Case Reports

Transradial Coronary Brachytherapy With the NovosteBeta-Rail System

Olivier F. Bertrand,1* MD, PhD, Robert De Larochelliere,1 MD, Onil Gleeton,1 MD,Sylvain Plante,1 MD, Michel Tessier,2 MD, MSc, and Jean Guimond,2 MD

We report our initial experience in 10 consecutive patients who underwent transradialcoronary brachytherapy for in-stent restenosis using a 90Sr/Y source and the NovosteBeta-Rail system. In all patients, procedures were successfully completed using a righttransradial approach. We performed the procedures with the Beta-Rail catheter using 7Fr (Zuma II, Medtronic, MN; n � 5) or 8 Fr (Cordis, Miami, FL; n � 5) guiding catheters. Alllesions were successfully dilated and no additional stent was inserted. We used a 40 mmsource (n � 3) or a 60 mm source (n � 7) with manual stepping in four cases. In threecases, we did one stepping, and in one case, we did three steppings. The mean dwell timewas 195 � 44 sec. The mean delivered dose was 23 � 3 Gy at 2 mm distance from thesource. No radiation treatment was interrupted. Mean fluoroscopy time was 26 � 13 min.Procedural success was achieved in all patients. Three patients had mild CK elevations(< 3 times upper normal limit). All patients were pretreated with clopidogrel (300 mg) andcombined treatment with aspirin � clopidogrel is to be continued for at least 1 year.Clinical follow-up up to 3 months has not yielded any complication and all patients haveremained free from angina. Cathet Cardiovasc Intervent 2002;55:362–366.© 2002 Wiley-Liss, Inc.

Key words: PTCA; IVUS; radiation; restenosis; isotope

INTRODUCTION

Catheter-based brachytherapy has become an effectivetreatment modality for patients presenting with in-stentrestenosis. Initial favorable results with a noncenteredcatheter and a 192Ir source were reported by Teirstein etal. [1] in 1997. To reduce radiation protection measuresin the catheterization laboratory, Novoste has developeda noncentered 5 Fr catheter that may accommodate atrain of radioactive seeds containing 90Sr/Y, a source ofpure �-emitters with a half-life of 28 years. The radio-active sources are safely kept in a transfer device withappropriate shielding. Once the catheter is positioned bythe interventional cardiologist at the target site, it isconnected to the transfer device. The seeds are senthydraulically by using a dedicated syringe through aspecific lumen by flushing with sterile water. After com-pletion of treatment, the seeds are sent back hydraulicallyto the transfer device. Seeds transfer from the angioplastysite to the transfer device typically lasts a few seconds.

This system has been tested in de novo lesions as wellas for the treatment of in-stent restenosis [2]. Followingthe favorable results of the START trial, we have been

authorized by the Canadian Ministry of Health to treat alimited series of patients with in-stent restenosis undercompassionate grounds. The size of the Beta-Rail cath-eter requires either 7 Fr large lumen (Medtronic Zuma II)or 8 Fr guiding catheters; thus far, no case has beenreported using a transradial access. Since in our institu-tion we perform more than 95% of our procedures usinga transradial technique, we considered this approach withvascular brachytherapy. It is the purpose of this article toreport our initial experience.

1Interventional Cardiology Laboratories, Quebec Heart-Lung In-stitute/Laval Hospital, Quebec, Canada2Nuclear Medicine Department, Quebec Heart-Lung Institute/Laval Hospital, Quebec, Canada

*Correspondence to: Dr. Olivier F. Bertrand, Quebec Heart-LungInstitute/Laval Hospital, 2725 Chemin Ste-Foy, Quebec G1V 4G5,Canada. E-mail: ofbertrand@videotron.ca

Received 19 September 2001; Revision accepted 2 October 2001

Catheterization and Cardiovascular Interventions 55:362–366 (2002)

© 2002 Wiley-Liss, Inc.DOI 10.1002/ccd.10083

METHODS

Patients suspected of in-stent restenosis underwentdiagnostic catheterization. Films were then reviewed byan interventional cardiologist and a nuclear medicinespecialist in order to plan the brachytherapy procedure,including the choice of source length (40 mm or 60 mm),decision of stepping, and dose prescription based onreference vessel diameter. All patients were pretreatedwith a loading dose of 300 mg clopidogrel, given the daybefore the procedure.

Palmar arch patency was verified using the modifiedAllen test with oxymetry-plethysmography as previouslydescribed [3]. After mild sedation (1 mg midazolam i.v.)and analgesia (50 mg fentanyl i.v.), local anesthesia wasperformed with xylocaine. After puncture of the radialartery, a 4 Fr introducer was used to predilate and a 7 or8 Fr sheath was inserted. A dose of 100 mg/kg of heparinwas then administered i.v. and 9.5 mg verapamil and 1mg nitroglycerin were injected intra-arterially throughthe side hole of the sheath. A perfusion of nitroglycerinwas then started. After multiple angiographic views, weperformed intravascular ultrasound (IVUS) imaging(CVIS, Boston Scientific, Sunnyvale, CA) before dilata-tion. This allowed better definition of the segment to betreated and detected underdeployment of the previouslyimplanted stent. To avoid slippage of the balloon andunexpected extension of the injured segment, we favoredinitial dilatation with cutting balloon catheters unless therestenotic region encompassed a very long segment. Todetermine the total injury length during the procedure,transparencies were superimposed on the angiographicscreen and each balloon extremities were marked duringinflation. Immediately before the brachytherapy proce-dure, IVUS was repeated. We avoided further manipu-lation at the dilated site after radiation delivery. At theend of the procedure, the arterial sheath was immediatelyremoved and a tourniquet was left in place until hemo-stasis is completed. Throughout the procedure, the acti-vated clotting time (ACT) was regularly measured andboluses of heparin were administered to maintain ACTabove 350 sec. Patients left the hospital the next dayunless significant rise in enzymes or troponins was de-tected. All patients were advised to continue aspirin �clopidogrel for at least 1 year. Regular follow-up wasperformed through telephone contact.

RESULTS

Thirteen patients were selected for vascular brachy-therapy and signed a written informed consent. Twopatients with multiple previous coronary interventionshad very low pulses in both radial arteries and we optedfor a femoral approach. One patient with recurrent in-

stent restenosis at the distal anastomosis between a veingraft and a marginal branch underwent a transradialapproach with successful IVUS and cutting balloon an-gioplasty. However, the prebrachytherapy IVUS re-vealed a significant mismatch between the lumens of alarge vein graft (� 3.0 mm) and a very small distal artery(1mm). Given the size of the Beta-Rail catheter (1.6mm), we felt that it was too hazardous to use it and wedid not perform brachytherapy. Therefore, this reportdeals with the initial 10 patients who were treated withthe Beta-Rail system via a transradial approach.

There were seven men and three women with a meanage of 60 � 13 years. The mean height was 167 � 9 cmand mean weight was 82 � 10 kg. In-stent restenosis waslocated in left anterior descending artery (n � 3), cir-cumflex artery (n � 3), marginal branch (n � 2), rightcoronary artery (n � 2), or vein graft (n � 1). Weperformed all procedures through the right radial artery.In seven cases, a 7 Fr sheath was initially installed andsuccessful dilatation was performed. In three cases, weselected an 8 Fr sheath. In two cases, we were unable toposition the Beta-Rail distally due to lack of backupsupport and we had to exchange for an 8 Fr left Amplatzguiding catheter to position the delivery catheter ade-quately into a distal circumflex artery. In one case, due tovigorous manipulation of the Beta-Rail catheter, wefeared minor kinks and exchanged for a new one (case 2).External testing with the dummy sources did not, how-ever, reveal malfunctioning. IVUS was successfully usedbefore PTCA (n � 8) and before brachytherapy (n � 10).In two cases, IVUS was not possible due to excessivetortuosity and a severe lesion (case 2) or was not at-tempted in one case since the patient presented with acutesevere chest pain and an occluded stent in a circumflexartery (case 5; Fig. 1). All PTCAs were successful andwe did not implant additional stents despite moderatedissections in two cases. Abciximab was used in one caseand eptifibatide in three cases. One patient underwentPTCA in a distal LAD artery and stent implantation in aproximal Cx artery immediately before the brachyther-apy procedure (case 6). In all cases, the Beta-Rail wassuccessfully positioned and the intended doses were de-livered. We used a 40 mm source in three cases and a 60mm source in seven cases. One manual stepping wasperformed three times and three steppings were per-formed in one case (case 5; Fig. 1). Repositioning duringirradiation had to be performed once (case 6). The meandwell time was 195 � 44 sec. The mean delivered dosewas 23 � 3 Gy at 2 mm distance from the source. Allirradiation procedures went uneventfully and a residuallesion � 50% with normal TIMI 3 flow was observed inall cases after irradiation. Early lumen loss after brachy-therapy was observed in one case but no further dilatationwas performed (case 5). Distal dissection after brachy-

Transradial Coronary Brachytherapy 363

Fig. 1. Case 5: Severe long in-stent restenosis in a large dominant Cx artery and in a marginalbranch. Four different irradiations were required to cover the injured vessel. There was someearly lumen loss at the bifurcation that occurred between the prebrachytherapy angiogram andthe final picture.

therapy in one case (case 9) required additional pro-longed dilatation but no stent was implanted. There wasno clinical complication and three patients sustained amild or moderate troponins I rise postintervention (case2, 114; case 5, 22.5; case 9, 23.2), but all maximum CKvalues remained below three times upper normal limit(Table I). The mean fluoroscopy time was 26 � 14 minand the mean procedure time was 138 � 37 min. Meancontrast volume was 296 � 84 ml. At clinical follow-upextending up to 3 months, all patients have remained inCanadian Cardiovascular Society angina class I.

DISCUSSION

Catheter-based brachytherapy is the first technology tohave demonstrated a significant benefit for the treatmentof in-stent restenosis [1]. In the past decade, severaldevices with different isotopes and designs have beenevaluated in animals and some have demonstrated favor-able results when applied to patients [4]. The 5 Fr non-centered catheter developed by Novoste uses a train ofseeds with pure �-emitters. This eases the use of radio-active sources in a catheterization laboratory but consid-eration of dosimetry at the presumed target tissue is morecomplex than for �-emitters [5]. Recent evidence, how-ever, suggests comparable results, at least in the short-term, between �-sources and �-sources [6]. In the re-cently completed START trial, 476 patients with in-stentrestenosis were randomized for treatment with the No-voste 90Sr/Y source or sham-treatment. At the 8-monthangiographic follow-up, in-stent restenosis rates were14.2% in the treatment group compared with 41.2% inthe sham-treatment group (P � 0.001) [7]. There was,however, some loss of the benefit at the stent edges andit has been speculated that geographical miss did occur ina significant number of cases with the use of the 30 mmsource. To overcome this limitation, a 40 mm and a 60mm source have recently been developed. In theSTART-40 trial, investigators used the 40 mm source

and longer lesions lengths were successfully treated [8].Still, the edge problem has not been completely resolvedand it is expected that the 60 mm source will furtherimprove the results. In this initial experience, bothsources have been successfully used and the intendeddoses could be delivered. To ensure good backup posi-tion of the guiding catheter, we selected right Amplatzcatheter for right coronary arteries and 7 Fr Extra BackUP (EBU) or left Amplatz (Zuma II, Medtronic) or 8 Frleft Amplatz catheter (Cordis) for left coronary arteries.In two cases, backup support with EBU catheters wasinsufficient and we had to exchange for an 8 Fr leftAmplatz catheter. It should be noted that these two caseswere related to very long in-stent restenosis in the Cxartery (cases 2 and 5).

As already shown with other percutaneous coronaryinterventions, transradial vascular brachytherapy offersto the patient significant advantages [9]. In this experi-ence, all patients underwent immediate or early ambula-tion and there was no local hemorrhagic complication. Itshould be noted, though, that it is not always possible touse 7 or 8 Fr sheaths in the radial artery [10]. Therefore,the awaited availability of the smaller 3.5 Fr catheter (6Fr compatible) with redesigned sources recently devel-oped by Novoste should further extend the use of tran-sradial vascular brachytherapy. It remains to be demon-strated whether the transradial approach carries the samerisks of geographical miss or edge restenosis than thefemoral approach [11]. In conclusion, transradial vascu-lar brachytherapy with the Novoste Beta-Rail systemappears feasible and safe, although excellent backupsupport is necessary in order to position the deliverycatheter optimally.

ACKNOWLEDGMENTS

Support from all nurses and radiology and nuclearmedicine technicians was greatly appreciated. The pres-

TABLE I. Procedure Details

Patient SexGuidingsize (Fr)

Targetvessel

Cuttingballoon

Balloonangioplasty Stepping

Source,mm Dose (Gy)

Procedureduration (min)

Maximum CK(U/L)

1 M 8 LAD Yes No 0 60 18.4 108 2142 M 73 8 Cx Yes Yes 1 60 18.4 and 23 186 3233 M 7 RCA Yes Yes 0 60 23 108 844 F 7 RCA No Yes 1 60 25.3 � 2 129 405 M 73 8 CX � Mg No Yes 3 40 25.3 � 4 212 1406 F 7 Mg Yes Yes 0 40 18.4 147 1207 F 7 LAD Yes Yes 0 40 25.3 86 318 M 8 SVG Yes Yes 0 60 25.3 140 489 M 8 Cx No Yes 1 60 23 � 2 134 224

10 M 7 LAD Yes Yes 0 60 18.4 135 103

*LAD, left anterior descending artery; Cx, circumflex artery; RCA, right coronary artery; SVG, Saphenous vein graft; Mg, marginal.

Transradial Coronary Brachytherapy 365

ence of Patrice Paiement from Novoste Corporation forthe initial cases was particularly helpful.

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366 Bertrand et al.