Optimal Pacing Site in the Atrium and the Ventricle for Patients with Sino-Atrial Disease

Patients with Sino-Atrial Disease

G. S

, C. A

, G. D

, B. G

, G. T

, J.I. R

, M. F

Patients with sick sinus syndrome (SSS) present symptoms due to bradycar- dia and chronotropic incompetence. Pacemaker implantation is indicated in these patients because it eliminates symptoms and improves quality of life.

Besides, many patients with sino-atrial disease have a high incidence of atri- al arrhythmias, mainly atrial fibrillation (AF; brady–tachy syndrome) [1]. In 1983, Coumel et al. were the first to observe the efficacy of overdrive atrial pacing to prevent recurrences of vagally mediated AF [2]. In the following years many studies were performed to investigate alternative pacing strate- gies to reduce the incidence of AF.

Atrial Pacing

Retrospective uncontrolled studies have yielded concordant results suggest- ing that AAI/R or DDD/R (physiological pacing) is associated with a lower incidence of chronic AF [3, 4]. Connolly et al. provided the first substantial evidence that atrial or dual-chamber pacing was useful in reducing progres- sion to permanent AF as compared to ventricular pacing in patients with SSS (2.6% vs 6.8%, respectively) [5]. Other studies confirmed a modest benefit offered by physiological pacing, significant after at least 2 years from implant [6–9]. Conclusions from these trials suggested that a history of AF and sinus node dysfunction represent major risk factors of recurrent chronic AF after pacemaker implantation. No difference was observed in the incidence of AF in patients paced for atrioventricular (AV) block according to pacing mode.

These beneficial effects of dual-chamber pacing in reducing AF recurrences may involve both mechanical and electrophysiological factors. Atrial or dual-

Division of Cardiology, Hospital of Cirie’ (Turin), Italy

chamber pacing provides synchronised filling patterns and ventricular con- traction, prevents consistent retrograde conduction, and reduces atrial over- load and stretch. In addition, atrial pacing can prevent AF by eliminating pauses caused by bradycardia and by suppressing atrial ectopic beats. In con- clusion, these studies proved a certain benefit conferred by atrial pacing in preventing AF in patients with SSS, and great interest was aroused in investi- gating the optimal pacing site.

The rationale for alternative site pacing is derived from the fundamental premise that conduction delays in the atrium are essential to the initiation of intra-atrial re-entrant mechanisms that underlie AF. These conduction delays may be in part anatomical and in part functional [10–12]. Besides, in patients with prolonged interatrial conduction time, a standard atrial lead position in the right appendage may produce deleterious left heart timing intervals, reducing the benefits provided by physiological pacing. Based on these observations, different pacing strategies were attempted in order to improve the modest benefit from right appendage pacing in patients with SSS.

- Biatrial pacing. This approach utilises synchronous atrial pacing from the high right atrium and the coronary sinus. The aim is to reduce pro- longed interatrial delay. D’Allones et al. reported a series of 86 patients with remarkable interatrial delay. After biatrial pacing, P wave duration was significantly reduced (187 ± 29 ms vs 106 ± 14 ms, P < 0.01) and 64%

of patients were in stable sinus rhythm [13].

- Dual-site right atrial pacing. Pacing is obtained from a first lead in the high right atrium and a second screw-in active fixation lead positioned at the coronary sinus ostium. Saksena et al. [14] reported a first experience with 30 patients. At 3-year follow-up 56% of patients were free from AF.

The DAPPAF investigators [15] enrolled 120 patients with recurrent AF and bradycardia requiring pacing. Dual-site pacing tended to prolong the time to first AF recurrence and to improve quality of life. The SYNBIA- PACE study [16] investigated 42 patients with a history of AF, prolonged duration of P wave, and intra-atrial conduction. At 9-month follow-up, dual-site pacing was shown to have increased the time to first AF recur- rence and reduced the AF burden.

- Bachmann’s bundle. Bachmann’s bundle (BB) serves to conduct cardiac

impulses from the right to the left atrium. Some studies of acute BB pac-

ing observed reduced P wave duration, increased symmetry of atrial acti-

vation, and decreased inducibility of AF [17, 18]. A multi-centre prospec-

tive randomised study compared the efficacy of BB regional pacing in 120

patients (57 patiens with pacing from atrial right appendage and 67

patients with pacing from BB). Investigators observed significant short- ening of P wave duration. At 1-year follow-up 75% of the patients paced at BB were free from chronic AF, compared with 47% paced at the tradi- tional site [19].

- Interatrial septum. Pacing at the interatrial septum is intended to achieve simultaneous pacing of both atria. Various approaches to atrial pacing have been evaluated. In 1997 Spencer et al. presented a initial experience with the atrial lead (Medtronic 4058) positioned in the most anterior region of the right interatrial septum. This approach allowed both atria to be paced simultaneously [20]. In patients with standard indications for pacemaker implantation and episodes of AF, the atrial septum was paced at the posterior triangle of Koch. This approach was safe and feasible and significantly reduced mean P wave duration and symptomatic episodes of AF [21]. Other reports, and our own experience, confirm the observation of clinical benefits in terms of reduction of AF recurrences in patients with a septal atrial lead [22, 23].

Besides alternative pacing sites, other strategies have been attempted in order to improve the efficacy of pacing in preventing AF recurrences. Several prospective studies have demonstrated that a faster atrial pace results in a higher percentage of paced beats and a reduction of AF recurrences. In order to increase the percentage of atrial pacing and to reduce sudden rate changes after premature beats, new algorithms have been proposed. These algorithms provide atrial pacing at a rate which is maintained only slightly higher than the intrinsic rate and reduces the dispersion of refractoriness. Many studies have evaluated the role of these algorithms in patients with AF recurrences.

Benefit derived from pacing at an alternative site could be increased with the use of algorithms, and several authors evaluated this combined strategy. The ASPECT trial evaluated the combined role of an atrial septal lead location and atrial pacing algorithms in the prevention of atrial tachyarrhythmias in 298 patients. The algorithms did not succeed in reducing AF burden and fre- quency, regardless of atrial lead position; however, prevention pacing was associated with a reduced frequency of premature atrial contractions and with a reduced frequency of symptomatic atrial tachyarrhythmia only in patients with atrial septal leads [24].

Finally, these studies demonstrated that interatrial septum pacing is safe

and feasible, avoids the technical problems due to the use of two atrial leads,

and permits simultaneous activation of both atria. Compared to the tradi-

tional right appendage pacing, septal pacing reduces AF recurrences and

progression to chronic AF. Patients with SSS and paroxysmal AF could be

suitable candidates for septal atrial lead pacing.

Ventricular Pacing

Although theoretically very attractive, atrial pacing for the prevention of AF has proved to be of quite modest benefit. A possible cause of this is the high percentage of ventricular pacing achieved in all studies, with a detrimental effect that could be reducing benefits from atrial pacing.

Four major clinical trials have been unable to demonstrate a clear benefit of DDDR pacing over VVIR pacing for the clinical endpoints of total mortal- ity, cardiovascular mortality, and stroke. The Danish Study [25] enrolled 225 patients with symptomatic bradycardia, randomised to undergo AAI pacing or VVI pacing, with long-term follow-up. Significantly, overall survival was higher in the AAI group, with fewer cardiovascular deaths, less AF, fewer thromboembolic complications, and less heart failure than in the VVI group.

However, AAI stimulation cannot be suitable for all patients with SSS: it requires stable long-term AV conduction and sinus rhythm, whereas SSS is a spectrum of electrical disorders including AF and AV block. For these rea- sons, other studies have considered the role of atrial pacing in DDD pace- maker versus ventricular pacing. In the CTOPP study [26] more than 2500 patients with all-cause bradycardia were randomised to undergo ventricular- based pacing or physiological pacing and followed for 3 years. The pacing mode did not produce a significant difference in the primary endpoint of stroke or cardiovascular death. Physiological pacing significantly reduced the cumulative risk of any AF and of chronic AF. In this study DDD pace- makers were not provided with algorithms to minimise ventricular pacing, with consequently a high cumulative percentage of ventricular pacing that could offset benefits from atrial pacing. Another large randomised study (MOST) [27] investigated more than 2000 patients with SSS randomised to receive DDDR or VVIR pacemakers, with as primary endpoint death from any cause or non-fatal stroke. At a median follow-up of 33 months no differ- ence in relation to total mortality or stroke was found; but dual-chamber pacing reduce newly diagnosed and chronic AF and progression to heart failure. A strong relation between the percentage of ventricular pacing (in both the DDDR and the VVIR group) and the risk of progression to heart failure was observed. Ventricular pacing in DDDR mode for more than 40%

of the time conferred a 2.6-fold increased risk of heart failure. Other inter- esting suggestions come from the DAVID trial [28], which has enrolled 506 implantable cardioverter–defibrillator (ICD) patients with no indication for antibradycardia pacing and left ventricular dysfunction (EF < 40%).

Patients were randomly assigned to receive an ICD with back-up VVI at 40

beats/min versus DDDR at 70 beats/min, with as primary endpoint a combi-

nation of death and heart-failure-related hospitalisation. At 18 months VVI 40 was associated with a 16% rate of heart-failure hospitalisation or death, versus 26.7% for DDDR 70 (P = 0.03).

In conclusion, in patients with SSS, ventricular pacing should be min- imised in order to maintain benefit produced by atrial pacing. Different strategies have been proposed to optimise right ventricular pacing: a novel right ventricular pacing site, manipulation of DDDR timing cycles to min- imise unnecessary right ventricular pacing, and the use of novel pacing algo- rithms.

Alternative pacing sites, such as right ventricular outflow tract or ventric- ular septum, are supposed to improve synchronous activation of the ventri- cle and thus avoid impairment of ventricular function. New active fixation leads guarantee feasibility, good thresholds, adequate sensing, and stability.

Initial experience with these new tools should be supported by large, long- term, randomised studies in order to demonstrate an advantage on the right ventricular apex.

A long AV delay did not succeed in reducing total ventricular pacing time.

The current generation of devices have new features to minimise ventric- ular pacing. The Search AV (SAV+, Medtronic EnPulse) offers the capability to search out longer AV intervals, up to 320 ms, in patients with intact or intermittent AV conduction. A prospective, multi-centre, non-randomised trial evaluated the ability of SAV+ ON to preserve intrinsic ventricular acti- vation in 194 patients with intact AV conduction. At 1-month follow-up patients with SAV+ ON had 76.3% ventricular sensing vs 2.8% in those with SAV+ OFF [29].

Another new algorithm is the minimal ventricular pacing mode (MVP,

Medtronic, Minneapolis) implemented in a dual-chamber ICD. This provides

AAI/R pacing with ventricular monitoring and back-up DDD/R pacing only

as needed during episodes of AV block. Single dropped ventricular beats are

permitted (Wenckebach behaviour), while higher-level AV conduction failure

causes mode switching to DDD/R to prevent asystole. Tests for a return to

normal AV conduction are made, and if AV conduction is detected, the ICD

returns to AAI/R mode. A randomised study with MVP was performed on 30

patients with DDD/R ICDs. Each patient spent a week in DDD/R mode and a

week in MVP. The cumulative percentage of ventricular pacing was signifi-

cantly lower during MVP than during DDD/R pacing (3.79% vs 80.6%,

P < 0.0001). Three patients (10%) presented transient AV block with switch

to DDD/R, confirming that a ventricular back-up could be opportune even in

patients without a history of AV block.

Conclusions

Patients with SSS should be implanted with a dual-chamber pacemaker.

Alternative sites appear superior to the traditional right appendage site since they improve atrial synchrony and may reduce AF recurrences. The hig per- centage of ventricular pacing in DDD mode in all studies is a common pitfall comparing physiological pacing and VVI mode is characteristic of a com- mon pitfall: ventricular pacing has a deleterious effect on both atrial and ventricular function that may mask the real beneficial entity of atrial pacing.

New pacing site in the right ventricle and use of algorithms to minimise ven- tricular pacing is likely to lead to more consistent positive results. In conclu- sion, data from the literature suggest that in patients with SSS atrial pacing from an alternative site should be used, employing algorithms to attain the highest possible percentage of atrial pacing and to reduce ventricular pacing as much as possible.

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