Indications of Angioplasty

1. To be candidate for revascularization procedure, one must have symptomatic or objective signs of ischemia.

2. Indications for PTCA or CABG may vary from one center to another according to experience, skills and results.

3. Definite indications for CABG: LM disease and 3 VD with proximal stenosis.

4. Definite indications for PTCA: SVD (apart from ostial LAD), with type A or B1 lesion.

• Are there still contra indications for angioplasty??– Almost every lesion can be treated

• Who needs surgery ??– Incomplete revascularisation– Mortality studies

New technologies were created to improve the PTCA balloon.

• Major limitations of PTCA– acute vessel closure during intervention– restenosis

• Intracoronary stenting has shown clinical efficacy

• First stents implanted in 1986

• High frequency of complications:– subacute stent thrombosis– stent misplacement– suboptimal deployment– bleeding complications

• In 1994 results of BENESTENT and STRESS were published showing a reduction in restenosis rate

• At that time early stent thrombosis remained a major drawback– Double antiplatelet therapy– High-pressure deployment

• CURRENT INDICATIONS OF STENTING:

– elective stenting : primary prevention of restenosis

– elective stenting : secondary prevention of restenosis

– bail-out stenting : management of acute or threatened vessel closure

• CURRENT INDICATIONS OF STENTING:

– saphenous-vein-graft disease– acute myocardial infarction– chronic total occlusion

• UNTIL NOW NO SCIENTIFIC PROOF EXISTS FOR STENT PLACEMENT IN:

– suboptimal angioplasty– long or diffuse disease or both– small vessels– aorto-ostial disease– bifurcation lesions

COMPLICATIONS OF ANGIOPLASTY

• The major complications of coronary interventions are:– death ( 0.5% to 1 % )– Q-wave myocardial infarction ( 1% to 3% )– need for emergent surgical coronary

revascularization ( about 1 % )

COMPLICATIONS OF ANGIOPLASTY

• Complications usually results from acute occlusion of the target vessel– causes include

• dissection• thrombosis• embolism• spasm

• Stenting is an effective therapy in treating acute and threatened coronary occlusion initiated by dissection

Other complications

• Vascular problems

• Rhythm disturbances

• Cholesterol embolization

• Cerebral problems

Evolution of PCI results

CARPORT VELVET

1987 2000

Failed PTCA 7.0% 0.0%

Death 1.4% 1.6%

MI 6.0% 0.8%

CABG 8.0% 0.0%

RePTCA 18.0% 2.5%

Angina at FU 26.0% 5.0%

Symptom free 56.0% 89.3%

PTCA results according toclinical presentation

RISK OF COMPLICATION IS INCREASED WHEN:. Multivessel disease. Old age. Diabetes. Unstable angina or recent MI ( < 3 Weeks). LV failure. Women. Prior bypass coronary surgery

Clinical Complications

1. . Death.2. . Non fatal myocardial infarction. 3. . CABG.4. . Repeat angioplasty.5. . Bleeding complications.6. . Intracranial event.7. . Anginal symtoms.8. . Puncture site complication.9. . Nephrotoxicity.10. . LV failure.11. . Allergic reaction.

Angiographic complications

1. (Sub)occlusion dissection

2. coronary perforation

3. no reflow

4. coronary spasm

5. transient occlusion of treated segment

6. coronary embolism

7. occlusion of side branch

8. occlusion of other vessel

Assessment of PTCA results

1. Angiographic assessment : pre - post - (3 - 6 mths)

Quantitative angiography : pre PTCA : 65 ± 10% post PTCA : 30 ± 10% F.U. : 45 ± 10%

2. Functional assessment

- Translesional gradient after adenosine (FFR)- Coronary flow reserve : Doppler- ETT pre post (24 - 48 h. or 1 week) F.U. (6 w - 3 mths)- Perfusion scan pre - 3 weeks - F.U. (3 mths)

3. IVUS assessment : pre - post

- Characterization of arterial wall and atheromatous plaque - assessment of PTCA result, stent expansion

MECHANISMS OF RESTENOSIS• Thrombosis (acute and subacute closure).• Early and late recoil (Balloon Angioplasty).• Neointimal proliferation (Stent, DCA,

Rotablator, Laser).

IVUS data:

Balloon PCI : 15% of restenosis due to tissue ingrowth 85% due to geometric remodeling

Stent PCI : 90% due to tissue ingrowth

10% due to late recoil

Mechanisms of restenosis.

• Acute recoil andVascular remodeling :

• Neointimal proliferation :

• Thrombus formation :c

c

c

c

c

c

c

c

c

Variables associated with restenosis

Clinical variables Anatomic variables Procedural variables Biological variables

Unstable angina prox LAD Undersized balloon Haemostatic Factors (?)tPa;PAI1;vWf;fibri

Variant angina Venous graft Extensive dissection Activated phagocytes (IL1B)

Diabetes Severe stenosis Residual stenosis ACE DD genotype

Renal failure Chronic occlusion Plaque burden (IVUS)

RESTENOSIS

• Stents will prevent vascular recoil and remodelingStents will prevent vascular recoil and remodeling • Active therapeutic agent (radiation or drug) is required Active therapeutic agent (radiation or drug) is required to block neointimal hyperplasiato block neointimal hyperplasia

• Neointimal Hyperplasia• Recoil & RemodelingCause:Cause:

Solution:Solution:

Prevention of restenosis• Oral (IV) medication : angiopeptine, abciximab,

diabetes control, probucol• Stents : importance of design (coil vs tubular),

struts width, alloy, passive/active coating.

• Ionization : brachytherapy, ultrasonotherapy.• Local drug delivery : catheter based, stent

loaded.

In-Stent Restenosis : the most important limiting factor of PCI

• A frequent problem

• Challenging to treat

Why ?Why ?

Characterization of in-stent restenosis

• Type I Focal.– Edge restenosis : proximal, distal or both (candy

wrapper).– Multifocal.

• Type II Diffuse .• Type III Proliferative.• Type IV Occlusive.

Treatment of in-stent restenosis

• Conventional balloon angioplasty.

• Cutting balloon.

• Brachytherapy.

• DES stent.

• Surgery.

(atherectomy, bare stent, drugs)

Prevention of thrombotic complications

• Anti-thrombins : heparin, LMWH (during the procedure).

• Anti-platelet agents :- Aspirin (procedure and long term)- Thienopyridines (procedure and long term?)- IIb/IIIa inhibitors (high risk procedures,

diabetics)

- (Thrombolytics)

• Direct stenting: placement of a coronary stent WITHOUT previous dilatation or previous intervention in the target coronary artery

• Primary stenting: 1. Cf. primary PTCA: placement of a coronary stent during an intervention for AMI.

• Elective stenting: 2. Cf. Debate II-trial: as a strategy compared with provisional stenting (guided by angiography and flow velocity measurement).

(Direct) Stenting: rationale

• Compared to PTCA, stenting reduces restenosis rate and improves the long-term clinical outcome in patients with de novo coronary lesions.

• Serruys et al., Benestent I, N Eng J Med 1994

• Fischman et al., STRESS, N Eng J Med 1994

• Macaya et al., 1 year follow-up of Benestent I,

J Am Coll Cardiol 1996

• Serruys et al., 5 year follow-up of Benestent I,

ESC congress Barcelona 1999

Direct Stenting: rationale

• Dissection/fissuring of the atherosclerotic plaque is immediately sealed, with less exposure of collagen and tissue factors

• Saving time and money…?Decreased risk of thrombosis/ Decreased risk of thrombosis/ acute occlusionacute occlusion

Advantage over Conventional Advantage over Conventional Stent ImplantationStent Implantation

COSTCOST

TIMETIME

SAFETYSAFETY

EFFICACYEFFICACY

DirectDirect

(1 balloon less)(1 balloon less) (1 Stent less in 50% of pts)(1 Stent less in 50% of pts)

(in well selected lesions)(in well selected lesions)

(in well selected lesions)(in well selected lesions)

PredilatationPredilatation

Direct Stenting or Predilatation? Direct Stenting or Predilatation? ConclusionsConclusions

DIRECTDIRECT Short lesions of Short lesions of

intermediate intermediate severity in healthy severity in healthy non calcified and non calcified and non tortuous non tortuous arteriesarteries

Unstable or Unstable or thrombus thrombus containing lesionscontaining lesions

PREDILATATIONPREDILATATION Total occlusionTotal occlusion Diffuse diseaseDiffuse disease Massive calciumMassive calcium Extreme tortuosityExtreme tortuosity Whenever in doubt Whenever in doubt

......

DRUG ELUTING STENTS:

INSIGHTS

FIM: FIRST IN MANFIM: FIRST IN MAN

Rapamycin experience:Rapamycin experience:15 patients (Sao Paulo, E. Sousa) ; fast15 patients (Sao Paulo, E. Sousa) ; fast releaserelease

15 patients (Sao Paulo, E. Sousa) ; slow release15 patients (Sao Paulo, E. Sousa) ; slow release

15 patients (Rotterdam, P W. Serruys); slow release15 patients (Rotterdam, P W. Serruys); slow release

12 12 months follow-up months follow-up No restenosis*, no TVR* No restenosis*, no TVR*

6 6 months follow-up No restenosis,no TVRmonths follow-up No restenosis,no TVR

12 12 months follow-up months follow-up No restenosis, no TVR* No restenosis, no TVR*

J.E.Sousa et al. Sustained Suppression of Neointimal Proliferation by Sirolimus-Eluting Stents; Circulation.2001;104:2007-2011

No Delayed Restenosis

18-month follow-up FIM Rotterdam

0% 17.3%

Best Results Worst Results

020406080

100

0 5 10 15 20

mean mean 0.8%0.8%

max max 17.3%17.3%

%%

%%

min min 0%0%

n=42n=42

Radical Abolition of RestenosisRadical Abolition of Restenosis

% obstruction volumeof the stent

The verdict of RAVEL

Sirolimus Eluting Bare stent

n=120 n=118

Vessel Size (mm) 2.60 2.64 ns

Event Free survival 97 72 .000

MLD f/u(mm) 2.42 1.64 .0000

Late Loss (mm) -0.01 0.80 .0000

Restenosis rate% 0 26 .0000

TLR % 0 22 .0000

MLD post(mm) 2.43 2.41 ns

What about the other early clinical results?

Eluting Stent programsQuanam Taxol derivative: Score

Cordis Sirolimus: FIM, Ravel, Sirius, SIRS

Boston Scientific Taxol: Taxus I ~ VI

Cook Taxol: Elutes, Aspect, Deliver

Guidant Actinomycin-D: Action

Biodyvisio Dexamethasone, Batimastat, Angiopeptin: Stride, Easter

Sorin Tacrolimus: Jupiter

Medtronic Zotarolimus: Endeavor

Conor Taxol: Pisces, Costar

Abbott Everolimus: Spirit

100

90

80

70

60

50

0 60 120 180 240 300 360

Days

%

Death / MI / CABG / Re-PTCA

CABRI: CABG (91%)

CABRI: PTCA (59%)32%

14%

Event free survival Event free survival Serruys’ rosy prophecySerruys’ rosy prophecy

ARTS2: Eluting STENT (95%)ARTS2: Eluting STENT (95%)

ARTS2: CABG (90%)ARTS2: CABG (90%)

CABRI: 1994CABRI: 1994ARTS: 1999ARTS: 1999ARTS2: 2006ARTS2: 2006

CABRI: 1994CABRI: 1994

ARTS: CABG (89%)

ARTS: STENT (75%)CABRI: 1994CABRI: 1994ARTS: 1999ARTS: 1999

- 5%

• Drug eluting stents: ‘the holy grail’??• So far only RCT data in ‘selected’ cohorts

of patients• The results of larger randomized safety and

cost-effectiveness trials are awaited (no angio fu...)

• Long term follow-up is needed• Drastic changes in policies and strategies of

revascularization have already occurred... too soon?

Coronary Artery Bypass Graft SurgeryCoronary Artery Bypass Graft Surgery

• Coronary artery bypass grafts (CABG) are intended to shunt blood from the aorta to the coronary artery, beyond an area of severe narrowing or occlusion

• CABGs can be constructed from veins or arteries

• Saphenous vein grafts (SVG) are conduits made by harvesting a piece of vein from the patient’s leg and attaching it between the aorta and coronary artery

• Arterial bypass grafts involve re-routing an artery from its normal course and attaching it to the coronary artery– Internal Mammary Artery– Gastroepiploic Artery– Radial Artery

Coronary Artery Bypass Graft SurgeryCoronary Artery Bypass Graft Surgery

• 1964: first aortocoronary saphenous vein graft implantation in a human by Garrett

• Subsequent pioneering work of Favaloro at Cleveland Clinic

• Effective treatment for intractable angina pectoris and a mean of improving long–term prognosis in certain patients subgroups.

• Despite its dramatic benefits it remains a palliative procedure due to accelerated atherosclerosis in the grafted saphenous vein conduits.

SVG Anatomy & PhysiologySVG Anatomy & Physiology

ProximalAnastamosis

VeinGraftBody

DistalAnastamosis

• Vein grafts are merely conduits – lack vascular tone found in

arteries– arterial bypass grafts (IMA) have

superior patency• preferred CABG for the LAD

• Vein grafts are prone to developing obstructive disease

• SVG disease is morphologically different depending on its location in the vein graft

Current Medical State of SVG DiseaseCurrent Medical State of SVG Disease

• Average lifespan for a vein graft is 5-10 years– 50% of SVGs will be occluded within 10 years– 75% will develop severe narrowing in same period

• SVG lesions presenting within the first year after surgery are typically caused by intimal hyperplasia– respond well to balloon dilatation

• Late vein graft stenoses are more commonly caused by diffuse atherosclerosis– friable plaque and thrombus tend to fragment and

embolize into distal coronary vessels

Coronary Artery Bypass Graft SurgeryCoronary Artery Bypass Graft Surgery

• Despite vein grafts are inferior to arterial grafts , they are still used :– Multivessel disease– Subclavian artery or internal mammary artery

disease– Emergency situations

Pharmacologic therapy:acute coronary syndromes

Acute myocardial infarction• Caused by an occlusion of a coronary

artery, mostly by a thrombus

• Clinically : longstanding, intense, oppressive chest pain, not responding on nitrates

Clinical presentation : myocardial necrosis

ECG features of myocardialischemia and infarction

Diagnosis• ECG

(ST elevation vs. Non ST elevation MI) • Enzymes

Troponines: highly specific but positive after 4 hoursCK-MB: not so specific and also positive after 4 hoursMyoglobine: low specificity, positive after 2-3 hours

• Echoif ECG is negative, Echo can show areas of hypo/akinesia

• Angiofinal “confirmation” of a stenotic/occluded vessel

Supportive therapy

• For all:– Rhythm control (continuous monitoring)– Intravenous line (glucose 5 %)– Oxygen (2 tot 4 l)– Pain control

• Pain killers: morphine• Beta-blockers• Sedation

– Aspirin at least 300 mg

Real treatment

• Open the occluded vessel as soon as possible

» Fibrinolysis

» PCI

Treatment of AMI30-day mortality based on level of risk

Low Intermediate High

2.9%

8%

12.7%

7.9%

13.1%

24.1%

%

PCR Lysis

PCAT

Equivalent time to reperfusion with fibrinolysis or primary PCI

WW3215

Reperfusion time(60’)

Start Tx(60’)

reperfusion time(30’)

Start Tx(30’)

TIMI 3 rateTreatment

Lysis

PTCA

Time0’ 90’

95%

70%

Fibrinolysis• Dissolution of fibrin thrombi

– Streptokinase first studied (90 minutes infusion)– tPA (alteplase) 1 hour infusion– rPA (reteplase) 2 boluses every 30 minutes– TNK (tenecteplase) 1 single bolus

• Works only in the first 6-12 hours after AMI– the sooner the better

• Risks: – Bleeding (cerebral ~1%)– Reocclusion of the artery

Primary PCI

• Immediate idea on the whole coronary anatomy• Better en faster reperfusion• Stents reduce reocclusion and restenosis• Glycoprotein receptor blockers (abciximab)

reduce mortality and reinfarctions

Distal protection devices ?? Thrombus aspiration devices ??

Microvascular obstructionPathophysiology

Distal embolization can result in microinfarctions

Zones ofMicroinfarction

Atheroemboli

Thromboemboli

MicrovascularPlugging

Microvascularspasm, edema, vasoconstriction

Plateletaggregation