First worldwide clinical experience with a new dual chamber implantable cardioverter defibrillator

Transcription

1 Europace (1999) 1, First worldwide clinical experience with a new dual chamber implantable cardioverter defibrillator Advantages and complications C. Sticherling, A. Schaumann*, T. Klingenheben and S. H. Hohnloser for the Ventak AV II DR investigators Department of Cardiology, J.W. Goethe University, Frankfurt, Germany; *Department of Cardiology, Georg-August University, Göttingen, Germany Aims The need for physiological pacing and for improving the ability to discriminate atrial from ventricular tachyarrhythmias has prompted the development of dual chamber implantable cardioverter/defibrillators (ICDs). Methods Fifty-two patients were implanted with a newly developed dual-chamber ICD providing rate-responsive physiological pacing (Ventak AV II DR). The device possesses two new arrhythmia detection algorithms ( atrial fibrillation rate threshold and ventricular to atrial rate relationship ) in addition to commonly used features such as onset and stability. During implantation, the atrial and ventricular lead impedances and pacing thresholds were determined together with the defibrillation threshold. Prior to discharge, attempts were made to induce both atrial and ventricular tachyarrhythmias in order to test those new detection criteria. All patients were followed for at least 3 months. Results The device was successfully implanted in all 52 patients. Placement of the atrial lead was successful in 50/52 patients (96%; P-wave mv; impedance Ω; atrial pacing threshold V). Prior to discharge, 32 episodes of atrial fibrillation (AF) alone, 38 episodes of AF with ventricular fibrillation and 10 episodes of AF with monomorphic ventricular tachycardia were induced in 33/50 patients (66%) and all were appropriately classified by the detection algorithm. During the 3 months follow-up, 12 patients (23%) had appropriate and successful therapies for ventricular arrhythmias, while four patients (8%) experienced inappropriate ICD therapies. Although all these episodes were detected correctly as supraventricular arrhythmias by the device, therapy was delivered because of incorrect or incomplete programming. In all cases reprogramming of the device resolved the problem. Conclusion Implantation of dual chamber ICDs is feasible and appears to improve discrimination of supraventricular from ventricular tachyarrhythmias. In addition, patients with tachyarrhythmias and concomitant bradyarrhythmias may benefit from simultaneous physiological pacing. However, implantation and follow-up of such patients should be performed at experienced centres since both surgical handling and programming of these devices is more difficult and complex than conventional ICDs. (Europace 1999; 1: ) Key Words: Implantable cardioverter/defibrillator, sudden cardiac death, dual chamber pacing, atrial fibrillation, discrimination of atrial and ventricular arrhythmias, inappropriate ICD shock. Introduction With the more widespread use of implantable cardioverter/defibrillator (ICD) therapy [1], an increasing number of patients will require concurrent therapy with Manuscript submitted 21 September 1998, and accepted after revision on 17 December Correspondence: Stefan H. Hohnloser, MD, FACC, FESC, J.W. Goethe University, Department of Internal Medicine, Division of Cardiology, Theodor-Stern-Kai 7, D Frankfurt, Germany. physiological antibradycardiac pacemaker systems. It has been estimated that up to 20% of ICD recipients are in the need of concomitant permanent antibradycardia pacing [2 4]. Concurrent therapy with ICD and separate antibradycardiac pacemaker systems, however, bears considerable risks for the patient; for instance, undersensing of ventricular fibrillation or oversensing of pacemaker spikes could result in inappropriate ICD therapy [5]. Although patients with life-threatening tachyarrhythmias benefit significantly from recent advances in ICD technology, such as reduction in /99/ $18.00/ The European Society of Cardiology

2 Dual chamber ICD therapy 97 generator size and transvenous implantation techniques [6], inappropriate ICD therapy for supraventricular tachyarrhythmias remains a significant clinical problem. Inappropriate shock therapy, mainly due to atrial fibrillation (39%), sinus tachycardia (30%) and oversensing (24%), occurs in up to 20% of all ICD recipients [7 10], and is associated with marked patient discomfort. Furthermore, inappropriately delivered antitachycardia pacing or shock delivery may result in the provocation of sustained ventricular tachyarrhythmias, an effect which has been referred to as ICDassociated proarrhythmia [11]. To improve differentiation between supraventricular and ventricular tachyarrhyhthmias, several enhanced detection criteria, such as onset, stability, QRS morphology or QRS width criteria have been implemented in new ICDs [12 18]. The development of new ICDs with dual chamber sensing and pacing properties offers the possibility of enhancing accuracy of arrhythmia detection by adding the analysis of atrial rhythms to the detection algorithms of the devices [19 21]. The present study examined the feasibility of implanting a novel dual chamber ICD with sequential pacing properties. During a limited follow-up of 3 months, the rate of complications and the ability to detect atrial arrhythmias safely, by means of two novel detection criteria based on direct sensing of the atrial rhythm, were studied. Methods Patient population This prospective study was carried out in 18 European investigational sites. Patients at high risk of sudden cardiac death were eligible if they had survived at least one episode of (1) cardiac arrest due to ventricular fibrillation (VF); (2) sustained ventricular tachycardia (VT) with haemodynamic deterioration or (3) a remote myocardial infarction resulting in a left ventricular ejection fraction of 35% and a documented episode of non-sustained VT; the latter patients had to have an inducible ventricular tachyarrhythmia not suppressible with intravenous procainamide on subsequent electrophysiological testing [22]. Exclusion criteria for the present study were (1) life expectancy less than 6 months; (2) patients on heart transplantation list; (3) previous implantation of unipolar antibradycardiac pacemakers; (4) previously documented ventricular arrhythmias due to a reversible cause; and (5) participation in other antiarrhythmic drug or investigational device trials. The study was approved by the local Institutional review boards of all participating centres. Written informed consent was obtained from all patients prior to enrollment in the study. The investigation was conducted conforming to EN 540 and the Declaration of Helsinki. Technical specification of the novel dual-chamber ICD The CPI Ventak AV II DR models 1821 and 1826 are dual chamber two-lead devices using ventricular defibrillation and bipolar pace/sense leads and atrial bipolar pace/sense leads with tip-to-ring electrode spacing of 8 15 mm for atrial sensing and pacing. To distinguish ventricular tachyarrhythmias of different rates from bradycardias, sinus rhythm or atrial tachyarrhythmias, the device employs different programmable detection criteria such as (1) the heart rate; (2) the onset, i.e. the relationship of the cycle length of the initial tachycardia cycle length to the previous cycle lengths; (3) the stability of cycle lengths within the tachycardia; (4) sustained rate duration (SRD); i.e. the duration for which therapy is withheld by one of the described inhibition criteria (5) the ventricular rate>atrial rate criteria; and (6) the atrial fibrillation rate threshold. The atrial fibrillation rate threshold (Afib threshold) feature is programmed in conjunction with the stability criterion and aims to suppress inappropriate therapy for fast ventricular rates secondary to fast atrial fibrillation or atrial flutter. If the ventricular rhythm is classified unstable and the atrial rate is higher than the programmed Afib threshold ( min), therapy is withheld. When the ventricular rate>atrial rate (V rate>a rate) criterion is programmed, onset and stability criteria are ignored and therapy is delivered. Thus, the potential advantage of the new enhancement criteria is to prevent underdetection of VT that is either irregular (Afib threshold) or does not fulfil the onset criterion (V rate>a rate). Accordingly, the new features cannot directly decrease the incidence of inappropriate shocks as compared with the criteria employed in single chamber devices. However, they allow more aggressive programming of the established features since these new criteria are likely to prevent fatal underdetection of VT that is either too irregular or does not fulfil the onset criterion. All mentioned detection enhancement criteria can only be activated in the lowest VT detection zone to avoid any potentially possible underdetection of fast VT or VF. The device terminates ventricular tachyarrhythmias by antitachycardia pacing (ATP) and/or high-voltage mono- or biphasic shock therapy. It provides bipolar atrial and ventricular, pre- and post-shock bradycardia pacing in a variety of modes, including dual chamber rate adaptive pacing. Implantation procedure and baseline measurements The devices were implanted under general anaesthesia by a surgeon or an electrophysiologist. During implantation, device lead measurements were performed in the final lead position as follows: amplitude of the R- and P-wave, QRS duration, atrial and ventricular pacing

3 98 C. Sticherling et al. impedances and pacing thresholds as well as the shock lead impedance. Step-down biphasic DFT testing, defined as the minimum energy yielding successful conversion of VF or polymorphic VT in a series of arrhythmia inductions with decreasing energy steps, was recommended for all patients. Pre-discharge measurements Prior to hospital discharge, atrial and ventricular lead measurements were performed to confirm appropriate sensing and pacing thresholds. Correct VF detection and conversion efficacy of the device had to be verified. Prior to VF conversion testing, the induction of atrial tachyarrhythmias was recommended by the protocol in order to examine the atrial fibrillation threshold detection enhancement features of the device. For this purpose, the device s tachycardia mode was programmed to monitor only to avoid inappropriate therapy delivery. In order to test in a worst case scenario for detection of VT, the atrial fibrillation rate threshold was programmed to 200 min, stability to 6 ms, onset to 250 ms, ventricular>atrial rate on and SRD off. The atrial fibrillation threshold feature is used in conjunction with the stability feature. If a ventricular rhythm is classified stable, therapy is delivered to terminate the arrhythmia. If the stability criterion indicates instability of a fast rhythm, the atrial fibrillation threshold algorithm confirms whether the atrial rate exceeds the programmed threshold, with therapy being inhibited in this case until either the ventricular rhythm becomes stable or the atrial rate falls below the threshold, at which point therapy will be delivered. Atrial fibrillation was induced using the atrial electrophysiological function of the device. If the induced atrial arrhythmia did not terminate spontaneously, the subsequent VF conversion testing was performed in the presence of the atrial tachyarrhythmia. 1 and 3 months follow-up The patients were seen in the outpatient arrhythmia services of the implanting centres 1 and 3 months after the implantation. Device interrogation was performed to document therapy history for any spontaneous arrhythmic episode. New arrhythmic episodes were retrieved and visually evaluated to verify appropriate detection and therapy by the device. Atrial and ventricular lead measurements were performed as described above. At 1-month follow-up, additional activity testing was performed to evaluate rate sensor performance with the device being programmed to DDDR. All stored arrhythmia episodes within the first 3 months were printed out and subsequently reviewed by an experienced electrophysiologist. Particular emphasis was given to verify appropriateness of ICD therapy Table 1 Demographic data of the patient population Age (years) (range: 30 78) Gender Male 46 (88 5%) Female 6 (11 5%) Left ventricular ejection fraction (%) (range: 14 76) New York Heart Association Classification Class I 13 (25%) Class II 25 (48%) Class III 13 (25%) Missing 1 (2%) Underlying cardiac disease Coronary artery disease 33 (63%) Non-ischaemic cardiomyopathy 12 (23%) Valvular heart disease 1 (2%) None 2 (4%) Other 4 (8%) Underlying arrhythmia VF 23 (44%) Polymorphic VT 5 (10%) Monomorphic VT 28 (53%)* Additional arrhythmias Paroxysmal atrial arrhythmias 10 (19%) Permanent atrial fibrillation/flutter 2 (4%) Other 3 (6%) Bradyarrhythmias II or III AV-block 16 (31%) Sinus node dysfunction 9 (17%) Atrial fibrillation with slow ventricular rate 1 (2%) *Patients may be counted in more than one category. delivery for arrhythmic episodes and to evaluate correct detection of supraventricular arrhythmias by the ICD. Statistical analysis Descriptive statistics were used to summarize the results. For continuous variables, mean standard deviations with 95% confidence intervals, and ranges were used to examine the data. Results Patient population The Ventak AV II DR ICD was successfully implanted in a total of 52 patients. The demographic data of the patient cohort are summarized in Table 1. In addition to the primary ventricular tachyarrhythmia (VF=44%, monomorphic VT=53% and polymorphic VT=10% of patients), 10 patients (19%) had a history of paroxysmal and two patients (4%) of permanent atrial fibrillation/ flutter. A total of 26 patients (50%) had a history of bradyarrhythmias (Table 1). Baseline measurements at implantation All patients were initially implanted with one transvenous lead. Intracardiac R- and P-wave signals could

4 Dual chamber ICD therapy 99 Table 2 Results of ICD-lead measurements At implantation At 3 months n Mean SD n Mean SD Atrial parameters P-wave (mv) Pacing impedance (Ω) Pacing threshold at 0 5 ms (V) Ventricular parameters R-wave (mv) Pacing impedance (Ω) Pacing threshold at 0 5 ms (V) not be measured in five patients who had an underlying rhythm with a heart rate <40 beats min 1. The atrial lead could be successfully placed in 50/52 patients (96%). Two patients were not implanted with an atrial lead but required rate responsive ventricular pacing (VVIR). Table 2 depicts results of device lead measurements obtained at the time of implantation. In 26/52 patients (50%), a step-down to failure DFT testing was completed, achieving a DFT 11 Joules (average values 10 4 J) in 21/26 patients (81%). Detection enhancement testing at pre-discharge Forty-two episodes of atrial fibrillation were induced in the described worst scenario setting for detection of monomorphic VT in 33 patients at the time of hospital discharge. For this purpose the ICD was programmed as a two-zone device with the VF zone beats. min 1 in the monitor-only mode. Atrial fibrillation was correctly identified by the device (i.e. therapy was withheld for atrial fibrillation) in all 42 instances. Subsequently, the tachycardia mode was activated, VF was induced, and therapy for the ventricular tachycardia was delivered. Antibradycardia pacing requirements and one month follow-up exercise testing Forty-four of the 52 devices (85%) were programmed in the DDDR or DDD-mode (DDDR=30 patients, Table 3 Cumulative incidence of atrial and ventricular pacing at 3 months Percentage of paced beats Atrial (n) Ventricular (n) 25% <50% % <75% % 3 19 n=patients. DDD=14 patients, DDI=2 patients, VVIR=5 patients; AAIR=1 patient). At 3 months follow-up, 19 patients had more than 75% of their ventricular beats and three patients of their atrial beats paced (Table 3). The appropriateness of the accelerator sensor function was tested in 40 patients (77%) who were able to undergo exercise testing. In 32 patients (80%), the nominal programming (maximal sensor rate: 120 min 1 ; activity threshold: medium; reaction time: 30 s; response factor: 8; recovery time: 5 min) yielded a rate response according to the individual patient s need during activity; in eight patients the sensor settings had to be reprogrammed. Spontaneous arrhythmia episodes and ICD measurements at 3 months follow-up At 3 months follow-up, 16 ICDs (31%) were programmed as a three-zone device, 24 (46%) as a two-zone device and 12 (23%) as a one-zone device. The detection enhancement criterion stability was activated in 27 patients (52%), A-rate threshold in 23 patients (44%), onset in 11 patients (21%) and V-rate>A-rate in 27 patients (52%). Device interrogation revealed a total of 217 arrhythmic episodes in 13/52 patients (25%). Twelve of 52 patients (23%) had a total of 139 episodes of ventricular tachyarrhythmias (VF=14, polymorphic VT=22, monomorphic VT=103). One hundred and eleven episodes (80%) were treated successfully with antitachycardia pacing (ATP), 13 episodes (12%) were converted by device shocks, and 15 episodes (14%) spontaneously converted. A total of 73 inappropriate therapies (ATP=71; shock=2) due to rapidly conducted atrial fibrillation occurred in two patients (4%). One patient had 67 ATP attempts during one day; in this case, the detection enhancement criteria stability, ventricular to atrial rate relationship and atrial fibrillation rate threshold had been programmed off. After activation of these ICD detection enhancement features, no further false treatment attempts were documented during an additional observation period of 6 weeks. The second patient experienced a total of six ICD therapies because the

5 100 C. Sticherling et al. therapy inhibition feature sustained rate duration (SRD) time had been programmed too short. Prior to therapy, all episodes had been classified appropriately through the novel detection algorithm. In addition, two patients (4%) had a total of five documented inappropriate ATP attempts for sinus tachycardia. In one case, SRD was programmed too short. The other treatment occurred in a patient with complex arrhythmias (frequent premature ventricular complexes, slow VT, sinus tachycardia) 25 min after ICD implantation. Analysis of this episode revealed that sinus tachycardia had been inappropriately treated with ATP, and subsequent ICD shock delivery had resulted in induction of VF which was appropriately detected and terminated by the device. At the time of this event, none of the ICD detection enhancement criteria had been activated. After device reprogramming, no further episodes of false ICD therapy were observed in this patient. There was no instance of inappropriate therapy secondary to lead-related problems or oversensing. Complications and clinical events during follow-up Two patients died during the observation period. One death occurred at day 7 following ICD implantation while the patient was at home. The death was unwitnessed and the device could not been interrogated prior to his funeral. At hospital discharge, his ICD was programmed as an one-zone device with a rate cut-off of 180 beats min 1, implying that none of the detection enhancement criteria could be activated. Accordingly, it appears unlikely that complex device programming was responsible for the death of the patient. Rather, it is conceivable that the lack of programming a VT zone could have resulted in the persistence of VT at a rate of <180 beats. min 1 with consecutive haemodynamic compromise. The second patient died 32 days after ICD implantation of a cerebral haemorrhage while she was treated with warfarin. Neither ICU monitoring nor final ICD interrogation showed an arrhythmic event preceding the patient s decease. (Final programming: 3-zone device; stability=16 ms, Afib threshold=off, onset=off, V rate>a rate=on, SRD=1 min.) Two patients developed ICD pocket infections (2 and 3 months after implantation) requiring system explantation with subsequent implantion of a new ICD system. Two patients received an additional subcutaneous array electrode due to inability to convert VF either during implantion or at the pre-discharge test. Four patients had atrial lead dislocation of their passive fixation-leads (two in-hospital; two during follow-up) and one patient had a fracture of both the atrial and ventricular lead secondary to a motor vehicle accident. One patient with a history of symptomatic paroxysmal atrial fibrillation went into chronic atrial fibrillation after discharge and underwent AV node ablation a few weeks after ICD implantation. Accordingly, in 10/52 patients (19%) a prespecified clinical event was observed which was related to the ICD system in at least eight patients (15%). Discussion To the best of our knowledge, the present study represents the largest consecutive series of dual chamber ICD-implantation and follow-up so far published. Several observations made deserve some comments. There are two main reasons for the development of these sophisticated two-lead systems. First, the number of ICD recipients (5 20%) [2 4] who in addition to therapy of life-threatening ventricular tachyarrhythmias are in the need of physiological permanent antibradycardia pacing (dual chamber) continues to increase with the more widespread use of device therapy. Although feasible, implantation of separate ICD and antibradycardia pacemaker systems bears considerable risks [5]. Secondly, the incorporation of direct atrial sensing in detection enhancement criteria to differentiate between supraventricular and ventricular tachyarrhythmias offers a new promising approach to reduce the incidence of inappropriate ICD therapy. Inadequate ICD therapy carries a considerable risk of proarrhythmic effects [11,23]. Direct simultaneous sensing of atrial and ventricular rhythms allows the application of novel detection enhancement criteria. Established criteria relying on ventricular sensing only (onset, stability) reduce the number of inappropriate therapies significantly but cannot completely avoid this important problem [15]. The more sophisticated detection parameter, QRS width, still shows considerable intra-individual variations and needs to be refined before being clinically applicable [16]. In contrast, dual chamber sensing allows the clinical application of an atrial fibrillation threshold in conjunction with stability or the ventricular-to-atrial rate relationship to withhold inappropriate therapy. In the present study, this feature correctly classified all induced and spontaneous atrial arrhythmias. As a potential limitation, however, it has to be emphasized that only those atrial arrhythmias occurring concurrently with a ventricular arrhythmia are stored by the device. Therefore, the precise number of atrial arrhythmias which could have potentially resulted in inappropriate therapies without the novel detection algorithms cannot be precisely determined. The new detection criterion atrial fibrillation threshold only became effective after the established feature, stability, had already classified the arrhythmia as unstable. Accordingly, there was no documentation of spontaneous VT episodes that had been inhibited or accelerated by the new detection enhancement criteria. To circumvent this limitation, respective changes in the ICD software have currently been commenced. The incidence of 8% of the patients experiencing inappropriate ICD therapies in the present study is in accordance with the results of previously published large

6 Dual chamber ICD therapy 101 series [6,24]. Since all of these inappropriate therapies observed in our study were related to incorrect or incomplete device programming, most of these episodes can be assumed to be potentially avoidable. It is important to note that there was no evidence that the device misclassified atrial arrhythmias or that therapy for ventricular arrhythmias had been incorrectly withheld. Even assuming that programming of onset or stability criteria could potentially withhold appropriate therapy, the addition of the dual chamber sensing feature ventricular rate>atrial rate will overrule the former. The present data clearly demonstrate that correct programming and use of the new detection enhancement criteria are crucial in order to maximize the potential benefits of new dual chamber ICDs. Moreover, the relatively high incidence of acute complications observed in our study probably reflects the fact that the handling of these new sophisticated devices is much more complex and challenging compared with the use of conventional single-chamber ICDs. In part, the high incidence of complications may also reflect the learning investigators. Accordingly, a word of caution seems appropriate in that patients benefitting from these devices should be implanted and followed only in experienced high-volume electrophysiological laboratories. Clinical implications Dual chamber lead ICD devices represent a promising new development for patients requiring simultaneous therapy for ventricular tachyarrhythmias and bradyarrhythmias [4,5,25,26]. Additionally, they provide a new approach to solve or at least to reduce the problem of inappropriate ICD therapy secondary to supraventricular arrhythmias, presuming correct device programming. However, they also bear the risk of higher acute complication rates mainly related to the implantation of two leads. Optimal programming of these devices is timeconsuming and requires experienced electrophysiologists. However, only such optimal device programming will offer maximal benefit of this sophisticated treatment modality. References [1] Garrat CJ. A new evidence base for implantable cardioverter defibrillator therapy. Eur Heart J 1998; 19: [2] Calkins H, Brinker J, Veltri EP et al. Clinical interactions between pacemakers and automatic implantable cardioverterdefibrillators. J Am Coll Cardiol 1990; 16: [3] Echt DS, Armstrong K, Schmidt P et al. Clinical experience, complications, and survival in 70 patients with the automatic implantable cardioverter/defibrillator. Circulation 1985; 71: [4] Higgins SL, Williams SK, Pak JP et al. Indications for implantation of a dual-chamber pacemaker combined with an implantable cardioverter-defibrillator. Am J Cardiol 1998; 81: [5] Sticherling C, Klingenheben T, Skupin M et al. Combined therapy with transvenous cardioverter/defibrillator and antibradycardia pacemaker systems. Z Kardiol 1997; 86: [6] Sticherling C, Klingenheben T, Cameron D, Hohnloser SH, for the Worldwide 7221 ICD investigators. First worldwide clinical experience with a new down-sized active can implantable cardioverter defibrillator in 162 consecutive patients. PACE 1998; 21: [7] Weber M, Block M, Brunn J et al. Inadequate therapies with implantable cardioverter-defibrillators incidence, etiology, predictive factors and preventive strategies. Z Kardiol 1996; 85: [8] Schmitt C, Montero M, Melichercik J. Significance of supraventricular tachyarrhythmias in patients with implanted pacing cardioverter defibrillators. PACE 1994; 17: [9] Grimm W, Flores BF, Marchlinski FE. Electrocardiographically documented unnecessary, spontaneous shocks in 241 patients with implantable cardioverter defibrillators. PACE 1992; 15: [10] Sticherling C, Klingènheben T, Hohnloser SH. An unusual cause of ICD shock. PACE 1997; 20: [11] Pinski SL, Fahy GJ. The proarrhythmic potential of implantable cardioverter-defibrillators. Circulation 1995; 92: [12] Olson WH, Bardy GH, Mehra R. Onset and stability for ventricular tachyarrhythmia detection in an implantable cardioverter-defibrillator. In: Computers in Cardiology, New York, NY, IEEE Press; 1987: 92: [13] Higgins SL, Lee RS, Kramer RL. Stability: an ICD detection criterion for discriminating atrial fibrillation from ventricular tachycardia. J Cardiovasc Electrophysiol 1995; 6: [14] Neuzner J, Pitschner HF, Schlepper M. Programmable VT detection enhancements in implantable cardioverter defibrillator therapy. PACE 1995; 18: [15] Schaumann A, von zur Muehlen F, Gonska BD et al. Enhanced detection criteria in implantable cardioverterdefibrillators to avoid inappropriate therapy. Am J Cardiol 1996; 78: [16] Klingenheben T, Sticherling C, Skupin M et al. Intracardiac QRS electrogram width a new arrhythmia detection feature for implantable cardioverter defibrillators. PACE 1998; 21: [17] Swerdlow CD, Chen PS, Kass RM et al. Discrimination of ventricular tachycardia from sinus tachycardia and atrial fibrillation in a tiered-therapy cardioverter-defibrillator. J Am Coll Cardiol 1994; 23: [18] Swerdlow CD, Ahern T, Chen PS et al. Underdetection of ventricular tachycardia by algorithms to enhance specificity in a tiered-therapy cardioverter-defibrillator. J Am Coll Cardiol 1994; 24: [19] Chiang CM, Jenkins JM, DiCarlo LA, The value of rate regularity and multiplicity measures to detect ventricular tachycardia in the presence of atrial fibrillation or flutter. PACE 1994; 17: [20] LeCarpentier GL, Baga JJ, Yang H et al. Differentiation of sinus tachycardia from ventricular tachycardia with 1:1 ventriculoatrial conduction in dual chamber implantable cardioverter defibrillators: feasibility of a criterion based on the atrioventricular interval. PACE 1994; 17: [21] Korte T, Jung W, Wolpert C et al. A new classification algorithm for discrimination of ventricular from supraventricular tachycardia in a dual chamber implantable cardioverter defibrillator. J Cardiovasc Electrophysiol 1998; 9: [22] Moss AJ, Jackson Hall W, Cannom DS et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. N Engl J Med 1996; 335: [23] Cohen TJ, Chien WW, Lurie KG et al. Implantable cardioverter defibrillator proarrhythmia: case report and review of the literature. PACE 1991; 14: [24] PCD Investigator Group. 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7 102 C. Sticherling et al. [25] Blanck Z, Niazi I, Axtell K et al. Feasibility of concomitant implantation of permanent transvenous pacemaker and defibrillator systems. Am J Cardiol 1994; 74: [26] Haffajee C, Casavant D, Desai P et al. Combined thirdgeneration implantable cardioverter defibrillator with permanent unipolar pacemakers: preliminary observations. PACE 1996; 19: Appendix Study centres: Austria: AKH Wien, Schmidinger (3 patients). France: Hôpital Cardiologique Lille, Kacet (2 patients). Hôpital Cardiovasculaire Lyon, Touboul (1 patient). Germany: University of Bonn, Jung (1 patient). University of Düsseldorf, Vester, Winter (1 patient). University of Frankfurt/M., Hohnloser, Klingenheben, Sticherling (5 patients). University of Göttingen, Herse, Schaumann (4 patients). University of Hamburg,Rüppel, Schuchert (4 patients). Marienhospital Herne, Trappe (4 patients). University of Magdeburg, Auricchio (7 patients). University of Mainz, Himmrich (1 patient). University of Münster, Block (1 patient). Kerckhoff- Klinik Bad Nauheim, Neuzner (5 patients). Israel: Neufeld Cardiac Research Institute, Tel Hashomer, Glickson (3 patients). Italy: Ospedale Consorziale Policlinico, Bari, Favale (2 patients). Ospedale Civile Piacenza, Capucci (5 patients). The Netherlands: Akademisch Ziekenhuis, Leiden, Schalij (1 patient). Akademisch Ziekenhuis, Maastricht, den Dulk (2 patients).