18 (Biotronik)

Diffusely diseased PTA

Pre-op Post-op

Revascularization existing feeding collateral

Additional focal stenting on areas of low success

pre-op

Dissection

after PTA

Multi-link

Vision

post-op

Dilation ATA

2.5x170

2 times

Resulting in distal flow

limiting dissection

cases of Dr . M.Manzi

Why and when endoluminal

atherectomy? M.Manzi, 2009

•Young patients •Popliteal tract •SFA intrastent reocclusion

In order to avoid stent !

• BTK high risk for PTA segments (bi-trifurcations)

•PTA restenosis •Light calcified distal plaques

Alternative to balloon

PTA

M.Manzi, 2009

ischemic rest pain, ulcers or Chronicgangrene attributable to objectively

proven arterial occlusive disease

and is to chronicityThe term CLI implies be distinguished from acute limb

ischemia

Ankle pressure

< 50 mm Hg

Toe pressure

< 30 mm Hg

TcpO2

< 30 mm Hg

Norgren et al. TASC II, Eur J Vasc Endovasc Surg 33, 2007

diabetes

neuropathy

trauma,

deformity

ulcer

lack of healing

infection

gangrene

1 million one mil. major amputations ww p/y

54% mortality, 46% amputation at 1y for untreated CLI

•www.iwgdf.org -International Working Group of Diabetic Foot

•Lepäntalo et al: EJVES 1996;11 (2): 153-157

http://www.iwgdf.org/

Revascularization + extra-Vascular care

Rogers LC, Armstrong DL: Podiatry Care, Chapter 113, Rutherford's Vascular Surgery, 7th

Edition, Cronenwett JL, Johnston KW, editors, Elsevier Inc, 2010

• Healing and Perfusion: non linear correlation

• Probability of healing:

– Suboptimal with suboptimal perfusion

– Maximized with optimal wound care and perfusion

– Best preserved in presence of optimal and durable perfusion

• Makes healing faster and better

O.Iida et al. angiographic restenosis and its clinical impact after infrapopliteal

angioplasty. Europ J of Vasc and Endovasc Surgery 2012

Reiber, et al. Diabetes Care, Vol 22, Number 1, January 1999

External Triggers of Ulceration

.1Durable perfusion is an insurance policy against the casual occurrence of new ulcers

.2Scarce Perfusion makes foot vulnerable to recrudescence and recurrencies

optimal Perfusion: F.Vermassen 2010

sub-optimal Perfusion:

Frequency and magnitude of reinterventions in CLI have a known bad implication on patient’s survival and QoL [1]

.1Conte M.S Suggested objective performance goals and clinical trial design for evaluating catheter-

based treatment of critical limb ischemia. JVS 2009;50:1462-1473

Ouriel K, Lancet 2001, data of ‘60

Limb Salvage correlates poorly with Primary Patency, less poorly with Secondary Patency

•Primary Patency reduces TLR, adds life and QoL to CLI Patients

T.Kudo et al. The effectiveness of percutaneous transluminal angioplasty for the treatment of

critical limb ischemia: A 10-year experience. J Vasc Surg 2005;41:423-35.)

Patency clinically relevant when WRA is involved [1-2]

.1Neville et al. Revascularization of a Specific Angiosome for Limb Salvage: Does the Target Artery Matter? Ann Vasc Surg 2009; 23: 367-373

.2Iida O. et al. Importance of the Angiosome Concept for Endovascular Therapy in Patients with Critical Limb Ischemia - Catheterization and

Cardiovascular Interventions 75:830–836 (2010)

[1] [2]

M.Manzi et al. 2009

• Improved functional outcome following re-establishment of the plantar arch due to suboptimal results of tibial revascularization

135 of 1331 CLI patients treated at Abano Terme Clinic (Italy) from 2007 to 2008) by pedal-

plantar-loop technique due to sub-optimal ATA revascularization and/or risk of amputation

Below-the-ankle run-off reduce MALE [1]

O.Iida et al. Anatomical Predictors of Major Adverse Limb Events after Infrapopliteal Angioplasty for Patients with Critical Limb

Ischaemia due to Pure Isolated Infrapopliteal Lesions. European Journal of Vascular and Endovascular Surgery 44 (2012) 318e324

Microcirculation to the wound related territory increase limb salvage

Utsunomiya M et al. Impact of wound blush as an angiographic end point of endovascular therapy for patients with critical limb

ischemia. J Vasc Surg 2012;55:113-21

Patency necessary but not sufficient for functional limb preservation (extravascular care = key therapy component)

Restenosis becomes clinically relevant

when involves the wound related artery

when occurs during the healing process

as new ulceration occur within the target angiosome, triggered by external factors

Prolonged better than short-term, Primary Patency better than Secondary Patency

Technically best fitting the extensive, multivessel, long diffuse BTK disease of real world CLI Patients

• 74% of all lesions in BTK

• 66% occlusions

• 50% occlusions >10 cm

• Tissue loss associated with significant worse, BTK concentrated disease [2-3]

• Arterial Disease extension and distribution in CLI and Diabetes [1]

.1Graziani L et al. Vascular Involvement in Diabetic Subjects with Ischemic

Foot Ulcer: a New Morphologic Categorization of Disease Severity Eur J

Vasc Endovasc Surg 33, 453 460 (2007)

.2Diehm N et al. Association of Cardiovascular Risk Factors with Pattern of

Lower Limb Atherosclerosis in 2659 Patients Undergoing Angioplasty. Eur J

Vasc Endovasc Surg 31, 59–63 (2006)

.3A.Bradbury et al. Bypass versus Angioplasty in Severe Ischaemia of the

Leg (BASIL) trial: A description of the severity and extent of disease using

the Bollinger angiogram scoring method and the TransAtlantic Inter-Society

Consensus II classification JVS 2010

.1D.Scheinert, J Am Coll Cardiol 2012;60:2290–5)

.2H.K.Soder, J Vasc Interv Radiol 2000; 11:1021–1031

.3F. Baumann, J Vasc Interv Radiol 2011; 22:1665–1673

.4F.Fanelli, J Endovasc Ther. 2012;19:571–580

.5F.Liistro, TCT 2012 oral presentation

.6A.Schmidt, Catheter Cardiovasc Interv. 2010 Dec 1;76(7):1047-54

101 Patients

12m Angio

PTA arm PTA arm

60 Patients

10m Angio

33 Patients

6m Angio

11 Patients

12m Angio

67 Patients

12m Angio

58 Patients

3m Angio

PTA arm

A.Schmidt LINC 2013

• Single Center Registry

• IN.PACT Amphirion

• Long BTK lesions > 80 cm

• 104 Patients

• Primary Endpoint: 3-month binary Restenosis rate

A.Schmidt JACC 2011

First DEB-BTK Experience in complex, real world BTK

lesions

IN.PACT (angio subgroup)

# patients / limbs 74 / 79

Male gender 51 (68.9%)

mean age (y) 73.5 ± 9.3

diabetics 54 (73%)

Renal insuff. 34 (45.9%)

RC 3 16 (20.3%)

RC 4 14 (17.7%)

RC 5 49 (62%)

RC 6 0 (0%)

avg lesion length 173±87 mm

Tot occlusions 61.9%


3m Ang. FU

Restenosis (>50%) 27.4%

Full-segm. Resten. 10%

Restenosis Length 64 mm

12m Clinical

FU

Deaths 16.3%

Limb Salvage 95.6%

Clinical Improv. (1) 91.2% (2)

Compl. wound heal. 74.2%

TLR 17.3%

(1) clinical improvement = reduction in size and/or depth of ulceration or improvement of rest-pain


PTA* (histor. group)

3m Angiographic FU

Restenosis (>50%) 27.4% 69%

Full-segm. Resten. 10% 56%

Restenosis Length 64 mm 155 mm

Clinical FU

12-month 15-month

Deaths 16.3% 10.5%

Limb Salvage 95.6% 100%

Clinical Improv. (1) 91.2% 76.5%

Compl. wound heal. 74.2% 78.6%

TLR 17.3% 50%

(1) clinical improvement = reduction in size and/or depth of ulceration or improvement of rest-pain

vs historical PTA cohort (A.Schmidt et al. CCI 2010)


PTA* (histor. group)

# patients / limbs 74 / 79 58 / 62

Male gender 51 (68.9%) 38 (65.5%)

mean age (y) 73.5 ± 9.3 70.5 ± 8.08

diabetics 54 (73%) 52 (89.7%)

Renal insuff. 34 (45.9%) 30 (51.7%)

RC 3 16 (20.3%) 0 (0%)

RC 4 14 (17.7%) 16 (25.8%)

RC 5 49 (62%) 46 (74.2%)

RC 6 0 (0%) 0 (0%)

avg lesion length 173±87 mm 183±75 mm

Tot occlusions 61.9% 64.9%

Compared to matched historical PTA cohorts, IN.PACT DEB

shows a remarkable (>60%) decrease in angiographic restenosis

at 3-month and TLR-rate at 12-15 months (65%) in the treatment

of long / complex BTK lesions

IN.PACT restenosis pattern presents more frequently focal

Single Center Randomized (1:1)

CLI, Diabetic patients

IN.PACT Amphirion vs. std PTA

Primary Endpoint: 12-month (>50%) Angiographic RR

F.Liistro LINC 2013

CLI + Diabetes

150 (Tibial) Lesions

DEB

(75 lesions)

Std PTA

(75 lesions)

12m Angio / Clinical FU

Aspirin + Clopidogrel (1 month)

24 m Duplex / Clinical FU

random (1:1)

First Randomized trial to assess DEB vs. PTA in a complex CLI–Diabetic population with 12-

month angiographic endpoint

DEB PTA p

Patients Nr 65 67

Mean age 74±9.4 y 75±9.6 y 0.7

Male gender 54 (83.1%) 52 (77.6%) 0.5

Diabetes 65 (100%) 67 (100%) 1

Hypertension 46 (70.8%) 52 (77.6%) 0.4

Smoking 13 (20.0%) 7 (10.4%) 0.1

Hypercholesterol. 23 (35.4%) 16 (23.9%) 0.1

Prev. PAD diagnosis 25 (38.4%) 23 (34.3%) 0.4

Serum creatinine 2.18±0.25 2.25±0.25 0.9

Dialysis 7 (10.8%) 7 (10.4%) 1

Obesity 23 (35.3%) 26 (38.8%) 0.5

Cor. Artery Disease 12 (18.5%) 10 (14.9%) 0.6

Cerebrov. disease 5 (7.7%) 7 (10.4%) 0.7

Limbs Nr 71 72 0.9

ABI 0.31±0.8 0.29±1.0 0.6

Concom. Fempop PTA 32 (49.2%) 35 (52.2%) 0.8

DEB PTA p

Lesions Nr 80 78

Tot Occlusions 62 (77.5%) 64 (82.1%) 0.5

Mean Length (mm±SD) 128±83 130±79 0.9

Severe Calcification 20 (25.0%) 22 (28.2%) 0.5

RVD (mm) 2.91±0.27 2.87±0.29 0.7

MLD (mm) 0.06±0.14 0.05±0.14 0.6

DS(%±SD) 97.2±7.7% 97.1±8.0% 0.9

DEB PTA p

IC 1 (1.4%) 3 (4.2%) 0.5

IIC 3 (4.2%) 5 (6.9%)

ID 7 (9.9%) 9 (12.5%)

IID 34 (47.9%) 32 (44.4%)

IIID 26 (36.6%) 23 (31.9%)

Texas Wound Class

DEB PTA p

Lesions Nr 80 78

pre-Dilatation 80 (100.0%) -

Subintimal Recanalization 17 (21.3%) 17 (21.8%) 0.8

Antegrade Recanalization 78 (97.5%) 75 (96.2%) 0.7

Retrograde Recanalization 2 (2.5%) 3 (3.8%) 0.7

Balloon Inflation Time (sec±SD) 142±38 140±50

0.5

Balloon Diameter (mm±SD) 2.90±0.39 2.85±0.36

0.4

Mean Balloon length (mm±SD) 148±83

140±79 0.5

Bailout Stenting 1 (1.3%) 1 (1.3%) 0.9

Technical Success [1] 80 (100%) 78 (100%) 1

Procedural Success [2] 65 (100%) 67 (100%) 1

.1Achievement of <30% residual stenosis by visual estimate

.2Achievement of Technical Success without procedural complications

DEB PTA p

Nr assessed Lesions 74 (92.5%) 74 (94.9%)

Lesion Assessment: ANGIO 67 (90.5%) 68 (91.9%) 0.8

DUPLEX 7 (10.0%) 6 (8.1%) 0.8

Restenosis (>50%) 20 (27.0%) 55 (74.3%) <0.001

Occlusion 13 (17.6%) 41 (55.4%) <0.001

Occlusion length (mm) 87±88 128±75 <0.001

12-month occl./baseline occl. %±SD 52±40 87±88 <0.001

Death 5(7.7%) 3(4.5%) 0.4

Major Amputation 0(0.0%) 1 (1.5%) 0.9

CVA 2 (3.1%) 3 (4.5%) 0.9

AMI 3 (4.6%) 3 (4.5%) 0.9

PCI 4 (6.2%) 3 (4.5%) 0.7

CLI recurrency 20(30.8%) 30(44.8%) 0.1

TLR 12 (18.5%) 29 (43.3%) 0.003

Non TLR 16 (24.6%) 23 (34.3%) 0.2

Cumulative MAE 19 (29.2%) 31 (46.3%) 0.05

Restenosis and Occlusion Rates TLR

Complete Wound Healing

12-month TLR

DEB vs. PTA:

18.5% vs. 43.3%

(p=0.003)

Major Adverse Events

.1F.Fanelli et al. J Endovasc Ther 2012;19:571–580

.2A.Cioppa – EuroPCR 2012

.3F.Liistro – TCT 2012

.4K.Suzuki – LINC Asia Pacific 2012

.5A.Schmidt et al. J Am Coll Cardiol 2011;58:1105–9 2011

10 Patients

12m Angio

75 Patients

12m Angio

65 Patients

12m Angio

20 Patients

4m Angio

74 Patients

3m Angio

A.Schmidt LINC 2013

Sustained Primary Patency should be the goal of modern revascularization therapies for CLI

Balloon-based technologies remain the most versatile solution to address the extent and burden of BTK arterial disease in CLI

IN.PACT DEB clinical evidence in complex, long BTK lesions shows significantly lower restenosis rate and burden, reduced TLR and improved wound healing vs. PTA

Patient #1

M, 32y/o,

17 y with DM type 1,

s/p kidney transplantation,

necrotic wound on the lt. foot

PRE

PTA with Balloonn 2.5X170 mm

END OF PROCEDURE

F, 81 y.o.

DM, type 2, 34 y.

HTN, IHD

Rest pain

necrotic wound on the lt. foot

Lt TFA antegrade admittance

Treatment

End of the

procedure

0-3 m

(89 patients)

0-6 m

(90 patients)

0-12 m

(92 patients)

Death

Amputation

TLR

1 (1.1%)

0%

1 (1.1%)

1 (1.1%)

0%

4 (4.5%)

2 (2.2%)

0%

8 (8.7%)

12M Survival from TLR, Occlusion, >50% Restenosis

83.7% Primary Patency (PSVR < 2.5)

PSVR ± SD

3,1

1,1 1,1 1,1 1,2

0

0,5

1

1,5

2

2,5

3

3,5

4

4,5

5

baseline discharge 3m 6m 12m

P < 0.0001

P = NS

Micari et al. Euro-PCR 2011 Micari et al. JACC Cardiovasc Intervent 2012

Sample case of restenosis following DEB administration

•CTO with significant calcium burden

•Efforts were made to avoid bail-out stenting, despite sub-

optimal acute results

•Further progression at later time points, especially around calcified segment

Angiograms Courtesy of Gunnar Tepe, MD

Background of Atherectomy

…Problem = recoil/ restenosis

…Problem = dissection

…Problem = vessel stretch

causes injury

…Problem = Intima Hyperplasia

usually after 3 - 9 months in

the SFA

…Problem = relative

contraindication in vessel

segments with high external

forces (knee)

…no dilatation - avoids

barotrauma and recoil

…smoothens the lumen

…reduces the need of stents

Angioplasty contemporarily

shifts the plaque…

Stenting permanently shifts

… the plaque

DCA removes the plaque…

Zeller et al. JACC 2006;48:1573-1578

Krankenberg et al. Circulation 2007

84

6168

0

10

20

30

40

50

60

70

80

90

1-yr patency

Silverhawk

POBA

stent

[%]

De novo lesions, 4.5mm length

Atherectomized Plaque

PHOTOPAC: Laseratherectomy & DCB

vs. DCB in instent-restenosis

PIs: Scheinert / Zeller

DEFINITIVE AR: DCA & DCB vs. DCB in native

vessels PIs: Tepe / Zeller

Entire cohort PTA DCB P

Primary patency @ 12 months [n/%/] 48/86 (55) 27/62 (43) 21/24 (88) <0.001*

TLR @ 12 months [n/%] 31/86 (36%) 29/62

(47%)

2/24 (8%) 0.001*

Restenosis@ 12 months [n/%] 39/86 (45%) 36/62

(58%)

3/24

(13%)

<0.001*

Secondary patency @ 12 months [n/%] 61/86 (71%) 39/62

(63%)

22/24

(92%)

0.015*

*: p<0.05; TLR: Target Lesion Revascularisation;

Sixt et al. JVS under revision

1. Hydrolyser

2. Oasis™ Thrombectomy System

3. Angiojet®

4. Amplatz Clot Buster (ATD)™

5. Trerotola Device

6. PMT™ Device

Mechanical Thrombectomy Local Thrombosis Straub-Rotarex (8F)

Micro Catheter

0.014” Guidewire

Dilatable Tip

FDA Cleared

CE approved

The Intraluminal Approach

The size and unique design of the Voletek™ peripheral

crossing system enables it to cross

in micro-channels

57y white male; 45mm total occlusion >9 months;

CiTop™ succeeded after standard GW failed; followed by x1 stent.

Crossing time: 3 min

Occlusion of the Rt. popliteal

FIM Peripheral Randomized Study

Operator: Dr. Alexander Belenky

DIRECTIONAL ATHERECTOMY

Endovascular Intervention offers a low risk

1-st choice therapy.

Surgery should be reserved for

– Diffuse severe vascular Calcification

– Failed endovascular intervention with

freq. restenosis

– Extensive gangrene with very prolonged healing

Michael Knizhnik — Endovascular treatment for patients with critical limb ischemia: yesterday,...

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