Impact of Interventional Strategy for Unprotected Left Main Coronary Artery Percutaneous Coronary Intervention on Long-term Survival

Canadian Journal of Cardiology 28 (2012) 553–560

Clinical Research

Impact of Interventional Strategy for Unprotected Left Main Coronary Artery Percutaneous Coronary Intervention on Long-term Survival Ralf Lehmann, MD,a Joachim R. Ehrlich, MD,a Salvatore De Rosa, MD, PhD,a Ioakim Spyridopoulos, MD,a Rafael Laskowski, MD,a Janine Kremer, MD,a Eva Herrmann, PhD,b Andreas M. Zeiher, MD,a Volker Schächinger, MD,a and Stephan Fichtlscherer, MDa a b

Department of Cardiology, Johann Wolfgang Goethe-University Frankfurt, Frankfurt, Germany

Institute of Biostatistics and Mathematical Modelling, Johann Wolfgang Goethe-University Frankfurt, Frankfurt, Germany

ABSTRACT

RÉSUMÉ

Background: Percutaneous coronary intervention (PCI) of unprotected left main coronary artery (ULMCA) is feasible. In cases involving the left anterior descending–left circumflex bifurcation, the optimal interventional strategy remains unclear. Randomized bifurcation trials in the past excluded ULMCA lesions. Methods: A single-centre registry study with retrospective analysis of the interventional protocols and procedural angiograms of 102 patients who underwent stent PCI of ULMCA was performed in order to evaluate the impact of the interventional strategy on long-term survival. Results: Isolated stenting of the ostium or mid ULMCA without bifurcation stenting was performed in 19 patients. Most interventions (n ⫽ 83) involved the left main bifurcation. Distal or bifurcation lesions were treated by provisional T-stenting in cases of single involved ostium (left anterior descending or right circumflex) or systematic T-stenting or V-stenting if both proximal coronary arteries were involved (n ⫽ 19).

Introduction : L’intervention coronarienne percutanée (ICP) du tronc commun coronaire gauche non protégé (ULMCA : unprotected left main coronary artery) est réalisable. Dans les cas impliquant la bifurcation entre la descendante antérieure gauche et la circonflexe gauche, la stratégie d’intervention optimale semble peu claire. Dans le passé, les essais aléatoires sur la bifurcation excluaient les lésions à l’ULMCA. Méthodes : Une étude rétrospective unicentrique des protocoles d’intervention et des angiographies interventionnelles de 102 patients ayant reçu une endoprothèse lors de l’ICP de l’ULMCA a été réalisée pour évaluer les conséquences de la stratégie d’intervention sur la survie à long terme. Résultats : L’implantation isolée d’un tuteur coronarien à l’ostium ou au milieu de la ULMCA sans implantation d’un tuteur coronarien à la bifurcation a été réalisée chez 19 patients. La plupart des interventions (n ⫽ 83) impliquaient la bifurcation du tronc commun coronaire

Coronary artery disease (CAD) involving unprotected left main coronary artery (ULMCA) is associated with poor prognosis, and surgery is considered the gold standard for treatment. The superiority of surgical revascularization over medical treatment is generally accepted.1 Nevertheless, data from trials comparing percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) regarding treatment of CAD with ULMCA involvement are scarce. LMCA appears to be an attractive PCI target because of proximity, lack of tortuosity, large diameter, and short lesion

length. In cases of hemodynamic instability due to acute myocardial infarction, PCI seems to be the only therapeutic option to treat LMCA stenosis, although it has similarly not yet been investigated in randomized trials. Data from a nonrandomized registry comparing PCI and CABG suggest similar outcome of patients undergoing ULMCA-PCI, even against the background of a greater proportion of high-risk patients.2 The randomized Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) trial also suggests similar survival for both treatment options in the left main subset.3 Recent data suggest good outcome of ULMCAPCI even in the setting of acute coronary syndromes (ACSs).4 Two main issues may complicate the treatment of LMCA stenosis: first, the occurrence of relevant lesion in additional coronary segments and, second, involvement of LMCA bifur-

Received for publication November 3, 2011. Accepted February 20, 2012. Corresponding author: Dr Ralf Lehmann, Department of Cardiology, University of Frankfurt, Theodor Stern-Kai 7, 60590 Frankfurt, Germany. E-mail: [email protected]. See page 559 for disclosure information.

0828-282X/$ – see front matter © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.cjca.2012.02.013

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The majority (96%) of patients received drug-eluting stents. The longterm survival (mean follow-up ⫽ 3.4 ⫾ 1.7 years) of patients was influenced by the interventional strategy. A single-stent strategy involving the bifurcation without side branch intervention was associated with less-favourable long-term survival (hazard ratio 4.08; 95% confidence interval, 1.91-8.69; multivariable Cox regression analysis). Conclusions: This prospective observational study suggests that single-stent PCI involving the bifurcation without side branch intervention of ULMCA is possibly associated with higher long-term mortality. ULMCA-PCI involving the bifurcation is possible with similar results compared with isolated PCI of ULMCA shaft or ostium. Large, randomized trials are warranted for comparison of optimal technical approach to LMCA interventions.

gauche. Les lésions distales ou de la bifurcation étaient traitées par la technique de T stenting provisionnel dans les cas où seul l’ostium était impliqué (descendante antérieure gauche ou circonflexe droite) ou par la pose systématique d’un T stent (tuteur coronarien en forme de T) ou d’un V stent si les deux artères coronaires proximales étaient impliquées (n ⫽ 19). La majorité (96 %) des patients recevaient des endoprothèses à élution de médicaments. La survie à long terme (suivi moyen ⫽ 3,4 ⫾ 1,7 ans) des patients était influencée par la stratégie d’intervention. Une stratégie utilisant un seul tuteur coronarien et impliquant la bifurcation sans intervention de la branche latérale était associée à une survie à long terme moins favorable (rapport de risque de 4,08; intervalle de confiance de 95 %, 1,91-8,69; analyse multivariée par le modèle de régression de Cox). Conclusions : Cette étude observationnelle prospective suggère que l’utilisation d’un seul tuteur coronarien lors de l’ICP impliquant la bifurcation sans intervention de la branche latérale de l’ULMCA est possiblement associée à une mortalité à long terme plus élevée. L’ICP de l’ULMCA impliquant la bifurcation est possible avec des résultats similaires comparativement à l’ICP isolée de l’arbre ou de l’ostium de l’ULMCA. Des essais aléatoires d’envergure sont justifiés pour comparer l’approche technique optimale aux interventions de la LMCA.

cation or trifurcation (left anterior descending [LAD], left circumflex [LCx], ramus intermedius). The need for bifurcation stenting may make percutaneous revascularization difficult and risky, and complex procedures may accordingly be necessary. Despite the increasing number of studies dealing with ULMCA-PCI, there is considerable debate regarding the optimal interventional approach (systematic T-stenting, provisional Tstenting, reverse Y-stenting, V-stenting, “trouser leg” stenting, culotte stenting, “crush” stenting) of left main bifurcation lesions.5 Difficulties regarding interpretation of existing data arise from many differently performed or not clearly defined interventional strategies. The lack of benefit from accelerated bifurcation procedures (systematic stenting of side branch [SB]) in non-ULMCA lesions in the past could have been due to the minor importance of SBs.6-9 So far, such strategies have not been compared systematically for LMCA bifurcation lesions. Randomized bifurcation trials excluded ULMCA bifurcation lesions. In addition, randomized trials dealing with bifurcation lesions were limited by high rates of crossover between initially planned and definitely performed strategy.10-11 Nonrandomized trials investigating ULMCA bifurcation intervention techniques support simpler techniques comparable to the randomized bifurcation trials.12-15 In summary, the optimal interventional strategy for ULMCA bifurcation lesions leading to the best long-term outcome is currently unclear. Giving the lack of data on the optimal interventional strategy for ULMCA bifurcation lesions and in light of the above mentioned evidence, the aim of the present study was to evaluate whether the interventional strategy during PCI of the LMCA has any influence on the clinical outcome.

terventional strategy and the interventional determinants of long-term prognosis.

Characteristics and Main Objective of the Study The goal of our observational study with retrospective analysis of interventional protocols and angiograms was to evaluate the distribution of different interventional strategies of patients undergoing PCI of ULMCA in the modern PCI era in a consecutive, daily-life, “all-comers” cohort. We additionally investigated the influence of initial clinical presentation on the in-

Methods Study population Inclusion criteria. The study population consisted of 102 consecutive patients undergoing LMCA-PCI at the University Hospital of Frankfurt, Germany. All patients were treated between March 2004 and July 2008. Indication for percutaneous revascularization was: (1) hemodynamic instability (emergency indication), (2) patient refusal of CABG, or (3) predicted high perioperative risk of CABG. A systemic review of all clinical records, interventional protocols, and interventional video documentation was performed. Exclusion criteria. We excluded patients with protected left main disease, defined as at minimum 1 intact aortocoronary bypass graft to LAD or LCx. Patients with prior LMCAPCI were also excluded. Procedures All procedural angiograms and interventions were analyzed retrospectively. We determined the angiographic parameters outlined in Table 1. The interventional strategy was primarily classified as “bifurcation involved” or “bifurcation not involved” (isolated ostial or shaft intervention), as illustrated in Figure 1. Furthermore, we divided bifurcation interventions, independently of sequence of stent implantation, into 1-stent-strategy (only main branch [MB] stented) and 2-stent-strategy (MB and SB stented). Finally, bifurcation interventions were distinguished as isolated MB stent-PCI without any SB-PCI and bifurcation interventions including SB-PCI (stent-PCI or “plain old balloon angioplasty” [POBA]). Follow-up Survival was assessed by telephone calls (to patients, relatives, physicians) and through queries to the resident’s registration office. Clinical long-term follow-up was available in 102 (100%) of the patients.

Lehmann et al. Interventional Strategy of LMCA PCI and Survival

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Table 1. Evaluation of angiogram Parameter

Specification

Left main length Branching Vessel diameter (LMCA, LAD, LCx)

Lesion location

⬍ 8 mm ⱖ 8 mm Bifurcation Trifurcation (RIM ⱖ 2.5 mm) ⬍ 2.5 mm 2.5-3.0 mm 3.0-3.5 mm 3.5-4.5 mm ⱖ 4.5 mm Ostial Shaft Distal (bifurcation) Equivalent (LAD and LCx ostium involved)

neoplastic disease). All calculations were performed first as univariable analysis and included only categorical variables. Therefore, continuous variables were dichotomized. Each factor was tested in the complete cohort, which means no patients were filtered for any analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. All parameters that reached statistical significance (P ⬍ 0.05) in the univariable Cox regression analysis were entered into the multivariable Cox regression analysis (forward selection). In addition, pairwise interactions of all tested parameters were included in this algorithm. Statistical significance was assumed at P ⬍ 0.05. SPSS for Windows 15.0 was used for statistical analysis.

LAD, left anterior descending; LCx, left circumflex; LMCA, left main coronary artery; RIM, ramus intermedius.

Results Statistical analyses

Baseline characteristics

Data are expressed as percentages for discrete variables and as median and interquartile range (IQR) for continuous variables. Continuous variables were compared by analysis of variance. Categorical comparisons were performed by chi-square analysis. Long-term overall survival of different interventional strategies was compared by Kaplan-Meier overall survival curves. The corresponding P value was obtained from the logrank test. A Cox regression analysis was conducted to identify predictors of adverse outcome (in addition to the interventional strategy, included factors were age ⬎ 75 years, severely reduced left ventricular ejection fraction, female gender, diabetes, indication for PCI [index event], presence of 3-vessel disease, number of treated lesions, total stent length per 10 mm, presence of

The baseline clinical, angiographic, and procedural characteristics of the study population were divided according to the identified relevant interventional strategy (Table 2). Angiographic assessment of lesion distribution The majority of the LMCA lesions involved the bifurcation (n ⫽ 83; 81%), with LAD mostly being classified as the MB (77%), depending on its diameter. Short LMCA (⬍ 8 mm; 34%) and trifurcation branching of LMCA (6%) were features of more-complex and risky interventions. Isolated stenoses of LAD and right circumflex ostia (LMCA equivalent) occurred in 15% of patients. Overall, the LAD ostium was involved in 48% and the LCx ostium was involved in 40% of patients.

Loca
on: isolated os
al or mid le main Single Singlestent Stent

N ==19 19 N

Loca
on: Loca
on:bifurca
on Bifurca
oninvolved involved Os
um of of LAD LAD or or LCX LCx not Os
um not involved involved

ProvisionalT-sten
ng T-stenting Provisional

83 NN==83 Os
um of of LAD LAD and and LCX LCx involved Os
um involved

N N ==64 64

Systematic T-stenting Systema
c T-sten
ng

accelera
on as needed

n = 23

N = 19

n = 20

14 NN==14

1. Side branch (to start with) 1. Side branch (to start with) 2. Main branch 2. Main branch 3. Kissing balloon encouraged 3. Kissing balloon encouraged

n = 21

V-sten
ng V stenting

N N ==55

Single Stent 2. Side branch 3.3. Sidebranch branchstent stent 1. 1. Single stent in 2. Side branch Side kissing in main branch (POBA) kissing (encouraged) main branch PCIPCI (POBA) balloonballoon (encouraged)

Figure 1. Distribution of interventional strategy. LAD, left anterior descending; LCx, left circumflex; PCI, percutaneous coronary intervention; POBA, “plain old balloon angioplasty.”

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Table 2. Baseline characteristics Single-stent bifurcation without SB-PCI, n ⫽ 23 Indication sCAD (%) ACS (%) AMI (%) Killip IV AMI (%) Age, mean (IQR) Male gender (%) LVEF At least moderate reduction (%) Severely reduced (%) SYNTAX score, mean (IQR) Diabetes (%) Tumour (%) 3-vessel disease (%) 3-vessel treated (%) No. treated lesions, mean (IQR) No. implanted stents, mean (IQR) Total stent length, mean (IQR) Complete revascularization (%) LMCA diameter ⬍ 2.5 mm (%) 2.5-3.0 mm (%) 3.0-3.5 mm (%) 3.5-4.5 mm (%) ⱖ 4.5 mm (%) LAD diameter ⬍ 2.5 mm (%) 2.5-3.0 mm (%) 3.0-3.5 mm (%) 3.5-4.5 mm (%) ⱖ 4.5 mm (%) LCx diameter ⬍ 2.5 mm (%) 2.5-3.0 mm (%) 3.0-3.5 mm (%) 3.5-4.5 mm (%) ⱖ 4.5 mm (%)

Ostium, shaft, or bifurcation with SB-PCI, n ⫽ 79

P 0.259

10 (44) 7 (30) 4 (17) 2 (9) 68 (61-79) 18 (78)

50 (63) 11 (14) 12 (15) 6 (8) 69 (61-77) 60 (76)

16 (70) 11 (48) 25 (19-33) 11 (48) 0 (0) 14 (61) 1 (4) 1 (1-2) 1 (1-2) 24 (13-38) 12 (52)

43 (54) 18 (23) 26.8 (21-34) 23 (29) 5 (6) 48 (62) 9 (11) 3 (2-3) 2 (1-3) 35 (24-56) 46 (58)

0 (0) 1 (4) 8 (35) 13 (57) 1 (4)

0 (0) 2 (3) 28 (35) 40 (51) 9 (11)

2 (9) 5 (22) 15 (65) 1 (4) 0 (0)

1 (1) 26 (33) 40 (51) 12 (15) 0 (0)

5 (22) 9 (39) 8 (35) 1 (4) 0 (0)

5 (6) 36 (46) 33 (42) 5 (6) 0 (0)

0.588 ⬎ 0.999 0.236 0.033 0.441 0.131 0.585 ⬎ 0.999 0.449 0.003 0.004 0.061 0.639 0.748

0.093

0.186

ACS, acute coronary syndrome; AMI, acute myocardial infarction; IQR, interquartile range; LAD, left anterior descending; LCx, left circumflex; LMCA, left main coronary artery; LVEF, left ventricular ejection fraction; SB-PCI, side branch percutaneous coronary intervention; sCAD, stable coronary artery disease; SYNTAX, Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery.

Interventional characteristics and treatment strategy Bare-metal stenting of the MB was performed in 4 patients. All others received drug-eluting stents (DESs; Cypher or Taxus) or circulating progenitor cell-capturing stents (Genous). Most patients (87%) received stents longer than 10 mm for the LMCA (median, 16 mm; IQR, 12-20 mm). Most commonly used balloon size in the MB was 3.5 mm (62% of cases). The stents used for the SB were shorter and smaller. Total stent length in the entire population was 32 mm (IQR, 20-52 mm). CAD involving LMCA was associated with multivessel disease in 40% of patients who received further PCI except LMCA. Most interventions (81%) were performed using a 6F guiding catheter (Medtronic Launcher). The remaining interventions were performed with 5F guiding catheters. Interventional strategy depended on lesion location (Fig. 1). Isolated stenting of the ostium or mid LMCA without bifurcation stenting was performed in 19 patients (19%). About 50% of the lesions involved ostia of proximal arteries (mostly LAD; 48%). Distal or bifurcation lesions were treated by provisional T-stenting in cases of single involved ostium (LAD or LCx). Systematic T-stenting was performed if 2 ostia of proximal coronary arteries were involved (n ⫽ 14), mostly with the

minicrush technique. V-stenting with consecutive creation of a neocarina in the LMCA was rarely used (n ⫽ 5). Final kissing balloon was performed in 37 cases (45% of bifurcation intervention). If the SB was stented, final kissing was performed in 73% of bifurcation interventions. Outcome depending on interventional strategy Long-term follow-up was available in 102 patients (100%), with a mean follow-up of 3.4 ⫾ 1.7 years (median, 3.7 years; 4.2 years for patients alive at end of follow-up; IQR, 2.5-4.7 years). Isolated ostium or shaft ULMCA-PCI (single-stent shaft or ostium) showed an excellent long-term outcome without any fatal event after hospital discharge (Fig. 2; 2 deaths occurring on day 4 and day 14 after PCI were associated to cardiogenic and septic shock, respectively). A single-stent strategy involving the bifurcation without SB intervention was associated with the less-favourable prognosis shown by continuously diverging Kaplan-Meier curves (Fig. 2; 14 events in 23 patients). All other interventional strategies in this observational study (systematic T- or V-stenting, provisional T-stenting, single-stent bifurcation POBA SB) revealed a long-term

Lehmann et al. Interventional Strategy of LMCA PCI and Survival

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Survival (%)

100

75

50

P p=0.002 = 0.002 (log-rank) (log-rank) 0

0

1

2

3

4

5

14 15 13 15 11

9 10 10 9 5

3 3 5 1 3

Years Systematic T- or V-stenting Provisional T-stenting Single-stent shaft or ostium Single-stent POBA side Single-stent bifurcation

19 21 19 20 23

19 19 17 19 16

18 18 16 16 13

Figure 2. Kaplan-Meier survival (event: all-cause mortality); patients were classified by the different interventional strategies. POBA, “plain old balloon angioplasty.”

survival comparable with that of the single-stent shaft or ostium strategy (17 events in 79 patients).

Baseline characteristics of single-stent bifurcation without SB-PCI vs the other strategies

Predictors of adverse outcome

The 2 groups were matched according to age, indication for revascularization, complexity of CAD shown by similar SYNTAX score, proportion of 3-vessel disease, and the dominant vessel of the coronary tree. Short LMCA (34%) and trifurcation branching of LMCA (6%) are features of more-complex and risky interventions. In particular, shortness of LMCA shaft usually leads to interventions involving bifurcation, even in the presence of isolated shaft or ostial lesions. DESs reduce the rate of restenosis and the need for later revascularization. The majority of patients received MB DESs to reduce the potential rate of restenosis, reflecting common clinical practice today. Nevertheless, recurrent target lesion revascularization became necessary in 8 patients (8%) during the first year. This rate of restenosis despite the use of DESs may be due to bifurcation involvement in most cases (81%). Rate of target lesion revascularization in clinical trials investigating stenting of bifurcation lesions ranges from 1.9% to 24.6% in the DES era.6-8,16-20 The majority of procedures were complex, with intervention of the SB. More than half (59%) of SBs were judged to be targets for intervention (20% POBA only). The interventional strategy was classified as bifurcation involved (which means overstenting SB) or not involved (isolated ostial or shaft intervention) according to Figure 1. Beyond plaque distribution, the decision of further SB intervention is dependent on the acute angiographic result. This means SB intervention was mainly avoided if no relevant stenosis in the SB could be detected angiographically. The classification of bifurcation lesions according distribution of plaque by angiography has known limitations. Additional diagnostic tools such as intravascular ultrasound (IVUS) or pressure wire could be helpful

The single-stent bifurcation strategy without SB-PCI was associated with a nearly 4-fold elevated risk of long-term mortality in univariable Cox regression analysis (HR 3.93; 95% CI, 1.93-8.01). Further relevant predictors of adverse outcome were severely reduced left ventricular ejection fraction (HR 2.44; 95% CI, 1.19-4.99), presence of neoplastic disease (n ⫽ 5; HR 3.66; 95% CI, 1.27-10.53), ACS (ST-segment elevation myocardial infarction and non–ST-segment elevation myocardial infarction) as indication for PCI (HR 3.20; 95% CI, 1.536.69), and diabetes (HR 2.79; 95% CI, 1.37-5.68). In contrast, factors such as age (⬎ 75 years, HR 1.33; 95% CI, 0.64-2.78), female gender (HR 1.23; 95% CI, 0.59-2.80), number of treated lesions (HR 0.84; 95% CI, 0.62-1.12), and total stent length (HR per 10 mm, 0.92; 95% CI, 0.80-1.08), as well as the presence of 3-vessel disease (HR 0.81; 95% CI, 0.39-1.66), were of no prognostic relevance in this population. In the multivariable analysis, single-stent bifurcation strategy (without SB-PCI) remained an independent predictor of long-term mortality (HR 4.08; 95% CI, 1.91-8.69; Fig. 3). In addition patients with ACS as indication for left main intervention, especially in combination with a neoplastic disease, experienced a dramatic elevation of long-term mortality (HR 5.22; 95% CI, 1.40-19.51).

Discussion Results of this prospective observational study suggest an untoward outcome related to the single-stent strategy without SB intervention in the context of ULMCA bifurcation lesions.

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HR (95% CI)

Univariable Cox regression analysis single stent bifurcation Single-stent bifurca
on

3.93 (1.93 - 8.01)

> 75 years Ageage > 75 years

1.33 (0.64 - 2.78)

female gender Female gender

1.23 (0.59 - 2.80)

Diabetes Diabetes

2.79 (1.37 - 5.68)

index event: NSTEMI / STEMI Index event: NSTEMI/STEMI

3.20 (1.53 - 6.69)

neoplastic disease Neoplas
c disease

3.66 (1.27 - 10.53) 2.44 (1.19 - 4.99)

LVEF severely reduced LVEF severely reduced of treated lesions No.No. of treated lesions

0.81 (0.39 - 1.66) 0.84 (0.62 - 1.12)

total stent lenght (per mm) Total stent length (per 1010mm)

0.99 (0.98 - 1.01)

3-vessel-disease 3-vessel disease

0.5

1

2

4

8

Multivariable Cox Cox-regression analysis(forward (forwardselec
on) selection) Mul
variable regression analysis Single-stent bifurca
on 4.08 (1.91 - 8.69)

Index event: NSTEMI/STEMI

2.37 (1.10 - 5.13)

Neoplas
c disease* index event: NSTEMI/STEMI

5.22 (1.40 - 19.51)

Figure 3. Predictors of long-term mortality (Cox regression analysis); interactions were tested pairwise in the multivariable algorithm. Squares express the HR, lines the 95% CI (red: P ⬍ 0.05; black P ⬎ 0.05). Asterisk indicates combination of neoplastic disease and acute coronary syndrome. CI, confidence interval; HR, hazard ratio; LVEF, left ventricular ejection fraction; NSTEMI, non–ST-segment elevation myocardial infarction; STEMI, ST-segment elevation myocardial infarction.

and give additional information. But IVUS was not standard during the study period in our centre. Do these results correspond to the data from controlled “bifurcation” trials? Up to now no definitive data are available to determine definitely the optimal intervention strategy of bifurcation lesions. The limitations of these trials have been discussed extensively in the literature.11 Several techniques have been evaluated for treatment of stenosis involving bifurcations. The most commonly used techniques mainly differ in the treatment strategy of the SB, ranging from simple POBA or POBA as final kiss to stent coverage (with or without final kiss). In the consensus paper of the European Bifurcation Club, final kiss was still deemed appropriate.21 But the underlying data need further confirmation by larger trials with harder endpoints.22 Nevertheless, some recently published data do not support general stent-PCI of the SB.23-26 Predictors of adverse outcome Beyond morphology and distribution of the target lesion, it is possible that interventions would be shortened because of instability or comorbidities of patients, and therefore SB interventions were avoided sometimes. But the groups we compared in this study were well matched for the majority of baseline characteristics, despite the nonrandomized study design. All baseline characteristics including discriminating factors were entered into the Cox regression analysis. The single-stent bifurcation strategy without SB-PCI was a strong predictor of

adverse outcome in our cohort. Multivariable analysis revealed this strategy as a better predictor than all other analyzed isolated parameters. Only the combination of ACS and neoplastic disease was a stronger predictor of adverse outcome. These data support and indicate the prognostic relevance of the selected interventional strategy. Underestimating the degree of stenosis in compromised SB by angiographic assessment might explain the prognostic importance of routine SB-PCI. The usage of postinterventional IVUS was not standard in the study period. Another interesting finding of the present study was the unexpected safety of drug-eluting stenting in patients with concomitant neoplastic disease, which lost its predictive value in the multivariable analysis as an isolated factor. Many interventional cardiologists avoid implantation of DESs in tumour patients because of the required prolonged dual antiplatelet therapy with clopidogrel and aspirin and the assumed elevated risk of bleeding. All of the 5 tumour patients received DESs in the LMCA. Our observational data suggest that other factors may be more important. In line with this finding, we found no fatal bleeding complication for those patients in the long-term follow-up, despite regular recommended duration of dual antiplatelet therapy for 6 to 12 months. The conclusion is certainly limited by the small patient number. Conclusions ULMCA-PCI involving the bifurcation is possible, with similar results, compared with isolated single-stent PCI of ULMCA shaft or ostium. In addition, this prospective observational study suggests that PCI of ULMCA is associated with

Lehmann et al. Interventional Strategy of LMCA PCI and Survival

higher risk regarding long-term mortality when a single-stent strategy involving the bifurcation without SB intervention is performed. SB intervention in the setting of LMCA bifurcation seems to be mandatory. Larger randomized trials including systematic technical approach are warranted to confirm this hypothesis. Limitations This was a nonrandomized, single-centre registry retrospective study with all-cause mortality as primary study endpoint. No systematic evaluation regarding cause of death (cardiac vs noncardiac death) was performed. In addition, a systematic evaluation of restenosis, occurrence of ACSs and bleedings would be desirable, but is not available because of the retrospective registry design of this study. But long-term follow-up as performed in this study, with survival as primary end point, includes several potential fatal risks of left main interventions: stent thrombosis including very late forms, left main restenosis with expected high rate of ACSs, and bleeding due to necessity of prolonged dual antiplatelet therapy. The study has all the limitations of a prospective registry without random assignment of patients to different treatment strategies. Today’s recommended advanced techniques of bifurcation treatment, namely, the provisional T-stenting and small protrusion technique and the proximal optimization technique, were not performed or evaluated systematically. The study involved a relatively small number of patients in each interventional group. Despite the study’s limitations, a survival difference was observed. The statistical model of the Cox regression analysis with 5 tested isolated parameters in the multivariable algorithm and 31 events is likely overfitted. This, plus the fact that these analyses have not been independently validated, justifies caution when one is interpreting our results, which are hypothesis generating rather than conclusive. Although patients were well matched regarding baseline characteristics, we cannot exclude that the choice of the PCI technique could have been influenced by hemodynamic conditions of the patients, occasionally demanding easier and quicker treatment. Consequences for our practice The consequences of these data and recently published trials and recommendations regarding the interventional strategy in our centre can be summarized as follows: all ULMCA-PCIs are now done under IVUS guidance for optimal stent choice; SB intervention with final kiss is mandatory; and final control by IVUS including SB is recommended to all operators in order to exclude inappropriate SB-PCI. The provisional T-stenting and small protrusion technique and the proximal optimization technique are the favoured strategies according to respective guidelines. Disclosures The authors state that there are no conflicts of interest. References 1. Eagle KA, Guyton RA, Davidoff R, et al. ACC/AHA guidelines for coronary artery bypass graft surgery: executive summary and recommendations: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to revise the

559 1991 guidelines for coronary artery bypass graft surgery). Circulation 1999;100:1464-80. 2. Lee MS, Kapoor N, Jamal F, et al. Comparison of coronary artery bypass surgery with percutaneous coronary intervention with drug-eluting stents for unprotected left main coronary artery disease. J Am Coll Cardiol 2006; 47:864-70. 3. Serruys PW, Morice MC, Kappetein AP, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med 2009;360:961-72. 4. Zhao C, Wang X, Wu X, Cui L. Early and long-term outcomes after percutaneous coronary intervention of unprotected left main coronary disease with drug-eluting stents in patients with non-ST-elevation acute coronary syndrome. Can J Cardiol 2011;27:743-8. 5. Park S-J, Kim Y-H. Percutaneous intervention for left main coronary artery stenosis. In EJ Topol, ed. Textbook of Interventional Cardiology. Philadelphia, PA: Saunders Elsevier, 2008:393-416. 6. Colombo A, Moses JW, Morice MC, et al. Randomized study to evaluate sirolimus-eluting stents implanted at coronary bifurcation lesions. Circulation 2004;109:1244-9. 7. Pan M, de Lezo JS, Medina A, et al. Rapamycin-eluting stents for the treatment of bifurcated coronary lesions: a randomized comparison of a simple versus complex strategy. Am Heart J 2004;148:857-64. 8. Steigen TK, Maeng M, Wiseth R, et al. Randomized study on simple versus complex stenting of coronary artery bifurcation lesions: the Nordic bifurcation study. Circulation 2006;114:1955-61. 9. Tsuchida K, Colombo A, Lefèvre T, et al. The clinical outcome of percutaneous treatment of bifurcation lesions in multivessel coronary artery disease with the sirolimus-eluting stent: insights from the Arterial Revascularization Therapies Study part II (ARTS II). Eur Heart J 2007;28: 433-42. 10. Moussa ID. Coronary artery bifurcation interventions: the disconnect between randomized clinical trials and patient centered decision-making. Catheter Cardiovasc Interv 2011;77:537-45. 11. Movahed MR. Major limitations of randomized clinical trials involving coronary artery bifurcation interventions: time for redesigning clinical trials by involving only true bifurcation lesions and using appropriate bifurcation classification. J Interv Cardiol 2011;24:295-301. 12. Kim WJ, Kim YH, Park DW, et al. Comparison of single- versus two-stent techniques in treatment of unprotected left main coronary bifurcation disease. Catheter Cardiovasc Interv 2011;77:775-82. 13. Kim YH, Park SW, Hong MK, et al. Comparison of simple and complex stenting techniques in the treatment of unprotected left main coronary artery bifurcation stenosis. Am J Cardiol 2006;97:1597-601. 14. Palmerini T, Marzocchi A, Tamburino C, et al. Impact of bifurcation technique on 2-year clinical outcomes in 773 patients with distal unprotected left main coronary artery stenosis treated with drug-eluting stents. Circ Cardiovasc Interv 2008;1:185-92. 15. Palmerini T, Sangiorgi D, Marzocchi A, et al. Ostial and midshaft lesions vs. bifurcation lesions in 1111 patients with unprotected left main coronary artery stenosis treated with drug-eluting stents: results of the survey from the Italian Society of Invasive Cardiology. Eur Heart J 2009;30: 2087-94. 16. Ge L, Airoldi F, Iakovou I, et al. Clinical and angiographic outcome after implantation of drug-eluting stents in bifurcation lesions with the crush stent technique: importance of final kissing balloon post-dilation. J Am Coll Cardiol 2005;46:613-20.

560 17. Ge L, Tsagalou E, Iakovou I, et al. In-hospital and nine-month outcome of treatment of coronary bifurcational lesions with sirolimus-eluting stent. Am J Cardiol 2005;95:757-60. 18. Hoye A, Iakovou I, Ge L, et al. Long-term outcomes after stenting of bifurcation lesions with the “crush” technique: predictors of an adverse outcome. J Am Coll Cardiol 2006;47:1949-58. 19. Moussa I, Costa RA, Leon MB, et al. A prospective registry to evaluate sirolimus-eluting stents implanted at coronary bifurcation lesions using the “crush technique.” Am J Cardiol 2006;97:1317-21. 20. Sianos G, Vaina S, Hoye A, Serruys PW. Bifurcation stenting with drug eluting stents: illustration of the crush technique. Catheter Cardiovasc Interv 2006;67:839-45.

Canadian Journal of Cardiology Volume 28 2012 treated with main vessel stenting: the Nordic-Baltic Bifurcation Study III. Circulation 2011;123:79-86. 23. Behan MW, Holm NR, Curzen NP, et al. Simple or complex stenting for bifurcation coronary lesions: a patient-level pooled-analysis of the Nordic Bifurcation Study and the British Bifurcation Coronary Study. Circ Cardiovasc Interv 2011;4:57-64. 24. Hildick-Smith D, de Belder AJ, Cooter N, et al. Randomized trial of simple versus complex drug-eluting stenting for bifurcation lesions: the British Bifurcation Coronary Study: old, new, and evolving strategies. Circulation 2010;121:1235-43.

21. Hildick-Smith D, Lassen JF, Albiero R, et al.; European Bifurcation Club. Consensus from the 5th European Bifurcation Club meeting. EuroIntervention 2010;6:34-8.

25. Colombo A, Bramucci E, Saccà S, et al. Randomized study of the crush technique versus provisional side-branch stenting in true coronary bifurcations: the CACTUS (Coronary Bifurcations: Application of the Crushing Technique Using Sirolimus-Eluting Stents) study. Circulation 2009; 119:71-8.

22. Niemelä M, Kervinen K, Erglis A, et al.; Nordic-Baltic PCI Study Group. Randomized comparison of final kissing balloon dilatation versus no final kissing balloon dilatation in patients with coronary bifurcation lesions

26. Ferenc M, Gick M, Kienzle RP, et al. Randomized trial on routine vs. provisional T-stenting in the treatment of de novo coronary bifurcation lesions. Eur Heart J 2008;29:2859-67.