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changes are generally reversible and seem to bear no definite relation to dose frequency or duration of therapy. Reports of agranulocytosis with levamisole have almost invariably been associated with the treatment of connective tissue or neoplastic diseases. The very low frequency of adverse events in this study is encouraging, and if one combines these data with those of previous reports a total of 140 patients may be analysed. In only 3 of these 140 patients < 2 x 109/1 documented, was a neutrophil count of and this effect was rapidly reversed when therapy was stopped. There were no cases of agranulocytosis in this patient population. Despite these encouraging data, regular full blood count monitoring should be undertaken during

therapy. The optimum dose frequency and duration of levamisole therapy in steroid-responsive nephrotic syndrome remain unclear. If this approach is successful, and provided adequate monitoring is undertaken, a longer period of alternate day therapy-eg, 6-12 months-may be justified in patients with steroid toxicity. results show that levamisole is effective in maintaining a steroid-free remission in patients with high-dose steroid dependency. This drug is worth considering as an alternative to further alkylating therapy or Thus

our

cyclosporin. The British Association for Paediatric Nerphrology acknowledge the expert statistical support given by Dr G. D. Murray, Senior Lecturer in Medical Statistics, University of Glasgow; the help and support given by Janssen Pharmaceuticats Ltd (UK); and the secretarial help of Mrs Lynda

McCarroll, RHSC, Glasgow.

REFERENCES 1. International Study of Kidney Disease in Children. Prospective, controlled trial of cyclosphamide therapy in children with the nephrotic syndrome. Lancet 1974; ii: 423-27. 2. Schnaper HW. The immune system in minimal change nephrotic syndrome. Pediatr Nephrol 1989; 3: 101-10. 3. Amery WK. The mechanism of action of levamisole through enhanced cell maturation. J Reticuloendothel Soc 1978; 24: 187-93. 4. Amery WK, Gough DA. Levamisole and immunotherapy: some theoretic and practical considerations and their relevance to human disease. Oncology 1981; 38: 168-81. 5. Tanphaichitr P, Tanphaichitr D, Sureeratanan J. Treatment of nephrotic syndrome with levamisole. J Pediatr 1980; 96: 490-93. 6. Niaudet P, Drachman R, Gagnadoux MF, Broyer M. Treatment of idiopathic nephrotic syndrome with levamisole. Acta Paed Scand 1984; 73: 637-41. 7. Pecoraro C, Usberti M, Guida B, et al. Levamisole in the treatment of frequently relapsing nephrotic syndrome. Kidney Int 1985; 28: 295

(abstr). 8. Mehta KP, Ali U, Kutty M, Kolhatkar U. Immunoregulatory treatment for minimal change nephrotic syndrome. Arch Dis Child 1986; 61: 153-58. 9. Drachman R, Schlesinger M, Alon U, et al. Immunoregulation with levamisole in children with frequently relapsing steroid responsive nephrotic syndrome. Acta Paed Scand 1988; 77: 721-26. 10. Mongeau JG, Robitaille PO, Roy F. Clinical efficacy of levamisole in the treatment of primary nephrosis in children. Pediatr Nephrol 1988; 2: 398-401. 11. Kirubakaran MG, Jacob GK, Date A, Shastry JCM. A controlled trial of levamisole in frequently relasping minimal change disease. Kidney Int 1984; 26: 240 (abstr). 12. International Study of Kidney Disease in Children. Nephrotic syndrome in children: a randomised trial comparing two prednisolone regimens in steroid responsive patients who relapse early. J Pediatr 1979; 93: 304-05.

Radiofrequency current catheter ablation of accessory atrioventricular pathways

Tachyarrhythmias mediated by an accessory atrioventricular pathway and which are refractory to drug therapy have been treated surgically with variable success. Early results of direct-current catheter ablation were encouraging but were associated with complications such as barotrauma and the need for a general anaesthetic. We have investigated the endocardial application of radiofrequency current which is a potentially safer technique. Of 105 patients with an accessory atrioventricular pathway, 79 were located on the left side of the heart and 32 on the right side. Accessory pathway conduction was permanently abolished in 93 (89%) patients. Complications developed in 3 patients: thrombotic occlusion of a femoral artery, arteriovenous fistula formation at the site of groin puncture, and left ventricular rupture with cardiac tamponade after direct-current shocks. There were no deaths from the procedure. We conclude that radiofrequency current catheter ablation is both effective and safe for patients with symptomatic tachyarrhythmias mediated by accessory atrioventricular pathways.

Introduction Catheter ablation is a new treatment for patients with refractory tachyarrhythmias. The technique was introduced in 19821 and initial clinical reports were encouraging,.3,4 However, the drawbacks of direct-current defibrillator shocks, such as lack of energy titration, risk of barotrauma, and the need for general anaesthesia, have led to the adoption of an alternative source of ablative energy, namely alternating current in the radiofrequency range (30 kHz to 300 MHz). The endocardial application of radiofrequency current to cardiac tissues has none of the disadvantages of direct-current shock therapy, and first reports on its successful use for the control of supraventricular5 and ventricular tachycardias6 have been promising. For tachyarrhythmias that are mediated by an accessory atrioventricular pathway, catheter ablation is especially valuable because of its potential to cure patients without recourse to

surgery. For selected anatomical locations of

accessory pathways, the direct-current approach has proved reasonably successful,’ although side-effects may occur.8

ADDRESS.

Department of Cardiology, University Hospital Eppendorf, 2000 Hamburg 20, Germany (K-H. Kuck, MD, M. Schluter, PHD, M. Geiger, MD, J Siebels, MD, W. Duckeck, MD) Correspondence to Dr K-H. Kuck.

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The first case of permanent interruption by radiofrequency current of a right-sided free-wall accessory pathway was reported in 1987,9 while we had previously introduced a catheter technique for potential interruption of left-sided free-wall accessory pathways. 10 Case reports have shown the efficacy of radiofrequency current in humans;",12 they form the basis for this study of transcatheter radiofrequency current ablation in symptomatic patients with accessory pathways at locations throughout both atrioventricular annuli.

Patients and methods Patients 105 consecutive patients (39 females, 66 males; mean [SD] age 40 [16] years) who were referred to our department because of symptomatic tachyarrhythmias related to an accessory atrioventricular pathway were studied. 83 patients had the WolffParkinson-White syndrome, while 22 were found to have a concealed accessory atrioventricular connection (retrograde conduction only). 100 patients were free of organic heart disease, 1 had hypertrophic obstructive cardiomyopathy, and 4 had coronary artery disease. In 2 patients, previous surgery for accessory pathway division had failed to interrupt accessory pathway conduction. Patients’ symptoms included disabling palpitations, nausea, dizziness, and feelings of faintness. Syncope took place in 16 patients, and 7 were survivors of cardiac arrest after ventricular fibrillation. Duration of symptoms ranged from three months to nearly 40 years. In most patients, the frequency and/or severity of

symptoms increased in the 3

to

12 months before referral.

Symptoms in 92 patients were caused by atrioventricular re-entrant tachycardia (paroxysmal in 91, incessant in 1); 39 patients had atrial fibrillation with or without a rapid ventricular response, and 2 patients had permanent junctional reciprocating tachycardia. Drug trials with a median of two antiarrhythmic agents (range 1-7) had failed in 90 patients before ablative therapy. Routine electrophysiological investigation before attempted ablation was completed in the first 20 patients, but in none of those remaining because it was clear that such information did not influence outcome of electrode catheter treatment. All patients were informed about the experimental nature of the catheter ablation procedure and gave their consent. Catheters For atrial and ventricular pacing, standard 6 French ’USCI’ quadripolar catheters were positioned in the high right atrium and at the right ventricular apex, respectively. A 6 F USCI hexapolar catheter with a 2 mm interelectrode distance was placed so as to record His-bundle activation. For coronary sinus mapping, a 6 F catheter with three sets of four circumferential electrodes arranged in an othogonal configuration (’Jackman’ catheter, Mansfield/ Webster, Billerica, Massachusetts) was advanced from the left subclavian vein into this vessel. The ablation catheter was a standard 6 F quadripolar catheter with a distal electrode of 2 mm in the first 13 patients, and a steerable 7 F quadripolar catheter with a tip electrode of 4 mm (Mansfield/Webster, Billerica, Massachusetts; or Dr Osypka GmbH, Grenzach-Wyhlen, Germany) in remaining patients. In those with a right-sided accessory pathway, the same catheter was used for mapping of the tricuspid annulus.

Fig 1-Preablation electrograms. Two sinus beats are shown in a patient with a right-sided accessory pathway The endocardial recording shows two potentials (AP, and APJ from different parts of the same accessory pathway, and which are between the local atrial (A) and ventricular (V) potentials III=Surface electrocardiographic lead. H RA = Endocardial electrogram from the high right atrium

repeated at the ostium and along the proximal part of the coronary sinus with a standard 6 F quadripolar or steerable 7 F large-tip catheter, introduced via the right femoral vein. area was

Ablation A custom-built generator supplying unmodulated 300 kHz alternating current at constant preset voltages for variable periods of time was used for accessory pathway ablation in the first 13 patients. A 500 kHz generator (’HAT 200’, Dr Osypka GmbH, GrenzachWyhlen, Germany) was used in all other subjects; this generator stores data of radiofrequency current delivery (power, duration, and cumulative energy) on a personal computer system that is unable to calculate voltage, current, or impedance. In patients with right-sided accessory pathways, radiofrequency current was applied between the tip electrode of the mapping/ ablation catheter and a back-paddle below the patient’s left scapula. The catheter was introduced via the right internal jugular vein in patients with pathways located on the right anterior (anterolateral, anterior, and anteroseptal) region of the heart, and via the right femoral vein in patients with pathways located on all other

right-sided areas of the heart. For ablation of left-sided free-wall accessory pathways, the ablation catheter was advanced from the right femoral artery into the left ventricle and positioned high against the mitral annulus, directly opposite the tip electrode of the coronary sinus mapping catheter. The procedure has been described in detail before.’2

Mapping Mapping of both atrioventricular rings was completed during orthodromic reciprocating tachycardia or right ventricular pacing, and during sinus rhythm or atrial pacing. The mapping technique for precise localisation of accessory pathways has been described before,13 and depends on the direct recording of an accessory pathway potential (fig 1). In case of a left posteroseptal pathway location, mapping for subsequent ablation of the left posteroseptal

Fig 2-Catheter ablation electrode). DC= Direct-current shock

in the first 13

patients (standard-tip

therapy; SD=sudden death

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Fig 5-Pre and post ablation electrograms.

Fig 3-Catheter ablation in 92 patients (large-tip electrode). AA=Antiarrhythmic drug therapy; DC=direct-current shock

This patient had a right-sided posteroseptal accessory pathway. Each panel shows two sinus beats. Note loss of accessory pathway potential (AP) postablation, whereas the local atrial (A) and ventricular (V) potentials remain almost unchanged. H His-bundle potential. =

therapy. In the first 13 patients with a left-sided free-wall accessory pathway, radiofrequency current was delivered between the tip

electrode of the left ventricular catheter and the coronary sinus catheter electrode that had located the accessory pathway.10-12 In all other patients with a left-sided free-wall accessory pathway (including one repeat ablation), radiofrequency current was applied between the tip eletrode of the left ventricular catheter and a back-paddle. This "ventricular" approach was also used in 4 patients with a left posteroseptal accessory pathway. In the other 10 patients with a left posteroseptal accessory pathway, radiofrequency current was applied between the tip electrode of the ablation catheter, introduced from the right femoral vein and curved towards the bottom of the proximal coronary sinus, and a back

paddle. In patients with the Wolff-Parkinson-White syndrome, radiofrequency current was delivered during sinus rhythm or during coronary sinus pacing at a rate slightly above that of the sinus rhythm. Concealed accessory pathways were ablated during orthodromic supraventricular tachycardia that allowed indirect assessment of conduction block in the accessory pathway by termination of the tachycardia. Ablation was thought successful in the electrophysiological laboratory if both antegrade and retrograde accessory pathway conduction was eliminated, or if retrograde conduction through concealed pathways was no longer present. After successful ablation of an accessory pathway, one additional "safety" application was given to minimise the possibility of late recurrence of accessory pathway conduction. In cases of an electrophysiological failure of the ablation attempt(s), ablation was taken to be a clinical success if accessory pathway conduction was lost spontaneously within three

months of the procedure, and the patient was free of arrhythmiarelated symptoms without antiarrhythmic medication. In these patients, loss of accessory pathway conduction was confirmed by a

postablation electrophysiological study. During the procedure some patients were either sedated with diazepam (5-15 mg) or lightly anaesthetised with fentanyl (0-1-0-5 mg). After catheter positioning, a bolus of 100 IU/kg heparin was given intravenously, followed by a second injection of 5000 IU after 4 h.

Follow-up After ablation, the first 50 patients were monitored in the intensive care ward for 48 h. Supraventricular or ventricular arrhythmias were never observed and remaining patients were transferred to the ward. A two-dimensional echocardiogram was completed each day, surface electrocardiograms were recorded twice daily, and serum creatine kinase was measured every 6 h for the first two days. All patients were discharged within two to five days on 300 mg acetylsalicylic acid daily.14 Patients were seen in the outpatient clinic after one and three months, and every six months thereafter. At each visit, the patient’s clinical course was assessed, a physical examination completed, and both a surface electrocardiogram and a two-dimensional echocardiogram recorded. Data are presented as mean [SD] values. In cases of a non-Gaussian distribution of measured variables, the median value is given instead of the mean.

Results Catheter treatment with radiofrequency current was aimed at a total of 111 accessory pathways. In 4 patients, two pathways each were subjected to radiofrequency current therapy;1 patient underwent ablation of three pathways. Of the 79 left-sided accessory pathways, 62 were overt (they had consistent antegrade and retrograde conduction properties) and 17 were concealed. Of 32 right-sided pathways, 24 were overt and 8 were concealed. A total of 131 ablation procedures was completed in the 105 patients. 20 patients underwent a single repeat session, and 3 consented to a third attempt at ablation. A median of 9

(range 1-53) radiofrequency current pulses were applied per

Fig 4-Radiofrequency current treatment. Electrograms from the same patient as shown in fig 1 are given. Radiofrequency current (RFC) is applied to the right anterior site of the accessory pathway during sinus rhythm. There is almost immediate loss (larger arrow) of the delta (A) wave indicating conduction block in the accessory pathway.

session. Cumulative electrical energy delivered per session ranged from 84 to 31587 J (median, 3503). Sessions lasted for a mean of 4-3 h [1°9] (range 1-10’5). Patients’ mean radiation exposure time per session was 53-2 min [32°8] (range 1’6-148’2). In each session, ablative therapy was directed towards a single accessory pathway, except in 2 patients in whom multiple pathways were destroyed in one session. In all patients, serum creatine kinase activities were within normal limits ( < 100 IU/1).

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Ablation with the standard-tip electrode catheter In the first 13

patients, 18 ablation procedures were with a standard-tip electrode catheter (fig 2). completed of 6-2 watts [2’ 3] per radiofrequency current A mean power pulse was applied for 17-6 s [3-9]. Abolition of accessory pathway conduction was achieved in 4 patients (31 %). 3 patients underwent a successful repeat ablation attempt with the large-tip electrode catheter, and 1 patient is scheduled for repeat ablation. 7 of 13 patients had a successful outcome of electrical ablative therapy. Ablation with the large-tip electrode catheter In 92 patients, the initial attempt at accessory pathway ablation was completed with the large-tip electrode catheter (fig 3). Successful radiofrequency current application led to accessory pathway conduction block within 3 s of onset of radiofrequency current (fig 4); this was associated with a loss of accessory pathway potentials without altering local atrial and ventricular potentials (fig 5). Mean pulse power and mean pulse duration were significantly higher compared with the standard tip electrode (26-7 watts [3’9] and 23-1 s [5-9], respectively; p

Radiofrequency current catheter ablation of accessory atrioventricular pathways.

Tachyarrhythmias mediated by an accessory atrioventricular pathway and which are refractory to drug therapy have been treated surgically with variable...
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