Treatment of In-Stent Restenosis Involving a Bifurcation Lesion With a Dedicated Bifurcation Device in Combination With Drug-Eluting Balloons

ABSTRACT: It can be difficult to find a good treatment strategy in cases with in-stent restenosis with involvement of a bifurcation lesion. To avoid multiple stent layers and to treat the bifurcation lesion properly, the patient described in this case report was treated with a Tryton side branch stent and drug-eluting balloons. Angiographic follow-up at 8 months showed an excellent result.

J INVASIVE CARDIOL 2012;24(8):E172-E175

Key words: in-stent restenosis, bifurcation, drug-eluting balloon, bifurcation device

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Treatment of coronary in-stent restenosis (ISR) with involvement of a bifurcation lesion can be very challenging. Drug-eluting stents (DES) are a good treatment option for in-stent restenosis.^1-3 However, placement of a DES for ISR results in a double layer of struts. The relatively new drug-eluting balloons (DEB) may provide a good alternative treatment option for in-stent restenosis, especially in bare metal stents (BMS). Treatment of ISR with DEB was superior to balloon angioplasty and the use of a paclitaxel-eluting stent with respect to the endpoint of late lumen loss in 2 different randomized studies in ISR of BMS.^4,5

Bifurcation lesions (BLs) account for up to 30% of all coronary lesions treated by percutaneous coronary intervention (PCI). The provisional single stent strategy is the preferred treatment of such lesions. However, even when this approach is used, PCI of BLs is still associated with poorer clinical outcomes compared to non-BLs. Therefore, several dedicated bifurcation devices were developed in an attempt to improve clinical outcomes. One of these devices is the Tryton Side Branch Stent (Tryton Medical). This stent consists of 3 zones: 1) the distal part, placed in the side branch; 2) the mid transition zone, which provides optimal scaffolding at the level of the carina; and 3) the proximal part (“the collar” or “wedding band”) with only 2 fronds, which ‘anchor’ the stent in the main branch. The transition zone consists of 3 elements, which can be independently deformed and connect the proximal with the distal part, and provide easy access to recross into the main branch for placement of additional stents (Figure 1).⁶ Previous smaller studies with this device have shown promising procedural and clinical outcomes.^7,8 Therefore, this new device could offer opportunities to treat highly complex BLs.

In the following case we demonstrate a successful treatment of ISR involving a bifurcation lesion, which was treated with a Tryton side branch stent in combination with SeQuent Please (BBraun) DEB.

Case report. A 63-year-old male patient suffered from non-ST-segment elevation myocardial infarction (N-STEMI). He had no other past medical history. He was treated initially medically with aspirin, clopidogrel, enoxaparin, bisoprolol, perindopril, and rosuvastatin. Peak level of CK-MB was 139.1 ug/L. Four days later, diagnostic coronary angiography was performed. Significant stenoses were seen in the ramus circumflex (RCx): a 40% stenosis of the ostium of the RCx and a proximal RCx lesion of 70% in a large posterolateral (PL) branch. We also saw 80% stenosis in the left anterior descending artery (LAD) just after the first diagonal branch (D1). The patient was referred to our center for an elective PCI of the lesions in the LAD and PL branch.

First, the lesion in the LAD was treated. Two guidewires were placed, 1 in the LAD and 1 in the D1 for protection because of its large size. This side branch was not involved (ie, Medina 0.1.0); a 3.0 mm x 18 mm Blazer (Orbus Neich) BMS was placed in the LAD across the D1 (provisional single stent strategy). A minor plaque shift was observed, but flow in the D1 was not compromised (TIMI 3 flow). Therefore, no additional side branch treatment was performed (Figure 2). In addition, the PL branch was treated with good result.

Eight months after the initial PCI, the patient complained of a recurrence of chest pains. We performed a diagnostic catheterization that showed ISR of the BMS in the LAD. Furthermore, progression of the side branch stenotic lesion was observed, resulting in a bifurcation lesion with both distal main branch and side branch involvement (ie, Medina Class 0.1.1, Figure 3).

PCI treatment. A 6 Fr CLS 3.5 catheter was inserted via a radial approach and 2 guidewires were placed: one in the D1 by fenestrating the struts of the BMS and the other in the LAD. Predilatation of the D1 was performed with a Sapphire balloon (1.0 mm x 10 mm at 16 atm; Orbus Neich), a Scoreflex balloon (2.0 mm x 15 mm at 10 atm; Orbus Neich), and a Trek non-compliant balloon (2.5 mm x 15 mm at 10 atm; Abbott Vascular). Then, a Tryton side branch stent was placed from the proximal main vessel (LAD) into the side branch (3.0/2.5 mm x 19 mm at 14 atm) (Figure 4). The jailed guidewire in the LAD was pulled back and recrossed through the Tryton transition zone into the LAD. After this, the restenosed BMS in the LAD was dilatated with a Voyager (Abbott Vascular) 3.0 mm x 15 mm non-compliant balloon at 14 atm. Next, the side branch, now scaffolded by Tryton, was further treated with a paclitaxel-eluting balloon (SeQuent Please, 2.5 mm x 20 mm at 7 atm for 65 seconds and at 12 atm for 65 seconds). In addition, the LAD BMS segment was treated with a paclitaxel-eluting SeQuent Please balloon (3.0 mm x 15 mm at 8 atm, for 60 seconds). Finally, the distal stent edge of the BMS was treated with a 3.0 mm x 10 mm SeQuent Please paclitaxel-eluting balloon at 8 atm for 60 seconds. The angiographic end result showed good flow in both main and side branch and less then 30% residual stenosis (Figure 5).

Follow-up. Eight months after the second procedure, the patient was referred again to our center. The patient had complaints of atypical chest pain, which was different than his previous presenting complaints. A diagnostic coronary angiogram was performed and showed very good result of the treaded ISR and bifurcation lesion of the LAD-D1; no new ISR was seen (Figure 6). The stent in the PL branch was also patent. Fractional flow reserve on the previously known 40% lesion of the ostium of the RCx was 0.95. In conclusion, there were no lesions found that could explain the atypical chest pain of the patient and the patient was referred back to his general cardiologist for further exploration of his complaints.

Discussion. After PCI of a lesion in the LAD with a BMS using provisional one-stent strategy across the D1, the patient was referred back to our center for an elective PCI due to an ISR with involvement of the diagonal side branch. Multiple treatment strategies were considered. Three issues were taken into account, which led to the final treatment strategy:

First, the provisional single stent strategy, which is the preferred treatment of BLs, was not considered as an option because it would be difficult to cross through 2 layers of struts (restenosed BMS and newly placed stent) to the side branch, if necessary, to perform balloon angioplasty or converting to 2-stent strategy due to acute side branch closure or flow compromise.

Second, the operator felt obliged to treat the side branch, because of its significance (the diameter of the D1 is more or less the same as the diameter of the distal LAD).

Third, the operator was concerned about the patient’s tendency to develop restenosis of bare metal stents.

We treated the now significantly diseased side branch with a dedicated bifurcation BMS and further applied DEB with paclitaxel to this side branch stent because of the patient’s tendency to restenose. In addition, the main branch was also treated with paclitaxel-eluting balloons, instead of a conventional DES, because this would have resulted in 3 layers of struts (old BMS, proximal part of Tryton, and conventional DES).

In our center, we have good experience with the Tryton side branch stent, which has been placed in more than 70 patients so far. The device has shown good clinical results in a first-in-man study of 30 patients and in a 2-center registry with 100 patients, showing target lesion revascularization rates at 6 months of 6.6% and 3.1%, respectively. The major adverse cardiac event rates in the 2 studies, defined as a composite of cardiac death, myocardial infarction, coronary artery bypass graft surgery, or target lesion revascularization, were 9.9% and 8.3%, respectively. Stent thrombosis did not occur in either of the studies.^7,8 These results suggest that Tryton is both safe and effective for the treatment of bifurcation lesions, but the results of the randomized trial are needed to further evaluate the performance of this new device in comparison with the provisional strategy (current standard of care).

We also have extensive and good experience with DEB use for the treatment of ISR. We consider the use of a DEB to be a good alternative treatment to stenting in ISR cases. A currently ongoing randomized multicenter trial, the DARE (Drug eluting bAlloon for in-stent REstenonis) trial, compares the SeQuent Please paclitaxel-eluting balloon to an everolimus-eluting stent (Xience Prime) in the treatment of ISR. Unverdorben et al and Scheller et al showed showed good results with DEB in ISR in BMS.^4,5 The use of DEB has some potential benefits in comparison to the use of DES in ISR including absence of multiple stent layers, a homogeneous delivery of the antiproliferative drug to the vessel wall, and potential decrease in late stent thrombosis events. Two studies reported the use of DEB in BLs: the DEBIUT registry (with the DIOR drug-eluting balloon) and the PEPCAD V study (with the SeQuent Please DEB presented by Mathey D at Transcatheter Therapeutics 2009). Both studies had relatively small patient groups (20 and 28 patients, respectively) and short follow-up (4 months and 9 months, respectively). In the DEBIUT study, the authors conclude that the DIOR DEB is safe and effective in BLs in short-term follow-up.9 The investigators of the PEPCAD V study concluded that there was efficacy but had their doubts about the safety because of the occurrence of late stent thrombosis in 2 patients.

Conclusion

To our knowledge, treatment of ISR and involvement of a bifurcation lesion with a combination of the Tryton side-branch stent and a SeQuent Please DEB has not been reported before. The patient in our case was successfully treated and angiographic follow-up at 8 months showed excellent result. The combination of the Tryton side-branch Stent and the SeQuent Please DEB may be a good alternative treatment for patients with ISR with involvement of a bifurcation.

References

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2. Singh IM, Filby SJ, El Sakr F, et al. Drug-eluting stents versus bare-metal stents for treatment of bare-metal in-stent restenosis. Catheter Cardiovasc Interv. 2010;76(2):257-262.
3. Stone GW, Ellis SG, O'Shaughnessy CD, et al. Paclitaxel-eluting stents vs vascular brachytherapy for in-stent restenosis within bare-metal stents: the TAXUS V ISR randomized trial. JAMA. 2006;295(11):1253-1263.
4. Scheller B, Hehrlein C, Bocksch W, et al. Treatment of coronary in-stent restenosis with a paclitaxel-coated balloon catheter. N Engl J Med. 2006;355(20):2113-2124.
5. Unverdorben M, Vallbracht C, Cremers B, et al. Paclitaxel-coated balloon catheter versus paclitaxel-coated stent for the treatment of coronary in-stent restenosis. Circulation. 2009;119(23):2986-2994.
6. Kaplan AV, Davis HR. Tryton side-branch stent. EuroIntervention. 2006;2(2):270-271.
7. Magro M, Wykrzykowska J, Serruys PW, et al. Six-month clinical follow-up of the Tryton side branch stent for the treatment of bifurcation lesions: a two center registry analysis. Catheter Cardiovasc Interv. 2011;77(6):798-806.
8. Onuma Y, Müller R, Ramcharitar S, et al. Tryton I, First-In-Man (FIM) study: six month clinical and angiographic outcome, analysis with new quantitative coronary angiography dedicated for bifurcation lesions. EuroIntervention. 2008;3(5):546-552.
9. Fanggiday JC, Stella PR, Guyomi SH, Doevendans PA. Safety and efficacy of drug-eluting balloons in percutaneous treatment of bifurcation lesions: the DEBIUT (drug-eluting balloon in bifurcation Utrecht) registry. Catheter Cardiovasc Interv. 2008;71(5):629-635.

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From the Department of Cardiology, Academic Medical Center-University of Amsterdam, Amsterdam, The Netherlands.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report research support/consultant grants for the Tryton Registry at AMC.
Manuscript submitted March 8, 2012, provisional acceptance given March 23, 2012, final version accepted April 4, 2012.
Address for correspondence: Joanna J. Wykrzykowska, MD, PhD, Department of Cardiology, Cardiac Catheterization Laboratory B2-127, Academic Medical Center – University of Amsterdam , Meibergdreef 9, 1105 AZ Amsterdam. Email: j.j.wykrzykowska@amc.uva.nl