The efficacy of therapeutic strategies mentioned in the guidelines for patients with
neurally mediated syncope (NMS) is limited. The first clinical study on cardiac
denervation in humans was published in 2005. Derived from this first method, different
approaches to cardioneuroablation (CNA) to treat NMS have been published. Such ablations
are complex, bi-atrial, and extensive. Cardio-neuromodulation (CardNM) is a less
extensive and right-sided approach to CNA, based on a tailored vagolysis of the
sinoatrial node through partial ablation of the anterior right-ganglionated plexus.
Evidence from a single-center, non-randomized, unblinded trial showed that CardNM was
associated with a reduction in syncope burden exceeding 90%.
This third study on CardNM (CardNMH3 study) is a multicenter, double-blind, randomized
trial with a sham control group investigating the efficacy and safety of a computed
tomography (CT)-guided, right-sided ablation of the anterior ganglionated plexus to
prevent recurrence of syncope in patients with neurally mediated syncope.
The primary goal of the study is to determine whether a CT-guided, right-sided ablation
of the anterior ganglionated plexus safely reduces the risk of recurrent episodes of
syncope in patients with a history of recurrent NMS.
Two-thirds of the patients will be randomized to the active arm and one-third to the
control arm (sham).
In all patients, the endocardial site to potentially target during ablation will be
annotated before the procedure by a target line (TL) on a computed tomographic image of
the heart imported into the CARTO system (Biosense Webster, Diamond Bar, CA), as detailed
in the 'intervention description'.
The study procedure will be performed under general anesthesia according to a
standardized protocol. In all patients, a diagnostic electrophysiology study (EPS) and
electroanatomical mapping of the right atrium and the surrounding veins will be performed
first. This image will be merged with the CT image and the TL will be visible.
Randomization will be performed electronically at this stage of the procedure.
In patients assigned to the active arm, the TL will be targeted by ablation as detailed
in the intervention description'.
The ablation procedure is considered complete when one of the following conditions is
fulfilled:
10 radiofrequency applications have been delivered;
After 5 radiofrequency applications, the P-P interval is <70% of the baseline
procedural P-P interval and remains >550 ms 5 min after the last radiofrequency
application;
≥5 radiofrequency applications have been delivered and the operator estimates that
no additional P-P interval shortening will be obtained by additional radiofrequency
applications;
3 radiofrequency applications have been delivered and the P-P interval is <550 ms
after the last radiofrequency application and remains stable after 5 min of waiting.
In all patients, a pharmacological evaluation and new diagnostic EPS will be performed to
further evaluate the sinus node and atrioventricular nodal intrinsic activity at the end
of the procedure, either after the diagnostic part of the procedure in the sham group or
after the ablation in the active arm.
Syncope burden, syncope occurrence and quality of life will be assessed by questionnaires
completed at baseline and at 1, 3, 6 and 12 months. A 24-h rhythm registration will be
performed at baseline and at 1-, 3- and 6-month follow-up to investigate the influence of
the intervention on heart rate.
The effect of CardNM on blood pressure and on chronotropic sinus node function will be
evaluated in 2 additional substudies. Patients enrolled in the blood-pressure substudy
will undergo a 24-h blood pressure monitoring at baseline and at 1, 3 and 6 months.
Participants in the sinus node competence substudy will undergo a bicycle exercise test
at baseline and at 1, 3 and 6 months.
Investigators aim to achieve complete follow-up for 110 patients who meet the study
enrollment criteria. If the syncope-free survival, the primary endpoint of the study, is
significantly different between the 2 arms after the enrollment of fewer than 110
patients (minimum 55 patients), enrollment into the trial will be prematurely stopped.
The study may also be terminated prematurely if safety concerns occur.