One-year clinical and angiographic outcomes after percutaneous coronary interventions in ostial versus distal left main lesions – a retrospective single center study

Background: Percutaneous coronary intervention (PCI) of left main coronary artery disease (LMD) is associated with appropriate clinical and angiographic outcomes, resulting in a class I recommendation in patients with less complex coronary anatomy. Due to higher SYNTAX scores and worse clinical outcomes, PCI in distal LMD is accomplished with a lower strength of recommendations for revascularization compared to ostial LM lesions. We compare angiographic and clinical outcomes of ostial/midshaft lesions versus distal lesion in LMD after PCI. Methods: This retrospective study included 176 patients with LMD undergoing PCI with drug-eluting stents. The study population was divided into 34 patients with ostial/midshaft LMD and 142 patients with distal LMD. Patients were routinely scheduled for 9 months of angiographic and 12 months of clinical follow-up. Quantitative coronary analysis (QCA) was performed for all lesions, using an 11-segment model. Primary outcome was MACE (major adverse cardiac events) defined as a composite of cardiac death, myocardial infarction and target lesion revascularization (TLR). Results: The primary outcome measure was comparable in both cohorts after 12 months follow-up (20.6% in ostial/midshaft LMD vs. 17.6% in distal LMD, P=0.71). As expected, TLR rates were increased in distal LM lesions compared to ostial LM lesions, but without reaching statistical significance (14.1% vs. 5.9%, P=0.15). Late lumen loss (LLL) in ostial/midshaft LMD was 0.42±0.33mm. In distal LM lesions value for LLL in the main vessel was 0.42±0.97 mm, with the highest values observed in segments adjacent to the bifurcation (0.37±1.13mm and 0.37±0.73 mm). On cox proportional regression analysis LLL in a bifurcation segment (P=0.03, HR 1.68 1.1-2.7) and diabetes mellitus (P=0.046, HR 2.77 1.0-7.5 were independent correlates for occurrence of MACE. Conclusion: PCI of distal LM to ostial lesions up to 12 months follow-up. In distal LM lesions segments nearest to the bifurcation show the highest for late lumen loss and binary restenosis. Presence of diabetes mellitus as well as


Background
Coronary artery bypass graft surgery (CABG) has been the standard of care for treatment of left main coronary artery disease (LMD) for nearly 40 years [1]. Nowadays, percutaneous coronary intervention (PCI) of LMD, using drug-eluting stents (DES), is associated with appropriate clinical results for the 4 safety composite of death, myocardial infarction (MI) and stroke at long-term follow-up [1,2]. Therefore, recent guidelines indicate that PCI is a suitable alternative to CABG in LMD with less complex coronary anatomy, resulting in a class I level A recommendation for patients with low SYNTAX score (0-22) and a class IIa level A recommendation for patients with intermediate SYNTAX score (23-32) [3].
The left main coronary artery can be divided into three segments: ostial, midshaft, and distal bifurcations. Due to the anatomical complexity, distal LM lesions result in higher SYNTAX scores than ostial and midshaft LM lesions and consequently in lower levels of evidence for revascularization with PCI [3]. Previous studies have reported that PCI of lesions not involving the distal LM has better outcomes than PCI of distal LM lesions, largely because of a lower need for repeat revascularization [4]. However, limited data are available regarding angiographic outcomes after PCI with DES implantation at different LM segments.
The aim of the present study was to compare angiographic and clinical outcomes in ostial/midshaft and distal lesions in left main coronary artery disease after percutaneous coronary intervention. and 2014, were retrospectively included in the present study. Based on lesion location, the population was divided into two groups: the group with an ostial or midshaft LMD and the group with a distal LMD. Pre-procedural parameters, procedural data and post-procedural clinical and angiographic outcomes were evaluated for both groups. All patients gave written informed consent and were clinically followed up for at least one year after intervention. The study was approved by the local ethics committee and has been performed in accordance with the ethical standards laid down in the Declaration of Helsinki.
Treatment strategy was to cover the stenotic segment with one or more stents. High-pressure implantation with at least 14 atm was mandatory to ensure a proper alignment of stent struts at the vessel wall and to avoid any residual stenosis. Dual antiplatelet therapy was prescribed for at least 12 5 months. Patients were routinely scheduled for 9 months angiographic follow-up. Furthermore, 12 months clinical follow-up was completed for all patients in outpatient visits or phone calls. Primary point of interest was the occurrence of major adverse cardiac events (MACE), defined as the composite of cardiac death, any myocardial infarction and target lesion revascularization (TLR).
Definite stent thrombosis was defined according to the ARC criteria [5]. Quantitative coronary angiography analysis (QCA) of the index procedure and the angiographic follow-up were performed with the current Cardiovascular Angiography Analysis System (CAAS 11.7, Pie Medical Imaging, Maastricht, The Netherlands), using the conventional single-vessel mode for ostial/midshaft lesions and the dedicated bifurcation algorithm for distal bifurcation lesions of the left main coronary artery [6]. Minimal lumen diameter (MLD) was measured in multiple projections, recording the results from the worst view. Late lumen loss (LLL) was defined as the difference between MLD post PCI and MLD at angiographic follow-up. LM bifurcation lesions were assessed according to the Medina classification [7].

Statistical analysis
Categorical parameters are presented as counts and percentages. Comparisons of proportions were carried out using the χ 2 -test. Continuous variables are presented as mean ± one standard deviation.
Continuous variables for two groups were compared with the unpaired U-test. Time-to-event analyses for one-year follow-up were performed using Kaplan-Meier estimates and were compared with the logrank test. Kaplan-Meier survival curves were generated for time-to-event outcomes.
Multivariate Cox proportional-hazards regression (full-model) analysis was performed for probable influential variables (P<0.20) of univariate analysis. A two-sided P-value < 0.05 was considered to indicate statistical significance. All statistical analyses were performed using the Statistica software
Lesion characteristics and procedural data are displayed in Table 2. Ostial/midshaft LM lesions were predominantly treated with a single stent strategy (stents per lesion: 1.0±0.2). Medina classifications of distal LM lesions are also shown in Table 2 Table 3.
Angiographic follow-up rate was 48.3% and comparable for both groups (ostial and distal lesions).
On Cox proportional regression analysis late lumen loss for segment 11 (P=0.03, hazard ratio 1.68, confidence interval 1.1 to 2.7) and diabetes mellitus (P=0.046, hazard ratio 2.77, confidence interval 1.0 to 7.5) were independent correlates for occurrence of MACE during 12 months follow-up.

Discussion
The main findings of the present study can be summarized as follows: PCI of both ostial/midshaft and distal LM lesions show acceptable and comparable angiographic and clinical results up to 12 months follow-up. Distal LM lesions led to numerically but not to significantly higher rates of repeat revascularization compared to ostial/midshaft lesions with highest values for late lumen loss and binary restenosis occurring in segments nearest to the bifurcation. Surprisingly, patients suffering from ostial/midshaft LM lesions had a four times increased rate of cardiac mortality as compared to patients with distal LM lesions. Finally, in distal LMD presence of diabetes mellitus as well as late lumen loss in a segment adjacent to the bifurcation were independent correlates for occurrence of MACE after PCI during 12 months follow-up.
Due to significant advances in device technology, increased operators´ expertise, and availability of improved antithrombotic therapy, PCI in left main coronary artery disease has emerged as a valid alternative technique to operative coronary artery bypass grafting [2,[8][9][10]. Current European and American guidelines recommend both CABG and PCI for treatment of LMD with overall less complex anatomy [3,11]. This is strengthened by encouraging recent data, showing equivalent results in terms of 'hard' endpoints such as incidence of myocardial infarction, stroke, or cardiac and all-cause mortality at long-term follow-up. Early safety advantages of PCI are subsequently offset by higher rates of repeat revascularizations [1,2,12,13].
In a recent meta-analysis of 6 randomized trials, including 4.717 patients with LMD, one year results revealed rates for all cause death of 5.4%, myocardial infarction of 3.4% and repeat revascularization (TVR) of 8.7% in the PCI group (compared to 6.6%, 4.3% and 4.5% in the CABG group) [14]. In this meta-analysis, the entire population was in the 60 th decade with a rather lower SYNTAX score in most of the included trials (for example in the EXEL and NOBLE trial SYNTAX score was 20 and 22, 8 respectively). In contrast to the mentioned analysis, we enrolled patients with a higher clinical risk profile. Patients in our study were older (mean age 72.3 years) and had a higher SYNTAX score with a mean of 28. In addition, mean EuroSCORE was 6.4 in the total cohort, 39.8% of patients had moderate to severe impairment of the left ventricular ejection fraction and 45.5% of patients were treated because of acute coronary syndrome. Especially due to these differences in baseline characteristics a comparison of the results with those of other trials is difficult. In our study 5.5% of patients died, rates of myocardial infarction and TLR were 6.8% and 12.5%, respectively.
Nevertheless, the results from our study are comparable to those of previous trials and registries, considering an older population with poorer health status, which represent real-world conditions. These results are encouraging and confirm PCI in LMD as a safe and durable alternative revascularization option to operative revascularization treatment.
Comparing the results between ostial and distal left main lesions, we observed comparable MACE rates in both groups up to 12 months follow-up. However, in detail we detected a four times higher death rate in the ostial LM group (12.2% vs. 2.9%, P=0.03), whereas TLR rates were rather the other way round, but without reaching significance (5.9% vs. 14.1%, P=0.15). The largest study that addressed this issue was the analysis from the DELTA registry (Drug-Eluting Stent for Left Main Coronary Artery Disease), including 1.612 patients with LMD [4]. In this multicenter registry 482 patients with ostial LM lesions were compared to 1.130 patients with distal LM lesions for a median follow-up of 1.250 days. Again, the study population was younger than ours with an average age of 65.7 years, EuroSCORE and SYNTAX score were comparable to our study population. This trial demonstrated that PCI for ostial/midshaft lesions was associated with better clinical outcomes at long term follow-up than for distal lesions in LMD, largely because of a lower need for repeat revascularization. Noteworthy, no significant differences were observed in terms of all-cause death and the composite endpoint of all-cause death and MI. The trial confirmed the results of previous studies, reporting better outcomes of PCI for lesions not involving the distal LM [15,16]. These findings don´t completely correspond to our results. Although baseline characteristics were equally distributed in both groups, death rates in ostial LMD were four times higher than in distal LMD. In 9 detail four cardiac deaths occurred in both groups. One death in the ostial LM group occurred as a result of a target lesion non-ST-elevating myocardial infarction after 239 days. One patient died in the distal LM group because of a target lesion ST-elevating myocardial infarction after 244 days follow-up.
The other 6 patients died due to decompensated heart failure without evidence for restenosis. In the end, these results might be a finding by chance and should not be overrated, but at least they disprove a tremendous clinical advantage for ostial lesions.
Altogether, our results are in line with the recommendations of recent guidelines on myocardial revascularization in LMD [3]. According to this, PCI has a class I level A recommendation for LMD with low SYNTAX score (0-22) and a class IIa level A recommendation for LMD with intermediate SYNTAX score (23-32). For patients with LMD and high anatomical complexity (SYNTAX score > 32) valid data are scarce due to the low number of patients studied in randomized controlled trials caused by exclusion criteria. Previous trials suggested a slightly trend towards better survival with CABG for this group [17]. Therefore, PCI in this setting cannot be endorsed in general by guidelines, as reflected by a class III level B recommendation. Due to the anatomical complexity, distal LM lesions result in higher SYNTAX scores than ostial and midshaft LM lesions and consequently in lower levels of evidence for revascularization with PCI. Our findings can possibly strengthen the role of PCI in distal LM lesions in the future, but further investigations are necessary.
In the present analysis revascularization rates were statistically not different in distal LM lesions as compared to ostial/midshaft LM lesions. According to this, the quantitative coronary analysis (QCA) revealed a comparable late lumen loss for ostial and distal LM lesions (0.42±0.33 mm and 0.42±0.97 mm in the main vessel, respectively). A trend toward higher rates of binary restenosis after PCI of distal LM lesions was already suggested in former analyses [4]. In our study, distal LM lesion segments nearest to the bifurcation showed the highest values for late lumen loss with highest values in segment 7 (0.37±1.13) and 11 (0.37± 0.73). This may be explained by involving the left anterior descending and left circumflex coronary arteries in case of distal LMD, being technically more challenging and associated with increased intra-and post-procedural complications [16,18].
Moreover, the development of atherosclerosis in the left main coronary artery has been linked to flow hemodynamics, with atherosclerotic plaques described at areas of low endothelial shear stress in the lateral wall of the bifurcation, opposite of the carina [19]. On the other hand, a lower lesion complexity often offers the use of shorter and larger stents, which are associated with better outcomes [4].
D'Ascenzo and colleagues revealed in a propensity score matched analysis with 440 patients that a planned angiographic follow-up after PCI of LMD results in more TLR, but may reduce mortality [20].
Up to date, the optimal choice for follow up these patients is still largely debated. While angiographic restenosis has been linked to mortality [21], angiographic control was associated with higher rates of revascularization without affecting mortality [22]. Consequently, routine angiographic follow-up for

Limitations
The present study is not a randomized trial. Nevertheless, the work reflects conditions and clinical outcomes from a real-world setting. We did not include intravascular imaging or optical coherence tomography at follow-up to measure neointimal proliferation. Lastly, angiographic follow-up rate was only 48.3%.

Consent for publication
Not applicable.

Availability of data and materials
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests
The authors declare that they have no competing interests.

Funding
No funding to declare.   --Data are presented as mean ± SD or n (%). LMD = Left main disease.