Important LM bifurcation studies update...M. Lee et al , Am J Cardiol 2010 ; 105:1070-1075 Meta-analysis of randomized controlled trials on the treatment of unprotected left main coronary

8th European Bifurcation Club 12-13 October 2012 - Barcelona

Important LM bifurcation studies update

I Sheiban

E-mail: [email protected]

 Assessment of left main Disease and lesion significance

 Procedural Challenges and Optimizing LM PCI

 Clinical outcomes vs surgical revascularization

 Present and Future: Impact on Clinical practice, Guidelines, trials….

Unprotected LM Percutaneous Revascularization What is important :






Visual Estimation QCA Stenosis

Angiographic measurements are unreliable in the assessment of intermediate LMCA lesions

Wide variability in visual and quantitative angiographic assessment of LMCA lesions with MLA <6 mm2

Left Main Lesion Assessment Angiography versus IVUS

LITRO Investigators. J Am Coll Cardiol 2011;58:351-8

Puri et al., J A C C Cardio vasc Interv 2012 : 6 9 7 – 7 0 7

IVUS Predictors of FFR in Angiographically Intermediate LM Disease

1999 - 2011

Left Main Lesion Assessment Angiography versus IVUS

From a clinical perspective, MLA ≥ 6 mm2 is a safe value for deferring revascularization of the LMCA LITRO Investigators. J Am Coll Cardiol 2011;58:351-8

IVUS Predictors of FFR in Angiographically Intermediate LM Disease Independent determinants of FFR (N=55) Plaque rupture Minimal luminal area FFR <0.80 MLA 4.8 mm2 Sensitivity 89%, Specificity 83% FFR <0.75 MLA 4.1 mm2 Sensitivity 95%, Specificity 83%

Kang et al. JACC Intvervent 2011

Minimal stent area threshold values for the prediction of angiographic in-stent restenosis

Kang S et al. Circ Cardiovasc Interv 2011;4:562-569

2-stent Cohort ( n = 104 ) 1-stent Cohort ( n = 289 )

Frequency of Stent Underexpansion 1 vs 2 Stent Techniques

2-stent: LCX stent most frequently underexpanded and results in ISR more than half of cases 1-stent: Underexpansion is less common compared with 2 stent techniques with lower ISR *P<0.05 for comparison of LAD and POC stent underexpansion

Kang S et al. Circ Cardiovasc Interv 2011;4:562-569;

Mechanisms of Luminal Loss at the LCX Ostium Morphometric Changes Pre/Post Crossover Stenting

Kang S et al. Circ Cardiovasc Interv 2011;4:355-361

•  80% of LCX ostia will have >10% reduction in MLA after crossover stenting

•  Carina shift is principal mechanism of lumen loss; less common is plaque redistribution

•  Narrow carina angle between LCX and LAD and wide angle between LCX and LM is associated with greater luminal loss


FFR Assessment for Angiographically

Intermediate LM Disease 2004 - 2009

A significant lesion at prox LAD or prox LCX can mask the true significance of the left main coronary artery lesion by compromising hyperemic flow and subsequent true maximal pressure gradient across this lesion. After treatment of the distal lesion, hyperemic blood flow through the vessel increasesn and he true fractional flow reserve (FFR) of the left main coronary artery lesion becomes apparent.

Limitations of FFR Assessment for

Angiographically Intermediate LM Disease

Fearon WF, 8th Annual CTO Summit and Left Main Interventions Course, 2011.







Mehilli et al. JACC , 2009; 19:1760–8

1-Year Incidence and Relative Risk of Death / MI/ TLR

Paclitaxel- Versus Sirolimus-Eluting Stents for Unprotected Left Main Coronary Artery Disease

( ISAR Left Main )

ISAR LEFT MAIN • True bifurcation and 2-stents, but not stent technique, predictive of ISR ISAR LEFT MAIN • Final kissing no additional benefit on ISR for single stent crossover or 2-stent if optimal angiographic results Tiroch et al. TCT2011; Tiroch et al. TCT 2011;

French Left Main Taxus Registry : Five-Year Outcomes 1stent vs 2 stents

D. Mylotte et al , EuroIntervention, 2012 ( ahead of publication )

MACE

Cardiac Death

Cardiac Death / MI / Stroke

Clinical and Angiographic Outcomes of Patients Treated With Everolimus-Eluting Stents or First-Generation Paclitaxel-Eluting Stents for Unprotected Left Main Disease

R Valenti et al , J Am Coll Cardiol. 2012;60:1217-1222

Clinical and Angiographic Outcomes

Adjusted hazard ratios of EES in the RECOMBAT-2 study compared with SES in the historical control of PRECOMBAT study for the risk of events

KIM YH et al ; J A C C CardioVac Interv 2012: 708-717

Everolimus-Eluting Stent Implantation for Unprotected Left Main Coronary Artery Stenosis

The PRECOMBAT-2

Lee, J.-Y. et al. J Am Coll Cardiol 2011;57:1349-1358

Left Main Surveillance Post Revascularization

PRE COMBAT Characteristics and Outcomes According to Angiographic Surveillance

Overall 2 Year Repeat Revascularization: LM, 4.5%, non-LM 2.5%

Park et al. NEJM 2011

Medical Therapy: Ostial LCx, Focal ISR, Less severe % diameter stenosis, silent ischemia/stable angina CABG: LAD ISR, diffuse ISR

UPLM DES Restenosis 71 Restenotic Cases (57 Focal, 14 Diffuse Pattern ISR) Timing of Presentation: 69% <1 year, 16.9% 1-2 years, 12.3% 2-3 years, 2.8% >3 years

Lee, J.-Y. et al. J Am Coll Cardiol 2011;57:1349-1358

PRECOMBACT 2 Angiographic Restenosis in the Subgroups Stratified By Stenting Technique


MAIN COMPARE Multivariate Predictors of In-Stent Restenosis

*Compared with simple cross-over stenting of distal bifurcation lesions

Lee et al. JACC Intervent 2011

Migliorini, A. et al. J Am Coll Cardiol 2011;58:125-130

Impact of Right Coronary Artery Total Occlusion on Survival Following LM PCI

N=330 (24% RCA CTO) Predictors of 3-Year Mortality : RCA CTO, EuroSCORE






ULM PCI with DES vs CABG Randomized Trial: Death or Myocardial Infarction

Boudriot et al. J Am Coll Cardiol 2011;57:538-545

ULM PCI with DES vs CABG Randomized Trial: Target Vessel Revascularization

Boudriot et al. J Am Coll Cardiol 2011;57:538-545

PRECOMBAT Death, MI, Stroke


PRECOMBAT Ischemia-Driven Repeat Revascularization


PRECOMBAT 2 Death, MI, Stroke


Death from any cause Death, MI, or Stroke

PRECOMBAT 2 Traget Vessel Revascularization & MACE

Ischemia-driven TVR MACE


D. C-apodanno , JACC 211, 54: 1426.32

Metanalysis of Randomizes Studies PCI Versus CABG in Left Main Disease

D. C-apodanno , JACC 211, 54: 1426.32



D. C-apodanno , JACC 211, 54: 1426.32

MACCE Between PCI and CABG in the Pooled Analysis of the SYNTAX Left Main and PRECOMBAT Studies

Chieffo et al , JACC Cardiovasc Interv 2012 : 718-730

DELTA Registry Multinational All-Comers Registry PCI = 1874 CABG= 900

- No difference between CABG and PCI in : Death, CVA and MI - An advantage of CABG over PCI in MACCE, (driven by the higher incidence of TLR/TVR in PCI Group )

Jang J-S, et al. Am J Cardiol. 2012;Epub ahead of print

Meta-analysis of 3 Randomized Trials and 9 Observational Studies Comparing DES vs. CABG for Unprotected Left Main Coronary Artery

Disease 5,079 pts treated with DES (n = 2,107) or CABG (n = 2,972), 2001-2011.

Death, MI, or Stroke Death TVR

Meta-analysis of 5674 patients treated with percutaneous coronary intervention and drug-eluting stents or coronary artery bypass graft surgery for unprotected left main coronary artery stenosis MP de Oliveira et al, Eur J Cardio thorac Surg 2012

Meta-Analysis of Clinical Studies Comparing Coronary Artery Bypass Grafting With Percutaneous Coronary Intervention and Drug-Eluting Stents in Patients With Unprotected Left Main Coronary Artery Narrowings M. Lee et al , Am J Cardiol 2010 ; 105:1070-1075

Meta-analysis of randomized controlled trials on the treatment of unprotected left main coronary artery disease: one-year outcomes with coronary artery bypass grafting versus percutaneous coronary artery intervention with drug-eluting stent. K Kaiimoto et al J Card Surg 2011

Comparison of one-year outcomes of percutaneous coronary intervention versus coronary artery bypass grafting in patients with unprotected left main coronary artery disease and acute coronary syndromes (from the CUSTOMIZE Registry). A. Caggegi et al , Am J Cardiol 2011 ;108(3):355-9 Stenting versus coronary artery bypass grafting for unprotected left main coronary artery disease: A meta-analysis of comparative studies H Takagi et al , J Thorac Cardiovasc Surg 2009 , 137:e54-e57

Percutaneous coronary intervention versus bypass surgery for left main coronary artery disease: a meta-analysis of randomised trials EuroIntervention 2011; publish-ahead-of-print August 2011

LM PCI vs CABG : Other Meta-analysis & Registries 2011-2012

No difference in Death , Death / MI / CVA

Significant increase in TLR in PCI patients

5-Year Outcomes Following Percutaneous Coronary Intervention With Drug-Eluting Stent Implantation Versus Coronary Artery Bypass Graft for Unprotected Left Main Coronary Artery Lesions: Title and subTitle BreakThe Milan Experience

A. Chieffo et al , J Am Coll Cardiol Intv. 2010;3(6):595-601. doi:10.1016/j.jcin.2010.03.014

MACCE at 5 Years Cardiac Death, MI, and CVA at 5 Years

Durable ……

French Left Main Taxus Registry : Five-Year Outcomes Syntax Score

D. Mylotte et al , EuroIntervention, 2012 ( ahead of publication )

Cardiac Death MACE

Cardiac Death / MI / Stroke

Durable ……

SYNTAX Trial LM Subgroup: 1 and 4 Year Outcomes

Serruys P. TCT2011

Cumulative KM Event Rate ± 1.5 SE; log-rank P value Site-reported Data; ITT population

Serruys P. TCT2011

MACCE at 4 Years Stratified by Baseline SYNTAX Score Tercile Tercile SYNTAX Low to Intermediate Scores 0-32

MACCE at 4 Years Stratified by Baseline SYNTAX Score Tercile SYNTAX High Score 33

Cumulative KM Event Rate ± 1.5 SE; log-rank P value Site-reported Data; ITT population

Serruys P. TCT2011

Overall TAXUS (N=290) CABG (N=315)

P<0.001

44.0%

26.8%

Core lab-reported Data; ITT population Cumulative KM Event Rate ± 1.5 SE; log-rank P value

CABG PCI P value

Death 11.4% 19.2% 0.005

CVA 3.7% 3.5% 0.80

MI 3.9% 10.1% 0.004

Death, CVA or

MI 17.1% 26.1% 0.007

Revasc. 12.1% 30.9% <0.001 Months Since Allocation

Cum

ulat

ive

Even

t Rat

e (%

)

0 12 24

50

0

25

48 36 60

MACCE at 5 Years Stratified by Baseline SYNTAX Score Tercile SYNTAX High Score 33

Serruys P. ESC 2012

The simple and extremely user-friendly ACEF score can accurately identify patients undergoing PCI for coronary bifurcation lesions at high risk of early fatal or non-fatal complications, as well as long-term fatality.

Biondi Zoccai G et al ,EuroIntervention 2012; Epub ahead of print May 2012

Girasis C et al. Eur Heart J 2011;eurheartj.ehr369

SYNTAX score and Clinical SYNTAX score as predictors of very long-term clinical outcomes in patients undergoing percutaneous coronary interventions: a substudy of SIRolimus-eluting stent compared with pacliTAXel-eluting stent for coronary revascularization (SIRTAX) trial

SYNTAX score and to a greater extent CSS were able to stratify risk for very long-term adverse clinical outcomes in an all-comers population receiving drug-eluting stents. Predictive accuracy for 5-year all-cause mortality was improved using CSS

Global Risk Classification and Clinical SYNTAX (Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery) Score in Patients Undergoing Percutaneous or Surgical Left Main Revascularization

D Capodanno et al , J Am Coll Cardiol Intv. 2011;4(3):287-297

In LM patients undergoing PCI, combined scores improve the discrimination accuracy of clinical or angiographic stand-alone tools. In LM patients undergoing CABG, the ACEF score has the best prognostic accuracy compared with other stand-alone or combined scores. The good predictive ability for PCI along with the poor predictive ability for CABG make the SYNTAX score the preferable decision-making tool in LM disease.






Indications for CABG versus PCI in stable patients with lesions suitable for both procedures

and low predicted surgical mortality

•  In the most severe patterns of CAD, CABG appears to offer a survival advantage as well as a marked reduction in the need for repeat revascularisation.

www.escardio/guidelines

2011 ACC/AHA PCI Guidelines

Levine et al. J Am Coll Cardiol 2011

Recommendations Pertaining to Unprotected Left Main Intervention in the American College of Cardiology Foundation /American Heart

Association /Society of Cardiovacular Angiography and Intervention 2011 Guidlines for PCI

P. Teirstein, MJ Price, JACC 2012 , 60:1605–13

  Clinical trials strongly support overall no differences in death or MI, possibly lower stroke but higher TLR with PCI and these outcomes are durable over time

  SYNTAX Trial does encourage expansion of PCI strategy to Low SYNTAX Score patients

  Beside SYNTAX Score Simple Risk models can help decision making for PCI vs CABG ( i.e. ACEF )

  Role for IVUS and FFR as diagnostic and guidance tools

  ‘Heart Team’ approach for PCI and CABG is recommend in overlapping subgroups with LM disease for an optimal clinical practice

Final Remarks

Documents

Important LM bifurcation studies update...M. Lee et al , Am J Cardiol 2010 ; 105:1070-1075 Meta-analysis of randomized controlled trials on the treatment of unprotected left main coronary