Discussion:
Although current guidelines recommend pacemaker implant in patients with severe symptomatic bradyarrhythmias, there is evidence that some of these disorders are related to functional imbalance in cardiac autonomic nervous system with a predominant excess of vagal tone(10). Cardiac parasympathetic drive occurs through efferent signals from vagal fibers, connected to postganglionic cells within atrial walls or in para-cardiac ganglia, mainly by decreasing automatism, excitability and conductivity. Cardiac modulation of parasympathetic GP abolishes the influence of excessive parasympathetic autonomic influence (4). Even though GP are located in epicardial fat pads, the extensive network of intramural atrial micro ganglia(2,7,12) renders endocardial ablation effective. Various reports (4,5,7,12) have shown that modulation of cardiac parasympathetic system supports this approach as an alternative strategy for these patients, particularly at younger ages for whom pacemaker implant is unwanted due to its potential lifelong complications. Similarly, in patients with vagally related AF in whom increased parasympathetic tone has an important role in initiation and perpetuation of AF episodes, modulation of parasympathetic drive in addition to PVI seems to confer increased arrhythmia free survival(2,13).
The exclusion of sinus and AV node intrinsic disease can be done non-invasively with Holter monitoring and exercise treadmill test. Maintained circadian variation of HR and normal chronotropic response to exercise are excellent surrogates of normal intrinsic sinus and AV node function. Previous studies have found comparable accuracy of Holter monitoring and treadmill exercise test with intrinsic HR measurements after pharmacological autonomic blockade. On the other hand, interpreting the measurement of baseline sinus node recovery time (SNRT) performed at electrophysiological study is difficult, as pacing suppression can be a normal phenomenon even in patients with normal sinus node function and because of existent overlap in recovery times between patients with normal and abnormal sinus node function. Additionally, it has sensitivity of only 70% (14). Furthermore, performing SNRT without pharmacological blockade is misleading and do no reflect the intrinsic properties of sinus and AV node and that is the reason why we didn“t performed SNRT.
In our study we included patients with suspected parasympathetic driven bradyarrhythmias, that showed adequate chronotropic response on non-invasive evaluation which otherwise would have indication for pacemaker implant due to the severity of the clinical symptoms or the rhythm disorder. Our results show that modulation of parasympathetic cardiac system is effective in treating functional bradyarrhythmias. It has shown good results in immediate period after ablation with increase in HR, in shortening of AH intervals and WBCL and on follow up, as none of the patients had recurrence of symptoms or severe bradyarrhythmias.
So far, targeting GP for parasympathetic modulation has been quite challenging. Most of previous studies have used complicated methodologies requiring appropriate specific systems for identification of GP site, leading to extensive ablation in the atria and predisposing patients to iatrogenic atrial arrhythmias (15).
Previous works (3,5,8,9,16,17) have shown that GP ablation can be achieved either using high frequency stimulation (HFS) (from epicardial or endocardial sides) to identify the GP or with an anatomical approach at known GP sites. Some works(3,9,12,18) have posteriorly shown that the sensitivity of HFS is low (21-71%) for the identification of GP sites and for assessment of the success of ablation. It is increasingly supported in the literature, the superiority of the anatomical approach over the HFS methodology due do the inconsistent parasympathetic response of the later. Besides, it allows avoidance of additional dedicated catheters and generators to perform HFS and spares the awake patient the unpleasant procedure (7,17,19). Our work pursued a simplified methodology to perform parasympathetic modulation, using only an anatomical approach with 3D electroanatomic mapping and geometry reconstruction. With this method the GP described location was easily accessible, as was precise delivery of radiofrequency lesions with homogenization of the created scars and reducing potential additional procedure complications, without compromising success. Likewise, endpoints of the procedure are not standardized and there is no current consensus on endpoints for successful procedures. The most used assessment of parasympathetic modulation by achieving a blunted HR response with atropine administration after ablation has low value because of the increase in sympathetic tone (8,19). So, in our study the endpoint of ablation was only anatomical deployment of lesion in pre specified sites and with pre specified settings, irrespective of any change in electrophysiological parameters.
Anatomic and physiological studies demonstrate that parasympathetic drive is predominantly located in the GP between the right superior pulmonary vein and right atria (which has most influence in cardiac parasympathetic innervation) and that the group of fibers located between the inferior vena cava and the right and left atria plays a major role in AV nodal innervation (4). Increasing clinical evidence, have also shown that the most important modification of parasympathetic autonomic response during ablation occurs by targeting the right GP and some authors additionally claim predominant modulation from the right atria side of GP, namely during ablation of the right side of the interatrial septum along the coronary sinus ostium(1,5,20). We used a simple and consistent method for GP ablation aiming at just the right GP with anatomical endpoints. Our results have shown that this strategy is feasible and effective, with less scar creation. In our patients, approaching the right GP alone seemed to be enough leading to abolishment of vagal cardiac tone, with significant shortening of RR and AH intervals and WBCL acutely. Also, we report a significant increase in minimal and mean heart rate 30 days after parasympathetic modulation, rendering patients asymptomatic with persistent effect in the medium-term. This data demonstrates that in the absence of standardized hard endpoints for GP ablation, an anatomic endpoint as surrogate of parasympathetic modulation and for simplification of the procedure purposes, with creation of a lesion subset in pre specified anatomic areas is enough.