Final thrombus burden

BALAKUMARAN. J
PGIMER & DR.R.M.L HOSPITAL
MANAGEMENT OF THROMBUS BURDEN
DURING PAMI

Introduction
 Thrombus containing lesions are well known predictors of complications
during primary angioplasty.
 The thrombus burden associated with an acute coronary syndrome may
vary depending on various factors, including size of the vessels, duration
of occlusion, prothrombotic state.
 Some of the clinical risk factors associated with higher thrombus burden
include hypercholesterolemia, smoking and male gender.

Thrombus causes complications during intervention
 3 times higher MACE – ischemic complications
 Lower procedural success.
 Higher distal embolization leading to slow/no flow
 High mortality
 ST elevation
 Longer hospital stays

 The right coronary artery tends to have a larger burden of
thrombus probably because of proximal propagation of
thrombus related to fewer branch points.
 During PCI, thrombus development may be triggered by
guidewires, stasis of blood, inadequate antithrombotic
/anticoagulant therapy, balloons or stent; the “angry clot”
phenomenon.

Composition of thrombus
Fibrin-increases with ischemic time (every 1hr-2 fold
increase in ischemic time)
Platelets-decreases with ischemic time
Erythrocytes
Cholesterol crystals
Leucocytes.
JACC march,2011.

With white thrombi-smaller, smaller vessels, lower ischemic time
Red thrombus- more death rate

Red vs white thrombus
Am. Heart Journal,oct-2012

Thrombus Grading for Coronary Interventions
 Thrombus grading scales are essential tools used for qualification
and quantification of the thrombus burden.
 They provide a platform for clinical assessment and subsequently
effect management decisions prior to and during interventions.
 The widely used TIMI thrombus grading scale was originally
created by the TIMI study group investigators

TIMI GRADING FOR THROMBUS
JACC vol.50,2007

 While this classification is user friendly and universally accepted, the accuracy of
the highest level, grade 5, is subject to interpretation challenges.
 With its hallmark characteristic of TIMI 0 flow, the ischemic vessel containing
grade 5 thrombus is totally occluded.
 Consequently, the histological relationship between the underlying plaque burden
and thrombus content is unknown, yet this grade supposedly represents the highest
thrombus load.

 To overcome the above mentioned limitation of TIMI grade 5, an
important modification was recently introduced by the Thoraxcenter
(Rotterdam, The Netherlands) investigators.
 Focusing on this specific grade, they added a much needed critical step to
the reclassification that significantly improves the determination of the
correct load of the underlying thrombus .
 Use either a guide wire or a 1.5 mm balloon for crossing and
recanalization of the target thrombus.

Sianos et al 2006
Large thrombus burden (TBL)
 Presence of thrombus with largest dimension >2 vessel diameters.
Small Thrombus Burden (TBS)
 No thrombus or thrombus present with largest dimension< 2 vessel diameters.

 Another practical grading classification was introduced by
Niccoli et al.

Yip criteria
YIP’S CRITERIA FOR HIGH THROMBUS BURDEN:
 1. Large infarct-related artery (visually estimated reference vessel diameter ≥ 4 mm)
 2. Angiographic thrombus with the greatest linear dimension > 3 times the reference vessel diameter;
 3. “Cutoff pattern” (lesion morphology with an abrupt cutoff without taper before the occlusion);
 4. Accumulated thrombus (> 5 mm of linear dimension) proximal to the occlusion;
 5. Floating thrombus proximal to the occlusion;
 6. Persistent dye stasis distal to the obstruction.
> 2 ABOVE = VERY HIGH THROMBUS BURDEN

Management of thrombus
 The mainstay pharmacological treatments for thrombus-containing
lesions include aspirin, heparin, glycoprotein IIb/IIIa platelet
receptor antagonists, thienopyridines, direct thrombin inhibitors, and
thrombolytic agents.
 The four main contemporary technologies for mechanical thrombus
extraction are manual aspiration catheters, power-sourced
thrombectomy devices, ultrasound sonication, and embolic
protection systems.

 A useful strategy for thrombus management and the restoration of
perfusion incorporates elements of pharmacotherapy and
mechanical thrombus removal.
 The route of administration, dosing of these agents, and selection of
a dedicated device vary according to the location of the thrombus,
burden of thrombosis, and resistance.

Role of GP IIb/IIIa Inhibitors

 The GP IIb/IIIa inhibitors play a central role in the armamentarium for treating thrombus-
containing lesions.
 IC and intravenous delivery routes have also been compared in several studies, with mixed
results.
 There are three intravenous GPIIb/IIIa receptor antagonists that have been approved by the
U.S. FDA
Abciximab
Tirofiban
Eptifibatide

 Despite the differences in structure and pharmacology of abciximab as
compared to eptifibatide and tirofiban, it is unknown if different IIb/IIIa
antagonists may provide different outcomes in relation to their structural
differences in patients with ACS.
 Abciximab has been associated with a long-term decrease in mortality, an
effect that cannot be entirely attributed to the suppression of acute
periprocedural ischaemic events, whereas mortality reduction has not been
observed to date with eptifibatide or tirofiban.
Eur Heart J Suppl (February 2007)

ABCIXIMAB
Abciximab was given as a 0.25-mg/kg intravenous bolus
followed by a 0.125-mg/kg per min infusion for 12 hours.

Trials in primary pci-abciximab
CADILLAC
 1036 PTS.
 Adjunctive abciximab treatment during primary percutaneous
coronary intervention significantly enhanced 30-day event-free
survival, predominantly by reducing ischemia-driven TVR.
 Abciximab treatment did not affect the composite end point at
1 year, reflecting a lack of effect on restenosis.

RAPPORT (483),ISAR-2(401)
30 DAYS –BETTER
6 MONTHS REDUCED BENEFIT.
ADMIRAL
300 PTS.
BENEFIT EVEN IN 6 MONTHS.

Tirofiban
 Tirofiban , a tyrosine derivative with a molecular weight of 495 kd, is a
nonpeptide inhibitor (peptidomimetic) of the platelet GPIIb/IIIa
receptor.
 Administer intravenously 25 mcg/kg over 3 minutes and then 0.15
mcg/kg/min for up to 18 hours.
 In patients with creatinine clearance ≤60 mL/min, give 25 mcg/kg
over 3 minutes and then 0.075 mcg/kg/min.

On-TIME 2 (Ongoing Tirofiban In Myocardial
infarction Evaluation 2)
 Pre-Hospital initiation of tirofiban (HDB) improves ST resolution
after primary PCI
 Combined secondary clinical endpoint reduced
 No increase in bleeding risk

AGIR-2 TRIAL
320 STEMI patients within six hours of symptom onset were randomized to the new
high-dose tirofiban infusion in the ambulance or in the cath lab.
All patients also received a prehospital loading dose of clopidogrel, aspirin, and
heparin. In the prehospital group, tirofiban was administered 48 minutes earlier than
in the cath-lab group.
Results showed no difference in TIMI 2-3 flow at initial angiography (the primary
end point) between the two groups. There was also no difference in ST-segment
resolution or peak levels of cardiac enzymes. Although not powered for clinical
events, these actually trended toward a worse effect in the prehospital group

1398 patients .
Tirofiban (25-g/kg bolus and 0.15-g/kg/min maintenance infusion)
Early pre-hospital administration of a HBD of tirofiban, in addition to
aspirin, high-dose clopidogrel and unfractionated heparin, improves
the clinical outcome after pPCI in patients with acute STEMI, with no
increased risk of major bleeding.
Journal of the American College of Cardiology Vol. 55, No. 22, 2010

High dose Tirofiban vs abciximab
The MULTISTRATEGY trial was an open-label, 2x2 factorial
trial comprising 745 STEMI patients undergoing PCI.
 Tirofiban enables non-inferior STR within 90 min after intervention
and similar outcomes at 8 months than Abciximab
 The safety profile favoured the use of tirofiban for a lower incidence
of thrombocytopenia which has prognostic implications
 Tirofiban appeared a more cost-efficient drug than abciximab

Eptifibatide
 Eptifibatide (Integrilin) is a nonimmunogenic cyclic heptapeptide with
an active pharmacophore from the venom of the southeastern pigmy
rattlesnake.
 Eptifibatide receives a lower level of recommendation in guidelines
regarding STEMI patients due to less scientific validation compared to
abciximab

Eptifibatide vs Abciximab
SCAAR REGISTRY (swedish registry)
A total of 11,479 patients with STEMI underwent Primary PCI with
adjunctive GPI therapy between 2004 and 2007.
This large registry study suggests that eptifibatide is noninferior to
abciximab in patients with STEMI undergoing primary PCI with
respect to death or MI during one year, thereby supporting the use
of either drug in clinical practice.

Intracoronary drug delivery.
 Though this approach has been used empirically in the past
and still continues to be used in cardiac catheterization
laboratories around the world, it has never been evaluated in a
large-scale randomized study.
 The rationale for this approach is the ability to achieve a very
high concentration of the drugs at the site of the thrombus
without significantly increasing the risk of bleeding.

Why favouring intracoronary
 Improve microvascular function and clinical outcomes.
 Concentration after IC administration depends on coronary blood flow. It has been estimated that
the concentration may be as much as 280-fold greater when compared to IV delivery, depending
on inflow and washout of blood.
 Facilitate the diffusion of the drug into the acute thrombus, with the potential of promoting clot
dissolution in the epicardial and microvessels.
 Moreover, a high local concentration leads to increased receptor occupancy in the case of GP
IIb/IIIa inhibitors.

INFUSE-AMI
 Patients randomized to intracoronary abciximab had a significant reduction in the
primary end point compared with patients who did not receive abciximab.
 Infarct size measured as a percentage of total left ventricular mass was 15.2% in
the abciximab-treated patients compared with 17.5% in those who did not receive
abciximab, a significant 2.3% absolute difference in infarct size .
 Regarding the thrombus aspiration arm, the investigators reported no difference in
infarct size between patients undergoing manual aspiration thrombectomy and
those who didn't receive thrombectomy.

All patients were given bolus only dose of intracoronary abciximab (0.25 mg/kg) using the
clearway catheter.
Intracoronary abciximab using local drug delivery catheter in patients with STEMI with
thrombus burden significantly improves TMP grading without increasing the risk of bleeding.
This benefit is achieved even in patients without thrombus aspiration.

Intracoronary vs intravenous trial

In conclusion, compared to IV administration , IC administration of GPIs has favorable
effects on TIMI flow, TVR, and short-term mortality after PCI, with no difference in rates
of bleeding.

CICERO TRIAL 534 PATIENTS
 CICERO trial is the largest clinical trial to date to determine the effect of intracoronary vs intravenous
administration of abciximab in STEMI patients undergoing primary PCI.
 Did not improve myocardial reperfusion as assessed by ST-segment resolution but did improve
myocardial reperfusion as assessed by myocardial blush grade and a smaller enzymatic infarct size in
STEMI patients undergoing primary PCI

AIDA STEMI TRIAL - negative
 2065 pts with STEMI <12 hrs rand to Pri PCI with IC vs IV bolus abciximab.
 Intracoronary versus intravenous abciximab bolus (0·25 mg/kg bodyweight) during percutaneous
coronary intervention with a subsequent 12 h intravenous infusion 0·125 μg/kg per min
(maximum 10 μg/min).
 The IC bolus delivered directly through the guiding catheter as well as the IV bolus were followed
by an IV infusion of abciximab for 12 h.
 Thrombectomy was used in about 20% of patients almost equally in both groups, particularly in
lesions with high thrombus burden.

 Intracoronary abciximab does not reduce rates of death or
myocardial infarction (MI) compared to standard intravenous
(IV) administration of the glycoprotein IIb/IIIa inhibitor in
patients with ST-segment elevation myocardial infarction
(STEMI) undergoing primary percutaneous coronary intervention
(PCI).
 IC decreases CHF.

Beneficial effects of intracoronary tirofiban bolus administration following
upstream intravenous treatment in patients with ST-elevation myocardial
infarction undergoing primary percutaneous coronary intervention: The
ICT-AMI study
 A total of 453 eligible STEMI patients were randomly allocated to
intracoronary bolus administration of tirofiban (10 μg/kg; during primary
PCI, followed by intravenous tirofiban infusion (0.15 μg/kg/min) for 24–
36 h.
 An intracoronary tirofiban bolus administration following upstream
intravenous treatment reduces coronary circulatory platelet activation and
inflammatory process, and significantly improves myocardial reperfusion
and left ventricular function as well as 6-month MACE-free survival for
STEMI patients undergoing primary PCI.
IJN MAY 2013

Bivalirudin during Primary PCI
 Even though it has been studied mostly in stable angina, unstable
angina,non-ST elevated MI, the large scale study in STEMI is
HORIZONS-AMI.
 The Harmonizing Outcomes with Revascularization and Stents in Acute
Myocardial Infarction (HORIZONS-AMI) study was a prospective, open-
label, randomized, multicenter trial that compared bivalirudin alone with
heparin plus a glycoprotein IIb/IIIa inhibitor in patients with ST-segment
elevation myocardial infarction who were undergoing primary PCI.
NEJM, May ,2008

 Bivalirudin was administered as an intravenous bolus of 0.75 mg/kgfollowed by an infusion of 1.75 mg
/kg/ hour.
 There is significant 1.0% absolute increase in stent thrombosis.The early increase in stent thrombosis
with bivalirudin alone may be explained by adenosine diphosphate–induced platelet activation before
maximal thienopyridine blockade of the P2Y12 receptor or by residual thrombin activity after the
discontinuation of bivalirudin.
 Patients with evolving ST-segment elevation myocardial infarction who are undergoing primary PCI, the
use of bivalirudin alone, as compared with heparin plus a glycoprotein IIb/IIIa inhibitor, results in
significantly reduced 30-day rates of major bleeding and increased event-free survival.

3 years follow up
 After 3 years, treatment with bivalirudin alone compared to heparin plus a GP IIb/IIIa
inhibitor resulted in significantly reduced rates of all-cause mortality (5.9% vs. 7.7%),
cardiac mortality (2.9% vs. 5.1%), reinfarction (6.2% vs. 8.2%) and major bleeding not
related to bypass graft surgery (6.9% vs. 10.5%). There were no significant differences in the
incidence of ischemia-driven target vessel revascularization, stent thrombosis, stroke, or
composite adverse events.
 In addition, at 3 years, the implantation of a paclitaxel-eluting stent compared to a bare-
metal stent resulted in significantly lower rates of ischemia-driven target lesion
revascularization (9.4% vs. 15.1%) with no significant differences in the rates of death,
reinfarction, stroke, or stent thrombosis.
Lancet .june 2011

Bivalirudin or heparin in primary angioplasty performed through the transradial
approach: results from a multicentre registry
 1009 patients underwent primary PCI through the transradial approach: 154
patients were treated with bivalirudin (males 79%, age 65±14 years) and 855 with
heparin (males 82%, 63±12 years).
 In group 1, the use of glycoprotein IIb/IIIa inhibitors was only 4%, compared to
55% (p<0.001) in group 2.
 In this registry of primary PCI performed through the transradial approach,
bivalirudin was not associated with a significant reduction in major bleeding or
MACE compared to heparin and provisional glycoprotein IIb/IIIa inhibitors.
European Heart Journal: Acute Cardiovascular Care January 7, 2014

 The role of thrombolytic therapy in patients with coronary artery disease continues to evolve. Early
clinical trials utilized direct intracoronary delivery of drugs and resulted in high patency rates.
 Subsequent trials demonstrated that intravenous thrombolytic therapy was also effective in opening
closed vessels.
 Because of its relative ease of use, intravenous administration quickly emerged as the preferred route.
Since then, the efficacy of intravenous thrombolytic therapy in reducing the mortality of acute
myocardial infarction has been clearly demonstrated.
 In recent years, however, there has been widespread application of newer interventional techniques in the
cardiac catheterization laboratory, renewing interest in the intracoronary use of thrombolytic agents.
Catheterization and Cardiovascular Diagnosis 34:196-201 (1 995)

 Intracoronary thrombus remains a major challenge despite the development of
mechanical approaches, including Angiojet rheolysis and thrombectomy devices.
 These devices, while beneficial in some cases, are limited by their size, cost, and
inability to treat thrombus that has embolized.
 The combination of newer, more fibrin-specific thrombolytic agents such as TNK
with potent platelet inhibition offers the potential to overcome many of the
limitations of intracoronary thrombolytic therapy.

 In the treatment of STEMI, both primary PCI and intravenous
thrombolytic therapy can effectively restore flow in the culprit
coronary artery.
 Studies examining the use of IC thrombolytics as a
prophylactic measure against acute closure after angioplasty
have not suggested a significant benefit in outcomes.

the administration of low-dose intracoronary streptokinase immediately after primary
PCI improved myocardial reperfusion but not long-term left ventricular size or function.

Intracoronary TNK was administered directly through the coronary guide catheter, an
Export catheter (Medtronic), or a Pronto Catheter (Vascular Solutions).
An initial bolus dose of 5 mg was given and the dose was repeated at 5-min intervals
if the angiographic appearance of thrombus and/or coronary blood flow did not
improve.
A maximum dose of 25 mg of TNK was given.
Safety of adjunctive intracoronary thrombolytic therapy during complex percutaneous
coronary intervention: Initial experience with intracoronary tenecteplase
Catheterization and Cardiovascular Interventions, November 2005.

 The indication for administering intracoronary TNK was angiographically visible
intracoronary clot in 12 patients (35%), no-reflow in 11 patients (32%), distal
embolization in 10 patients (29%), and subacute stent thrombosis in 1 patient (3%)
 Death occurred in three patients who presented with cardiogenic shock in the
setting of acute anterior myocardial infarction
 In conclusion, the administration of intracoronary TNK in complex PCI after the
onset of thrombotic complications is safe and may even improve the success rate in
PCI complicated by thrombus.

Thrombosuction devices
 Contemporary mechanical thrombus removal or dissolution devices can be
categorized into four main types, according to their activation mode:
 Manual aspiration catheters,
 Power-sourced thrombectomy,
 Ultrasound-induced sonication, and
 Excimer laser.
 Embolic protection.

BENEFITS
 Shortening of door-to-thrombus clearance time
 Allow selective infusion of thrombolytics, platelet aggregation inhibitors
and vasodilators through the device
 Removal of thrombus-related prothrombotic coagulants and promoters of
vasoconstriction and platelet aggregation
 Reduction of distal embolization and “no reflow”
 Restoration or antegrade flow, improved myocardial blush score.
 Enable accurate assessment of the underlying plaque morphology and
stenosis
 Facilitate stenting.

LIMITATIONS
 May prolong PCI duration
 Higher dependency on operator`s technique
 May not achieve complete thrombus removal
 Can cause distal embolization due to device manipulation
 Do not completely eliminate “no reflow”
 Do not reduce the need for adjunctive stenting
 Increased cost

Thrombosuction catheters
 They are user-friendly because of their low crossing
profile, hydrophilic coating, flexibility, and tapered distal
tip.

MANUALASPIRATION CATHETERS
 Export (Medtronic, Minneapolis, MN),
 Pronto Extraction Catheter (Vascular Solutions, Minneapolis,
MN),
 Diver CE (Invatec, Roncadelle, Italy),
 Xtract (Volcano, Rancho Cordova, CA),
 QuickCat (Kensey Nash, Exton, PA), and
 Fetch (Possis, Minneapolis, MN).

 Use 6 Fr system in the small/mid size vessel, 7 Fr in the large vessel.
 Start aspiration 2 cm before the lesion with the thrombus, move the catheter forward very
slowly and pass the lesion with continuous aspiration (if too quickly - the risk of distal
thrombus dislocation)
 Remove the catheter with aspiration even into the guiding catheter, aspirate the blood from
the guiding catheter
 Remove the catheter outside slowly if a large thrombus is caught on the tip of catheter and
completely block the aspiration Two or three passages are recommended

 A new feature of the Export Advance aspiration catheter is a pre-loaded stylet, a
core wire that runs through the middle of the shaft to provide more support during
delivery.
 This feature increases the deliverability and kink resistance of the device when
traversing the anatomy to reach the aspiration site.
 The Export Advance aspiration catheter is also constructed with full-wall variable
braiding technology that provides variable levels of stiffness along the length of
the device to enhance flexibility and pushability for optimal catheter performance.

TAPAS
 Used export catheter.
 Thrombus aspiration is applicable in a large majority of
patients with myocardial infarction with ST-segment
elevation, and it results in better reperfusion and clinical
outcomes than conventional PCI, irrespective of clinical
and angiographic characteristics at baseline.

Thrombus aspiration results in a lower mortality and in lower combined
mortality and non-fatal reinfarction at 1 year. Thrombus aspiration does not
result in lower TVR rate.

All-cause mortality at 30 days
HR 0.94 (0.72 - 1.22), P=0.63

 The primary end point was all-cause mortality at 30 days.
All-cause mortality was 2.8% in thrombus aspiration
group as compared to 3.0% in the PCI-only group .
 No increased risk of stroke or neurological complications
was observed with thrombus aspiration

TASTE -results
 This large, prospective, registry-based randomized
clinical trial showed:
 no reduction of mortality at 30 days
 no significant reduction of hospitalization for MI or of stent
thrombosis at 30 days
 no reduction of other important clinical endpoints during
hospitalization

 An additional thrombus aspiration study, known as a Trial of
Routine Aspiration Thrombectomy With Percutaneous
Coronary Intervention versus PCI Alone in Patients With
STEMI Undergoing Primary PCI (TOTAL), is ongoing.
 The primary end point of that is a composite of cardiovascular
death, recurrent MI, cardiogenic shock, or new or worsening
NYHA class IV heart failure at six month

 Need to add GP IIb/III antagonists to this treatment to further
improve survival.
 Thrombectomy during primary PCI improves one-year
survival.
 Survival benefit is confined to manual thrombectomy only.

Cardiovascular Revascularization Medicine-2013
Mother-in-child’ thrombectomy technique: a novel and effective approach to
decrease intracoronary thrombus burden in acute myocardial infarction
 The procedure was performed using a 5 F-‘Heartrial’ multipurpose
guiding catheter (Terumo Medical, Somerset, NJ, USA) advanced
into a 6 F-guiding system over a standard coronary wire before
reaching the angiographic location of the thrombus.

‘Mother-in-child’ thrombectomy technique: a novel and
effective approach to decrease intracoronary thrombus
burden in acute myocardial infarction.

Mother –child technique
 Mother and Child Technique with 6F and 8F catheters was used to retrieve thrombus.
 A 100 cm JL 3.5 8F (cordis), I.D,Guiding catheter was cut from proximal end at about 20 cm and mouth
of the proximal end was opened using the dilator of 8F femoral sheath.
 This catheter was used as “mother catheter”. A 100 cm multipurpose A1 (MPA1) 6F (cordis), was used as
“child catheter”.
 This was introduced through proximal end of 8F JL3.5 8F catheter. The 6F MPA1 tip was kept inside the
tip of 8FJL3.5 catheter and left main vessel was engaged with JL3.5 8F catheter. LAD was wired again
with Cougar XT(HT) wire. Over the wire 6FMPA1 catheter advanced into the LAD and passed up to the
mid LAD.
 Aspiration was done with th ehelp of a 20 cc syringe through MPA1 6F catheter.

Rheolytic thrombectomy - ANGIOJET
The AngioJet rheolytic thrombectomy system (Medrad
Interventional/Possis, Minneapolis, Minnesota) consists of a
drive unit console, a disposable pump set, and a 4-F
disposable catheter.
Thrombectomy is accomplished with high-velocity saline
jets contained within the distal catheter tip.

Rheolytic thrombectomy
 Designed to remove thrombus with the Venturi-Bernoulli effect, with multiple
high-velocity, high-pressure saline jets which are introduced through orifices in the
distal tip of the catheter to create a localized low-pressure zone, resulting in a
vacuum effect with the entrainment and dissociation of bulky thrombus.
 Rheolytic thrombectomy with the AngioJet catheter can reduce the thrombus
burden in the setting of AMI and degenerated SVGs.
 The long-term follow-up appears to be favourable in patients treated with rheolytic
thrombectomy in the setting of acute myocardial infarction over conventional
primary angioplasty.

This technique includes:
1) catheter activation at least 1 cm proximal to the thrombus, to create a suction vortex before
advancing the device;
2) advancing the thrombectomy catheter slowly (1 to 3 mm/s) to and through the thrombosed
segment; and
3) restarting the thrombectomy at the end of the proximal-to-distal pass, with a distal-to-
proximal pullback. After the first pass, the device was retrieved into the guide catheter, and an
angiographic check was performed to assess restoration of TIMI flow.
If a TIMI flow grade 2 or 3 was restored and there was no more evidence of residual thrombus,
thrombectomy treatment was stopped, whereas a second or third pass could be made if there
was evidence of residual thrombus or a TIMI flow grade <2.

ANGIOJET
The AngioJet® (MEDRAD, PA, USA) rheolytic thrombectomy system. Active thrombus fragmentation by pressurized,
heparinized saline. (A) Saline jets travel backwards at high speed to create a negative pressure zone (less than -600
mmHg), causing a powerful vacuum effect. (B) Cross-stream® windows optimize the fluid flow for more effective
thrombus removal. (C) Thrombus is drawn into the catheter where it is fragmented by the jets and evacuated from the
body.

AIMI Trial: Secondary Endpoint
• The rate of MACE
was higher in
patients undergoing
thrombectomy
(6.7% v. 1.7%;
p=0.01).
6.7%
1.7%
0%
2%
4%
6%
Angiojet Primary PCI
Rate of MACE in Patients Undergoing Throbectomy
p=0.01
J Am Coll Cardiol 2006;48:244–52

AIMI Trial: Mortality
• Mortality rates at
30 days were higher
in those undergoing
thrombectomy
(4.6% (n=11) v.
0.8% (n=2);
p=0.01).
4.6%
0.8%
0%
2%
4%
6%
Rate of Mortality in Patients Undergoing Throbectomy
p=0.01

AIMI Trial: Secondary Endpoint
0%
20%
40%
60%
80%
100%
Rate of TIMI 3 Flow
p<0.02

JETSTENT TRIAL
the results of this study support the use of RT before infarct artery stenting in patients with
acute myocardial infarction and evidence of coronary thrombus.

Diff. outcomes of AIMI AND JETSTENT TRIALS?
AiMI enrolled patients regardless of whether there was visible thrombus present, while
JetSTENT enrolled only patients with visible thrombus.
In AiMI, the AngioJet was usually passed beyond the coronary occlusion before activation,
which may predispose to distal embolization, while in the JetSTENT Trial the AngioJet was
activated before antegrade passage.
In AiMI, balloon pre-dilatation was usually performed before RT, which may predispose to
distal embolization, while in JetSTENT pre-dilatation was not performed.
In addition, the mortality in the control arm of AiMI was extremely low and may have occurred
by chance. These reasons may explain some of the differences in outcomes between AiMI and
JetSTENT.

Thrombectomy during AMI by manual catheter aspiration, but not mechanically, is beneficial in
reducing MACE, including mortality, at 6 to 12 months compared with conventional primary PCI
alone.

X- SIZER
 The X-sizer catheter system (EndiCOR Medical Inc) consists of a dual-lumen
catheter shaft connected to a handheld control module. Two catheter sizes, 1.5 mm
(7F compatible) and 2-mm (8F compatible), with a helical shape cutter at its distal
tip were used .
 The X-sizer catheter was inserted over a 0.014-inch guidewire and was gently
advanced to the culprit lesion. The inner lumen contains a helical cutter rotated at
≈2.100 rpm. Activation of the system leads to fragmentation of the thrombus,
which is consecutively removed by vacuum through the outer lumen.

X-SIZER
 Thrombectomy was performed using the X-Sizer catheter system.
 One catheter lumen is connected to a 250-ml vacuum bottle, and
aspirated debris is collected in an in-line filter.
 Two or more passages across the lesion from proximal to distal were
performed by slowly advancing the activated catheter.

RINSPIRATOR
 The Rinspiration™ System (Kerberos Proximal Solutions Inc., Sunnyvale, California) consists of two components: a
Rinspiration catheter and a Rinspirator™ device.
 The hand-activated Rinspiration device allows for simultaneous irrigation and aspiration at the treatment site by
activating two syringes, one for infusion and one for aspiration. This coordinated action of both rinsing and aspirating has
been designated as “rinspiration”.
 The Rinspiration catheter has three lumens . A monorail wire lumen is 25 cm in length and allows passage over a
standard 0.014-inch coronary guidewire. A second lumen allows distal aspiration. A third lumen allows injection of a
rinsing solution through perforations located proximal to the aspiration lumen.
 The perforations are distributed circumferentially along a short length of the catheter. The catheter includes a small
radiopaque marker band at the distal tip adjacent to the aspiration port, and two radiopaque marker bands designating the
infusion portion of the catheter. The multilumen catheter has a working length of 135 cm and a diameter of 5.3 French
(Fr), or 1.78 mm.

 The infusion delivery syringe is fed from a reservoir of heparinized
Ringer’s lactate solution or saline.
 As the handle of the Rinspirator is released, the infusion syringe is
automatically filled from the reservoir, while the aspirant is emptied into a
second reservoir bag. This allows for temporary storage, inspection,
analysis, transport and/or disposal of the aspirated materials.

VAMPIRE TRIAL
J Am Coll Cardiol Intv. 2008

RESCUE DEVICE
 The Rescue device (Boston Scientific Scimed, Inc. Maple Grove, Minn., USA) is
a monorail system consisting of a catheter with 2 leads one for passing the guide
catheter, and the other through which aspiration of the intracoronary material is
performed and is joined at the proximal end of the catheter, to an extension tube,
which is in turn connected to a vacuum bottle.
 The bottle empties through another connecting tube that is connected, via a
hydrophobe filter, to an aspiration console that increases the vacuum in the bottle.
The aspiration rhythm is controlled by external compression of the catheter with a
clamp.

Thrombectomy as an adjunct to pPCI in patients with high thrombus load was associated
with better myocardial reperfusion, in terms of better TIMI flow, higher STR, and reduced
no rfelow but was not associated with a reduction in infarct size at 3-month MRI or with
better clinical outcome at 1 year.
Rheolytic thrombectomy was more effective than MT in removing thrombus and showed a
nonsignificant reduction in infarct size.
J Am Coll Cardiol Intv. 2012;
Thrombectomy was performed with either the manual aspiration Export catheter (Medtronic
CardioVascular, Santa Rosa, California) or the RT AngioJet Ultra catheter (Possis Medical,
Inc., Minneapolis, Minnesota) in a sequential alternating fashion.

ACOLYSIS
 Coronary ultrasound thrombolysis uses an acolysis probe to deliver
low-frequency ultrasound at the treatment site, which will lyse or
liquefy thrombus to subcapillary size.
 Acolysis system (Angiosonics Inc., Morrisville, NC, USA) consists
of a control unit that generates ultrasound energy at 35±50 kilohertz,
which is transmitted to the distal tip of a catheter.
 Probe is 0.018 compatible with 2.2 mm Z-tip.

 The Acolysis Probe tip (positioned 2mm away from the
proximal end of the thrombus) produces cavitation and a
resulting vortex which pulls the thrombus toward the
distal tip of the Probe.
 The fibrin holding the thrombus together is selectively
lysed—even fibrin within clots of various ages.
 Because the System works from the proximal end of the
thrombus, this precludes the need to cross the clot with
the probe before treatment.

Acolysis
In the multicenter Acolysis during Treatment of Lesions Affecting Saphenous vein
bypass grafts (ATLAS) trial, patients with ACS undergoing SVG lesion treatment
were randomized to receive either acolysis or abciximab .
Acolysis was inferior to abciximab, with angiographic procedural success in 63% of
Acolysis patients versus 82% of abciximab patients (p = 0.008), with a higher
incidence of 30-day MACE (25% with Acolysis and 12% with abciximab)

Analysis of Coronary Ultrasound Thrombolysis Endpoints in Acute
Myocardial Infarction (ACUTE Trial):
 15 PATIENTS.
 Coronary ultrasound thrombolysis was found to attain device success (TIMI grade
3 flow) in 87% of patients, angiographic success in 87%, and clinical success in
80%.
 Final angiographic results revealed minimal residual stenosis (20%) with no
adverse morphological signs on angiography.
 No adverse clinical side effects were observed during sonication in the coronary
tree. CIRCULATION 1997

Excimer laser
 The Excimer laser ( Spectranetics CVX-300, Spectranetics,
Inc., Colorado Springs, Colorado) works on the principle that
ultraviolet laser light of mid-ultraviolet wavelength is well
absorbed by thrombus, induces thrombolysis, inhibits platelet
aggregation and may ablate the atherosclerotic plaque.
 Works because both atherosclerotic plaque and thrombi avidly
absorb laser energy in the ultraviolet wavelength

EXCIMER LASER.
 A pulse-wave xenon chloride excimer laser (Spectranetics CVX-300,
Spectranetics, Colorado Springs, Colorado) was applied, with a 308-nm
wavelength, pulse duration of 135 ns, and an output of 165 mJ/pulse.
 The laser catheters contain flexible optic fibers, with either concentric tip
configuration in sizes of 0.9, 1.4, 1.7, and 2.0 mm (Vitesse C,
Spectranetics) or eccentric tip sizes 1.7 and 2.0 mm (Vitesse E,
Spectranetics).
 The laser catheter was advanced slowly at a speed of 0.2 to 0.5 mm/s

PRINCIPLE
 Adequate absorption of laser energy within thrombus and an atherosclerotic plaque is required for debulking. Lasers
in the near and mid-ultraviolet wavelength (excimer) rely on absorption in the nonaqueous components of the
atherosclerotic plaque (e.g., proteins and nucleic acids).
 Absorption within the atheromatous, thrombotic material results in photomechanical (breaking of chemical bond)
and photothermal (increase in the target's temperature) processes that lead to vaporization and removal of the
irradiated lesion.
 The interaction of excimer laser energy with thrombus has 2 effects: the first, typical for pulsed-wave lasers,
includes induction of acoustic shock waves propagating onto fibrin strands leading to their fracture and dissolution.
 The second phenomenon is suppression of platelet aggregation kinetics, an effect termed the “stunned platelet
phenomenon. The products of in vitro excimer laser thrombolysis are mainly small particulates of <10 μm in size

The Effect of Interventional Treatment in Acute Myocardial
Infarction on ST Resolution: A Comparison of Coronary Angioplasty
with Excimer Laser Angioplasty-36 VS 44 PATIENTS
The treatment methods for acute myocardial infarction (MI) have started to change in the new millennium.
Myocardial perfusion (ST-segment resolution) is the target rather than achieving TIMI-III flow in the infarct-
related artery.
In this study the authors compared the effect of percutaneous transluminal coronary angioplasty (PTCA) and
excimer laser angioplasty (ELCA), which was accepted as one of the thrombolysis methods, on ST-segment
resolution.
ST segment resolution, which is a good predictor of tissue perfusion, was higher with ELCA than with
balloon angioplasty. These findings should be supported by large randomized studies.
ANGIOLOGY July/August 2005

Excimer Laser Angioplasty in Acute Myocardial Infarction
(The CARMEL Multicenter Trial)
 151 Patients.
 Baseline left ventricular ejection fraction was 44 + 13%, and 13% of patients were in
cardiogenic shock.
 Excimer laser light is an effective and safe revascularization modality for treatment of AMI.
 Maximal thrombus dissolution in lesions with extensive thrombus burden, significant
increase in minimal luminal diameter, and adequate restoration of anterograde TIMI flow in
the infarct-related artery all support successful debulking facilitated by excimer laser energy.
Am J Card March 2004

EMBOLIC PROTECTION DEVICES
 Despite early perceptions that distal embolization of atherosclerotic plaque
contents was a rare event during balloon angioplasty, it has now become
clear that manipulation of atherosclerotic lesions with wires, balloons,
atherectomy catheters, or stents does liberate plaque debris.
 The concept of distal occlusion is to block the vessel being treated several
centimeters beyond the target lesion so that plaque liberated from the
lesion during angioplasty or stent placement remains suspended in the
resulting stagnant column of blood.
 If that column of blood (and the suspended debris it contains) can be
aspirated completely before the distal occlusion is relieved and antegrade
flow is restored, distal embolization of debris will be prevented.
Circulation.2006; 113: 2651-2656

DISTAL OCCLUSION DEVICES
 The concept of distal occlusion is to block the vessel being treated
several centimeters beyond the target lesion so that plaque liberated
from the lesion during angioplasty or stent placement remains
suspended in the resulting stagnant column of blood.
 If that column of blood (and the suspended debris it contains) can
be aspirated completely before the distal occlusion is relieved and
antegrade flow is restored, distal embolization of debris will be
prevented.

 The occlusive systems have at least 2 theoretical advantages over
the filters.
 First, they have a lower crossing profile, which may lead to less
embolization of thrombus while crossing the lesion.
 Second, the aspiration of stagnant blood allows for the removal of
humoral mediators released during PCI that may also contribute to
microvascular dysfunction.

(Medtronic, Minneapolis, Minn)

WHY EMERALD NEGATIVE
The GuardWire wasn’’t efficient enough
Embolization occurred during guidewire passage
GuardWire delays caused harm
Procedural inflations/deflations caused harm
Couldn’’t protect prox side branches/bifurcation

 The frequency of in-hospital MACE was similar among the
protected and control groups, which may indicate that there was no
detrimental influence associated with PercuSurge system
 A tendency to have higher incidence of Blush 3 has been observed
in the group treated with distal protection device, especially in the
cases with proximal RCA lesions

Distal Embolic Filter Devices
 These devices permit anterograde flow and hence are less
likely to induce ischemia; they also allow contrast injections
for imaging of the vessel during the procedure.
 The efficacy of the FilterWire has been investigated in 2
randomized trials.

SPIDER FX
Works with any 0.014" or 0.018" guidewire to cross the most challenging lesions
Enhanced Visibility
Clearly visible radiopaque markers and direct mouth indicator enable quick and
controlled positioning of the filter throughout the intervention
Excellent Stability
Controlled filter positioning throughout the intervention and during device exchanges
.
Braided nitinol design provides full-wall apposition.
Capture wire designed to rotate and move longitudinally independent of the filter
Heparin coated filter provides up to 60 minutes patency

3.2 F
Retrieval-Catheter 3.2 F
Filter3-7 mm
Micropores 48-167μ

PROMISE
 Among patients with myocardial infarction (MI) undergoing direct PCI,
use of the FilterWire distal protection device was not associated with
improvements in microvascular reperfusion or reductions in infarct size
compared with conventional PCI.
 The lack of benefit in the present PROMISE trial parallels the results of
the recent EMERALD trial, which also showed no improvement in infarct
size or myocardial perfusion associated with use of a balloon distal
protection device in acute myocardial infarction patients.

Explanations for the lack of efficacy.
 First, the devices themselves may promote distal embolization while crossing the culprit lesion.
 Second, the removal of debris may be insufficient, with inadequate ability to aspirate large
particles with the occlusion devices or failure to capture particles <100 μm with the filter systems.
 Third, the potential exists for embolization into side branches that are proximal to the device.
 Fourth, predilation is often required to facilitate delivery of the device, which may negate the
benefit because of the embolization that occurs during the initial balloon inflation.

 The recent trials of routine use of embolic protection devices for
primary percutaneous coronary interventions (PCI) (the
EMERALD, PROMISE, and AIMI trials) have demonstrated neutral
or even negative effects of these devices on myocardial reperfusion
and final infarct size.
 Despite these results, there is still ground to believe that PCI-
induced embolization may be clinically relevant in specific subsets
of patients with acute myocardial infarction (AMI).

 Overall, the larger clinical trials of distal protection devices have consistently
demonstrated that this strategy for adjunctive thrombectomy does not improve
microvascular perfusion or clinical outcomes during primary PCI.
 Although the precise reasons why such a promising concept has failed to prove
effective remain unclear, what has been established is that distal protection is
not an adjunctive strategy that can be recommended for primary PCI on a
routine basis.
 Distal protection may still offer benefit in selected cases with high thrombus
burden

Proximal Protection Device
 A system for proximal (to the culprit lesion) embolic
protection has been developed
(Proxis system, St Jude’s Medical, Minneapolis, Minn).
 Proximal occlusion is based on the principle of suspending anterograde blood flow before PCI
and then aspirating the stagnant column of blood that contains the embolic debris before restoring
flow.
 This approach offers the theoretical advantage of protecting distal side branches. The Proxis
system is not widely used in clinical practice, and its role in primary PCI has not been
investigated. Preliminary experience suggests that the device requires further refinements to make
it suitable for use in unstable patients.

 6F and 7F GC compatible
 Sealing balloon at the tip
 CO2 based inflation device
 Complete STR was faster and more frequent in Proxis treated patients.
 The results of the PREPARE trial suggest that primary PCI with combined proximal
embolic protection and aspiration leads to better immediate microvascular flow in
STEMI patients.

PREPARE Trial
 PRoximal Embolic Protection in Acute MI and
Resolution of ST-Elevation

Stents with Thrombus Capturing Mechanisms
 A dedicated thrombus-trapping stent could offer a targeted approach to the
management of thrombus and reduction of embolization.
 The MGuard stent (Inspire-MD, Tel-Aviv, Israel) was developed for this purpose.
 It provides a unique stainless steel bare metal stent covered with an ultrathin,
micrometer-level (150 × 180 micrometer), flexible mesh net fabricated by circular
knitting .
 During stent deployment, the net stretches and slides over the expanding stent
struts, creating custom-designed pores parallel to the vessel wall.

Stent
Stent material: Stainless steel
Stent design: Low profile, open cell
Strut thickness: 100µm
Catheter
0.014” guide wire compatible
Guiding catheter: 6F or higher
Nominal Pressure: 8 atm.
Radio-opaque markers: Proximal and Distal
Balloon Characteristic: Semi-compliant

 The sleeve is designed to expand seamlessly when the stent is deployed, without
affecting the structural integrity of the stent, and to prevent plaque detachment
during and post procedure.
 The MGuardTM Coronary stent provides long acting embolic protection, without
adding complexity in deliverability. The sleeve is designed to diffuse stent pressure
on the vessel wall, thereby may reduce injury and lower the likelihood of
restenosis.

 Reducing the chance of embolization by maintaining plaque’s stability and
preventing rupture.
 Once deployed, the MGuard stent seals the thrombus and accompanying
plaque and captures potential embolic debris between the fiber net and the
arterial wall.

 MAGICAL TRIAL- 60 PTS SUPERIOR –FIRST
STUDY
 INSPIRE MD TRIAL
 GUARDIAN TRIALS-NONINFERIOR
 MASTER TRIAL- SUPERIOR

Prospective, Randomized, Multicenter Evaluation of a Polyethylene Terephthalate Micronet Mesh–
Covered Stent (MGuard) in ST-Segment Elevation Myocardial Infarction.
The MASTER Trial
Among patients with acute STEMI undergoing emergent PCI, the MGuard micronet mesh–
covered stent compared with conventional metal stents resulted in superior rates of epicardial
coronary flow and complete ST-segment resolution. A larger randomized trial is warranted to
determine whether these benefits result in reduced infarct size and/or improved clinical
outcomes.

If MGS implantation is noninferior to a strategy of MT pretreatment followed by BMS
deployment, it will lend support to the use of this treatment as another possible option
for STEMI patients undergoing PCI.

NO REFLOW
 The no-reflow phenomenon is defined as a profound reduction in antegrade
coronary blood flow (TIMI flow grade ≤ 2 ) despite vessel patency and the
absence of dissection, spasm, or distal macroembolus, which is defined as a
distal filling defect with an abrupt "cutoff" in one of the peripheral coronary
artery branches of the infarct-related vessel, distal to the site of PCI.
 The concept of “no reflow” refers to a state of myocardial tissue
hypoperfusion in the presence of a patent epicardial coronary artery

No reflow
 NO RFLOW-term was first given by majno and coleagues in view of
cerebral ischemia in 1967.
 No-reflow is more common after mechanical revascularization of
thrombus-containing lesions (i.e., acute MI) and degenerated vein grafts
containing friable debris.
 No-reflow is associated with adverse clinical outcomes and is caused by
MVO (<200 μm), which may result from multiple pathophysiological
mechanisms.
Eur Heart J (2001) 22 (9

 Nitroprusside and nitroglycerin are nitric oxide donors that
vasodilate conductance vessels >200 μm.
 Microvessels are unable to metabolize nitroglycerin to nitric oxide;
in contrast, nitroprusside does not require metabolism.
 Calcium channel blockers may attenuate microvascular spasm and
reduce myocardial ischemia and infarct size by lowering heart rate
and blood pressure.

 Nicorandil is a hybrid drug of ATP-sensitive K+ channel
opener and has been shown to decrease infarct size and
incidence of arrhythmias probably by suppressing free
radical generation and by modulation of neutrophil
activation.
 It also exerts stimulating effect on preconditioning and
has vasodilator properties.

Reverse Superimposed Spasm.
 Intracoronary nitroglycerin (200-800 mcg) rarely has any
effect on no-reflow but may reverse superimposed spasm.
 Since its use is not associated with unnecessary delay or
enhanced risk, it should be used in all cases.

Administer Intracoronary Calcium Antagonists.
The most important strategy in the treatment of no-reflow is the use of intracoronary
calcium antagonists.
Intracoronary administration of verapamil (100-200 mcg, total dose up to 1.0-1.5
mg) or diltiazem (0.5-2.5 mg bolus, total dose up to 5-10 mg) has been shown to
reverse no-reflow in 65-95% of cases.
Although high-degree AV block is unusual following intracoronary calcium
antagonists, a temporary pacemaker should be readily available. Hypotension caused
by no-reflow is not a contraindication to intracoronary CCBs.

Adenosine, an endogenous nucleoside with a short half-life, improved ST-segment
resolution more than angiographic indices of reperfusion suggests that its benefit extends
beyond brief vasodilation.

Patients were randomized to
intracoronary adenosine (120 µg as fast bolus, then 2 mg in
33 mL of saline in 2 minutes as slow bolus vs
nitroprusside (60 µg as fast bolus, then 100 µg in 33 mL of
5% glucose in 2 minutes as slow bolus given distal to the
occlusion.

Conclusion
 Optimizing myocardial perfusion during STEMI for management of thrombus burden is
challenging.
 Pharmacotherapy: the new anti-platelet agents clearly have an advantage over past ones.
 GP IIb/IIIa inhibitors, antithrombotics inhibitors is of use.
 IC GP IIb/IIIa inhibitors- administration appears to have an advantage over IV, but to be studied in
larger population.
 No-reflow should be prevented

CONCLUSION
 Manual thrombus aspiration appeared promising especially from initial studies
(TAPAS), but recent studies (INFUSE-MI, TASTE) and following trial failed
to duplicate the favorable effect.
 Rheolytic thrombectomy is of use in large thrombus burden.
 Embolic protection devices are of doubtful benefit for STEMI PCI .
 DES preferred stents; MGuard stent may be beneficial in STEMI PCI but
needs to be tested in further clinically powered trials.

Final thrombus burden

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