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.

ESC-2012

Intracoronary

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.

Decreases the greater risk of bleeding.

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

AHA -2013

Fibrinolytics

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. 

THROMBECTOMY DEVICES

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.

MANUAL ASPIRATION 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

EXPORT CATHETER

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.

Major trials

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.

Came the trendsetter

Nejm ,Oct 2013

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

ATTEMPT EHJ 2009

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-2013Mother-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.

ANGIOJET

AIMI TRIAL

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;48:244–52J 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%

Angiojet Primary PCI

Rate of Mortality in Patients Undergoing Throbectomy p=0.01

J Am Coll Cardiol 2006;48:244–52J Am Coll Cardiol 2006;48:244–52

AIMI Trial: Secondary Endpoint

0%

20%

40%

60%

80%

100%

Angiojet Primary PCI

Rate of TIMI 3 Flow p<0.02

J Am Coll Cardiol 2006;48:244–52J Am Coll Cardiol 2006;48:244–52

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.

X-SIZER

X-SIZER - X AMINE ST TRIAL

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.

Rinspirator

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 TRIALJ 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

ASPARAGUS trial

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

DPO DEVICES

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.

DISTAL EMBOLIC FILTERS

FILTERWIRE

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.

TRIALS IN FILTERS

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.

PROXIS SYSTEM

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.

MANAGEMENT OF NO RELOW

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.