Adjunctive Atrial Pacing

Holter monitor recordings from patients with AF have revealed that episodes may be initiated by absolute or relative bradycardia, by postectopic pauses, and/or by increasing atrial ectopy (33,34). However, the prevalence of bradycardia- or pause-dependent AF onset in patients with AF may be relatively low in untreated patients (34). Regardless of the prevalence, relatively rapid atrial pacing may prevent bradycardia-dependent onsets for AF and overdrive suppress atrial ectopy (34,35). In addition, relatively rapid atrial pacing rates may decrease the dispersion of atrial refractoriness which electrically stabilizes the atria and facilitate rate-dependent antiarrhythmic drug effects (34,35). Thus, there are several reasons that pacing the atria at relatively rapid rates (60-80 BPM) or consistently faster than the underlying sinus rate could result in a decreased frequency of AF.

Previous retrospective studies and some prospective studies comparing single-chamber ventricular pacing (VVI) vs physiologic pacing (DDD or AAI) in patients with sick sinus syndrome (most of whom do not have AF) have suggested that physiologic pacing approaches decrease the likelihood of AF developing during long-term follow-up (36-40). However, the retrospective trials are limited by a number of methodological flaws (40). Only one prospective trial has shown a clinically significant benefit to physiologic pacing (41,42). Other prospective trials have shown only modest benefits (43) or no advantage (44,45) (Fig. 1). These studies have not confirmed whether the decrease, if any, in AF is a result of a beneficial effect of physiologic pacing or the negative effects of ventricular pacing in facilitating the occurrence of AF. Ventricular pacing may cause manifest or occult pacemaker syndrome (46), exacerbate mitral regurgitation (15), and cause electrical and mechanical remodeling of the atria that facilitate the genesis of AF (47).

Recent prospective trials targeting patients with AF have raised serious questions regarding the benefit of right atrial pacing for prevention of AF (45,48). In the Atrial Pacing Periablation for Prevention of Atrial Fibrillation Trial, patients with planned AV-junction ablation had a dual-chamber pacemaker implanted 3 mo prior to ablation. Patients were randomized to continue their medical management of AF or to receive aggressive atrial pacing in addition to the medical therapy (48). Recurrence rates of AF were identical in paced and nonpaced patients (Fig. 2), indicating no benefit when single-site pacing is used for AF suppression for patients with no bradycardia-pac-ing indication.

Several innovative pacing algorithms for the prevention of AF recurrences have been proposed. Overdrive atrial pacing simply involves pacing the atrium at a rate higher than would be typical. Consistent atrial pacing involves increasing the atrial rate in response to premature atrial contractions (PACs), in an effort to suppress atrial ectopy. Current clinical trials are addressing these algorithms. More sophisticated pacing prevention algorithms have been incorporated in the Medtronic Jewel AF 7250 atrial/ ventricular defibrillator, although efficacy data are not yet available.

Fig. 1. Cumulative risk of AF in patients with sick sinus syndrome randomized to receive a single-chamber ventricular pacemaker (VVI) or an atrial-based pacemaker (either AAI or DDD) in the Canadian Trial of Physiological Pacing. Note that there is no difference in AF occurrence until after 2 yr of follow-up, at which point atrial-based pacing is associated with a small, decreased risk of AF. (Reproduced with permission from ref. 43.)

Fig. 1. Cumulative risk of AF in patients with sick sinus syndrome randomized to receive a single-chamber ventricular pacemaker (VVI) or an atrial-based pacemaker (either AAI or DDD) in the Canadian Trial of Physiological Pacing. Note that there is no difference in AF occurrence until after 2 yr of follow-up, at which point atrial-based pacing is associated with a small, decreased risk of AF. (Reproduced with permission from ref. 43.)

Fig. 2. Survival free of recurrent AF in patients with AF and no indication for pacing randomized to DDD-R pacing or no pacing in the Atrial Pacing Periablation for Prevention of Atrial Fibrillation Trial. There is no difference in risk of recurrent AF in either group. (Reproduced with permission from ref. 48.)

Fig. 3. Actuarial curves demonstrating the percentage of patients free of recurrent AF with dual-atrial-site pacing (DAP) and single-atrial-site pacing (SAP) from the high right atrium compared to the baseline before pacing. Note that both decrease the risk of recurrent atrial fibrillation, but that dual-site pacing is more effective in preventing AF than single-site pacing in this study. (Reproduced with permission from ref. 53a.)

Fig. 3. Actuarial curves demonstrating the percentage of patients free of recurrent AF with dual-atrial-site pacing (DAP) and single-atrial-site pacing (SAP) from the high right atrium compared to the baseline before pacing. Note that both decrease the risk of recurrent atrial fibrillation, but that dual-site pacing is more effective in preventing AF than single-site pacing in this study. (Reproduced with permission from ref. 53a.)

The site of pacing within the right atrium may also be important. In a retrospective study, Seidl et al. demonstrated that AF occurred in 28% of patients in whom the atrial lead was placed along the right atrial freewall, compared to only 5% when the lead was placed in the right atrial appendage (49). More recent prospective studies have demonstrated a decreased incidence of AF with septal atrial pacing, presumably a result of the rapid and more simultaneous activation of both atria (50). More uniform activation of both atria may decrease the dispersion of electrical refractoriness, decrease intra-atrial conduction, and decrease AV mechanical dys-synchrony, and concomitantly decrease compensatory sympathetic stimulation, all of which may prevent AF initiation or maintenance. Papageorgiou et al. demonstrated that there may be key zones of slow conduction along the tricuspid valve, inferior vena caval isthmus, and intra-atrial septum, which greatly facilitate AF maintenance (50). More uniform activation of these regions may decrease the probability of creating conditions appropriate for intra-atrial reentry and AF initiation maintenance.

Another means of achieving more uniform atrial activation is to pace two atrial sites simultaneously. Dual-site atrial pacing has been clinically evaluated, either by pacing the right atrial appendage and distal coronary sinus (CS) or pacing the right atrial appendage and CS ostium. Preliminary data suggests that either form of dual-site pacing may decrease the risk of AF as compared to the unpaced state and, to a lesser extent, to single-site pacing (Fig. 3) (51-53). This effect may be more dramatic for patients with marked intra-atrial conduction delay (52). However, others have found a benefit to dual-site pacing, even for AF patients with no detectable profound atrial conduction delays (53). Studies have not yet revealed which patient characteristics (if any) suggest a high rate of response to dual-site atrial pacing for suppression of AF in conjunction

Table 4

Factors Relevant to Direct Current Cardioversion Success

Procedural

Patient-specific

Waveform (biphasic vs monophasic) Pad/paddle position Electrode size Energy

Conductive medium

Chronicity of AF Left atrial size Body habitus

Hemodynamic/metabolic issues

Mitral-valve disease

Left ventricular dysfunction with continued antiarrhythmic drug therapy. Multicenter prospective, randomized trials DAPPAF (dual-atrial vs single-atrial) and SYNBIAPACE (dual-atrial vs single-atrial vs no atrial) are currently being performed to further address the preventative role of multi-site pacing in larger patient populations with AF (54,55). However, given the uncertainties surrounding adjunctive pacing for AF suppression, studies should still be considered investigational unless the patient has an established indication for pacemaker insertion.

Atrial fibrillation may occur in up to 40% of patients after open-heart surgery. Temporary single- or dual-site pacing using epicardial wires placed at the time of open-heart surgery may also be useful for prevention of postoperative AF. However, the results of published studies to date are conflicting, with some showing no benefit to pacing and some showing benefit only with dual-site or with single-site pacing (56-60).

Direct current (DC) cardioversion, initially introduced by Lown and colleagues for AF in the early 1960s, remains the most effective means of restoring sinus rhythm (61). DC cardioversion is generally performed using transient intravenous (iv) deep sedation or general anesthesia. Success rates for external cardioversion using standard monophasic energies up to 360 J have varied. Lown's initial series reported a success rate of 89% (62), but more recent series have typically reported success rates of 80% or less (63). One of the problems with external cardioversion is that only about 4% of the delivered current passes through the heart (64). For this reason, a number of related approaches have been developed, including internal cardioversion, intracardiac cardioversion, external cardioversion using sequential shocks, and pharmacologic pre-treatment prior to cardioversion. The incorporation of biphasic waveforms in external defibrillators has markedly increased the efficacy of external cardioversion, limiting the necessity of these adjunctive techniques. The increased efficacy offered by biphasic external cardioversion and the option to cardiovert internally if necessary have changed the focus from whether or not sinus rhythm can be restored to whether sinus rhythm can be maintained.

A number of variables may affect the success of DC cardioversion, including both patient-specific and procedure-specific issues (63) (see Table 4). An anterior-posterior pad placement appears optimal; it remains uncertain whether the best initial choice is right anterior-left posterior or left anterior-left posterior. If the initial electrode position is unsuccessful, cardioversion can be reattempted following a change in electrode

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