Long-Term Use of the Atrial and Dual Defibrillator: What Have We Learned?

We Learned?

J.M. M

, A.S. T

, D.A.M.J. T

, L.J. J

Background

Persistent atrial fibrillation represents a management problem for the physi- cian and a condition associated with considerable morbidity. The results of anti-arrhythmic therapy are disappointing [1]. In the 1980s the rapid devel- opments in implantable device technology, combined with the knowledge that atrial defibrillation thresholds were far lower with internal cardiover- sion than with transthoracic cardioversion [2] and the rationale for applying early cardioversion of atrial defibrillation to limit electrical remodelling, led to the development of the implantable atrial defibrillator or atrioverter. The first commercially available device was only capable of delivering low-energy shocks, specifically for atrial defibrillation; later, high-energy devices became available that could accomplish atrial and ventricular defibrillation.

Electrode configurations are variable, with shock coils positioned in the right atrium and coronary sinus or only in the right ventricle or different combinations.

Stand-Alone Atrial Defibrillators

The InControl Metrix Atrioverter system (Guidant Corp., St Paul, Minn., USA) consists of an implantable atrial defibrillator connected to right atrial and coronary sinus defibrillation leads and a right ventricular pacing lead (Fig. 1). It is capable of delivering a maximum of 6 J of energy. This system was evaluated acutely in a study of 51 patients [3] and demonstrated the

Department of Electrophysiology, Erasmus Medical College, Rotterdam, The

Netherlands

capability of the device to deliver promptly and safely internal shocks for the acute treatment of recurrent episodes of atrial fibrillation. These patients were subsequently also evaluated in the ambulatory setting [4].

Dual-Chamber Defibrillators

A number of implantable cardioverter defibrillators (ICDs) capable of deliv-

ering shock therapy for atrial and ventricular tachyarrhythmias have been

developed, including the Jewel AF model 7250 ICD and GEM III AT

(Medtronic, Inc., Minneapolis, Minn., USA), and the Prizm AVT and Vitality

AVT (Guidant Corp., St Paul, Minn., USA). In addition, these devices can

deliver overdrive pacing therapy in the atrium which may obviate the need

Fig. 1.Chest radiograph of a patient with an implanted atrioverter with leads in the right

atrium, the coronary sinus, and the apex of the right ventricle. The right atrial and coro-

nary sinus leads are used for arrhythmia recognition and defibrillation. The right ven-

tricular lead is used for shock synchronisation and, if needed, ventricular pacing

to administer a shock. The largest amount of data published has been on the Jewel AF, a dual-chamber defibrillator also capable of delivering preventive pacing therapies and atrial overdrive pacing. It delivers a maximum of 27 J of electrical energy. This device is combined with pace-sense electrodes in the right ventricle and atrium together with one ventricular and one supraventricular shocking electrode and an optional third high-voltage elec- trode in the coronary sinus. It may be employed as an active can device or subcutaneous patches may be added. The device uses algorithms to distin- guish between atrial tachycardia, atrial fibrillation, and ventricular tach- yarrhythmias. It may be programmed to deliver atrial shock therapy auto- matically (Fig. 2) after a variable interval or only in response to a patient- initiated request given by means of a manual activator. The former program- ming allows for automatic shocks to be delivered at a moment when the patient is least likely to experience it as painful, uncomfortable, or inconve- nient; the latter programming allows the patient to optimise conditions for delivery of the shock, including taking a sedative or analgesic prior to shock delivery. To minimise the risk of inducing a ventricular tachyarrhythmia the device synchronises the shock with an R wave and will only deliver therapy after a relatively long R-R interval, nominally 500 ms in this device. This device was evaluated in the Worldwide Jewel AF-Only Trial [5].

Safety and Efficacy of Cardioversion of Atrial Fibrillation by Implantable Devices

In the study by the Metrix investigators [3] the device delivered a total of 670 shocks for 227 spontaneous episodes of AF in 41 patients during a mean fol- low-up of 259 days (2 SD = 138 days). A further 3049 shocks were delivered for induced episodes of AF during testing of the synchronisation adequacy

Fig. 2. Intracardiac electrogram and a marker channel showing the detection and shock termination of an episode of atrial tachycardia in a Jewel AF dual-chamber defibrillator.

TF interval below atrial tachycardia detection interval, TD atrial tachycardia detection, AS atrial sensed event, VS ventricular sensed event

and atrial defibrillation threshold. There was not a single instance of ventric- ular arrhythmia induced by shocks delivered for atrial fibrillation, confirm- ing that R wave synchronisation was adequately achieved by the device. It is important to note that the trial excluded patients with anything more than mild structural or ischaemic cardiac disease as well as patients with a docu- mented episode of ventricular tachyarrhythmia. As regards efficacy, 96% of the spontaneous episodes of atrial fibrillation were successfully cardioverted by the device, but in 27% of episodes several shocks were required because of early recurrence of atrial fibrillation (ERAF). Arrhythmia recognition occurred with high specificity.

In the Worldwide Jewel AF-Only Trial [5] a total of 1036 shocks were delivered for atrial tachyarrhythmia without a single instance of induced ventricular dysrhythmia. The efficacy of delivered shocks in terminating atrial tachyarrhythmias was 86.7%. The efficacy of atrial overdrive pacing was 40%, a high percentage, explained by the fact that many episodes of atri- al tachyarrhythmia started as a well-organised atrial tachycardia. The mean follow-up period was 12.6 ± 6.2 months. Based on analysis of available stored electrograms, the positive predictive accuracy of the detection algo- rithm was 98.9%. Fifty-four episodes of delivered therapy were inappropri- ate, caused by sensing of far-field signals or multiple premature atrial beats.

After 1 year, 94% of the patients remained in sinus rhythm, and 91% still had atrial therapies enabled.

Again, this trial excluded patients with documented ventricular tach- yarrhythmias, but moderate to severe heart disease was not an exclusion criterion (except for NYHA class IV symptoms). Of 67 episodes of ventricu- lar tachycardia or fibrillation, 58 were successfully terminated by device intervention; the remaining 9 terminated spontaneously. The incidence of ventricular tachyarrhythmia (6.7%) was relatively high, a fact which casts doubt on the wisdom of implanting a stand-alone atrial defibrillator.

However, this high incidence may have arisen from selection bias and fur- ther, a significant proportion of patients had NYHA class III symptoms and/or left ventricular ejection fraction (LVEF) of less than 35% – charac- teristics that in 2005 are accepted as indications for ICD implantation [6, 7].

An intriguing finding from this study is that 75% of ventricular tach- yarrhythmias started during an episode of atrial tachyarrhythmia. Other studies [8] have also described a temporal relation between atrial fibrilla- tion and ventricular tachyarrhythmia.

Anti-tachycardia pacing and shock therapy resulted in a significant

reduction in the atrial tachyarrhy thmia burden from a mean of 58.5

h/month to 7.8 h/month [9].

Long-Term Follow-Up of the Dual Defibrillator

Longer-term follow-up in a smaller group of patients [10] revealed a very high rate of successful device intervention, with 96% of episodes successfully terminated with a single shock. This study revealed three different patterns of atrial fibrillation recurrence, with a trend to longer duration of sinus rhythm after successful cardioversion in only a minority of patients, provid- ing limited evidence for the concept that ‘sinus rhythm begets sinus rhythm.’

Timmermans et al. [11] similarly reported a decrease in the number of episodes requiring therapy and an increase in the time between episodes after 260 ± 144 days in patients implanted with the Metrix device.

Modern devices are also capable of delivering overdrive pacing in the atrium in order to terminate episodes of more organised atrial tachycardia, hopefully preventing the rhythm from degenerating into atrial fibrillation.

Most can also deliver 50 Hz pacing in an attempt to convert atrial fibrilla- tion to sinus rhythm before proceeding to shock therapy. The efficacy of these modalities is 71.3% for anti-tachycardia pacing (ATP) on atrial tachy- cardia and 36.2% for 50 Hz pacing for atrial fibrillation [12, 13].

Early recurrence of atrial fibrillation (ERAF) after successful ambulatory cardioversion is common [14], reaching 70% at 24 h, and is commoner with an episode duration of less than 3 h, with episodes where multiple shocks are required, and in the absence of a history of myocardial infarction.

In a long-term follow-up of 136 patients with the Metrix device [15], at a median of 40 months after implantation only 39 of 106 (37%) for whom data was available were still actively delivering therapy with the device. In 14 patients (13%) the device was being used to monitor the arrhythmia, with action taken in the event of a recurrence, either as a device-delivered or transthoracic cardioversion under the supervision of the treating physician.

In 53 patients the device had either been turned off or explanted for a vari- ety of reasons including: a rise in the defibrillation threshold, rendering the device incapable of performing successful cardioversion in 7 patients; intol- erance of shocks due to frequent atrial fibrillation recurrences in 15 patients;

significant bradycardia necessitating atrioventricular sequential pacing, of

which this device was incapable, in 12 patients; and battery depletion in the

remaining 19 patients. Of these 19 patients, 7 refused implantation of a new

defibrillator due to intolerance of shocks, 9 received a second-generation

dual-chamber defibrillator, 6 received a dual-chamber pacemaker (with or

without preventive or therapeutic pacing algorithms) and 2 received anti-

arrhythmic drug therapy (in combination with a Maze procedure in 1). In 36

patients rhythm control was abandoned in favour of a strategy of rate con-

trol (including ablate-and-pace therapy in 13).

Device-Related Complications

In the study by the Metrix investigators [3] there were 8 system-related com- plications, including 2 cases of lead displacement. In the Worldwide Jewel AF-Only Trial [5] there were 26 system-related complications in 23 patients.

Lead displacement was the commonest complication, occurring in 11 instances; 5 of these were displacements of the atrial tripolar lead, which is heavier than a standard bipolar lead. This incidence should be much less if a standard dual-coil ventricular defibrillation lead is used.

Tolerability of Delivered Shocks and Quality of Life

The tolerability of this device therapy is highly variable. Anti-tachycardia pacing is generally tolerated well, shocks less so. Nevertheless, a careful analysis of measures of quality of life in the Jewel-AF trial [16] demonstrated a convincing improvement in all subgroups of patients, with no evidence of an attenuation of this improvement in those who received shocks. Indeed, the proportion of episodes for which patients used the activator increased during the course of the study. Follow-up in this report, however, was short (6 months). In a study with a longer follow-up, Ricci et al. reported signifi- cant improvement in the quality of life and decreased hospitalisation in a group of 40 patients with the Jewel AF device implanted [17]. In one survey, acceptance of device therapy is good at 18 months after implantation [18]

but does correlate with a number of patient characteristics with which the physician should be familiar, such as lower psychosocial distress, lower anxi- ety score, and lesser atrial fibrillation symptom burden. Automatic night- time shocks are significantly less acceptable to patients than patient-activat- ed shocks with pre-medication [19]. Pre-medication with sedation is pre- ferred to that with analgesia [20].

Patient Selection

The trials conducted to date have limited the use of the atrial or dual defib-

rillator to patients with recurrent atrial fibrillation refractory to combina-

tion or sequential drug therapy. Patients with permanent atrial fibrillation

are clearly not candidates. From the long-term follow-up data [15, 16, 18] it

appears that therapy is better tolerated by patients with a lower atrial fibril-

lation burden.

Future of the Atrial Defibrillator

The advent of ablation techniques for atrial fibrillation [21] with good short- term and medium-term results heralds a new era in the treatment of this condition in patients with symptomatic paroxysmal or persistent atrial fib- rillation in the absence of severe structural heart disease [22]. No doubt improvement in techniques with a commensurate increase in success and decrease in complications will mean this modality will be applicable in a larger group of patients, including those with more severe structural cardiac disease [23].

What then is the role for the atrioventricular defibrillator in 2005 and beyond? Patients who were previously candidates for the stand-alone atrial defibrillator, i.e. those with minimal cardiac disease but symptomatic drug- refractory paroxysmal atrial defibrillation, should nowadays have a pul- monary vein isolation procedure performed. Patients with more severe structural heart disease probably have an indication for implantation of an ICD in light of the results of the more recently published trials [6, 7]. The incorporation of atrial defibrillation modalities into ICDs (a development of the philosophy that spawned the Jewel AF device) for a select group of patients with recurrent symptomatic drug-refractory atrial fibrillation may ensure the survival of the atrial defibrillator. In particular, patients with hypertrophic obstructive cardiomyopathy, who are at risk of sudden death from ventricular tachyarrhythmias, and who can develop rapid haemody- namic deterioration with the onset of atrial dysrhythmias, may benefit remarkably from this device, especially if paced from the apex of the right ventricle with a short atrioventricular delay. A large number of patients with congenital heart disease, who are also at high risk of developing atrial and ventricular tachyarrhythmias, likewise form a particular target group.

Conclusions

Atrial and dual defibrillators held great promise when they were introduced in the 1990s.

The devices are effective and safe in selected patients. Tolerability and

acceptance by patients is good in the short term but only moderate in the

longer term. The complication rate is relatively low. However, advances in

ablation techniques for the treatment of atrial fibrillation have limited and

will continue to limit the use of implantable atrial defibrillators. In combina-

tion with ICDs they may find a continued role in a patient group that should

be further defined.

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