Thrombus Management in the Cath Lab David A. Cox, MD FSCAI FACC Lehigh Valley Health Network Director, Cardiovascular Research Institute Associate Director of Cardiac Catheterization Laboratory Allentown, PA CRT 2017

Disclosures Advisory Board: Abbott Vascular Medtronic,Inc. Boston Scientific Speaker: Medicure

We All Agree Dealing with thrombus still a real challenge “Why are trials negative? I do thrombectomy and it works!” Doctor feels good, any benefit for patient?

What PCI doc’s already know Is the size and amount of thrombus really that important? YES! WE ALL WANT LESS DISTAL EMBOLI, NO-REFLOW, AND STENT THROMBOSIS

Lots of papers in this area

Inaba Yet al. Eurointervention; 2009;5:375-83 Embolic Protection During Primary PCI: Impact of single vs. multicenter studies 25 RCTs, 5919 pts 2460 pts in single center trials, 3459 pts in multicenter trials Study design Single center Multicenter Overall (I2=0, P=0.51) RR (95%) 0.58 (0.37, 0.90) 1.01 (0.67, 1.54) 0.81 (0.72, 0.91) Predictors of mortality Study design Single center Multicenter Overall (I2=84.8%, p<0.001) RR (95%) 0.58 (0.37, 0.90) 1.01 (0.67, 1.54) 0.75 (0.72, 0.79) 2 1 4 Predictors of ST resolution 0.3 1 2 Inaba Yet al. Eurointervention; 2009;5:375-83

Filters…no data for use

Some exceptions Massive thrombus in proximal vessel……. Run manual thrombectomy device over filter placed distally. OR Some reports of literally catching the clot with the filter as a butterfly net!!! DATA-FREE ZONE!

What’s new in embolic protection?

MGuard Concept STENT + EMBOLIC PROTECTION STENT + EMBOLIC PROTECTION

The MGuard and MGuard Prime Embolic Protection Stent (EPS) MGuard MGuard Prime Metallic frame 316L stainless steel L605 cobalt chromium Strut width 100 µm 80 µm Crossing profile 1.1 – 1.3 mm 1.0 – 1.2 mm Shaft dimensions 0.65 – 0.86 mm 0.65 – 0.86 mm Mesh sleeve PET** PET** - Fiber width 20 µm 20 µm - Net aperture size 150 - 180 µm 150 - 180 µm *InspireMD, Tel Aviv, Israel; **Polyethyleneterephthalate

MGUARD for Acute ST Elevation Reperfusion II The MASTER II Trial STEMI with symptom onset within 12 hours - 1,114 pts at 70 sites in 11 countries - R Stratified by LAD vs. non-LAD infarct vessel and intended DES vs BMS PCI with BMS or DES PCI with MGuard Prime Follow-up: 30 days, 6 months, 1 year, 2 years, 3 years 1 efficacy endpoint: ST-segment resolution at 60-90 minutes (Sup) 1 safety endpoint: Death or reinfarction at 365 days (NI) 2 efficacy endpoint: Infarct size day 3-7 MRI (n=352 P/MLAD) (Sup) 2 safety endpoint: In-stent late loss 12 months (n=200 BMS strata, NI)

MASTER II Primary Endpoint Complete ST-segment resolution MGuard Prime (n=144) Control (n=145) 10.4% 11.0% Difference [95%CI] = -2.4% [-14.5,9.7] P=0.68 59.3% 56.9% 29.7% 32.6%

AngioJet Rheolytic Thrombectomy 16

Why Angiojet Rarely Used? Set up more complex Heart Block, hypotension Deaths in AiMI often related to procedural complications Manual Aspiration…must be better

Manual Thrombectomy

Tale of 4 Trials TAPAS INFUSE AMI TASTE TOTAL

Why might manual aspiration work? Easy to use Can chase clot down artery Direct Stenting? Why not? Technique not defined, thrombus often left, catheters not ideal

TAPAS: 1,071 pts with STEMI undergoing PCI randomized in the ER to aspiration (Export) vs. control Myocardial Blush (1 EP) ST-segment Resolution P<0.001 P<0.001 Thrombus aspiration Conventional PCI Thrombus aspiration Conventional PCI Svilaas T et al. NEJM 2008;358;-557-67

TAPAS: 1,071 pts with STEMI undergoing primary PCI randomized in the ER to manual aspiration (Export) vs. control 30 days 4.0% vs. 2.1% P=0.07 Time (days) Mortality (%) Conventional PCI Thrombus-Aspiration 100 200 300 400 2 4 6 8 10 12 1 year 7.6% vs. 4.0% P=0.04 Vlaar et al. Lancet 2008;371:1915-20

INFUSE-AMI Ant MI 452 pts PCI <6 hrs after symptoms Manual aspiration vs. no aspiration Pooled across the abciximab randomization

INFUSE-AMI: STR 60 minutes post-PCI* [55.8, 87.4] [45.2, 87.2] ST-segment resolution (%) *Core laboratory assessed

Ole Fröbert, MD, PhD - on behalf of the TASTE investigators UCR Uppsala Clinical Research Center Thrombus Aspiration in ST- Elevation myocardial infarction in Scandinavia (TASTE trial): Results and Methodology of a Registry based Randomized Clinical Trial (RRCT) Ole Fröbert, MD, PhD - on behalf of the TASTE investigators Departement of Cardiology Örebro University Hospital Sweden

TASTE and previous studies

All-cause mortality at 30 days HR 0.94 (0.72 - 1.22), P=0.63 Per protocol analysis based on actual treatment: HR 0.88 (0.66 - 1.17), P=0.38 Fröbert, O. et al. N Engl J Med 2013; 369:1587-97

Additional results

TASTE vs. TAPAS

TASTE 12 mo: NO BENEFIT

TOTAL Trial Flow and Adherence 10,732 enrolled and randomized Cross-over to Thrombectomy as initial strategy in 70 (1.4%) Bailout Thrombectomy in 354 (7%) Crossover to PCI alone in 231 (4.6%) TOTAL 5035 Manual Thrombectomy 5029 PCI Alone 5029 included in analysis 5035 included in analysis 10,064 underwent PCI for STEMI

Primary Outcome (CV death, MI, Shock or CHF) at 1 year

Primary Outcome at 1 year Thrombectomy (N=5033) (%) PCI alone (N=5030) (%) HR 95% CI p CV death, MI, shock or class IV heart failure 395 (7.8) 394 (7.8) 1.00 (0.87 – 1.15) 0.99 CV death 179 (3.6) 192 (3.8) 0.93 (0.76 – 1.14) 0.48 Recurrent MI 125 (2.5) 118 (2.3) 1.05 (0.82 -1.36) 0.68 Cardiogenic Shock 95 (1.9) 105 (2.1) 0.90 (0.68 – 1.19) 0.47 Class IV heart failure 106 (2.1) 96 (1.9) 1.01 (0.83 – 1.45) 0.50

Safety Outcomes at 1 year   Thrombectomy (N=5033) (%) PCI alone (N=5030) (%) HR 95% CI p Stroke at 1 year 60 (1.2) 36 (0.7) 1.66 (1.10 – 2.51) 0.015 Stroke or TIA at 1 year 73 (1.4) 44 (0.9) 1.6 5 (1.14 – 2.40) 0.008 Landmark Analyses Stroke 180 days to 1 year 7 (0.1) 10 (0.2) 0.7 0 (0.27 – 1.83) 0.46

TOTAL one year: subgroups Jolly et al. Lancet 2016; 387(10014): 127

2015 ACC/AHA/SCAI Focused Update on Primary PCI for Patients with STEMI: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention and the 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction Developed in Collaboration with the American College of Emergency Physicians © American College of Cardiology Foundation, American Heart Association, and Society for Cardiovascular Angiography and Interventions

Aspiration Thrombectomy COR LOE Recommendations IIb C-LD The usefulness of selective and bailout aspiration thrombectomy in patients undergoing primary PCI is not well established.1 III: No Benefit A Routine aspiration thrombectomy before primary PCI is not useful.2 1. Modified recommendation from 2013 guideline (Class changed from IIa to IIb for selective and bailout aspiration thrombectomy before PCI) 2. New recommendation

Thomas Stiermaier, MD; Suzanne de Waha, MD; Effect of Thrombus Aspiration in Patients With Myocardial Infarction Presenting Late After Symptom Onset Steffen Desch, MD Thomas Stiermaier, MD; Suzanne de Waha, MD; Philipp Lurz, MD, PhD; Matthias Gutberlet, MD; Marcus Sandri, MD; Norman Mangner, MD; Enno Boudriot, MD; Michael Woinke, MD; Sandra Erbs, MD; Gerhard Schuler, MD; Georg Fuernau, MD; Ingo Eitel, MD; Holger Thiele, MD

Background Hypothesis Design Routine thrombus aspiration reduces microvascular obstruction (MVO) assessed by cardiac magnetic resonance imaging (CMR) in patients with subacute STEMI presenting between 12 and 48 hours after symptom onset. Design This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) Prospective, randomized, controlled, single-blind Single-center 41

Primary Endpoint: Microvascular Obstruction Results Primary Endpoint: Microvascular Obstruction on MRI Day 1-4 Thrombus aspiration Microvascular obstruction, %LV Standard PCI only p=0.47 5 4 3 1 2 3.1 ± 4.4 2.5 ± 4.0 This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 42

The Third DANish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction: DEFERred stent implantation in connection with primary PCI: DANAMI 3-DEFER

Aim of DANAMI-3-DEFER study To evaluate whether the prognosis of STEMI patients treated with pPCI can be improved by deferred stent implantation

Methods N=1207 DEFER: Minimal acute manipulation to restore stable flow in IRA Stent implantation 48 hours later Conventional PCI: Immediate stent implantation

Primary endpoint

Components of the primary endpoint

Routine deferred stenting was associated with an increased rate of target vessel revascularisation, mainly due to premature stent implantation but Slight improvement in EF (3% pts)

A prospective, randomized trial of TATORT-NSTEMI: A prospective, randomized trial of Thrombus Aspiration in ThrOmbus containing culPriT lesions in Non-ST-Segment Elevation Myocardial Infarction Holger Thiele, MD Ingo Eitel, MD; Suzanne de Waha, MD; Steffen Desch, MD; Bruno Scheller, MD; Bernward Lauer, MD; Meinrad Gawaz, MD; Tobias Geisler, MD; Oliver Gunkel, MD; Leonhard Bruch, MD; Norbert Klein, MD; Dietrich Pfeiffer, MD; Gerhard Schuler, MD; Uwe Zeymer, MD on behalf of the TATORT-NSTEMI Investigators

Study Design, Flow, and Compliance Methods 460 NSTEMI patients 20 not randomized 440 NSTEMI patients 221 assigned to thrombectomy 219 assigned to standard PCI No CMR (n=40) Claustrophobia (n=11) PM/ICD (n=2) Obesity (n=1) Death (n=3) Renal insuff. (n=0) Other (n=23) No CMR (n=27) Claustrophobia (n=5) PM/ICD (n=3) Obesity (n=1) Death (n=3) Renal insuff. (n=1) Others (n=14) Primary endpoint analysis MO (n=181) Secondary endpoint MBG (n=221) Secondary endpoint TIMI-flow (n=221) Clinical follow-up 6 months (n=218) Primary endpoint analysis MO (n=192) Secondary endpoint MBG (n=219) Secondary endpoint TIMI-flow (n=219) Clinical follow-up 6 months (n=216)

Primary Study Endpoint – MO in MRI Results Presence of MO Extent of MO Thrombectomy Standard PCI Median [IQR] 1.95% [0.80;4.10] 1.40% [0.70;2.60] Extent of MO, %LV p=0.17 2 4 6 8 10 p=0.74 Presence MO, % 30.8% 29.2% Thrombectomy Standard PCI Core lab assessed

Clinical Outcome 6 Months Results Clinical Outcome 6 Months Thrombectomy Standard PCI HR 95% CI P Death/Reinfarction/TVR/new CHF 7.3% 10.1% 0.72 0.37-1.41 0.34 Death 3.0% 3.3% 0.83 0.28-2.48 0.74 Reinfarction 2.1% 2.7% 0.78 0.21-2.89 0.70 TVR 1.6% 1.30 0.29-5.80 0.73 New CHF 1.8% 4.4% 0.43 0.13-1.40 0.15 Evtl. weglassen und nur die Kaplan Meier Kurven zeigen

Which Intraprocedural Thrombotic Events Impact Clinical Outcomes After Percutaneous Coronary Intervention in Acute Coronary Syndromes? A Pooled Analysis of the HORIZONS-AMI and ACUITY Trials Jeffrey D. Wessler, MD, MPH; Philippe Généreux, MD; Roxana Mehran, MD; Girma Minalu Ayele, PhD; Sorin J. Brener, MD; Margaret McEntegart, MD, PhD; Ori Ben-Yehuda, MD; Gregg W. Stone, MD; Ajay J. Kirtane, MD, SM J Am Coll Cardiol Intv. 2016;9(4):331-337

Results 6591 pts PCI for NSTEMI or STEMI IPTE 7.7% 12/2% STE 3.5% NSTEMI

Use what works for you!

Should we stop thrombectomy? Oculothrombotic reflex Allows direct stenting May reduce distal embolization but CVA Techniques in trials poorly defined J Blankenship JACC Int Jan 2016: Why we will never stop aspirating coronary thrombi….selectively