Drug-Eluting Stent Implantation in Coronary Trifurcation Lesions

Lesions at coronary divisions, either bifurcation or trifurcation, represent a challenging area in interventional cardiology. Indeed, it has been shown that percutaneous coronary intervention (PCI) in this anatomical setting using bare-metal stents (BMS) has a poor rate of procedural success and a high rate of restenosis.^1–3 More recently, the use of drug-eluting stents (DES), either sirolimus-eluting stents (SES) (Cypher™, Cordis Corp., Miami, Florida) or paclitaxel-eluting stents (PES) (Taxus^®, Boston Scientific Corp., Natick, Massachusetts), is associated with a lower event rate and reduction in restenosis compared with historical controls in this complex lesion subset.^4–7
Technically, for trifurcation lesions, simultaneous triple-balloon angioplasty has been previously utilized with good immediate angiographic success.^8,9 More recently, El-Jack et al reported 2 cases of coronary trifurcation lesions treated with PES with initial angiographic success.¹⁰ However, no specific study is available on acute and mid-term outcomes of treatment of trifurcation lesions with either BMS or DES. In this study, we report our experience with DES implantation in coronary trifurcation lesions.

Methods

Study population. From April 2002 to April 2006, a consecutive series of patients with de novo trifurcation lesions was retrospectively identified from our database. Anatomically, coronary trifurcation was defined as a close origin of 2 side branches (SB) from the main branch (MB), identified as the distance of both the SB take-off <3 mm and a branch size of at least 2.25 mm at baseline angiography or after predilatation (by visual estimation). A trifurcation lesion was defined as a diameter stenosis >50% within 5 mm to the carina involving the MB, associated or not with disease in either one or both SBs. In addition, the analysis included any trifurcation lesion for which branch protection with wiring in each of 3 branches was necessary, irrespective of the diameter stenosis. The MB was defined as the bigger branch with the largest perfusion territory. Between 2 SBs, the one with a narrower angle from the distal MB was defined as “SB1” (i.e., for the left main coronary artery [LMCA] trifurcation, the LMCA-left anterior descending artery [LAD] is the MB, the intermediate branch [IM] is “SB1”, and the left circumflex artery [LCX] is “SB2”). To better describe the lesion distribution, we modified the Medina classification of bifurcation lesions to render it suitable for trifurcations, adding information regarding “SB2” (Figure 1).¹¹ A binary value of 1 or 0 was given in case of either presence or absence of a stenosis >50% in each branch, according to the following sequence: proximal MB, distal MB, “SB1” and “SB2”. Patients with a myocardial infarction (MI) within the last 24 hours were excluded from the analysis.
Procedure. The operator’s judgement determined the strategy of trifurcation stenting and the use of final kissing balloon inflation (FKB). The operator decided, based on vessel anatomy, to implant either 3 stents, 2 stents or 1 stent, and to perform provisional SB stenting. The decision to use multiple stenting was based on the fact that the SB was significantly narrowed at the ostium or within a few millimeters of it and/or if significant plaque shift was expected. Either crush, culotte, V-stenting or T-stenting were utilized, as previously described.^12,13 When stenting all 3 branches, the “double-crush” technique or the “modified-V” technique were used.
-crush” technique description. Briefly, after coronary selective engagement with a 9 Fr guiding catheter and lesion preparation, 3 stents are commonly placed in the MB and 2 SBs. The stent to be positioned in the most distal SB is deployed first and then its balloon and wire are removed. The stent in the other SB is subsequently deployed (first “crush”) and its balloon and wire are then removed. Finally, the stent in the MB is deployed, flattening the protruding struts of the SB (second “crush”). At this point, FKB can be performed utilizing 3 balloons simultaneously. “Modified-V” technique description. After selective cannulation of a 9 Fr guiding catheter and lesion preparation, proximal markers of 3 stents are positioned together with a slight protrusion in the MB in order to create a proximal carina. Each stent is separately deployed and FKB is performed using 3 balloons.
All patients were pretreated with aspirin and either ticlopidine or clopidogrel. A minimum of 300 mg loading dose of clopidogrel was administered before the procedure if patients were not pretreated. During interventions, patients received intravenous unfractionated heparin (100 IU/kg) to maintain an activated clotting time between 250–300 seconds. Administration of glycoprotein IIb/IIIa inhibitors was left to the operator’s discretion. Double antiplatelet therapy with aspirin and a thienopyridine (ticlopidine 250 mg twice daily or clopidogrel 75 mg/day) was continued for at least 6 months after DES implantation.
The decision to perform PCI in unprotected LMCA lesions instead of coronary bypass graft surgery (CABG) was taken when one of the following two conditions was present: (1) suitable anatomy for stenting and patient and referring physician preference for a percutaneous approach; or (2) suitable anatomy for stenting and contraindication for CABG because of the presence of comorbidity. Follow up. Clinical follow up was conducted by telephone contact or office visit at 1, 6, and 12 months. After 12 months, annual follow up was continued. Angiographic follow up was planned 6 months after the procedure unless clinically indicated earlier.
Definitions. Chronic renal failure was defined as the presence of previously-documented renal failure and/or a baseline serum creatine level >2 mg/dl. Angiographic success was defined as a final residual stenosis <50% and grade 3 Thrombolysis In Myocardial Infarction (TIMI) flow in all branches. Major adverse cardiac events (MACE) were defined as cardiac death, Q-wave MI, target lesion revascularization (TLR) and target vessel revascularization (TVR), either percutaneous or surgical. A non-Q-wave MI was defined as a CK-MB concentration rise >3 times the upper limit of normal in the absence of pathological Q-waves. TLR was defined as a repeat revascularization with a stenosis >50% in the target segment. TVR was defined as any repeat revascularization within the treated vessels.

Stent thrombosis was defined as follows:
1. Definite/Confirmed: in cases where the patient presented with an acute coronary syndrome and either angiographic confirmation of stent thrombus or occlusion, or pathologic confirmation of acute stent thrombosis.
2. Probable: defined as unexplained death within 30 days or target vessel MI without angiographic confirmation of stent thrombosis or other identified culprit lesion.3. Possible: defined as unexplained death after 30 days. Quantitative coronary angiographic analysis. Cineangiograms were analyzed with a validated edge detection system (CMS, version 6.0; MEDIS, Leiden, the Netherlands) at baseline, after the procedure, and at follow up. Binary restenosis was defined as diameter stenosis >50% within a target segment at the follow-up angiogram. Analysis was performed inside the stent and in the 5 mm segment proximally and distally to the stented segment including the origin of the SB, even when this vessel was not stented. Focal restenosis was defined as a restenotic lesion <10 mm long. Diffuse restenosis was defined as a restenotic lesion >10 mm long.¹⁴ Statistical analysis. Descriptive analyses were used. Continuous variables are presented as mean ± standard deviation (SD), and categorical variables are presented as frequencies with percentage.

Results

Overall baseline and procedural characteristics. A total of 15 consecutive patients undergoing PCI with DES in trifurcation lesions were identified. SES were implanted in 9 patients with 9 trifurcation lesions, and PES in 6 patients with 6 trifurcation lesions. Baseline clinical characteristics are reported in Table 1. Four patients (26.7%) had diabetes mellitus and 2 patients (13.3%) had chronic renal failure.
Procedural characteristics are reported in Table 2. Thirteen (86.7%) trifurcation lesions were located at the distal LMCA comprising the LAD, LCX, and the IM: 1 between the LAD, diagonal and septal branches, and 1 between the LCX, obtuse marginal and posterior lateral branches. All LMCA lesions were unprotected. Lesion distribution in the modified Medina classification is reported in Table 2. The combinations of diseased branches were the MB and both SBs in 1 patient (6.7%), the MB and 1 of the SBs in 10 patients (66.7%), the MB only in 2 patients (13.3%), and both SBs in 2 patients (13.3%). Because of heavy calcium burden, lesion preparation with rotational atherectomy was performed towards the “SB2” in 1 patient (Patient #3). Stenting was performed in all 3 branches in 8 patients (53.3%), in 2 branches in 6 patients (40%), and in 1 branch in 1 patient (6.7%). Among patients treated with stents in all 3 branches, in 6 of them, the procedure was performed as intention-to-treat with a 9 Fr guiding catheter (Patients #1, 3, 6, 7, 9, and 12). In the other 2 patients, a third stent was placed following an unsatisfactory result after balloon angioplasty in the SB (Patients #4 and 8). The stenting techniques applied were: “crush or double-crush” in 9 patients; “V or modified-V” in 4 patients; “culotte” in 1 patient; and “single” in 1 patient. FKB was performed in 12 patients (80%): triple FKB in 6 patients, and double FKB in 6 patients. An IVUS-guided procedure was performed in 4 patients (26.7%). Among those, IVUS examination was performed only in the MB and “SB2” in 1 patient (Patient #4) and only in the MB in the other 3 (Patients #1, 3, and 7). Seven patients received additional balloon angioplasty and/or stenting for nontrifurcation lesions during the index procedure. Glycoprotein IIb/IIIa inhibitors were electively utilized in 4 patients treated with a double- or triple-stenting technique for LMCA lesions (26.7%) (Patients #1, 2, 9, and 12). Intra-aortic balloon pump (IABP) therapy was electively inserted in 3 patients treated with the triple-stenting technique for LMCA lesions (20%) (Patients #1, 7, and 12).
The number of lesions treated per procedure was 1.8 ± 1.0. The numbers of stents implanted per lesion was 2.5 ± 0.6, and the total stent length per lesion was 57.5 ± 16.3 mm. Procedure time, fluoroscopy time, and dose of contrast media used were 97.0 ± 41.5 minutes, 31.1 ± 17.5 minutes, and 348.7 ± 139.5 ml, respectively. In-hospital and clinical outcome. Angiographic success rate was 93.3% because a final stenosis >50% in a nonstented septal branch was observed in 1 patient with a LAD trifurcation lesion (Patient #13). No complications such as coronary perforation, cardiac tamponade, or coronary dissection were recorded during the procedure. No Q-wave MI, and1 non-Q-wave MI occurred during hospitalization.
The mean clinical follow-up period was 19.0 ± 8.3 months (range 6.0–35.1). No MI occurred within the follow-up period. Clinical outcome is shown in Figure 2. TLR occurred in 3 patients (20%). Of those, 2 underwent repeat PCI (Patients #7 and 14), and 1 underwent CABG in another hospital (Patient #12). All TLR were performed for symptoms and/or signs of ischemia secondary to restenoses in the LMCA trifurcation. TVR occurred in 6 patients (40%). Of those, 3 were due to TLR, while the other 3 for progression of nontarget lesions in the LAD (Patients #3, 5, and 8). The rate of cumulative MACE was 40%. During the entire study period, no deaths or stent thromboses were recorded. The mean duration of dual antiplatelet therapy was 11.4 ± 3.5 months (range 6.0–20.5).
Angiographic outcome. In 4 patients, the baseline reference vessel diameter of the SB was <2.25 mm (Patients #7, 8, 9, and 15). However, after predilatation, all of them were treated with a stent or a balloon of at least 2.25 mm nominal size. Angiographic follow up was available for 13 patients (86.7%) at a mean period of 7.7 ± 2.0 months after the index procedure. Binary restenosis occurred in 4 patients (Patients #1, 7, 12, and 14). All restenoses were focal and observed in stented branches of the LMCA trifurcation: 1 at the proximal edge of the stent in the LMCA (Patient #7), 1 at the in-stent segment in the LMCA (Patient #12), 1 at the LCX ostium (Patient #1), and 1 at the IM ostium (Patient #14). In particular, restenosis occurred in 2 patients treated with the “crush or double-crush” technique (Patients #1 and 14), and in 2 treated with the “modified V” technique (Patients #7 and 12). Of those, systematic triple-stenting was performed in 3 patients (Patients #1, 7, and 12). Among the 4 patients who developed restenosis, IVUS was performed in 2 of them, and only in the MB (Patients #1 and 7). The total in-segment restenosis rate per lesion was 26.7% (4 of 13 lesions with angiographic success and angiographic follow up). Repeat revascularization was performed for 3 restenotic lesions. The patient with restenosis at the LCX ostium (Patient #1) did not undergo TLR since his symptoms and sign of ischemia were fully controlled by medical treatment.
Outcome in trifurcation lesions involving the LMCA. Among 13 patients with LMCA trifurcation lesions, 3 patients (23.1%) had diabetes mellitus and 1 patient (7.7%) had chronic renal failure. The lesion distribution according to the modified Medina classification is presented in Table 2. The combinations of diseased branches were the MB and both SBs in 1 patient (7.7%), the MB and 1 of the SBs in 9 patients (69.2%), the MB only in 2 patients (15.4%), and both SBs in 1 patient (7.7%). Stenting was performed in all 3 branches in 8 patients (61.5%), in 2 branches in 4 patients (30.8%), and 1 branch in 1 patient (7.7%). The stenting techniques used were: “crush or double-crush” in 7 patients; “V or modified-V” in 4 patients; “culotte” in 1 patient; and “single” in 1 patient. FKB was performed in 10 patients (76.9%): triple FKB in 6 patients and double-FKB in 4 patients. TLR and TVR occurred in 3 patients (23.1%) and 6 patients (46.2%), respectively. The rate of cumulative MACE was 46.2%. No deaths or Q-wave MIs occurred. Angiographic follow up was available in 12 patients (92.3%). The total in-segment restenosis rate per lesion was 33.3%.

Discussion

The results of the present study can be summarized as follows. First, the majority of noteworthy coronary trifurcation lesions were found in the distal LMCA. Second, DES implantation in trifurcation lesions using current stenting techniques could be performed with the low incidence of major complications, such as death, Q-wave MI or stent thrombosis. Third, compared to prior studies on bifurcation treatment with DES, the incidence of TLR was more frequent; however, restenosis when it occurred, was a focal phenomenon occurring mainly in the in-stent segment.
PCI for trifurcation lesions is one of the most difficult procedures to achieve angiographic, procedural, or clinical success. Yet, the approach to coronary trifurcation lesions, as well as results of trifurcation treatment, has been less well described. Few case reports of simultaneous triple-balloon angioplasty for trifurcation lesions have been reported with good angiographic results.^8,9 More recently, El-Jack et al reported 2 cases of PCI for coronary trifurcation lesions using 3 PES with initial angiographic success.¹⁰ Between 2 patients, 1 developed subacute stent thrombosis 6 days after the procedure, and the other had no event at 3-month clinical follow up.
In the present study, we found that PCI in trifurcation lesions was safe when utilizing the current approach, despite procedural complexity. In addition, TLR occurred in 20% of patients, which is a high incidence compared to the results of DES implantation in bifurcation lesions (8.2–14.9%).^4–7 This may be due to a high frequency of restenotic lesions at the level of the LMCA, which triggers the need for repeat treatment in most cases. Focusing on 13 lesions in the LMCA, the rate of TLR reached 23.1%. This is in agreement with the results of other studies on unprotected LMCA treatment with DES. In particular, the rates of TLR after DES deployment in the distal LMCA were 38.3% by Price et al, and 19.5% by Chieffo et al.^15,16 It is not completely clear to us the reason for the relatively high restenosis rate we found. Among possible explanations, we favor incomplete dilatation and stent expansion at the level of the SB ostium.¹⁷ In this setting, increased utilization of an IVUS-guided procedure in each of 3 branches may overcome this problem in the future. As a matter of fact, in our report, IVUS was mainly used only in the MB. The encouraging aspect is that all the restenotic lesions were focal and therefore quite simple to treat. Of the 3 TLRs performed, only 1 patient underwent CABG in another hospital. and the other 2 patients were treated with repeat PCI.
In the present study, restenosis was observed in 4 patients. Of those, a systematic triple-stenting approach was selected in 3 patients, and none of them underwent IVUS in any SB. Furthermore, the restenosis rate of lesions treated with a systematic triple-stenting approach was 50%. Despite the interest in speculating that provisional stenting is always the best initial approach, we cannot make a definite statement unless we can demonstrate by IVUS that the results in the SB in patients treated with stents are acceptable. Different approaches may also be chosen according to the extent of the disease in the SB: focal ostial disease may be best suited for provisional stenting, while disease extending into the SB may call for elective placement of multiple stents.
Study limitations. The present study has some limitations. First, it only reflected the experience of a single institution with a small sample size. The choice of stenting strategy was at the operator’s discretion, and the crush or double-crush technique was predominantly used in 60% of patients. In addition, IVUS was limited and performed mainly in the MB. However this is the first large series reporting on trifurcation treatment utilizing DES.

Conclusion

In conclusion, implantation of DES in trifurcation lesions appears to be feasible and safe, with a low incidence of cardiac death, Q-wave MI and stent thrombosis. However, the rate of TLR is higher compared to that of simpler lesions.

References

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