Interventional Cardiology Live Case Study Series: A Master Class in Procedural Techniques Samin K. Sharma, MD Director Cardiac Cath Lab and Intervention Professor of Medicine Co-Director Cardiovascular Institute Mount Sinai Medical Center New York, NY Annapoorna S. Kini, MD Associate Director Cardiac Cath Lab Mount Sinai Medical Center New York, NY Sameer K. Mehta, MD Voluntary Associate Professor of Medicine University of Miami - Miller School of Medicine, Miami, Florida

September 21, 2010: Case #1: NJ, 72-y-o man Presentation: Crescendo exertional angina and SOB for 2 months and stress MPI revealed moderate-to-severe multivessel ischemia and TID History: Hypertension, hyperlipidemia, ex-smoker, colon ca s/p colectomy & chemotherapy 2006 CRi Medications: ASA, clopidogrel, simvastatin, metoprolol, amlodipine SOB = shortness of breath; MPI = myocardial perfusion imaging; TID = transient ischemic dilation; Cri = incomplete blood cell count recovery; ASA = acetylsalicylic acid

Case #1 (cont) Cardiac Cath: 8/6/2010: PCI 8/6/10: Plan Today: Three-vessel CAD with LVEF 65% Left main: no obstruction LAD: 80% long calcified lesion of proximal LAD (large) with 70% apical lesion and mild diffuse first diagonal LCx: 50% prox LCx, 80% OM1 & 50% distal LCx (Medina 1,1,1) RCA: 70%-99% multiple lesions in RCA, fills via LAD PCI 8/6/10: PCI of RCA (XienceV® x 4, 3-3.5 mm size) Plan Today: PCI of calcified LAD lesion using RotaDES and LCx bifurcation SYNTAX Score 26 CAD = coronary artery disease; LVEF = left ventricular ejection fraction; LAD = left anterior descending; LCx = left circumflex; OMI = first obtuse marginal; RCA = right coronary artery; PCI = percutaneous coronary intervention; RotaDES = rotablation and drug-eluting stent implantation ® Abbott Laboratories, Abbott Park, Ill.

Issues Involving the Case Choice of Antithrombotic Therapy Treatment of Calcified Lesions Bifurcation Lesion Intervention

REPLACE-2 vs ACUITY PCI: 30-day Events REPLACE-2 PCI ACUITY PCI Heparin + GP IIb/IIIa (n = 3008) Bivalirudin alone (n = 2994) Heparin + GP IIb/IIIa (n = 2619) Bivalirudin alone (n = 2561) P = .49 % P = .30 % P = .45 11.1 P = .40 10.0 10.5 9.2 8.8 8.2 7.6 7.0 P < .001 P < .001 4.1 4.2 2.4 2.1 Ischemic Major Net Clinical Composite Bleeding Outcomes Ischemic Major Net Clinical Composite Bleeding Outcomes Lincoff AM, et al. JAMA. 2003;289:853-863 Stone GW, et al. N Engl J Med. 2006;355:2203.

HORIZONS AMI Trial: 30-Day Mortality of PCI Heparin + GPIIb/IIIa inhibitor (n = 1662) Bivalirudin monotherapy (n = 1678) HR = 0.63 [0.40, 0.99] P = .049 2.8% Death (%) Cardiac 1.8% Noncardiac 0.2% 0.1% Time in days Number at risk Bivalirudin 1678 1647 1640 1635 1632 1620 1563 Heparin + GPIIb/IIIa 1662 1631 1615 1604 1598 1583 512 From Stone GW, et al. N Engl J Med .2008;358:2218. © 2008 Massachusetts Medical Society. All rights reserved.

HORIZONS AMI Trial: 30-Day Mortality of PCI This higher early events in bivalirudin group were due to higher acute stent thrombosis and can be eliminated by extended (1-3 hours) infusion after PCI or by prasugrel load instead of clopidogrel load. Heparin + GPIIb/IIIa inhibitor (n = 1662) Bivalirudin monotherapy (n = 1678) HR = 0.63 [0.40, 0.99] P = .049 2.8% Death (%) Cardiac 1.8% Noncardiac 0.2% 0.1% Time in days Number at risk Bivalirudin 1678 1647 1640 1635 1632 1620 1563 Heparin + GPIIb/IIIa 1662 1631 1615 1604 1598 1583 512 From Stone GW, et al. N Engl J Med .2008;358:2218. © 2008 Massachusetts Medical Society. All rights reserved.

HORIZONS-AMI: Clinical Follow-Up 1-Year FU 2-Year FU % P = .98 % 20 18.8 Heparin+GP IIb/IIIa (n = 1802) Bivalirudin group (n = 1800) Heparin+GP IIb/IIIa (n = 1802) Bivalirudin group (n = 1800) 18.7 P = .98 15 P < .001 11.9 11.9 P < .001 9.2 9.6 10 P = .03 P = .04 P = .03 P = .22 6.9 6.4 P = .005 5.8 P = .005 6.1 4.8 5.1 4.4 4.6 3.8 5 4.2 3.6 3.5 2.1 2.5 Major Bleeding Cardiac Mortality All-Cause Mortality MACE Major Reinfarction Cardiac All-Cause MACE Bleeding Mortality Mortality Reinfarction Data presented by Stone GW, Trans Catheter Cardiovascular Therapeutics, 2009, San Francisco, Calif. Mehran R, et al. Lancet. 2009:374:1149

Major Bleed only -Without MI Without Major Bleed (n = 611) ACUITY Trial: Impact of MI and Major Bleeding (non-CABG) in the First 30 Days on Risk for Death Mortality at 390 Days % Both MI and Major Bleed (n = 94) Major Bleed only -Without MI (n = 551) MI only- Without Major Bleed (n = 611) No MI Major Bleed (n = 12,557) Stone G, et al. N Engl J Med. 2006;355:2203-2216.

Significant Net Clinical Benefit with Prasugrel TRITON-TIMI 38 Trial: Net Clinical Benefit Bleeding Risk Subgroups – Therapeutic Consideration Avoid Prasugrel Prior CVA/TIA Reduced maintenance dose guided by PK Age ≥ 75 or Wt < 60 kg 4% 16% Subgroups With Positive Benefit: STEMI Multivessel/diabetes SAT on clopidogrel Clopidogrel non-/hypo-responders Clopidogrel allergy Complex or high-risk lesions Significant Net Clinical Benefit with Prasugrel 80% Maintenance Dose 10 mg CVA = cerebrovascular accident; TIA = transient ischemic attack; SAT = subacute stent thrombosis Wiviott S, et al. Circulation. 2007;116:2923.

Updated Dual Anti-Platelet Therapy (DAPT) Post Stenting Incorporating Prasugrel: Optimal DAPT post stenting continues to evolve with aspirin (81-325 mg PO daily) lifelong and clopidogrel (600 mg load/75 mg PO daily) for 1-12 months being used routinely. Two new recommendations have emerged from the results of major randomized trials: Increasing clopidogrel dose to 150 mg for 1 week as per OASIS-7 trial. Use of prasugrel (TRITON TIMI-38 trial): Prasugrel (60 mg load/10 mg PO daily for 1-15 months) is more effective than clopidogrel in reducing primary endpoints of death, MI, stroke, and stent thrombosis. The relative benefit of prasugrel was higher in patients with STEMI and in diabetes. But prasugrel use was associated with higher fatal, major and minor bleeding vs clopidogrel especially in patients with prior CVA (also less effective in this subgroup), age > 75 years and weight < 60 kg.

Updated DAPT Post Stenting Incorporating Prasugrel Therefore in following subgroups of PCI patients, prasugrel will be preferred over clopidogrel: STEMI Multivessel patients with diabetes Clopidogrel allergy Clopidogrel nonresponders Stent thrombosis in clopidogrel compliant pts Even in these PCI patients, prasugrel should be absolutely avoided in those with prior CVA and with history of major vascular or nonvascular bleeding (such as GI or GU bleeding) and prasugrel maintenance dose should be decreased to 5 mg PO daily in those > 75 years old or < 60 kg. Patients should be strictly monitored and instructed for signs and symptoms of bleeding. Routine use of PPI for GI prophylaxis is indicated with prasugrel. For staged procedures in patients on maintenance dose of prasugrel, an extra loading dose of 10 mg before PCI will suffice. To switch patients who are taking clopidogrel maintenance dose, prasugrel loading dose of 30mg followed by 5-10 mg PO daily (as indicated) maintenance is advised.

Issues Involving the Case Choice of Antithrombotic Therapy Treatment of Calcified Lesions Bifurcation Lesion Intervention

Treatment of Calcified Lesions Interventional Techniques Noncompliant (NC) balloon (high pressure inflation up to 20-24 atm) NC balloon with another side-by-side wire in the vessel and high pressure inflation Cutting balloon (up to 8-12 atm) AngioSculpt® balloon (up to 16-20 atm) Rotational atherectomy (heavily calcified) ® AngioScore Inc., Fremont, Calif

Atherectomy: Rotablator® Diamond microchips Differential cutting PTCA PRCA Rotablator®; Boston Scientific, Inc., Natick, Mass.

Rotational Atherectomy (RA, PRCA, PTRCA) Indications: Calcified lesion Undilatable/chronic lesion Diffuse long lesion Small vessels (< 2.5 mm) In-stent restenosis Bifurcation lesion Ostial lesion Rotastent (SPORT trial) Limitations: Slow flow / No flow Perforation CK-MB release Wire bias and dissection Technically challenging PRCA = percutaneous rotational coronary atherectomy; PTCRA = percutaneous transluminal coronary rotational ablation; CK-MB = creatine kinase-MB isoenzyme

Rotational Atherectomy: Current Issues Slow / no-flow CPK, CK-MB release Coronary spasm Intimal dissections and acute closure Perforation Wire bias problems Heat generation CPK = creatine phosphokinase

Rotational Atherectomy: Complications Mechanism of No/Slow-flow Atheromatous debris embolism Platelet and microthrombi Platelet activation, aggregation, lysis (by rota burr) Microcirculatory (vasculature) spasm Heightened microvasculature reactivity / tone Microcavitation Impaired local synthesis of EDRF Neuro-humoral reflex Lower epicardial vessel pressure and higher LVEDP Extreme cases: free radical injury, local edema, microvascular plugging, no-reflow EDRF = endothelium-derived relaxing factor; LVEDP = left ventricular end-diastolic pressure

Rotational Atherectomy: Complications Slow-flow Settings: Long calcified lesions Total occlusion and right coronary artery Poor LV function and hemodynamic instability Thrombotic lesions (also post-MI) ? on -blockers Technical modifications: Small initial burr size and small upsizing Short ablation runs and avoid RPM drops ?Slow-speed Avoid hypotension and bradycardia Rota flush & GP IIb/IIIa inhibitors Treatment: verapamil, nitro, adenosine, nitroprusside, IABP Best treatment to prevent slow flow is to avoid it from happening. IABP = intra-aortic balloon pump

Activation of Platelets by Rotablation Is Speed-Dependent Rotational Atherectomy and GPIIb/IIIa Inhibitors Activation of Platelets by Rotablation Is Speed-Dependent Transmission electron micrography: Platelet-rich plasma through chamber with rota burr held stationary (0 rpm) and stirred in an aggregometer for 5 minutes: Intact platelet membrane, intracellular granules, and clear background. Platelet-rich plasma was subjected to rotablation at 180,000 rpm and stirred in an aggregometer for 5 minutes: Ruptured platelet membranes, depletion of intracellular organelles (“ghost platelets”), and cloudy background. From Williams MS. Circulation. 1998;98:742-748.

Rotational Atherectomy and Platelets Effect of Rotablation on Platelet Aggregation Initial Aggregation Slope (units/min) Rotablation Speed (rpm x 10-3) From Williams MS, et al. Circulation. 1998;98:742-748.

Rotational Atherectomy Activation of Platelets by Rotablation Is Speed-Dependent Rotational Speed (rpm) Platelet Aggregates (> 20 m)/mL blood 180,000 7434  2193 140,000 2269  627 Control 633  258 P < .0001 for all groups Slower rotational speed results in a significantly lower number of platelet aggregates. Porcine blood exposed to a rotating burr resulted in: Platelet aggregation and red blood cell crenation. From Reisman M, et al. Cathet Cardiovasc Diagn. 1998;45:208-214.

STRATAS Trial Technique Matters: Incidence of Slow-Flow % P = .008 Predictors of CK-MB release: deceleration > 5000 rpm > 5 sec Predictors of restenosis: deceleration > 5000 rpm LAD location P = .008 % Current optimal Burr-to-Artery Ratio (BA): 0.3-0.5 Aggressive strategy (n = 249) BA: > 0.9 Routine strategy (n = 248) BA: < 0.8 Whitlow PL, et al. Am J Cardiol. 2001;87:699-705.

Rotational Atherectomy: Complications Perforation Settings: Lesion in a bend > 90 Calcified lesion Large burr-to-artery ratio Total occlusion Wire - bias situations Technical modifications: Smaller initial burr size (start with 1.25 mm burr) Bending the wire technique Rota extra support wire ?Predilatation with a smaller balloon Avoid abciximab before rotablation

---DES--- Rotational Atherectomy Mount Sinai Hospital Experience (6%-9% of PCI) Complications % ---DES--- short burr runs, rota-flush, abciximab, stent, experience slow speed (140-150,000 rpm) rotational atherectomy, BA: 0.4-0.5

STEPS for Rotational Atherectomy Mechanism of action: Plaque ablation and pulverization by the abrasive diamond-coated burr: Physical principles: 1. Differential cutting is defined as the ability to ablate one material selectively while sparing and maintaining the integrity of another, based on differences in substrate composition, resulting in a polished smooth lumen compared with multiple intimal tears/dissections with balloon angioplasty; ie, able to ablate inelastic tissue selectively (ie, plaque) while maintaining the integrity of elastic tissue (ie, the normal vessel wall) due to the principle of differential cutting.

STEPS for Rotational Atherectomy (cont) Physical principles: 2. Orthogonal displacement of friction at rotational speeds > 60,000 rpm; the friction, which occurs when sliding surfaces are in contact, is virtually eliminated. As a result, there is reduced surface drag and unimpeded advancement and withdrawal of the burr, allowing the rotating burr to pass through tortuous and diseased segments of the coronary tree. The abraded plaque is pulverized into microparticles (size of RBCs), which are 5–10 μm in diameter. These particles are small enough to pass through the coronary microcirculation and ultimately undergo phagocytosis in the liver, spleen, and lung.

STEPS for Rotational Atherectomy (cont) Indications: Severely calcified lesions Undilatable/inelastic lesions Diffuse recurrent In-stent restenosis with multiple jailed side branches Contraindications: Acute myocardial infarction Saphenous vein graft/thrombotic lesions Presence of dissection

STEPS for Rotational Atherectomy (cont) Preparation for procedure: Proper burr size selection (~0.5:1 burr-to-artery ratio). Proper guide catheter size selection (6F for up to 1.75 mm burr and 7F for 2.0 mm or bigger burr). Additional guidewire (Runthrough NS®/Fielder®) with J-tip prepped. Noncompliant balloon (1:1 balloon size-to-artery ratio) prepped. Temporary pacemaker for RCA/dominant LCx lesions (optional at attending discretion). Make connections to tachometer, NO tank, and flush solution (use the 3-way stopcock for flush). Gently remove the rota-floppy wire from the packing (first remove distal wire tip from the back-stopper), and wipe with generously wet 4x4. It is a very delicate wire, so handle with care and loop the wire making only 3 loops. Runthrough NS®; Terumo Interventional Systems, Somerset, NJ . Fielder®; Abbott Vascular, Redwood City, Calif.

STEPS for Rotational Atherectomy (cont) Steps for operator: Place the rota-floppy guidewire beyond lesion (direct wire placement/wire exchange with over-the-wire 1.5 mm balloon / fine cross). Backload and advance the burr over the guidewire to the co-pilot. Place the wire-clip at the end of rota-wire, and reconfirm verbally that wire clip is in place. Turn on the flush solution and do RPM check while holding the co-pilot in the hand (to prevent entanglement of rota burr and blue drape/4x4 gauze). Press foot pedal to activate dynaglide mode.

STEPS for Rotational Atherectomy (cont) Steps for operator: (cont) Advance the burr inside the guiding catheter to the ostium of the coronary artery. Three steps to remove tension/inertia from the system: Move advancer knob back and forth to remove tension between drive shaft and Teflon® sleeve. Open copilot and move burr back and forth under fluoroscopic guidance to remove tension between guidewire and rota burr. Brief Dyna-tap under fluoroscopic guidance. If there is residual tension/inertia and there is sudden burr advancement/jump – it occurs at low speed and therefore is safer; ie, prevents dissection. For distal lesions: advance the burr manually/at dynaglide mode to just proximal to lesion.

STEPS for Rotational Atherectomy (cont) Technique of rotablation: Slow burr advancement To-and-fro pecking motion of the burr Shorter burr run times (15–20 sec) Low burr speeds (140,000–150,000 RPM) Strict avoidance of significant drops in rpm (> 5000 RPM for > 5 sec) Flush the system with diluted contrast (1:10 dye-to-saline ratio) during the ablation runs. Keep systolic blood pressure > 100 mm Hg during the procedure, use 1-2 cc of diluted IV neosynephrine 100-200 ug as needed (neosynephrine may cause reflex bradycardia).

STEPS for Rotational Atherectomy (cont) After completion of rotablation: 1. Activate the dynaglide mode and remove the burr from the guiding catheter on dynaglide mode, while pressing brake release (the black button on the Rotablator® console), and advancing the wire as the burr is withdrawn. 2. Three steps after completion of procedure: Remove wire clip Turn off the flush solution Remove the burr from the wire 3. Take a cine image to rule out complications 4. Advance another guidewire (Runthrough NS®/Fielder®) across the lesion, parallel to rota-floppy wire 5. Use NC balloon for post-rota PTCA (modified CB-PTCA with rota-floppy wire in-situ) to prepare lesion for stent delivery. 6. Remove rota-floppy after stent placement, and before deploying the stent.

Rota+BMS vs Rota+DES Procedural and Clinical Results Rota + BMS (n = 284) Rota + DES (n = 130) P = NS P = NS P < .01 P = .62 P = .09 % % P = NS Procedural Clinical Success Success CK-MB 30-day Stent TVR >3x MACE Thrombosis MACE = major adverse cardiac events; TVR = target vessel revascularization Data presented by Sharma S, et al. American College of Cardiology Scientific Sessions, Chicago, Ill, 2008

RotaDES Issues Procedural and clinical results — as restenosis will be determined by stent expansion What should be DES length post-rotablation? All ablated areas or lesion coverage only No randomized trial yet — ongoing ROTAXUS Trial

Issues Involving the Case Choice of Antithrombotic Therapy Treatment of Calcified Lesions Bifurcation Lesion Intervention

Medina Classification Bifurcation Lesion Classification Duke’s Classification Medina: 1,0,0 Medina: 1,1,1 Medina: 0,0,1 Medina: 1,0,1 Medina: 1,1,0 Medina: 0,1,0 Medina Classification Prebranch Postbranch Pre- and postbranch Ostial and Ostial True Bifurcation A B C < 5% 5%-10% 10%-15% 15%-20% D E F Causes: Plaque shift Spasm Dissection Most common = 45%

MADS (Main, Across, Distal, Side) Classification of Techniques Based on the Manner in which First Stent Is Implanted With Multiple Final Stent Strategy M Main prox. first A Main Across side first D Distal first S Side branch first Reprinted from EuroIntervention Vol 5(1), 39-49, Stankovic G, et al. © 2009, with permission from Europa Edition.

Complex Bifurcation Lesion Interventions Technical Issues How big is the sidebranch(es). Ready to lose the sidebranch (SB)? Wire both branches. Difficult wiring? Jailing the sidebranch wire(s). Hydrophilic? Good back-up support guide catheter: 6, 7, or 8Fr? Optimal views. Orthogonal projections? Provisional or systematic SB stenting (1 vs 2 stents?) Dedicated 2/3 stent technique (T, Culotte, Crush, SKS, V or W?)

Various Techniques for Stenting Trifurcation/Bifurcation Lesions Stent the MV + balloon or debulk SB Bifurcation Lesion ..and stent the SB only if suboptimal results: CP, EKG , < TIMI III flow, > 90% stenosis SB MV Provisional/ Conventional Stent Technique Stent + stent (“T stenting”) (“reverse-T”) MV = main vessel; CP = chest pain

Various Techniques for Stenting Bifurcation Lesions Stent + stent (“T stenting”) Stent + stent (“reverse-T”) Bifurcation Lesion Stent + PTCA SB MV Stent + stent (“Culotte”) 1 2 Stent + stent (“Kissing”) Stent + stent (“Y” or “V”) “V” 2 1 Stent + stent (“Crush”) 2 1

Bifurcation Lesion Intervention Using DES “Simultaneous Kissing Stent” (SKS) Technique Pre Post

Clinical Outcomes in Trials Comparing 1 DES (1S) vs 2 DES (2S) Strategy in Treating Coronary Bifurcations MACE TLR % 1S 2S 1S 2S 1S 2S 1S 2S 1S 2S 1S 2S 1S 2S Colombo A, et al. SES stents (n = 85) Pan M, et al. SES stents (n = 91) Ferenc M, et al. T-stenting (n = 202) Steigen TK, et al. NORDIC Trial (n = 413) Colombo A, et al. CACTUS trial (n = 85) Hildick-Smith D, et al. BBC ONE (n = 500) Sharma SK, et al. PRECISE-SKS (n = 100)

Clinical Outcomes in Trials Comparing 1 DES (1S) vs 2 DES (2S) Strategy in Treating Coronary Bifurcations (cont) Incidence of Reported Stent Thrombosis 1S group 2S group % 1S 2S 1S 2S 1S 2S 1S 2S 1S 2S 1S 2S 1S 2S Colombo A, et al. SES stents (n = 85) Pan M, et al. SES stents (n = 91) Ferenc M, et al. T-stenting (n = 202) Steigen TK, et al. NORDIC Trial (n = 413) Colombo A, et al. CACTUS trial (n = 85) Hildick-Smith D, et al. BBC ONE (n = 500) Sharma SK, et al. PRECISE-SKS (n = 100)

a complex strategy (done correctly) Clinical Outcomes in Trials Comparing 1 DES (1S) vs 2 DES (2S) Strategy in Treating Coronary Bifurcations (cont) Incidence of Reported Stent Thrombosis 1S group 2S group % Therefore while simple approach of one stent in the main vessel may suffice in most bifurcation lesions, a complex strategy (done correctly) of 2 stents by one’s preferred technique may be required especially if SBr is large size (>3mm) or lesion is long/angulated 1S 2S 1S 2S 1S 2S 1S 2S 1S 2S 1S 2S 1S 2S Colombo A, et al. SES stents (n = 85) Pan M, et al. SES stents (n = 91) Ferenc M, et al. T-stenting (n = 202) Steigen TK, et al. NORDIC Trial (n = 413) Colombo A, et al. CACTUS trial (n = 85) Hildick-Smith D, et al. BBC ONE (n = 500) Sharma SK, et al. PRECISE-SKS (n = 100)

Newer Interventions and Stents in 2010 Bifurcation Stents A B C D E F G I J H

Interventional Cardiology Live Case Study Series: A Master Class in Procedural Techniques Samin K. Sharma, MD Director Cardiac Cath Lab and Intervention Professor of Medicine Co-Director Cardiovascular Institute Mount Sinai Medical Center New York, NY Annapoorna S. Kini, MD Associate Director Cardiac Cath Lab Mount Sinai Medical Center New York, NY Sameer K. Mehta, MD Voluntary Associate Professor of Medicine University of Miami - Miller School of Medicine, Miami, Florida

Take-Home Message: Techniques of Rotational Atherectomy in DES Era Rotational atherectomy is a useful adjunctive device in interventional treatment of heavily calcified lesions Optimal technique and strategy are crucial to avoid any potential complications Properly performed rotational atherectomy followed by DES implantation (RotaDES) may translate into excellent long-term results and will broaden our scope of lesions we can take care of safely

Tuesday October 19th Interventional Cardiology Live Case Study Series: A Master Class in Procedural Techniques Please join us for our next live case: Tuesday October 19th at 8:00 AM EST