Georgios Katsimagklis M.DAssociate Director of Cardiology Clinic and

Cath-lab in Naval Hospital of Athens

I, Georgios Katsimagklis,don’t have a financial interest or affiliation with one pr more organizations probably related to the subject of this presentation

Significant unprotected left main coronary artery (ULMCA) disease occurs in 5-7% of patients undergoing coronary angiography

Patients with ULMCA disease treated medically have been reported to have a three-year mortality rate of 50%

CABG has historically been regarded as the gold standard treatment for ULMCA disease

The LMS is generally divided into three anatomical regions: the ostium (arising from the left aortic sinus), a mid and a distal portion

The distal portion of the LMS bifurcates into the LAD and LCx arteries in approximately two thirds of patients, and trifurcates into the LAD, LCx, and ramus intermedius in approximately one third of patients

The greater elastic tissue content in the LMS (particularly the ostium) may historically explain the elastic recoil and greater restenosis rates observed following balloon angioplasty

Intimal atherosclerosis is accelerated in low shear stress areas in the lateral walls of the LMS (i.e., opposite the flow divider – carina) close to the LAD and LCx bifurcation; conversely the carina is frequently free of disease due to its being a high shear stress area

IVUS studies have shown that plaque burden in the LMS bifurcation is more frequently diffuse rather than focal, with continuous plaque from the LMS into the proximal LAD artery occurring in approximately 90% of cases

Meta-analyses(18studies-5483 patients- and 4 randomised trials-1611 patients) have consistently shown comparable mortality rates between CABG and PCI at atleast 1 year in patients with ULMCA disease, with greater rates of CVA with CABG and repeat revascularisationwith PCI. These meta-analyses have not looked at selecting patients by anatomical complexity or clinical comorbidity, which appears to enhance the appropriate identification of patients suitable for CABG or PCI

ULM PCI in the setting of acute coronary syndrome or primary PCI have demonstrated in-hospital mortality rates of 21%(Pappalardo et al-5261 patients) and 11%(Pedrazziniet al-6666patients) respectively in registry studies, and lend support to the continued adoption of this practice

A pilot study (n=215) has suggested a higher longer-term mortality and stent thrombosis-free survival in patients with a low residual platelet reactivity compared to patients with a high residual platelet reactivity undergoing ULM PCI. Further study is awaited

Routine surveillance angiography post ULM PCI is no longer recommended, with comparable clinical events to patients who undergo PCI for non-left main lesions

Anatomical based scores

Functional SYNTAX score

Clinical based scores

Combined (anatomical and clinical) risk scores

PRECOMBAT trial Park SJ, Kim YH, Park DW, Yun SC, Ahn

JM, Song HG, Lee JY, Kim WJ, Kang SJ, Lee SW, Lee CW, Park SW, Chung CH, Lee JW, Lim DS, Rha SW, Lee SG, Gwon HC, Kim HS, Chae IH, Jang Y, Jeong MH, Tahk SJ, Seung KB. Randomised trial of stents versus bypass surgery for left main coronary artery disease. N Engl J Med. 2011;364:1718

PRECOMBAT-2 trial

DELTA Registry Chieffo A, Meliga E, Latib A, Park SJ, Onuma

Y, Capranzano P, Valgimigli M, Jegere S, Makkar R, Palacios I, Kim YH, BuszmanP, Chakravarty T, Sheiban I, Mehran R, Naber C, Margey R, Agnihotri A, MarraS, Capodanno D, Leon M, Moses J, Fajadet J, Lefevre T, Morice MC, Erglis A, TamburinoC, Alfieri O, Serruys PW, Colombo A. Drug Eluting stent for LefT main coronary Artery disease: the DELTA Registry A Multicenter Registry Evaluating PCI vs. CABG for Left Main Treatment. JACC Cardiovasc Interv.

Fame study.(a retrospective sub-analysis of almost 500 patients with multivessel disease from the FFR-guided arm of the FAME study, the primary benefit appeared in reclassifying higher-risk groups into lower-risk categories without any adverse sequelae, in terms of MACE and death or MI at 1 year [77]. However, it should be emphasised that no patients with LMS disease were involved in this study and prospective validation of the Functional SXscore in LMS -and multivessel disease-is required. )

Combination of SXscore and Modified ACEF.

ACEF( age/ejection fraction+1 point for every 10 ml/min reduction in creatinine clearance below 60 ml/min/1.73m2 (up to a maximum of 6 points).

Similar results as SXscore alone

The Parsonnet

EuroSCORE

The SXscore has proven to be a clinically useful anatomical scoring system to risk stratify patients with ULMCA disease to determine the optimal revascularisation modality

A low to moderate SXscore in patients with ULMCA disease has been shown to have comparable outcomes in terms of efficacy and safety in the SYNTAX trial at up to 4 years in patients undergoing surgical or percutaneous revascularisation. This has been validated in several registries at short and longer-term follow-up, and is now subject to the ongoing EXCEL trial

The outcomes of patients undergoing ULM PCI appears to be affected by a higher SXscore and its association with anatomical complexities and clinical comorbidity

The “Functional SXscore” (a fractional flow reserve-derived SXscore) may improve the risk stratification of patients with ULMCA disease. Further study is on-going

Clinical based scores, such as the Parsonnet score and EuroSCORE, or clinical variables per se have been shown to improve the predictive ability of the SXscore in patients with ULMCA disease. No clear consensus currently exists on the most appropriate combined anatomical and clinical based score

The European and American Revascularisationguidelines regard ULM PCI as a Class IIa indication in appropriately selected patients with suitable anatomical conditions. Both guidelines suggest the use of the SXscore in guiding risk stratification

IVUS is superior to QCA in terms of assessing reference diameter, MLD and diameter stenosis of the LMS

IVUS provides a high tissue penetration that allows for a visualisation of the entire vessel wall and thus the assessment of vessel remodelling and total atheroma burden

To date, only one propensity-matched RCT has observed superiority in terms of clinical outcome with an IVUS-guided PCI strategy(a substantial long-term (3-year) mortality benefit) compared to conventional angiography

In angiographically ambiguous LMS lesions, an IVUS-derived MLA cut-off of 5.9 mm2 has been associated with an FFR of 0.75.

Due to the discrepancies in the best IVUS MLA cut-off that correlates with FFR, the undertaking of FFR or non-invasive stress testing has been suggested if the IVUS derived MLA is <6.0 mm2 pre-intervention. Revascularisation can be safely deferred if the MLA value ≥6.0 mm2

The criteria for the minimum stent areas (MSA) post ULM PCI have been shown to be approximately 8 mm2, 7 mm2, 6 mm2 and 5 mm2 in the proximal LMS, polygon of confluence, ostial LAD, and ostial LCx, respectively These cut-off values have been associated with reduced ISR at 9 months and freedom from MACE at 2 years

LCx ostial measurements cannot be reliably assessed obliquely from the LAD to LMS on IVUS pullback. Evaluation of the LAD and LCx ostia is recommended by the pull-back in the respective vessels

If clinically indicated, MSCT can allow for reliable non-invasive evaluation after LMCA stenting and can safely exclude significant left main in stent restenosis

Within angiographically intermediate ULM lesions a number of studies have shown that revascularisation of the LMS can safely be deferred if the FFR value ≥0.80, with comparable mortality rates to patients with significant ULM stenoses treated with CABG at up to 5 years follow-up.

Hamilos M, Muller O, Cuisset T, Ntalianis A, Chlouverakis G, Sarno G, Nelis O, Bartunek J, Vanderheyden M,

Wyffels E, Barbato E, Heyndrickx GR, Wijns W, De Bruyne B. Long-term clinical outcome after fractional flow reserve-guided treatment in patients with angiographically equivocal left main coronary artery stenosis.Circulation 2009;120:1505-12. A study demonstrating the long term safety of deferring LMS revascularisation if the FFR value ≥0.75.

Angiographic stenotic appearances of the Side B ostiumafter cross-over stenting have previously been demonstrated to be unreliable with only a quarter (27%) of cases with a residual angiographic narrowing of ≥75% in the Side B being found to have a functionally significant narrowing in pressure wire studies. This is probably equally relevant in the distal LMS

EXCEL (Evaluation of Xience Prime versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularisation) Trial, investigating patients with a low-intermediate SXscores (i.e., SXscore <33) with the next-generation DES, will help define the optimal revascularisation modality for patients with ULMCA disease.

Main areas of FUTURE RESEARCH:Riskstratification models, Advances in intravascular imaging, advances in stent design with dedicated devices, bioabsorbable materials ,new antiplatelets.

My personal opinion, the near future guidelines are not going to be further than today’s.