Introduction

Percutaneous coronary intervention (PCI) in left main coronary artery (LM) disease is widely used worldwide with documented favorable results in large studies. However, the impact of left circumflex coronary artery (LCx) ostium atherosclerosis in LM bifurcation disease is not well-known. Evidence from computed tomography angiography and fractional flow reserve (FFR) shows that the side branch supplies a smaller portion of the myocardium compared to the main branch and that a stenosis in the side branch is less likely to result in significant ischemia compared to a similar stenosis in the main artery [1]. Nevertheless, side branch occlusion is one of the most significant potential complications after LM stenting and may be a major reason why operators choose the two-stent technique [2]. Significant ostium stenosis of the side branch has also been reported to be a frequent source of side branch occlusion after stent implantation in the main vessel [3]. The European Bifurcation Club advocates use of the “jailing wire” technique which involves leaving a wire in the side branch while a stent is implanted in the main branch [4]. The study based on a small group showed that the patients with higher FFR in the jailed LCX had better long-term results than those with low FFR [5]. In terms of the one-stent technique in LM PCI, two mechanisms of acute luminal loss at the ostium of the left circumflex coronary artery have been suggested, i.e. carina shift and plaque shift [6–8]. Angioplasty in the area of huge atherosclerotic plaque around the bifurcation often results in plaque burden shifting to the coronary branch, sometimes causing subsequent occlusion [9]. However, recent articles demonstrated that the carina shift was the principal mechanism of ostial LCX lumen loss during LM PCI [10]. In the study performed by Kang et al., carina shift was associated with a narrow distal angle between the LAD and the LCX and a wide proximal angle between the LCX and the LM [10].

In this study, we aimed to assess whether the involvement of LCX ostium carries prognostic implications in patients undergoing unprotected LM PCI.

Methods

Our study is part of a larger project concerning LM disease [11–13]. Currently, we analyzed all 564 patients with unprotected LM (ULMCA) disease PCI and with at least 1 year of available follow-up. Patients with significant LM stenosis (≥50% diameter) were prospectively enrolled in the study between January 2015 and February 2021 [14]. An ostial LCX lesion was defined as a lesion with at least 50% diameter stenosis by visual assessment and within 3 mm of the left main stem. Patients were divided into two groups: the first group was composed of 145 patients with unprotected LM disease with LCX ostium stenosis and the second group consisted of 419 patients with unprotected LM disease without LCX ostium stenosis. Established primary outcomes were in-hospital death, in-hospital myocardial infarction (MI), and long-term all-cause death (median [interquartile range (IQR)] follow-up was 1411 (IQR, 908 [max 2553] days). Survival analysis data were gathered by telephone contact or with the use of National Health Fund information. IVUS or OCT imaging were used in 202 (35.8%) patients and were not analyzed in great detail. The antiplatelet regimens were low-dose aspirin (75 mg daily) and clopidogrel (75 mg daily) for a minimum of 6 months after PCI, with the intention of 12 months of dual antiplatelet therapy. In patients without contraindications, a switch to ticagrelor or prasugrel was allowed.

Statistical analysis

All continuous variables were presented as medians (interquartile range [IQR]). Categorical variables were presented as numbers and percentages and were compared using the test for proportions or Fisher’s exact test. The normality of the distribution of variables was assessed using the Shapiro-Wilk test. Differences between continuous variables were evaluated with a nonparametric Mann-Whitney test. The survival probability at follow-up was calculated using the Kaplan-Meier method. Log-rank tests were used to compare survival between different groups. P-values below 0.05 were considered significant. We used STATISTICA 13.7 (StatSoft, Inc., Tulsa, OK, US).

Results

Patients in the group with ULMCA disease with LCX ostium stenosis were older (median [IQR], 69.0 [65.0–79.0] years vs. 68.0 [62.0–74.0] years; P = 0.002) (Table 1).

In this group, comorbidities such as chronic kidney disease (44.8% vs. 28.6%; P <0.001), diabetes (46.9% vs. 36.8%; P = 0.03), and previous stroke (13.1% vs. 7.9%; P = 0.06) were found more often. Naturally, the SYNTAX score was higher in the group with LCX ostium stenosis (28.0 [22.25–34.0] vs. 21 [14.0–28.0]; P <0.001), also LM calcifications were found more often in this group (19.3% vs. 11.5%; P = 0.02). The number of implanted stents (2.0 [2.0–3.0] vs. 1.0 [1.0–2.0]; P < 0.001), total stent length (46.0 [36.0–64.0] vs. 33.0 [22.0–50.0]; P <0.001), radiation time (19.5 [14.0–26.0] vs. 15.0 [11.0–21.0]; P <0.001), and radiation dose (1436.5 [969–2151] vs. 1120.5 [706.5–1722.5]; P <0.001) were higher in patients with LCX ostium lesions (Table 2).

The two-stent technique was used more often in the group with LCX ostium stenosis (62.8% vs. 14.6%; P <0.001). The trend toward more frequent use of crush techniques was observed in the group with LCX ostium involvement. Provisional stenting was performed more often in the group without LCX ostial disease. There were no differences between two study groups in terms of periprocedural complications, periprocedural mortality, and myocardial infarction type 4a. Median patient (IQR) follow-up was 1411 (908–2553) days. At 7-year follow-up, all-cause mortality between groups with and without LCX ostium stenosis did not differ (P = 0.50) (Figure 1).

Figure 1. Kaplan-Meier analysis of all-cause mortality: patients with unprotected LM disease with LCx ostium stenosis vs. patients with unprotected LM disease without LCx ostium stenosis

Abbreviations: see Table 1

There was no difference in long-term all-cause mortality in patients with LCX ostial lesions who underwent procedures with either one-stent or two-stent technique (P = 0.75) (Figure 2).

Figure 2. Kaplan-Meier analysis of all-cause mortality: one-stent vs. two-stent technique in patients with unprotected LM disease with LCx ostium stenosis

Abbreviations: see Table 1

In our cohort, there were some patients without significant LCX ostium disease who underwent LCX stenting during LM PCI (13.4% of patients from the group without LCX ostium involvement) because of the plaque

burden shift or carina shift; long-term results of these patients were satisfactory (Figure 3).

Figure 3. Kaplan-Meier analysis of all-cause mortality: patients without LCx ostium disease with LCx ostium stenting during LM PCI

Abbreviations: see Table 1

Subanalysis for three groups of patients: (1) patients with LM plus LCX ostium stenosis, (2) LM plus LAD ostium stenosis, (3) LM plus LCX ostium plus LAD ostium stenosis was performed. Long-term mortality rates also did not differ in these groups (P = 0.63) (Figure 4).

Figure 4. Kaplan-Meier analysis of all-cause mortality: LM + LCx ostium stenosis vs. LM + LAD ostium stenosis vs. LM + LCx ostium + LAD ostium stenosis

Abbreviations: see Table 1

Discussion

The choice of stenting strategy in LM PCI is generally determined by the stenosis at the LCX ostium, atherosclerotic lesion length, and/or difficult coronary artery side branch access. These situations generally require initial use of two-stent strategies. Bailout stenting of a diseased coronary side branch can often be more demanding than opting for an up-front two-stent strategy. In other LM bifurcation cases, a provisional stenting strategy is usually chosen [15]. In the study performed by Park et al. [16], a group of patients with true bifurcation lesions had a significantly higher risk of major adverse cardiovascular events than those with non-true bifurcations (HR, 1.39; 95% CI, 1.08–1.80; P = 0.01); however, this study was not performed only on the LM disease population. Moreover, patients with Medina 1-0-1 had a lower risk of cardiac death and MI than other patients with true bifurcation lesions [16]. Nevertheless, the LCX is not always last in the order of numbers in the Medina classification. In subanalysis from the EXCEL trial in 524 patients, both LM major side branches i.e. the LAD and LCX had ostial diameter stenosis ≥50% in 34.7% of cases [17]. In patients who underwent provisional stenting, a bailout stent was implanted in 28.6% of those with and 12.1% without both side branches ostium stenoses (P = 0.0005) [17]. Bailout stenting was performed in 1 in 6 cases in EXCEL, although it was needed more often when the major coronary side branch, usually the LCX, had ostium stenosis. In EXCEL, all-cause mortality rates were insignificantly lower in the group with LM bifurcation without involvement of both side branches ostia treated with the provisional approach vs. planned two-stent technique (6.1% vs. 13.0%; hazard ratio [HR], 0.46; 95% CI, 0.21–1.01). However, one- and two-stent techniques in LM disease, where both ostial coronary side branches were affected, resulted in comparable mortality rates [17]. In the EBC MAIN study, patients with true bifurcation of left main stem lesions who underwent PCI using the stepwise layered provisional method had fewer major cardiac incidents compared to planned dual stenting, although the difference was not statistically significant [18]. Therefore, the stepwise provisional approach should continue to be the preferred option for intervention in bifurcation of the distal left main stem [18].

Study limitations

One limitation of our study was the absence of a surgical group for comparison. Nevertheless, examining such a group alongside the coronary artery bypass grafting (CABG) group was not within the study’s intended scope. Additionally, while the study was based on a prospective registry, not all clinical data were accessible. Thirdly, the follow-up did not include analysis of the antiplatelet regimen or duration of dual antiplatelet therapy (DAPT) after discharge. Lastly, intravascular imaging (IVUS or OCT) were not analyzed in great detail.

Conclusions

In this study, we evaluated whether the involvement of LCX ostium significantly influences the results in real-world patients undergoing unprotected LM PCI. As far as we know, this is the first study to assess this issue broadly. The main finding of the study is that the LCX ostium involvement in LM disease PCI is not associated with increased long-term mortality, which is highly beneficial for the Heart Team’s decision-making process. Moreover, in patients with LM disease and LCX ostium stenosis, there was no significant difference in long-term mortality between groups operated on using one-stent or two-stent techniques. Also, there were no significant differences in long-term mortality regardless of coexisting LCX ostium or LAD ostium lesions. An interesting subgroup of patients without significant LCX ostium disease who underwent LCX stenting during LM PCI, because of the plaque burden shift or carina shift, also presented good long-term outcomes.

Article information

Acknowledgments: The abstract was published in the Journal of the American College of Cardiology abstracts book: https://doi.org/10.1016/j.jacc.2022.08.175

Conflict of interest: None declared.

Funding: None.

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