Transcript Microembolization

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
Failed PTCA
Death
MI
CABG
RePTCA
Angina at FU
Symptom free
CARPORT
1987
7.0%
1.4%
6.0%
8.0%
18.0%
26.0%
56.0%
VELVET
2000
0.0%
1.6%
0.8%
0.0%
2.5%
5.0%
89.3%
PTCA results according to
clinical 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 and
Vascular remodeling :
c
c
c
• Neointimal proliferation : c
c
c
c
c
• Thrombus formation :
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
Cause:
• Recoil & Remodeling
• Neointimal Hyperplasia
Solution:
• Stents will prevent vascular recoil and remodeling
• Active therapeutic agent (radiation or drug) is required
to block neointimal hyperplasia
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
Why ?
• A frequent problem
• Challenging to treat
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
Decreased risk of thrombosis/
acute occlusion
• Saving time and money…?
Advantage over Conventional
Stent Implantation
Direct
Predilatation
COST
(1 balloon less)
TIME
SAFETY
(in well selected lesions)
EFFICACY
(in well selected lesions)
(1 Stent less in 50% of pts)
Direct Stenting or Predilatation?
Conclusions
DIRECT
PREDILATATION


Short lesions of
intermediate
severity in healthy
non calcified and
non tortuous
arteries
Unstable or
thrombus
containing lesions





Total occlusion
Diffuse disease
Massive calcium
Extreme tortuosity
Whenever in doubt
...
DRUG ELUTING STENTS:
INSIGHTS
FIM: FIRST IN MAN
Rapamycin experience:
15 patients (Sao Paulo, E. Sousa) ; fast release
12 months follow-up
No restenosis, no TVR*
15 patients (Sao Paulo, E. Sousa) ; slow release
12 months follow-up
No restenosis*, no TVR*
15 patients (Rotterdam, P W. Serruys); slow release
6 months follow-up
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
Radical Abolition of Restenosis
Best Results
Worst Results
% obstruction volume
of the stent
%
100
80
60
40
20
0
mean
0.8%
max
17.3%
min
0%
0
5
10
n=42
15
20
%
0%
17.3%
The verdict of RAVEL
Sirolimus Eluting
n=120
Bare stent
n=118
Vessel Size (mm)
2.60
2.64
ns
MLD post(mm)
2.43
2.41
ns
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
97
72
.000
Event Free survival
What about the other early
clinical results?
Eluting Stent programs
Quanam
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
Event free survival
Serruys’ rosy prophecy
%
ARTS2: Eluting STENT (95%)
100
CABRI: CABG (91%)
- 5%
ARTS:CABG
CABG (90%)
(89%)
ARTS2:
90
14%
80
ARTS: STENT (75%)
32%
CABRI: PTCA (59%)
60
CABRI: 1994
ARTS: 1999
ARTS2: 2006
50
Death / MI / CABG / Re-PTCA
70
0
60
120
180
Days
240
300
360
• 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 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 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 & Physiology
• Vein grafts are merely
conduits
Proximal
Anastamosis
– 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
Vein
Graft
Body
Distal
Anastamosis
Current 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 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 myocardial
ischemia and infarction
Diagnosis
• ECG
(ST elevation vs. Non ST elevation MI)
• Enzymes
Troponines: highly specific but positive after 4 hours
CK-MB: not so specific and also positive after 4 hours
Myoglobine: low specificity, positive after 2-3 hours
• Echo
if ECG is negative, Echo can show areas of hypo/akinesia
• Angio
final “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 AMI
PCAT
30-day mortality based on level of risk
PCR
Lysis
24.1%
25
20
%
12.7%
13.1%
15
7.9%
10
5
8%
2.9%
0
Low
Intermediate
High
WW3215
Equivalent time to reperfusion with
fibrinolysis or primary PCI
Treatment
TIMI 3 rate
Start Tx
(30’)
Lysis
Reperfusion time
(60’)
Start Tx
(60’)
PTCA
0’
70%
reperfusion time
(30’)
Time
95%
90’
Fibrinolysis
• Dissolution of fibrin thrombi
–
–
–
–
Streptokinase
tPA (alteplase)
rPA (reteplase)
TNK (tenecteplase)
first studied (90 minutes infusion)
1 hour infusion
2 boluses every 30 minutes
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 obstruction
Pathophysiology
Microvascular
Plugging
Atheroemboli
Microvascular
spasm, edema,
vasoconstriction
Platelet
aggregation
Thromboemboli
Zones of
Microinfarction
Distal embolization can
result in microinfarctions