Second Study on Cardio-neuromodulation in Humans
Second Study on Cardio-neuromodulation in Humans
Different approaches to cardio-neuroablation (CNA) to treat neurally mediated syncope, sinus
 node dysfunction, and functional atrioventricular block have been published. Investigators
 have developed a more limited and specific approach of CNA, called cardio-neuromodulation
 (CardNM). This treatment is based on a tailored vagolysis of the sinoatrial node through
 partial ablation of the anterior right ganglionated plexus (ARGP); it is also based on an
 innovative anatomic strategy. The feasibility of CardNM has already been tested in our center
 in a limited first study in humans (CardNMH1), with a favorable outcome for the patients
 involved. The results of CardNMH1 have been submitted for publication. The purpose of this
 second study of CardNM in humans (CardNMH2) is to collect more procedural and clinical data
 in well-defined patient groups.
This is a phase II A prospective, interventional study. All patients will undergo CardNM. The
 study will involve eight different steps, from the screening procedure through study
 completion: screening, enrollment, pharmacological testing, group allocation, preprocedural
 assessment, procedure, follow-up, study completion.The dedicated study nurse and the PI are
 responsible for recording all data from the trial on the case report forms (CRFs) and
 completing the study database. A dedicated independent physician will be responsible for the
 safety monitoring. The PI will permit inspection of the trial files and the database by
 national or international official controlling scientific authorities, if required. The PI
 will review and monitor completed CRFs and the database at regular intervals throughout the
 trial.
Inclusion Criteria:

 Candidates must meet all of the inclusion criteria required for inclusion in one of the two
 groups (summarized in Table 2). All of the patients need to have a positive P wave of > 0.5
 mm in lead 2. Patients must have had ≥ 1 syncope during the 6 months preceding enrollment
 and ≥ 2 syncopes in their lifetime except if the last syncope was complicated by an injury
 or an accident, in which case further waiting for CardNM may be less desirable. Patients <
 18 years must have least 3 syncopes with an interval exceeding 1 month unless 1 syncope was
 complicated by an injury or an accident.

 If a significant rate drop (> 15%) is noted during head-up tilt test (HUT), either isolated
 or combined with vasoplegia, and associated with syncope or severe presyncope, patients
 will be eligible for inclusion in group A. If the HUT is negative and a pause > 3 seconds
 has been documented, patients will be assigned to group B. If both conditions are present,
 patients will be eligible for inclusion in either group but will be preferentially assigned
 to group A.

 Exclusion Criteria:

 Candidates will be excluded if ANY of the following criteria apply (detailed in Table 3):

 -  < 14 years of age;

 -  Inability to provide consent;

 -  Chronotropic negative medications (excepted in patients with a previous history of
 atrial fibrillation);

 -  4 g amiodarone intake during the 2 months preceding enrollment;

 -  Alternating right bundle branch block (RBBB) and left bundle branch block (LBBB), HV
 interval > 70 ms;

 -  LBBB, bifascicular block (RBBB + left anterior hemiblock [LAHB], RBBB + left posterior
 hemiblock [LPHB]);

 -  PR interval permanently > 240 ms;

 -  Permanent AF, PAF or electrical cardioversion during the last 6 months;

 -  Valvular or subvalvular aortic stenosis, mitral stenosis;

 -  Any unstable medical condition, life expectancy < 12 months;

 -  Syncopes due a non-cardiac disease (excepted NMS) or advanced neuropathy;

 -  Current pregnancy;

 -  glaucoma.

 Patients with transient atrioventricular conduction disturbances and normal
 atrioventricular conduction during an exercise test and normal QRS complexes are eligible
 for this study.

 Patients with a high risk of bleeding are eligible, but clopidogrel (75 mg daily, 1 month
 of treatment) will then be preferred to oral anticoagulants.