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Case Report

Recurrent In-Stent Restenosis With Total Occlusion Remedied With Drug-Eluting Balloon Angioplasty

A Case Report

Shah Mohd Shah Azarisman,1 MD, Mahmood Zulkifli Sabruddin,2 MD, and Mohd. Ali Rosli,2 MD

Summary

We report a 69 year old female who presented with chest pain to the Emergency Department of the National Heart Institute Malaysia. Her history revealed that she had had 2 separate episodes of chest pain beginning in 2002, resulting in total occlusion of her mid left anterior descending artery (LAD) requiring percutaneous coronary intervention and stent-ing on both occasions. Cine angiogram on her current admission revealed recurrent target lesion in-stent restenosis with total occlusion of the distal LAD. Intravascular ultrasound revealed multilayered suboptimally deployed stents in the LAD. Successive drug-eluting balloon deployments resulted in sustained patency of the LAD after 1 year. (Int Heart J 2011; 52: 61-63)

Key words: In-stent restenosis, Angioplasty, Drug-eluting balloon

Stents are a crucial and indispensible tool for coronary in-terventionists. Their efficacy, however, has been limited by the development of in-stent restenosis (ISR) second-

ary to neointimal proliferation.1) Drug-eluting stents (DES) have, in the past decade, markedly reduced the incidence of bi-nary restenosis and repeat coronary revascularization.2) How-ever, there is limited data on optimal management of DES re-stenosis. Some studies have shown similar benefits between repeat DES stenting and conventional balloon angioplasty, whereas others have shown clear benefit for repeat DES stent-ing.2-4) Percutaneous coronary balloon angioplasty has been largely superseded by repeat DES stenting or the ‘sandwich stenting’ technique, which is steadily gaining prominence.5) We report a case of recalcitrant target lesion ISR which was suc-cessfully treated with drug-eluting balloon deployment. A re-peat coronary angiogram 1 year later revealed sustained target lesion patency and the patient remains symptom free.

Case Report

A 69-year-old female with a history of diabetes, hyper-tension, and hyperlipidemia since 1990 and on regular medica-tion, has had recurrent episodes of stable angina since 1997. She was put on aspirin but was never investigated for coronary artery disease due to patient refusal to consent for further eval-uation or intervention.

In 2002, she had a severe episode of chest pain which ne-cessitated admission to a peripheral hospital from where she was eventually referred to the National Heart Institute in Kuala Lumpur. Her coronary angiogram then revealed a total occlu-sion of the left anterior descending artery (LAD) which was

remedied with two overlapping Cypher DES extending from the mid to distal LAD (2.5 × 33 mm and 2.75 × 33 mm, Cy-pherTM sirolimus-eluting stent; Cordis Corp., Miami, FL) (Fig-ures 1A-F). She was discharged with dual antiplatelet therapy.

In 2003, she had recurrent symptoms and a repeat angi-ogram showed ISR with total occlusion of the mid LAD. Per-cutaneous coronary intervention (PCI) was attempted with a cutting balloon (3.0 × 15 mm, 3.5 × 15 mm and 4.0 × 10 mm; InterVentional Technologies Inc., San Diego, CA). This was followed by two bare-metal stents (BMS), Multi-Link PentaⓇ (Guidant Corp., Indianapolis, IN) 4.0 × 13 mm in the proximal LAD, overlapped distally with the proximal Cypher. A DriverⓇ (Medtronic, Santa Rosa, CA) 3.0 × 18 mm was also deployed into D1.

The PCI was complicated by perforation in the mid LAD distal to D1 which was bailed out using the ‘sandwich stenting’ technique with 2 Jomed covered stents (Abbott Vascular De-vices, Redwood City, CA) 4.0 × 12 mm across D1 and 3.5 × 12 mm overlapped distally. The final angiographic result was ac-ceptable with TIMI III flow to distal LAD and patent septals/D2 despite an obliterated D1. The patient was discharged well and remained asymptomatic for many years.

In 2008, she again developed recurrent symptoms of se-vere chest pain necessitating hospital admission. Electrocardi-ography (ECG) showed sinus rhythm with no ST-T changes and an echocardiogram (ECHO) revealed a good left-ventricu-lar ejection fraction of 64%, concentric left ventricular hyper-trophy with mild diastolic dysfunction, but no regional wall motion abnormality.

Coronary angiography revealed recurrent mid LAD ISR with total occlusion distal to D2 (Figures 2A-B). The presence of overlapping Cypher DES and sandwiched Cypher/Jomed

From the 1 International Islamic University Malaysia and 2 National Heart Institute, Malaysia.Address for correspondence: Shah Mohd Shah Azarisman, MD, International Islamic University Malaysia, Jalan Sultan Ahmad Shah, Bandar Indera Mahkota, 25200

Kuantan, Pahang, Malaysia.Received for publication May 28, 2010.Revised and accepted November 4, 2010.

62Int Heart J

January 2011AZARISMAN, ET AL

covered stents from the proximal to mid LAD precluded the use of further DES stenting and necessitated the use of drug-eluting POBA. A conventional antegrade approach via a 6 Fr LauncherTM Extra Back-Up (EBU) 3.5 guide (Medtronic, USA) for the LAD was performed with a RunthroughTM Inter-mediate wire (Terumo Inc, Japan). Sequential low-pressure dilatation was performed with a SeQuentⓇ CTO 2.0 × 15 mm balloon (B. Braun Medical Inc., Bethlehem, PA). Intravascular ultrasound (IVUS) revealed multilayered suboptimally de-ployed stents in the LAD but neither stent fractures nor over-lap-free segments were present. Furthermore, there was mod-erate neointimal hyperplasia but no thrombus-like images were seen (Figures 3A-B).

POBA was performed with sequential, distal to proximal, dilatation of the SeQuentⓇ Please (B. Braun Medical Inc.) pa-clitaxel-eluting balloon 2.5 × 30 mm deployed at 8 atm/45 sec-

onds, 3.0 × 26 mm at 16 atm/45 seconds and 3.5 × 26 mm at 16 atm/45 seconds (Figures 2C-E). Postdilatation IVUS re-vealed proper stent expansion and apposition (Figures 3C-D). Final cine confirmed TIMI III flow to the distal LAD, patent septals and D2 (Figures 2F-G).

She was then discharged well with medications. She re-mained asymptomatic under regular follow-up for the succeed-ing year. Repeat angiogram on 15th January 2009 revealed a

Figure 1. A: Left-sided diagnostic angiogram (AP cranial view) showing stenosed mid left anterior descending (LAD) artery at first diagonal (D1) level and total occlusion of the mid LAD at D2 level. B: Right-sided diagnostic ang-iogram (AP cranial view) showing the right coronary artery (RCA) with ret-rograde collateralization of the distal-mid LAD. C: Distal stent placement with CypherⓇ 2.5 mm × 33 mm drug-eluting stent (DES) deployed at 18 atm/10 seconds. D: Proximal stent placement with CypherⓇ 2.75 mm × 33 mm drug-eluting stent (DES) deployed at 14 atm/10 seconds. E: Per-cutaneous coronary intervention (PCI) ended with kissing balloon tech-nique, 3.0 mm × 15 mm into LAD and 2.5 mm × 10 mm into D1 deployed at 6 and 14 atm respectively. F: Post-PCI cine (RAO cranial view) show-ing stent deployment from mid to distal LAD with mild stenosis proximal to the 1st stent just distal to D1.

Figure 3. A, B: Intravascular ultrasound (IVUS) showing multilayered stents in the pre-DEB LAD proximally (A) and distally (B). C, D: Post-DEB IVUS showing better stent apposition and deployment.

Figure 2. A: Repeat right-sided cine (AP cranial view) showing the RCA with retrograde collateralization of the distal-mid LAD. B: Repeat left-sided cine (AP cranial view) showing significant in-stent restenosis of the mid LAD stent and total occlusion of the D1 stent and distal LAD stent just beyond D2. C-E: Successive distal to proximal deployment of the Se-quent PleaseⓇ drug-eluting balloons (DEB). (C: 2.5 mm × 30 mm at 8 atm/45 seconds, D: 3.0 mm × 26 mm at 16 atm/40 seconds and E: 3.5 mm × 26 mm at 16 atm/40 seconds) F: Post-DEB cine (RAO caudal view) showing patent stents with moderate ISR of the proximal stent but TIMI III flow to the distal LAD. G: Post DEB cine (AP cranial view) showing occluded D1 stent but patent LAD stents.

63Vol 52No 1 RECURRENT ISR REMEDIED WITH DRUG-ELUTING BALLOON

patent LAD with moderate ISR and TIMI III flow (Figure 4).

Discussion

Our patient had several factors associated with higher risk of restenosis, namely, age, female sex, and diabetes. Nonethe-less, these factors are thought to have diminished with the ad-vent of DES wherein vessel characteristics and type of DES used became stronger predictors of both angiographic and clinical restenosis.1) However, despite dual antiplatelet therapy, utilisation of sirolimus-coated stents, in a large calibre coro-nary artery and achieving good post-PCI angiographic results following the first PCI, our patient still had recurrent target le-sion ISR in 2003.

She did not display any of the usual causes of DES ISR such as stent fracture, edge proliferation, overlap-free areas, or bifurcation stenting. Furthermore, neither cutting balloon utili-sation nor sandwich stenting managed to prevent further recur-rent target lesion ISR following the second PCI. Both methods have been described as therapeutic breakthroughs in treating ISR.2,6) Following the second PCI in 2003, however, the risks for ISR increased substantially due to the anatomic location (LAD), vessel geometry, the number and length of stents, and the presence of multiple overlaps.7)

Many studies have shown good results for the sandwich stenting technique in which a DES is implanted into a BMS ISR.8,9) However, the data for such a procedure or any other in-travascular intervention for that matter, in a DES ISR are still limited, although some reports are encouraging.2,3,10) Paclitaxel-coated balloon catheters (DEB) offer more therapeutic advan-tages through immediate drug delivery on inflation, adminis-tration of a controlled dose, and homogeneity of vessel wall

exposure without the disadvantages of a polymeric matrix that may induce inflammation and thrombosis.11)

In addition, intracoronary delivery of paclitaxel by a DEB catheter results in concentrations of the drug in vascular tissue that are high enough to have antiproliferative effects, thus lead-ing to a significant reduction in neointimal proliferation.6) Re-sults from the Paccocath ISR I/II and the PEPCAD II studies have shown that the DEB is associated with greater procedural success, lower binary restenosis rates, and lower major adverse cardiovascular event rates.12,13) These factors point towards a promising future for the DEB in treating ISR.

We have shown that despite multiple complicated PCI at-tempts on a recalcitrant target lesion, satisfactory results were achieved through preemptive deliberation and utilization of the DEB, a novel breakthrough for the treatment of ISR.

References

1. Kastrati A, Dibra A, Mehilli J, et al. Predictive factors of resteno-sis after coronary implantation of sirolimus- or paclitaxel-eluting stents. Circulation 2006; 113: 2293-300.

2. Sardella G, Colantonio R, De Luca L, et al. Comparison between balloon angioplasty and additional coronary stent implantation for the treatment of drug-eluting stent restenosis: 18-month clinical outcomes. J Cardiovasc Med 2009; 10: 469-73.

3. Kitahara H, Kobayashi Y, Takebayashi H, et al. Re-restenosis and target lesion revascularization after treatment of sirolimus-eluting stent restenosis: retrospective analysis of 4 Japanese hospitals. Circ J 2009; 73: 867-71.

4. Lee CW, Park CB, Kim YH, et al. Incidence and predictors of re-current restenosis following implantation of drug-eluting stents for in-stent restenosis. Catheter Cardiovasc Interv 2007; 69: 104-8.

5. Alfonso F, Zueco J, Cequier A, et al. A randomized comparison of repeat stenting with balloon angioplasty in patients with in-stent restenosis. J Am Coll Cardiol 2003; 42: 796-805.

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8. Holmes DR Jr, Teirstein P, Satler L, et al. Sirolimus-eluting stents vs vascular brachytherapy for in-stent restenosis within bare-metal stents: The SISR randomized trial. JAMA 2006; 295: 1264-73.

9. 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: 1253-63.

10. Mishkel GJ, Moore AL, Markwell S, Shelton MC, Shelton ME. Long-term outcomes after management of restenosis or thrombo-sis of drug-eluting stents. J Am Coll Cardiol 2007; 49: 181-4.

11. Scheller B, Speck U, Abramjuk C, Bernhardt U, Böhm M, Nick-enig G. Paclitaxel balloon coating, a novel method for prevention and therapy of restenosis. Circulation 2004; 110: 810-4.

12. Scheller B, Hehrlein C, Bocksch W, et al. Treatment of in-stent restenosis with a paclitaxel-coated balloon catheter. New Engl J Med 2006; 355: 2113-24.

13. 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: 2986-94.

Figure 4. Repeat coronary angiogram in January 2009 shows patent LAD with moderate ISR and TIMI III flow.