Bifurcation Overview A comprehensive overview of Bifurcation disease, treatment options and techniques

Bifurcation Overview Prevalence of Bifurcation lesions Anatomy of Bifurcation lesions Bifurcation Lesion and Technique Classification Systems Medina System MADS System Important Stent Attributes for treating Bifurcation lesions Bifurcation Treatment Techniques Provisional Stenting Two-stent Kissing Balloon Clinical Evidence impacting current techniques Summary

Recent All-Comers Trials and Registries Bifurcation Overview Bifurcation Lesions - Prevalence Based on recent trials which included bifurcation treatment, bifurcation lesions occur in about 25% of PCI cases. Several large recent trials have enrolled an all-comer population allowing bifurcation lesion treatment Recent All-Comers Trials and Registries Study # Patients % Bifurcations RESOLUTE All Comers1 2265 17% RESOLUTE International2 2349 18% TWENTE3 1391 26% LEADERS4 1707 29% NOBORI 25 3067 20% Real-world representation of bifurcation lesions is about 25% of all PCI’s. A Bifurcation lesion is a narrowing at the takeoff of a significant side-branch 1 Diletti R, et al. Heart 2013;99:1267–1274. 2 Neumann, F. et al. EuroIntervention 2012 Feb;7(10):1181-8 3 von Birgelen et al. J Am Coll Cardiol 2012 Vol 59, Issue 15 4 Garg et al. EuroIntervention 2011 Mar;6(8):928-35. 5 Danzi , GB, et al EuroIntervention2012 May15;8)1):109-16

Bifurcation Overview The Goal of Bifurcation PCI Bifurcation PCI aims to restore the natural configuration of the bifurcation, including: Optimal blood flow Well apposed stent Easy access to the SB in the future Pre Treatment* Post Treatment* *A. Colombo

Bifurcation Overview Bifurcation treatment may be complicated by: Lesions are difficult to treat Bifurcation treatment may be complicated by: Vessel geometry: different angles and tapers affect the shape of the ostium Variable stenting techniques Procedural success is low while complications and MACE rates are high for bifurcation as compared to non-bifurcation lesion treatment 1,2 Stankovic, EBC 2012 Vessel geometry – vessel diameters and branches have different angles and tapers which affect the shape of the ostium Variable stenting techniques – many variations of techniques and approaches currently exist to treat bifurcation lesions Adverse event rates – procedural success is low while complications and MACE rates are high for bifurcations as compared to non-bifurcation lesion treatment Images – Louvard Y. SEOUL 2009. Classification and Treatment Strategy of Bifurcation Lesions 1 Hildick-Smith, D. Bifurcation Stenting: Should You Keep it Simple. theheart.org 2 Stankovic et al. EuroIntervention 2009;5(1):39-49

Bifurcation Overview Classification of Bifurcation Lesions – Medina System The Medina System uses the proximal and distal main branches and the side branch as reference for the location of significant stenosis (>50%). The system cannot be used to describe the angles, the calcifications and length of the lesions. A “true” bifurcation involves both the main and side branch Medina System: The binary number corresponds with the presence or absence of a lesion within main, distal and side branches, respectively. In the majority of bifurcation lesions, one stent or “Provisional Stenting” is the treatment of choice;1 however, in true bifurcations (large diameter vessels and significant ostial side branch length), two stents may be needed2 1 Legrande et al. EuroIntervention 2007;3:44-49 2 Hildick-Smith et al. EuroIntervention 3010;6:34-38 Y. Louvard, T. Lefevre EuroIntervention 2011; 7(1): 160-163 Stankovic et al. EuroIntervention 2009;5(1):39-49

Bifurcation Overview Classification of Bifurcation Techniques - MADS The MADS System highlights classification of a number of bifurcation techniques, but does not reflect every possible bifurcation treatment strategy Main – stenting of the proximal main first; Across - stenting of the proximal main to the distal main, across the SB; Distal – historically starts with simultaneous stent placement at the ostium of both distal branches; Side – side branch is stented first Y. Louvard, T. Lefevre EuroIntervention 2011; 7(1): 160-163

Bifurcation Overview Important Stent Attributes in Provisional Stenting Side branch access and stent apposition are key attributes in provisional stenting and are dependent on several factors:1 Strut shape/size: smaller, smoother struts are easier to cross; apposition can be affected by torsion of the rectangular stent struts at the peaks leading to a ‘bumpy’ stent surface2 Cell shape/size: smooth round struts allow for easy wire and balloon sidebranch access; complex irregular cell shape may obstruct wire or catheter advancement through the stent3 1 Stankovic EBC 2012 2 Mortier EBC 2012 3 Carrie TCT Mediterranean 2012

Bifurcation Overview Important Stent Attributes in Provisional Stenting Cell expansion area: larger maximum achievable cell area allows for less obstruction into the side branch Number of Links: connections hold rings together, provide longitudinal strength, control flexibility, cell size and SB access2,3 Conformability: well apposed stent struts minimize the risk of wire or catheter snagging 1 Mortier EBC 2012 2 OrmistonT CT 2012 3 Stankovic EBC 2012

Bifurcation Overview Techniques – Provisional Stenting The preferred treatment approach for bifurcation disease known as provisional stenting, accounts for 80% of bifurcation lesion treatement:1 Provisional stenting uses only one stent, is not as technically difficult compared to two-stent techniques, procedure times are shorter and patients are exposed to less contrast and fluoroscopy In this NORDIC/BBC1 subgroup analyses there remained an increased risk of the primary end point associated with the complex group3 Provisional stenting - The technique starts with a single-stent approach for the main vessel (MV) and ignore side branch (SB) disease unless clinical circumstances warrant placement of an SB stent - Stankovic ESC 2012 Clinical circumstances include: Presence of chest pain, EKG changes, <3 TIMI flow, unstable dissection, severe residual stenosis, large (>2.5mm) SB with >5mm ostial disease, very difficult SB access Subgroup Analysis: from 2011 -Simple or Complex Stenting for Bifurcation Coronary Lesions: A Patient-Level Pooled-Analysis of the NORDIC and BBC1, 1 Routledge H. Interventional Cardiology. 2011;6(2):150–3 2Louvard & Lefèvre. EuroIntervention 2011;7:160-163 3 Behan, M. Circulation: Cardiovascular Interventions. 4(1):57-64, February 2011. Figure 2 . Odds ratio plot of the primary outcome for individual subgroups. Equivalence indicates that the SB is <0.25 mm smaller than the MV. Size of data markers indicates the number of patients in that subgroup. SB indicates side branch; MV, main vessel; CI, confidence interval.

Bifurcation Overview Techniques – Provisional Stenting Provisional stenting steps include stenting the MB and optimizing flow and access to the side branch Both branches are wired starting with the most difficult one MB is stented (stent sized according to MB distal reference) and SB wire is jailed The stent is post-dilated using the Proximal Optimization Technique (POT) to maximize stent apposition Stent is now well apposed proximally, while the SB is partially covered by scaffolding MB wire is pulled back and re-inserted through the most distal strut of the SB opening scaffold Jailed wire is removed and re-inserted in the distal MB (with a formed loop at the distal end) The Kissing Balloon inflation is done to optimize side branch flow and access Final result (if suboptimal, can then place additional stents) Louvard & Lefèvre. EuroIntervention 2011;7:160-163

Bifurcation Overview Techniques – Provisional Stenting The key steps to provisional stenting include: distal main branch sizing and proximal main branch proximal optimization technique (POT) and/or Final Kissing balloon (FKB) Proximal Proximal POT FKB No carina shift Carina shift In single stent techniques, the primary stent should be sized according to the distal main vessel diameter. This avoids the risk of carina shift, which can lead to occlusion of the side branch.1 1 Stankovic EBC 2012 Postdilitation (POT) or kissing balloon inflations (FKB), are required to optimize the proximal main vessel stent diameter.2 2 Stankovic ESC 2012 Distal Distal Stankovic EBC 2012

Strut expansion at carina Bifurcation Overview Techniques – Proximal Optimization Technique (POT) The proximal optimization technique (POT) is a variation of the provisional stenting technique and expands the stent at the carina, using a short oversized balloon. This optimizes the proximal main vessel stent diameter and produces curved expansion of the stent into the bifurcation point, which facilitates: Proximal oversizing - Re-crossing into the SB - Distal re-crossing - Kissing inflations - Ostial stent coverage of the side branch Opinion remains divided as to whether POT should be a part of the standard approach to bifurcation lesions, but there is consensus that this technique should be used in any case of difficulty re-crossing into a side branch with either a wire or balloon. Strut expansion at carina Hildick-Smith et al. EuroIntervention 2010;6:34-38

Bifurcation Overview Techniques – Two Stent Approach The following are required for a 2-stent approach: Final kissing balloon inflations High pressure ostial and proximal stent inflations to correct stent deformation Figure depicts the most common two stent techniques that can be used after provisionally stenting the main branch. Out of these options, crush is the least-preferred 2-stent technique. Main branch stenting first The range of potential steps and techniques to treat bifurcation lesions is extremely complex No consensus exists on the ideal 2-stent technique and each operator has their own tips and tricks on how to overcome technical challenges. Stankovic ESC 2012

Bifurcation Overview Techniques – Two Stent Approach (T-stenting, Culotte, Crush) The range of potential steps and techniques to treat bifurcation lesions is extremely complex – no consensus exists on the ideal 2-stent technique and each operator has their own tips and tricks on how to overcome technical challenges. T-Stenting Technique Culotte technique Crush technique Gutersohn TCT 2012, Adapted from A. Colombo

Bifurcation Overview Final Kissing Balloon (FKB) Kissing balloon technique is done mainly to optimize the proximal main vessel stent diameter as well as side branch flow and access. Advantages of final kissing inflations:1,2 Correction of the main vessel stent distortion Expansion/apposition of the main vessel stent Better scaffolding at the side branch ostium Correction of carina shift Future access to the SB Systematic kissing balloon inflation Routine use of Final Kissing Balloon (FKB) did not improve clinical (MACE) outcomes but did reduce angiographic side branch restenosis, especially in patients with true bifurcation lesions3 Kissing balloon inflations, or pressure wire interrogation, should be used when an angiographically significant (>75%) side branch lesion remains after main vessel stenting.4 1 Stankovic et al. EuroIntervention 2009;5:39-49 2 Darremont EBC 2012 3 Niemela, M. et al Circulation 2011 Jan 4;123(1):79-86. 4 Hildick-Smith et al. EuroIntervention 2010;6:34-38

Bifurcation Overview Final Kissing Balloon (FKB) Crossing of the distal side cells of the main vessel stent is associated with better ostium scaffolding and reduced need for side branch stenting1 Image adapted from Carrie TCT Mediterranean 2012 Although it remains up to physician preference, to prevent overdilation during kissing inflations EBC recommends the use of non-compliant balloons2 Image from Darremont EBC 2012 1 Burzotta et al. EuroIntervention Supplement (2010) Vol. 6 (Supplement J) J72-J80 2 Hildick-Smith et al. EuroIntervention 2010;6:34-38

Bifurcation Overview Clinical Data’s impact on Bifurcation techniques? Prior to 2008, there was limited clinical data on the treatment of bifurcation lesions with specific bifurcation techniques. Up to that time, 2-stent techniques were often thought to be an optimal treatment for true bifurcations. In 2008 the NORDIC and BBC trials shifted the perception and practice to the simpler, provisional strategy by showing first generation DES are effective at treating bifurcation lesions. Prior to 2008, the Crush technique was a highly preferred 2-stent technique. Based on BBC ONE outcomes, the investigators went as far as labeling Crush stenting as ‘dead’.

Bifurcation Overview Provisional Stenting as the Gold Standard Randomized bifurcation trials comparing provisional 1-stent vs. systematic 2-stent strategy have shown no benefit using two stents. Stankovic ESC 2012

Bifurcation Overview NORDIC I - Overview NORDIC I was a randomized trial of 400 patients (200 to simple – provisional stenting and 200 to a complex – dual stent strategy with either crush, culotte, T, or Y stenting using SES (Cypher)). The Primary Endpoint was MACE at 6 months and 5-year follow up. Figure 1 5-Year Follow-Up Patient Flow Chart of the Nordic Bifurcation Study ∗ A total of 307 patients had a quantitative coronary assessment at the index procedure and after 8 months. MV = main vessel; SB = side branch. M. Maeng, et al. Journal of the American College of Cardiology, Vol 62, Issue 1 2013 30-34

Bifurcation Overview NORDIC I – Study Conclusions Short and long-term follow-up showed no difference in MACE. Both stenting strategies have a high and similar procedural success, but simple stenting is associated with reduced procedure and fluoroscopy time as well as significantly lower incidence of increased levels of biomarkers (possible infarctions). M. Maeng, et al. Journal of the American College of Cardiology, Vol 62, Issue 1 2013 30-34

Bifurcation Overview BBC ONE - Overview BBC ONE was a randomized trial of 500 patients (250 to simple – provisional stenting and 250 to a complex – dual stent strategy with either crush or culotte, stenting using PES (Taxus)). The Primary Endpoint was MACE at 9 months. Hildick-Smith theheart.org HildickSmith TCT 2008

Bifurcation Overview BBC ONE – Study Conclusions A systematic 2-stent technique resulted in longer procedures, higher x-ray doses, more procedural complications, and a higher rate of in-hospital and 9-month MACE. Hildick-Smith theheart.org HildickSmith TCT 2008

Bifurcation Overview NORDIC III - Overview NORDIC III was a randomized trial comparing final kissing balloon (FKBD) vs. no FKBD in patients treated with main vessel stenting using SES (Cypher) 1 Erglis Korea 2010 2 Niemela, M. et al Circulation 2011 Jan 4;123(1):79-86. 3 Hildick-Smith TCT 2011

Bifurcation Overview NORDIC III – Study Conclusions Similar 6-month clinical outcome with and without FKBD Angiographic restenosis was significantly less in the FKBD group Simple no-FKBD strategy was associated with shorter procedure and fluoro times and reduced use of contrast media.1,2 It has been proposed that FKBD should be used in cases where the side branch ostial narrowing is >75%.3 Secondary end point P=0.039 1 Erglis Korea 2010 2 Niemela, M. et al Circulation 2011 Jan 4;123(1):79-86. 3 Hildick-Smith TCT 2011

Bifurcation Overview European Bifurcation Club What is EBC? A “think-tank” of cardiologists with a particular interest in bifurcations Independent club with a yearly scientific meeting and publication of consensus statement (established 2004) Educational collaboration with EuroPCR http://www.bifurc.net/ Based on current clinical evidence and expert consensus, EBC provides recommendations to help improve bifurcation treatment technique and outcomes. Lassen EBC 2012