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 [2,8-10]. 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) . In this meta-analysis, the entire population was in the 60th 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, 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 . 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 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 . 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 . 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 . 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 . On the other hand, a lower lesion complexity often offers the use of shorter and larger stents, which are associated with better outcomes .
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 . Up to date, the optimal choice for follow up these patients is still largely debated. While angiographic restenosis has been linked to mortality , angiographic control was associated with higher rates of revascularization without affecting mortality . Consequently, routine angiographic follow-up for LMD is actually not recommended by guidelines . However, high risk patients need close clinical follow-up after PCI, as they may have a higher need for repeat revascularization. Nowadays, the recommendation of angiographic follow-up after PCI is based on patient-associated factors, lesion-specific characteristics and procedural variables. Distal LM lesion segments nearest to the bifurcation showed the highest values for late lumen loss in our trial. It has been shown that angiographic LLL seems to correlate with the occurrence of important clinical events such as binary restenosis and TLR [24-26]. Especially LLL in segment 11 was an independent predictor for the occurrence of MACE in distal LM lesions in our study. Hence, our findings may simplify the indication of angiographic follow-up in future, but further investigations are necessary.
The multivariate analysis resulted in findings that besides late lumen loss for segment 11, diabetes mellitus is a predictor of MACE. This is not surprising, as cardiovascular risk factors, especially diabetes mellitus, are generally considered as markers of poorer prognosis even in non-PCI populations. A more diffuse and accelerated form of atherosclerosis, accompanied by small vessels size, long lesions and greater plaque burden are well documented in these patients .