Role of AV junction ablation and cardiac resynchronisation pacing in patients with permanent atrial fibrillation 

Background

Largest trials limit cardiac resynchronisation therapy (CRT) to patients with sinus rhythm, excluding patients with atrial fibrillation (AF) because in these, the effect of cardiac resynchronisation is potentially limited by rate irregularity, interference of the intrinsic rhythm with pacing that causes incomplete biventricular (BiV) pacing and impossibility to perform atrioventricular (AV) resynchronisation. Nevertheless, in clinical practice, up to 40 % of patients with drug-refractory congestive heart failure have permanent atrial fibrillation (AF) and physicians are seeking advice as to how to deal with their patients.

There are two main components for optimal cardiac resynchronisation therapy (CRT) in patients with permanent AF: ventricular rate control and regularisation; and, resynchronizing the contraction of the left ventricle (LV).

When rate control and regularisation cannot be achieved with drugs, AV node ablation and permanent pacing from the right ventricular (RV) apex provides highly efficient rate control and regularisation of AF. The prerequisite and the rationale for the benefit of biventricular pacing (BiV) is that it is able to resynchronise LV walls that have delayed activation.

Therefore, three possible treatment scenarios arise from these considerations:
1. AV junction ablation alone
2. BiV pacing alone
3. BiV pacing on top of AV junction ablation

1) AV junction ablation alone  

Is rate regularisation achieved by AV junction ablation effective?

AV junction ablation and RV pacing are perceived by certain physicians as palliative therapy (i.e., an old disease -rate irregularity- is replaced by another disease, iatrogenic AV block) that causes pacemaker dependency and may even worsen heart failure. For these reasons it is perceived as a potentially harmful therapy that should be avoided as much as possible. Nevertheless, a few randomised and several observational studies in the last two decades have included thousands of patients. They have consistently shown that, in selected patients, AV junction ablation and permanent pacing from the RV apex provides highly efficient rate control and regularisation of AF and improves symptoms without ventricular function deterioration (1,2,3,4,5,6,7,8).

In reality, AV junction ablation is easily performed, it has a low complication rate, and is highly effective in controlling specific symptoms, it improves quality of life, does not worsen or even improve cardiac performance, doesn’t increase morbidity and mortality over long-term follow-up. In brief, AV junction ablation and RV pacing are a very effective and attractive therapy for patients with permanent AF and refractory heart failure. Nevertheless, large randomised controlled clinical trials comparing AV junction ablation with conventional pharmacological therapy are warranted in order to definitely assess the efficacy of such a therapy on hard clinical outcomes, i.e., mortality, hospitalisation and quality of life (8).

2) CRT alone

Is CRT alone effective ? (or do we have to perform AV junction ablation together with BiV pacing in AF patients to avoid interference of the intrinsic rhythm with pacing?). 

The figure below shows a typical case of a patient with permanent AF undergoing BiV pacing. In panel A, BiV is almost always inhibited by a higher intrisic ventricular rate; no resynchronisation pacing is possible. In panel B, sophisticated algorithms have been enabled in order to synchronise BiV pacing to intrinsic rhythm. The result is an imperfect fusion between some intrinsic and paced beats despite an iatrogenic increase in heart rate, some beats still remain unpaced and ventricular rate remains irregular and high. The resulting resynchronisation effect is surely partial. Finally, in panel C, BiV pacing is performed on top of AV junction ablation that causes a complete AV block; no interference with the intrinsic rhythm is possible, a full simultaneous BiV pacing is now achieved and rate is regular. This example clearly shows that achieving complete AV block forms a prerequisite for optimal BiV pacing.

Based on this pathophysiological background, Gasparini et al (9) compared the efficacy of BiV pacing in 48 patients with permanent AF in whom ventricular rate was controlled by drugs, thus resulting in apparently adequate delivery of biventricular pacing (>85% of pacing time), and in 114 permanent AF patients, who had undergone AV junction ablation (100% of resynchronization therapy delivery). During up to 4 years of follow-up, only patients who underwent ablation showed a significant increase in ejection fraction, reverse remodeling effect and improved exercise tolerance; no improvements were observed in AF patients who did not undergo ablation. The improvements of left ventricular function and functional capacity was similar to that observed in patients in sinus rhythm only if AV junction ablation was performed.
In brief, strong pathophisyological background and clinical results suggest the utility of AV junction ablation in order to assure constant BiV stimulation.

3) CRT on top of AV junction ablation

Do we need to perform CRT on top of rate regularisation achieved by AV junction ablation?

Although AV node ablation and permanent RV pacing is very effective, nevertheless, RV pacing is not considered optimal, since it provides a non-physiologic asynchronous contraction which might partly counteract its beneficial effects (1,10). On RV pacing, the ventricular activation sequence resembles that of left bundle branch block, i.e. the right ventricle is activated before the left (inter-ventricular dyssynchrony) and the LV septum before the LV free wall (intraventricular dyssynchrony). RV pacing has been seen to induce LV dyssynchrony in an acute setting (11) and after long-term pacing therapy (12) in approximately 50% of patients. Some small acute studies (13,14) suggest that BiV pacing may exert an additive beneficial hemodynamic effect to that of rate regularisation achieved through AV junction: AV junction ablation plus RV pacing increased ejection fraction and reduced the magnitude of mitral regurgitation, BiV pacing doubled these effects.

Three randomised trials (15,16,17), with 347 patients in all, compared BiV pacing vs RV pacing in AF during a short-term clinical follow-up. These trials did not individually report a statistically significant improvement in survival, stroke, hospitalisation, exercise capacity, or healthcare costs. BiV was associated with a statistically significant improvement in ejection fraction in two of the three trials. Thus, although BiV pacing doubles the acute hemodynamic effects of AV junction ablation, the additive short-term clinical benefit of BiV after rate regularisation achieved with AV junction ablation seem modest. On the other hand, upgrading to BiV pacing those patients who developped heart failure months or years after AV junction ablation resulted in a great clinical benefit (18,19). For example, Leon et al (18) upgraded to BiV pacing 20 patients who became severely symptomatic 17 months after AV junction ablation and RV pacing; they observed an improvement of NYHA class of 29%, of Mineesota LHFQ score of 33% and a reduction of hospitalisation of 81%. Simlar results were obtained by Valls-Bertault V et al (19).
In brief, no definite conclusion from available data can be drawn and large-scale randomised trials are needed to assess the efficacy of these therapies (8).