Clinical Trial: Comparison of the Efficacy and Safety of Cardioneuroablation to Permanent Pacing in Patients With an Implanted Pacemaker for Symptomatic Bradycardia.

Study Status: NOT_YET_RECRUITING
Recruit Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL



Official Title: A Multicenter, Randomized, Double-blind, Research Study comparinG the Efficacy and Safety of cardioneuroablaTion vs Permanent Pacing in Patients With an implantabLE PACEmaker for Symptomatic Bradycard

Brief Summary:

Background Sinus node dysfunction (SND) and atrioventricular block (AVB) are significant diagnostic and therapeutic problems.
The primary method of their treatment is cardiac pacemaker implantation (PM).
Although PM remains the main therapeutic approach for most patients with SND/AVB, long-term PM therapy can be associated with various limitations, complications, and the need for device and electrode replacement.
There is increasing evidence for the effectiveness of an alternative approach to functional bradycardia associated with excessive vagal activation - cardioneuroablation (CNA).
The method leads to the alleviation or complete resolution of bradycardia symptoms, as well as reflex syncope, providing an opportunity to discontinue PM therapy.

Primary aims

1. Evaluation of the efficacy and safety of CNA as a therapy allowing for discontinuation of PM therapy in patients with SND or AVB.

Secondary aims

  1. Evaluation of the efficacy and safety of CNA as a therapy allowing for the optimization of PM therapy in patients with SND and AVB.
  2. Development of a diagnostic algorithm allowing for the identification of patients with SND and/or AVB suitable for CNA and discontinuation of PM and TLE therapy.
  3. In addition, blood samples will be collected for future analysis and biobanking.

Methodology

Inclusion criteria

  1. Patients up to 50 years old who underwent pacemaker implantation due to sinus node and/or atrioventricular node dysfunction
  2. Positive response to atropine test
  3. Age between 18-65 years
  4. Signed informed consent to participate in the study

Exclusion criteria

  1. Own heart rate <30/min
  2. Fainting after pacemaker therapy initiation
  3. Persistent and sustained atrial fibrillation
  4. History of myocarditis
  5. History of cardiac surgery
  6. History of ablation procedures
  7. Congenital heart defects
  8. Congenital atrioventricular block
  9. Neuromuscular and neurodegenerative diseases
  10. Indications for expanding the pacemaker system to ICD/CRT-D
  11. Pregnancy
  12. Renal insufficiency with GFR <30 ml/min/1.73m2

Randomization, study scheme Qualified patients will be randomly assigned (1:1:1) to group 1 undergoing first-stage invasive electrophysiology study (EPS), extracardiac vagus nerve stimulation (ECVS) and CNA with continued PM therapy and implantable loop recorder (ILR) implantation, to group 2 undergoing first-stage EPS and ECVS with continued PM therapy, ILR implantation, and no CNA, and to group 3 where patients will undergo observation only for the entire study period.
The follow-up time will be 18 months.
Groups 1 and 2 will be blinded.
Two months after the first invasive procedure, the secondary endpoint-stimulation rate in all groups will be assessed.
In addition, a non-invasive evaluation of the efficacy of CNA and the incidence of syncope (MAS) and collapse (paraMAS) will take place in group 1, as well as an evaluation of the pacing percentage.
After another month during the second hospitalization, the following will be performed: EPS and ECVS, and repeat CNA if ECVS does not show full parasympathetic cardiac denervation.
In group 2, after 2 months, non-invasive tests will also be performed to assess and presence of MAS, paraMAS symptoms, and to assess pacing rates.
After another month, during the second hospitalization, the following will be performed: EPS, ECVS and CNA.
Group 1 and 2 patients with an effective CNA confirmed on ECVS will have their pacemaker set to VVI/AAI 30/min.
Group 3 patients will then be evaluated for pacing rates and MAS, paraMAS symptoms.
At the third visit, one month after the second invasive procedure in group 1 and 2 patients, the pacing percentage will be assessed.
Patients with zero pacing percentage PM will be put on ODO/OVO/OAO-pacing off mode.
Patients with a pacing percentage greater than zero PM will be set to their optimal mode.
A pacing percentage of <0.1% will be treated as 0%, which will be confirmed in the ILR control.
For the next 12 months, patients will be observed.
During this period, at the next 4 visits repeated every 3 months, groups 1 and 2 will undergo a non-invasive assessment of CNA efficacy and bradycardia symptoms, while group 3 will be evaluated for MAS, paraMAS and pacing percentage assessment.
At the 7th visit, the qualification of patients in groups 1 and 2 for discontinuation of continued pacing treatment will take place, with possible qualification for TLE.

Justification Early and late results of a new strategy which is CNA, indicate the possibility of developing an new approach that allows patients with functional bradycardia to decide whether to discontinue or optimize PM therapy.
However, standardized approaches based on noninvasive and invasive techniques have not yet been validated and evaluated in a prospective, multicenter, randomized, controlled trial with long-term remote follow-up, including ILR.