Circumferential Versus Ganglionated Plexi Ablation for Atrial Fibrillation (AF)
Condition: Atrial Fibrillation
MeSH terms: Atrial Fibrillation
Study type: Interventional

Summary: 
      The investigators have recently shown that anatomic ganglionated plexi (GP) ablation is
      inferior to circumferential pulmonary vein (PV) ablation for the treatment of paroxysmal AF.
      In this study, however, 26% of patients subjected to GP ablation alone without
      circumferential lesions were free of AF-recurrence up to one year after the ablation
      procedure. The investigators hypothesized that a combination of circumferential ablation with
      high-frequency-stimulation-identified GP ablation is superior to conventional circumferential
      ablation for the prevention of recurrences of paroxysmal atrial fibrillation (AF). The
      investigators are, therefore, conducting a randomized study comparing conventional
      circumferential ablation to a combination of circumferential ablation plus specific right and
      left atrial GP ablation in patients with drug-refractory paroxysmal AF.
    

Detailed description: 
      Introduction:

      In clinical studies, epicardial or endocardial partial ganglionated plexi (GP) ablation may
      prevent AF,1-4 and parasympathetic denervation has been proposed as a potential mechanism of
      circumferential or antral pulmonary vein (PV) ablation for the treatment of atrial
      fibrillation.5,6 However, there have also been reports of a temporary only 7 or even
      proarrhythmic effect of this approach by means of increased vulnerability of vagally-mediated
      AF,8,9 or ablation-related macro-reentrant left atrial tachycardias.10 Thus, the potential
      contribution of GP modification to clinical success of circumferential or antral pulmonary
      vein ablation that unavoidably affects adjacent GP is not known. Few publications exist on
      isolated GP ablation with variable results in terms of eliminating paroxysmal or persistent
      AF.11-13 We have recently shown that anatomically-oriented regional ablation at the areas of
      GP is superior to selective GP ablation, following identification of GP by high-frequency
      stimulation, conferring success rates comparable to these of pulmonary vein (PV) isolation
      procedures.13 We hypothesized that GP ablation guided by both HF stimulation and anatomical
      orientation is superior to PV isolation in patients with paroxysmal AF. We also aimed at
      comparing these two approaches with a combination of GP ablation and PV isolation. We are,
      therefore, conducting a randomized study comparing the three techniques in patients with
      drug-refractory paroxysmal AF.

      Methods:

      Patients with symptomatic, paroxysmal AF were randomized to three groups:

      Group 1. Patients are subjected to conventional PV isolation through circumferential ablation
      1-2 cm from the PV ostium.

      Group 2. Patients are subjected to specific, HF stimulation-guided and anatomic ablation of
      the main right and left atrial GP.

      Group 3. Patients are subjected to specific, HF stimulation-guided and anatomic ablation of
      the main right and left atrial GP followed by PV isolation.

      Group 1. PV isolation. Circumferential ablation around the antra of the PV with the aid of
      electroanatomical mapping (Carto, Biosence-Webster) at a distance of approximately 1-2 cm
      from the ostia of the left and right PVs (46°C, 35W, 17 mL/min, Stockert, Biosense Webster),
      aimed at a voltage reduction by > 80% or a peak to peak bipolar electrogram <0.1 mV.
      End-point of both approaches is verification of PV isolation with demonstration of entry and
      exit block. The area encircled by circumferential ablation will be calculated using the
      software provided by the CARTO system.

      Group 2. GP ablation. The anatomic areas of GP are identified in the right and left atrium.
      Anatomic locations of GP were considered around the PV: anterior right (ARGP), inferior right
      (IRGP), left superior (LSGP), and left inferior GP (LIGP). In addition the following GP were
      considered: The GP at the crux of the left atrium which is probably near or in continuation
      with the IRGP (2-3 cm below the lower edge of RIPV), expanding both toward the mitral annulus
      and inferior aspect of the LA posterior wall (cruxGP). This GP was also approached from the
      crux of the RA, behind the tendon of Tadaro/Eustachian ridge and the coronary sinus ostium.
      The GP at the septal-posterior aspect of the junction of the RA with the SVC (this GP may
      actually correspond to the 3rd fat pad located at the junction of SVC-RA-right
      PA-aorta).14-18 Following anatomic orientation, precise determination of the location of
      parasympathetic GP is accomplished by high-frequency stimulation.19 Patients are deeply
      sedated with diamorphine and diazepam without intubation, and high-frequency stimulation is
      delivered with a Grass stimulator at 1,200 bpm (20 Hz) with a pulse width of 10 ms at 20 V. A
      predominant parasympathetic response is defined as induction of AV block (> 2 sec) and
      hypotension or prolongation of the R-R interval by >50% during AF, following a 5 seconds
      application of high-frequency stimulation.19 Before applying high-frequency stimulation to
      inferior GP, extra care is taken to ensure that the catheter tip is not on the annulus to
      avoid induction of ventricular fibrillation. Verification of catheter position is
      accomplished by examination of recorded electrograms and anatomic location on both lateral
      views on CARTO. The sequence of GP ablation is: LS GP, LI GP, ARGP GP, IRGP, right anterior
      GP and the crux GP situated in the RA. After each ablation lesion (46°C, 35W for 60 seconds,
      17 mL/min), parasympathetic response is reassessed by high-frequency stimulation. End-point
      for radiofrequency delivery is abolition of parasympathetic response. Following specific GP
      ablation, anatomical ablation is performed as previously described, in a way that the
      designated anatomic areas of GP are ablated.

      Group 3. GP ablation and PV isolation. Following specific and anatomic GP ablation as
      previously described, PV isolation is accomplished either by circumferential or antral
      ablation.

      At the end of the ablation procedure in both groups, AF or atrial flutter induction is
      attempted by isoproterenol infusion and high left atrial pacing. Induction of atrial
      fibrillation is registered but does not necessitate additional ablation. Induction of right,
      isthmus-dependent atrial flutter is dealt with cavotricuspid isthmus ablation. Left atrial
      flutters will be studied by means of entrainment from the mitral isthmus and the adjacent
      posterior wall. Since a considerable percentage of these arrhythmias disappear with time,20
      they will be ablated only if sustained (> 3 minutes) and associated with 1:1 ventricular
      response.

      Follow-up. Patients will be prospectively assessed for recurrence of AF or other atrial
      arrhythmia. As part of our routine AF ablation protocol, all patients are receiving beta
      blockers, whereas all patients are kept on amiodarone and warfarin for 3 months
      post-ablation. Patients will be subjected to monthly clinical assessment and ambulatory
      electrocardiographic monitoring for 2 years. All patients are instructed to maintain personal
      records with descriptions of every episode of symptomatic palpitations and, in case of
      persistent arrhythmia episodes, to obtain trans-telephonic or electrocardiographic
      documentation of the underlying rhythm. Patients will be encouraged to use trans-telephonic
      monitoring even when their symptoms are not typical for recurrent AF. A successful outcome
      over the follow-up period is defined as the lack of electrocardiographically recorded AF, and
      no AF or other atrial arrhythmia on Holter, and subjective symptomatic improvement after a
      3-month blanking period.

      Heart rate variability will be measured at 6, 12, 18 and 24 months after ablation.
    

Intervention name(s): GP ablation; PV isolation
Intervention type(s): Procedure; Procedure
Intervention description(s): HF stimulation-guided and anatomic ablation of the main right and left atrial GP; Circumferential PV isolation
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: atrial fibrillation; PV isolation; ablation; ganglionic plexi; parasympathetic denervation