Damage to Polymer of Undelivered Sirolimus-Eluting Stents

A sirolimus-eluting stent (SES) consists of 3 components: 1) metallic stent; 2) sirolimus as an antiproliferative agent to inhibit neointimal formation; and 3) a polymer coating used as a drug-carrier vehicle (Figure 1).¹ Polymer also plays an important role in controlling the release of sirolimus. Thus it may be released in an uncontrolled manner when damage to the polymer of SES occurs. The present study evaluated damage to the polymer coating of SES that could not be delivered into lesions.

Methods

SES that could not be delivered into lesions were prospectively collected and examined using a scanning electron microscope (S-800, Hitachi, Tokyo, Japan).
Case 1. A 68-year-old male was admitted due to exertional angina. Coronary angiography demonstrated a 90% diffuse stenosis with severe calcification in the proximal-to-mid left anterior descending coronary artery (LAD) (Figure 2A). The patient was referred for coronary angioplasty. A 6 Fr BL 3.5 guiding catheter (Terumo, Tokyo, Japan) was positioned at the left main ostium and a 0.014 inch Runthrough guidewire (Terumo) was advanced into the distal LAD. Predilatation was performed using a 2.5 mm Sprinter balloon catheter (Medtronic, Inc., Minneapolis, Minnesota) inflated at 14 atm (Figure 2B). Intravascular ultrasound (IVUS) imaging using a 40 MHz Atlantis IVUS catheter (Boston Scientific Corp., Natick, Massachusetts) was performed and demonstrated severe calcification in the proximal LAD (Figure 2C). An attempt was made to deliver a 23 mm Cypher^™ stent (Cordis Corp., Miami Lake, Florida), premounted on a 3.0 mm balloon catheter, into the mid-LAD. However, it would not cross the proximal segment of the LAD. Another 0.014 inch Whisper guidewire (Guidant Corp., Santa Clara, California) was advanced into the distal LAD. However, the SES would not cross it (Figure 2D). A 23 mm Multi-Link Vision stent (Guidant), premounted on a 3.0 mm balloon catheter, was delivered into the mid-LAD. It crossed the proximal LAD and was deployed in the mid-segment of the LAD using an inflation pressure of 14 atm. An 18 mm Multi-Link Vision stent, premounted on a 3.0 mm balloon catheter, was deployed in the proximal LAD using an inflation pressure of 14 atm. The final angiogram showed a good result (Figure 2E). The undelivered Cypher stent was examined using a scanning electron microscope, which showed damage to the polymer coating of the stent (Figure 3A).

Case 2. A 75-year-old female who had exertional angina was referred for coronary angiography, which revealed a 90% stenosis in the mid-right coronary artery (RCA) (Figure 4A). The patient was referred for coronary angioplasty. A 6 Fr AL1 guiding catheter (Boston Scientific) was positioned at the RCA ostium and a 0.014 inch Balance Middle Weight guidewire (Guidant) was advanced into the distal RCA. Predilatation using a 3.0 mm Voyager balloon catheter (Guidant) inflated at 10 atm was performed. An attempt was made to deliver an 18 mm Cypher stent, premounted on a 3.5 mm balloon catheter, into the mid-RCA. However, it would not cross the proximal RCA due to severe angulation and moderate calcification. Another 0.014 inch Balance Middle Weight guidewire was advanced into the distal RCA. The SES would not cross the proximal RCA (Figure 4B). Next, we attempted to deliver an 18 mm DRIVER stent (Medtronic), premounted on a 3.5 mm balloon catheter, into the mid-RCA. It crossed the proximal RCA and was deployed in the mid-RCA using an inflation pressure of 10 atm. Postdilatation using a 3.5 mm Quantum Maverick balloon catheter (Boston Scientific) inflated at 16 atm was performed. The final angiogram showed a good result (Figure 4C). IVUS imaging using a 40 MHz Atlantis IVUS catheter was performed and demonstrated optimal stent expansion in the mid-RCA and moderate calcification in the proximal RCA (Figure 4D). The undelivered Cypher stent was examined using a scanning electron microscope. It demonstrated damage to the polymer coating of the Cypher stent (Figure 3B).

Case 3. A 68-year-old female with previous stent placement in the proximal-to-mid left circumflex artery (LCx) was admitted due to exertional angina. Coronary angiography revealed subtotal occlusion of the stents implanted in the proximal-to-mid LCx (Figure 5A). The patient was referred for coronary angioplasty. A 6 Fr JL3.5 guiding catheter (Asahi Intec, Seto, Japan) was positioned at the left main ostium and a 0.014 inch Balance Middle Weight guidewire was advanced into the distal LCx. Predilatation was performed using a 1.25 mm Ryujin balloon catheter (Terumo) inflated at 10 atm, and a 2.5 mm Vento Speeder balloon catheter (Invatec, Bresia, Italy) was inflated at 10 atm (Figure 5B). An attempt was made to deliver an 18 mm Cypher stent, premounted on a 2.5 mm balloon catheter, into the proximal LCx. However, it would not cross the bend between the left main and the LCx, where severe calcification was observed (Figure 5C). A 0.014 inch Whisper guidewire was advanced into the distal LCx. The SES would not cross it, however (Figure 5D). Further conventional balloon angioplasty was done using a 2.5 mm Vento Speeder balloon catheter inflated at 12 atm. The final angiogram showed a good result (Figure 5E). The undelivered Cypher stent was examined using a scanning electron microscope, which demonstrated damage to the stent’s polymer coating (Figure 3C).

Results

Between August 2004 and January 2007, percutaneous coronary intervention using SES was planned in 1,042 lesions. Unsuccessful delivery of the SES occurred in 5 lesions (0.47%) of 5 patients. Table 1 shows the details of these 5 cases. In all patients, moderate or severe calcification with and without vessel tortuosity were the reasons for unsuccessful delivery. A scanning electron microscope demonstrated damage to the polymer coating in 4 out of the 5 undelivered Cypher stents (Figure 3).

Discussion
Recently randomized trials^2,3 have demonstrated that drugeluting stents (DES) substantially reduce in-stent restenosis compared to bare-metal stents. However, in-stent restenosis remains an important clinical problem, especially in highly complex lesions.⁴ Previous studies have demonstrated risk factors associated with restenosis after DES implantation: stent underexpansion,⁵ stent fracture,⁶ nonuniform strut distribution⁷ and incomplete lesion coverage with DES.⁸
SES have two non-erodable polymer layers (basecoat and topcoat).¹ The basecoat is a drug-polymer matrix and serves as a reservoir of sirolimus. The topcoat is a layer of drug-free polymer applied on top of the basecoat. It is a diffusion barrier to prolong the release of sirolimus. SES were designed to release approximately 80% of sirolimus within 30 days after implantation. We previously reported damage to the polymer coating of SES that would not cross the segment of another newly-deployed SES.⁹ Sirolimus may be released in an uncontrolled manner through the damaged topcoat polymer. The scraped-off basecoat polymer might cause the lack of sirolimus itself. Polymer damage would likely result in nonuniform local drug distribution that might then enable neointimal hyperplasia. Calcification may be the most likely cause of damage to the polymer of SES. In Cases 2 and 3, delivery of the SES was attempted through a bent portion of a coronary artery. There may be greater friction at a bent portion between the SES and coronary atheroma, especially with calcification, which might result in damage to the polymer coating of the SES. To facilitate SES delivery,¹⁰ the buddy wire technique was used in 3 of the 4 patients in whom damage to the polymer layer of the SES was observed. There was a possibility that the guidewire along the SES caused the damage to the polymer. Another possible cause of damage to the polymer could have been two-stent deployment and/or kissing balloon inflation in bifurcation lesions, but this could not be evaluated because there were no such cases in the present study. We previously reported a high restenosis rate after SES implantation in patients on dialysis whose coronary arteries often have severe calcification.⁴ One of possible mechanisms of a high restenosis rate in dialysis patients might be damage to the polymer of the SES that were delivered through calcified coronary arteries. Operators must be aware of the possibility of damaging the polymer coating while deploying SES. Forceful delivery of a SES should therefore be avoided. To prevent damage to the polymer, predilatation and use of rotational atherectomy, as well as a 5 Fr inner guiding catheter as a protective sheath, may be considered when SES are delivered through moderately or severely calcified coronary arteries, or if there is difficulty in SES delivery.^10,11
Study limitations. There are some limitations in the present study. First, the number of undelivered stents is small. Second, only undelivered SES were examined. Third, other DES such as paclitaxel-eluting stents, everolimus-eluting stents and zotarolimus-eluting stents use different polymers.¹ Thus, it is unknown if damage to the polymer layer of these stents occurs.

Conclusion
This study shows that damage to the polymer coating of a SES may occur when it is delivered through a calcified coronary artery. Operators should always be careful not to damage the polymer of SES.

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