Debate #4: CTO Revascularization CCCSymposium 2014 Debate #4: CTO Revascularization Most CTO Should be Opened: Samin K Sharma, MD Only Limited CTO Should be Opened: Carlo Di Mario, MD Samin K Sharma, MD, FACC, FSCAI Director Clinical & Interventional Cardiology Zena and Michael a Weiner Professor of Medicine Mount Sinai Hospital, NY

I will make my point for; Most CTOs Should be Opened

Chronic Total Occlusion (CTO) Presence of CTO in CAD Imparts Adverse Prognosis

Impact of Completeness of PCI Revascularization on Long-Term Outcomes in the Stent Era HRs for Mortality for Various Subgroups of Incomplete Revascularization N Unadjusted HR Compared with CR [95%CI] Adjusted HR Compared with CR [95%CI] Complete Revascularization 6817 1.00 1 IR vessel with no CTO 8518 1.20 [1.04-1.38] 1.00 [0.87-1.15]  2 IR vessel with no CTO 2057 1.88 [1.57-2.27] 1.25 [1.03-1.50] 1 IR vessel CTO 3232 1.81 [1.53-2.13] 1.35 [1.14-1.59]  2 IR vessels at least 1 CTO 1321 2.77 [2.29-3.35] 1.36 [1.12-1.66] Hannah, Holmes, King, Sharma et al. Circulation 2006;113:2406

Incomplete Revascularization in the Era of DES: NY State Database Report Conclusion: Pts with ≥2 IR vessels with a CTO, have the worst long-term prognosis and greater need for CABG or re-PCI Hannan, Sharma et al. JACC Cardio Interv 2009;2:17

Effect of a Concurrent CTO on Long-Term Mortality and LVEF in Pts After Primary PCI in AMI 3277 STEMI pts 1997-05: SVD 65%, MVD 22%, MVD + CTO 13% Landmark Survival Analysis Endpoint: Survival at 5 yrs, LVEF at 12 mo (median F/U 3.1 yrs) Claessen et al. JACC Cardio Interv 2009;2:1128.

Temporal Trends in Cumulative Angiographic Success Rates and Major Procedural Complication Rates 80% 0.5% Patel et al., JACC Cardiovasc Interv 2013;6:128 7

Incidence of Procedural Complications in Successful vs Incidence of Procedural Complications in Successful vs. Unsuccessful CTO PCI Complications Successful Unsuccessful p value MACE (%) 3.7 4.3 0.68 Death (%) 0.4 1.5 <0.0001 Emergent CABG (%) 0.03 0.17 0.74 Stroke (%) 0.07 0.04 MI (%) 2.8 3.0 0.87 Q-wave MI (%) 0.3 0.5 0.26 Coronary perforation (%) 10.7 Tamponade (%) 0.0 1.7 Vascular complication (%) 0.9 0.20 Contrast nephropathy (%) 5.0 4.6 0.86 Patel et al., JACC Cardiovasc Interv 2013;6:128 8

CTO: Anatomic Descriptors of Procedural Success In the current ERA; Severe calcification Key Message: XIENCE V® provides the right combination of technology with a deliverable, efficacious, and safe platform. Throughout this section you will present the key features of XIENCE V®, including the Multi-Link vision stent, the Multi-Link Vision stent delivery system, the everolimus elution profile, and the fluorinated copolymer. You will also show how these features work together to provide deliverability, efficacy, and safety. 9 9

Chronic Total Occlusion (CTO) Why Bother to do PCI? Presence of CTO in CAD Imparts Adverse Prognosis Because successful CTO recanalization may result in Angina/Ischemia relief Freedom from subsequent CABG Improved LV function Improvement in event-free survival

Chronic Total Occlusion (CTO) CTO Recanalization and Angina Relief Series Name/Year Successful PCI (N) FU (months) Asymptomatic (%) Olivari, 2003 248 12 89 Berger, 1996 139 6 87 Ivanhoe, 1992 264 36 69 Ruocco, 1992 160 24 Bell, 1992 234 32 76 TOTAL >1000 >24 mo >80%

TOAST-GISE 1 Year Clinical Status of Complication Free Patients CTO Success (n = 248) CTO Failure (n = 60) P Value No angina 220 (88.7%) 45 (75.0%) 0.008 ETT performed 210 (84.7%) 42 (70.0%) 0.010 Maximal ETT 155 (62.5%) 20 (33.3%) <0.0001 Negative ETT 181 (73.0%) 28 (46.7%) 0.0001 Olivari Z et al, J Am Coll Cardiol 2003;41:1672

Meta-Analysis of CTO Outcomes 13 Observational Studies, 7288 patients weighted averaged follow-up 6 years OR for Success vs. Failure 95% Cl p Value Mortality 0.56 0.43-0.72 <0.001 MI 0.74 0.44-1.25 0.26 Subsequent CABG 0.22 0.17-0.27 Residual Angina 0.45 0.30-0.67 0.001 Joyal et al., Am Heart J 2010;160:179. 13

Evaluation of LV Function 3-Yrs after Percutaneous Recanalization of CTO Changes in LV Volume Indexes and EF between Baseline and 3-Yr FU Measured Using Magnetic Resonance Imaging (N=21) 86 63 78 60 35 30 Mean ejection fraction improved slightly, but end-systolic and end-diastolic volume indexes decreased significantly. Kirschbaum S et al, Am J Cardiol 2008;101:179

MRI Predicts LV EF & Wall Motion Improvement with CTO Revascularization (N=21) with prior MI SWT at Baseline (n=21) SWT 5 mths post Stent Implantation P=ns P<0.001 SWT 3 yrs post stent Implantation 90 P=ns P<0.05 80 P<0.05 70 60 P<0.05 P<0.001 50 P<0.05 Segmental wall thickening (%) 40 P<0.05 P=ns 30 P=ns 20 P=ns 10 -10 -20 <25% 25-75% >75% Remote Transmural extent of infarction Kirschbaum et al, Am J Cardiol 2008;101:179

Effect of Successful vs Effect of Successful vs. Failed CTO PCI in All-Cause Mortality During Long-Term Follow-up Author, Year Yr Follow-up PCI Success (n) PCI Failure (n) OR/HR, 95% CI Finci, et al., 1990 2 100 OR: 1.70, 0.40 - 7.32 Warren et al., 1990 2.6 26 18 N/A Ivanhoe et al., 1992 4 317 163 OR: 0.21, 0.05 - 0.83 Angioi et al., 1995 3.6 93 108 OR: 0.37, 0.10 - 1.40 Noguchi et al., 2000 4.3 134 92 OR: 0.28, 0.11 – 0.72 Suero et al., 2001 10 1,491 514 OR: 0.67, 0.54 – 0.83 Olivari et al., 2003 1 289 87 OR: 0.19, 0.03 – 1.14 Hoye et al., 2005 4.5 567 304 OR: 0.52, 0.32 – 0.84 Drozd et al., 2006 2.5 298 161 OR: 0.74, 0.23 – 2.37 Aziz, et al.,2007 1.7 377 166 OR: 0.31, 0.13 – 0.76 Prasad et al., 2007 914 348 OR: 0.82, 0.62 – 1.08 Valenti et al., 2008 344 142 OR: 038, 0.19 – 0.77 de Labriolle et al., 2008 127 45 OR: 1.25, 0.25 – 6.27 Mehran et al., 2011 2.9 1,226 565 HR: 0.63, 0.40 – 1.0 Jones et al., 2012 3.8 582 254 HR: 0.28, 0.15 – 0.52 Joyal et al., 2010 5,056 2,236 OR: 0.56, 0.43 – 0.72 Moses et al., JACC Cardio Interv 2012;5:389 16

Successful Recanalization of CTO Associated with Improved Long-Term Survival Jones et al., JACC Cardio Interv 2012;5:380 17

Advanced Techniques for Chronic Total Occlusion Japanese Specialized Technique Anchor balloon technique Mother-Child catheter technique Parallel wire IVUS guidance Retrograde approach

Retrograde Wire Technique for Chronic Total Occlusion Recanalization Four Patterns of Success in Retrograde CTO Recanalization Sumitsuji et al. J Am Coll Cardiol Intv 2011;4:941.

Increased Use of Retrograde Approach and Technical Success Rate Over Time 2006 2007 2008 2009 2010 2011 ≈35% % Michael et al., Am J Cardiol 2013;112:488 20

Appropriateness Score (1-9) ACCF/SCAI/STS/AATS/AHA/ASNC 2012 Appropriateness Criteria for Coronary Revascularization Chronic Total Occlusions: Indications for PCI INDICATION Appropriateness Score (1-9) CCS Angina Class Asymptomatic I or II III or IV • Chronic total occlusion of 1 major epicardial coronary artery, without other stenoses • Low-risk findings on noninvasive testing • Receiving no or minimal anti-ischemic medical therapy I • Receiving a course of maximal anti-ischemic medical therapy U • Intermediate-risk findings on noninvasive testing • Intermediate-risk criteria on noninvasive testing A • High-risk findings on noninvasive testing • High-risk criteria on noninvasive testing Patel et al. JACC 2012;53:530-553

Chronic Total Occlusions IIa IIb III PCI of a CTO in patients with appropriate clinical indications and suitable anatomy is reasonable when performed by operators with appropriate expertise B

Fundamental Wire Technique and Current Strategy for Chronic Total Occlusion PCI Procedural Steps of Current CTO-PCI Cotralateral Dual Injection CTO - PCI Single Wire Technique Antegrade approach x2 Parallel Wire Technique Retrograde approach (ostial) Retrograde Wire Cross Kissing Wire Cross IVUS guide re-entry CART Reverse CART Success Failure

Procedural Success of CTO PCI at MSH Asahi wires Retrograde technique Planned 2nd (18%) or 3rd (8%) attempt 93 86 78 68 EXPERT CTO US Trial: 90+ success % 397 806 665 782 2003-2005 2006-2008 2009-10 2011-12

Conclusions: Rationale for CTO Recanalization in ALL Presence of a CTO imparts adverse prognosis. Non randomized data support improved overall CV outcomes (including mortality) with successful CTO procedures. A randomized trial will be needed to establish the PCI efficacy in CTO pts. Therefore developing technical skills (dedicated centers and dedicated Interventionalists) is essential to tackle this “last frontier of Interventional Cardiology” to improve overall outcomes of our complex CAD pts. KEY to better CTO outcomes is successful recanalization