LCX. President / Director of Cardiology / New Tokyo Hospital

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LCX President / Director of Cardiology / New Tokyo Hospital Professor of Department of Advanced Cardiovascular Medicine: Kumamoto University Consultant / National Cardiovascular Center / Osaka Sunao Nakamura FACC, FAHA, FESC, FSCAI

72yo F. LMT-CTO, Very Low EF(EF20%) Dx: Course: Coronary Risk F: Renal F: LV Function: Euroscore: UAP/ Chronic Heart Failure 2003 (67 yo) Admission doe to AHF on CHF CAG (LMT CTO EF:19%) Admission due to re-acute HF 2004 (68 yo) re-cag consult Cardiac Surgeon Refuse, refer to Dr. Nakamura HL,Obesity, Current Smoker, FH Cr: 1.12 EF: 20 % 11.50.42%

72yo F. LMT-CTO, Very Low EF(EF20%) LVG (EF: 19%) LMT CTO

72yo F. LMT-CTO, Very Low EF(EF20%) Collateral angiogram Post PCI

72yo F. LMT-CTO, Very Low EF(EF20%) 1 year later No Restenosis, LVEF 19 40%

10 Years Later... (after open LMT Chronic Total Occlusion)... -At the same hospital, I met her again, because she wanted to meet me...?? :act of grace by Taiwan Dr.- She survived...

Pre

Pre Post

Pre Post F/U

Pre Post F/U EF: 66% No change: pre and post Patients: No Symptom

Japanese multicenter registry of CTO PCI 6 Institutions New Tokyo Hospital Department of Cardiology Kumamoto University Department of Cardiovascular Medicine Yamanashi University Department of Cardiovascular Medicine Fukuyama Cardiovascular Hospital Department of Cardiovascular Medicine Suzumoto Genaral Hospital Department of Cardiovascular Medicine Tenyoukai Central Hospital Department of Cardiovascular Medicine Success rate 92.5% Successful CTO PCI 1317 lesions PCI for CTO Jan. 2008 Dec. 2012 1273 patients 1424 lesions Unsuccessful CTO PCI 184 lesions Without Clinical follow-up 77 patients/ 80 lesions

Long-Term Outcome of Percutaneous Coronary Intervention For Chronic Total Occlusions with DES in New Tokyo Hospital Unpublished Data : Satoru Mitomo, Sunao Nakamura, et al Interestingly, Impact of after procedural revascularization success of cardiac CTO at mortality LAD and RCA fatal prognosis in CTO was PCI improved, according however to CTO it vessels was not changed in the case of CTO at LCX. Cumulative incidents of Cardiac death P=0.005 LAD RCA LCx success unsuccess 20.7% vs. 12.5% Log Rank p=0.005 P<0.001 success unsuccess 25.6% vs. 5.8% Log Rank p<0.001 success unsuccess 0.0% vs. 4.2% Log Rank p=0.55 Follow-up days Follow-up days Follow-up days

Hypothesis?? Degree of improvement of fatal prognosis brought by CTO revascularization may differ depending on which artery among coronary arteries is re-vascularized. LCX??

The MIlan and New-TOkyo (MITO) Registry Among LMT PCI, some specific cases are still challenged with restenosis and MACE. Seeking for solution of these unsolved challenges, we decided to conduct data review of our own cases. Under the guidance of Dr. Antonio Colombo and Dr. Alaide Chieffo, our staff compiled data of our hospital and that of Milan as MITO Registry. Me Toru DR.Colombo DR. Chieffo

MIlan and New-TOkyo (MITO) Registry Between April 2002 and Jun 2015 New-Tokyo n=990 Milan n=520 From 2005 April 2002 April MITO Registry Total 1510 patients 1 st DES N=765 2 nd DES N=745

About Long-term Survival After LMT PCI

The impact of Main Branch Restenosis on Long Term Mortality Following Drug-eluting Stent Implantation in Patients with De Novo Unprotected Distal Left Main Bifurcation Coronary Lesions: The MIlan and New-TOkyo (MITO) Registry Catheter Cardiovasc Interv. 2013 Sep 2 by K.Takagi, S.Nakamura A.Colombo et.al Distal LAD-ISR Both LAD and LCX-TLR LCx ostial ISR alone 30% LAD-TLR 9.2% at 2-years 60% LCX-TLR

Kaplan Meier 8-year patients survival n=753 No restenosis N=318 Cumulative Event Rate No Angio F/U N=318 No angiographic FU N=64 LCX-ISR alone N=64 LAD+LCX ISR N=30 LAD-ISR alone N=23 Log rank P<0.001 Days Since PCI

Lesson 1 Among restenosis after LMT PCI, restenosis at LCX ostium is not directly link to fatal prognosis in most of the cases. Therefore our focus should be shift to restenosis at LM toward LAD, which strongly affect on patientsʼ fatal prognosis. Letʼs think about RCA???

Impact of residual chronic total occlusion of right coronary artery on the long-term outcome in patients treated for unprotected left main disease: the Milan and New-Tokyo (MITO) registry. Circ Cardiovasc Interv. 2013 April;6(2);154-60 by K.Takagi, S.Nakamura A.Colombo et.al 523 Pts LMT-PCI No CTO RCA 46 Pts LMT-PCI Residual RCA CTO

Cumulative event rate at 5 years follow-up by Kaplan-Meier Method: No RCA CTO and RCA CTO (A) Cardiac-death (B) Cardiac-death + MI (C) MACE Log Rank P=0.001 Log Rank P<0.001 Log Rank P=0.861 Log Rank P=0.001 Log Rank P<0.001 Log Rank P=0.861 30.0% at 5-years Residual RCA-CTO 20.8% at 5-years 22.7% at 5-years 28.4% at 5-years NO 6.2% RCA-CTO at 5-years 8.1% at 5-years No at Risk (1) (2) 1-year 494 44 3-years 440 36 5-years 162 21 No at Risk (1) (2) 1-year 491 44 3-years 437 36 5-years 160 21 No at Risk (1) (2) 1-year 414 42 3-years 349 33 5-years 128 18 (1) ULM without residual CTO-RCA (ULM with no CTO-RCA + ULM with treated CTO-RCA ) n=522 (2) ULM with residual CTO-RCA n=46

Lesson 2 Following PCI of LMT, cardiac-death occurred more frequently in patients with residual CTO-RCA, v while a few cardiac death occurred in patients without residual CTO-RCA. These findings may suggest that recanalization of CTO-RCA may impact v on the long-term cardiac mortality in patients with LMT-PCI.

Long-term Clinical Outcome of Single-stent Crossover Technique from Unprotected Left Main Coronary Artery to the Left Circumflex Coronary Artery Naganuma T, Chieffo Alaide, Nakamura S, Colombo A, et al. Catheter Cardiovasc Interv. 2013 Comparison of LCX ost and LAD ost after Stenting LMCA * LAD LMCA * LAD LCx LCx Ø Restenosis at the LCx-ostium in LMT-LCx stenting group Ø Restenosis at the LAD-ostium in LMT-LAD stenting group

Cumulative event rate of TLR at 3 years follow-up by Kaplan-Meier Method 40 30 Log-rank p <0.001 LMCA-LCx LMCA-LAD TLR(%) 20 Restenosis at LCx-ostium 18.2% 10 Restenosis at LAD-ostium 3.0% No. at risk LMCA-LCx LMCA-LAD 0 0 1 2 3 Follow-up (years) 31 27 23 15 553 512 400 279

Lesson 3 LCX ostium itself independently shows high restenosis rate in patients with LMT-PCI. Now we donʼt have consensus for treating LCX ost. Prox. How about BRS???

Previous DES 3.0 NC Balloon pre Dilatation BVS 3.5 x 12mm 3.5mm NC balloon

Final Angiogram

Only 6month later Severe Restenosis in LCX ost.

A LAD previously implanted DES 3.5x12mm BVSLCx C D E F GH I C D E F G H I B LAD Small SB LCx J LAD F F overlapping struts LAD Small SB J no struts LM LM LCx LCx C D E F G H I C D E F G H I C D E neo-carina C D E neo-carina overlapping struts LAD G H I SD: 3.03/3.14mm SA: 7.45mm 2 LAD G H I SD: 2.26/2.71mm SA: 5.01mm 2 Small SB overlapping struts Small SB

BVS may not be an optimistic solution for an ostial LCX lesion F F overlapping struts no struts

Do not chase to much!! LCX is a different animal This is very unique part of coronary artery!!! So called, HINGE POINT... But point is moving and Twitching And not so much important as compared with LAD and RCA for keeping Ejection fraction of the patientʼs HEART

About Endothelial activation?? - Letʼs Think about Jailed Strut in LCX Ost.- Letʼs think about 2 stent technique? Is it related with restenotic event?? Yusuke Fujino M.D.

3D OCT Image After SES Implantation with inappropriate KBT LCX Malapposed stent struts LMCA Malapposed stent struts LMCA LCX LAD Y Fujino, Marco. A Costa, S Nakamura et al. AHA 2013 scientific session

OCT Assessment of LCX ostium at F/U Post PCI malapposed stent struts 9M follow-up A B C Neointimal proliferation over the malapposed stent struts A B C Y Fujino, Marco. A Costa, S Nakamura et al. AHA 2013 scientific session

Area Narrowing of LCX ostium by 3D-OCT Post PCI Follow-up 8.85mm 2 4.38mm 2 We calculated area narrowing(%) with this formula Area (post) Area (follow-up) Area Narrowing (%) = 100 Area (post) Y Fujino, Marco. A Costa, S Nakamura et al. AHA 2013 scientific session

Area Shrinkage of LCX Ostium Sirolimus-Eluting Stent Cypher: Johnson and Johnson Everolimus-Eluting Stent Xience V: abott vascular SES (n=10) EES (n=15) p Value Post-PCI LCX ostium area, mm 2 5.41±1.81 5.14±2.59 0.785 9M follow-up LCX ostium area, mm 2 3.52±1.03 4.46±2.59 0.220 Area Shrinkage (%) 32.4±15.73 9.78±23.08 0.013 Y Fujino, Marco. A Costa, S Nakamura et al. AHA 2013 scientific session

Case: LMT ost.~body stenosis: EES single crossover stenting without KBT LMT Ost~Body Lesion Single Stenting with Xiemce POT, Full Cover W/O KBT

EES single crossover stenting without KBT Post F/U E C A E C A B D D B A Post B C D E FFR; 0.78 Neointimal proliferation over the malapposed stent struts A B C D E F/U

Lesson 5 How many jailed struts, or how much area that jailed struts occupies in the area of ostium of LCX seems to be a determinant factor of Future Endotherialization for the coverage of these jailed struts. Finishing the case with optimum KBT is very indispensable for LMT bifurcation PCI

Optical coherence tomography assessment of in-stent restenosis after percutaneous coronary intervention with two-stent technique in unprotected left main. Fujino Y, Nakamura S, et al Int J Cardiol. 2016 May 20;219:285-292 After 2 Stent Implantation We can see NIH at CARINA area I 90 FD FD FD FD LW LW LW LW A B C D II LAD A B C D FD LMC A LW LCX

OCT Findings of ISR after Two-Stent Technique Fujino Y, Nakamura S, et al Int J Cardiol. 2016 May 20;219:285-292 Protruded NIH of LCX ostium at flow divider side uncovered stent strut LAD C Flow Divider D Flow Divider LMCA Flow Divider A B C D Lateral Wall LCX Lateral Wall Lateral Wall

Pre Stent Implantation (physiological) After Stent Implantation (non-physiological) Low Shear Stress Plaque accumulation LW (lateral wall) Implanted Stent Struts accumulation Low Shear Stress Plaque accumulation LW (lateral wall) High Shear Stress FD (flow divider) Neointimal Hyperplasia Neointimal Hyperplasia Uncovered Stent Struts Malapposed Stent Struts

Experimental model to study flow pattern Without stent placement Blood flow at carina is quite fast. After stent implantation Flow is delayed, causing turbulence. Without Stent High shear stress (high coronary flow) Culotte Stent Low shear stress (Low coronary flow) This is so-called low shear stress status. It is speculated that stent struts remaining at orifice of circumflex negatively affect the flow.

Without stent T- stent Accumulated stent struts might impact the flow pattern then progress the NIH in 2 stent PCI case Crush stent Culottes stent

OCT LAD LCX LMCA LCX Unfavorable culotte LAD LMCA Favorable culotte Home Data

Favorable culotte Unfavorable culotte LMCA LMCA LAD LAD LCX LCX LMCA LAD LMCA LAD LCX LCX Home Data

OCT TAP stenting

Follow-up CAG after PCI ISR of LAD proximal ISR of LCX proximal

Experimental model to study flow pattern Without stent placement Blood flow at carina is quite fast. Unfavorable TAP stent Flow is roiling, causing turbulence. High shear stress (high coronary flow) Flow Disturbance Home Data

Lesson 6 1. As far as bifurcation lesion is untreated, its flow around carina is fast and plaque is not accumulated. 2. However once two stents are placed, flow is delayed and causing turbulence, which is so called low shear stress area, susceptible to plaque deposition. 3. Depending on which double stenting technique is used, flow of CX would be different, and... even whether favorable stenting is achieved or not makes flow pattern different.

Happy End... Not Always!!