Cardioneuroablation Versus Pacemaker Implantation for the Treatment of Symptomatic Sinus Node Dysfunction

Sick Sinus Syndrome Clinical Trial

— DINERVAPACE  

Official title:

Endocardial Ablation of Ganglionated Plexi Versus Pacemaker Implantation in Patients With Symptomatic Sinus Node Dysfunction

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05186220
• Other study ID #: 2021/307
• Status: Recruiting
• Phase: N/A
• Start date: November 1, 2021
• Est. completion date: November 1, 2023

Study information

• Verified date: January 2022
• Source: Hospital Clinico Universitario de Santiago
• Contact: Carlos Minguito Carazo, MD
• Phone: 981 95 07 93
• Email: carlosminguito[@]hotmail.es
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Endocardial ganglion plexus ablation (cardioneuroablation) represents a promising therapeutic technique for the treatment of vasovagal syncope (VV), functional atrioventricular block (AVB) and sinus node dysfunction (SND) with a component of vagal hypertonia. Nevertheless, there is currently a paucity of literature about the results according to the type of presentation (VV, AVB or SND). The investigators aim to assess the safety and efficacy of cardioneuroablation for the treatment of symptomatic SND.

Description:

Sinus node dysfunction (SND), also known as sick sinus syndrome, comprises a wide spectrum of sinoatrial dysfunctions, ranging from sinus bradycardia, sinoatrial block, and sinus arrest to bradycardia tachycardia syndrome. An additional manifestation of SND is an inadequate chronotropic response to exercise, reported as chronotropic incompetence. Since the first cardiac denervation was reported in 2005, several registries and retrospective studies using this therapeutic approach for reflex syncope, SND and functional atrioventricular block have been published. However, due to the lack of randomized studies, current guidelines recommend permanent pacemaker implantation for patients with symptomatic SND in order to improve symptoms. Therefore, the purpose of the present study is to assess the safety and efficacy of cardioneuroablation versus permanent pacemaker implantation for the treatment of symptomatic SND.

This is a multicenter, randomized, open, interventional study. After being informed of the study and potential risks, participants will undergo a one week screening period to determine eligibility for the study entry. During this week, participants will undergo an exercise test, atropine test, and a 24 hour-holter electrocardiogram. Then, participants who meet the eligibility criteria, will be randomized 1:1 to receive permanent pacemaker implantation (control group) or cardioneuroablation (interventional group).

The primary endpoint (improve in quality of life assessed with 36-Item Short Form Survey (SF-36)) will be evaluated at six months since randomization.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: November 1, 2023
• Est. primary completion date: November 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria:

• Symptomatic sinus node dysfunction (dizziness, asthenia or syncope) clearly related to an abnormal electrocardiogram finding (sinus arrest, sinoatrial block, extreme bradycardia (<40 bpm) or chronotropic incompetence in the exercise test).

• Absence of structural cardiopathy

Exclusion Criteria:

• Left ventricular ejection fraction <50%

• Severe valvular disease

• Any type of cardiomyopathy such as hypertrophic cardiomyopathy

• Previous ischemic heart disease

• QRS interval >130 ms

• Atrioventricular conduction disorder with a former indication of pacemaker implantation (atrioventricular block Mobitz II, advanced atrioventricular block, complete atrioventricular block)

• Lifetime expectance <12 months

Related Conditions & MeSH terms

• Sick Sinus Syndrome
• Sinus Node Dysfunction

Intervention

Procedure:
• Cardioneuroablation
After 3D mapping of the surface of the left and right atrium and the superior vena cava (Ensite Navx, Carto), localization of ganglion plexus (GP) will be performed either anatomically and/or by means of high frequency stimulation (HFS). The anterior and superior right sided GP will always be ablated per protocol. Other GP will be ablated according to interventional electrophysiologist judgement. The endpoint of the ablation procedure will be 1) absence of a vagal response after HFS from the right jugular vein and 2) an increase in at least 10 bpm as compared to baseline.

Device:
• Permanent dual chamber pacemaker implantation
Under local anesthesia and using a subclavian or cephalic vein approach a dual chamber pacemaker implantation with a lead in the right atrium and a lead in the right ventricle will be performed. The device will be programmed in a AAI-DDDR mode to avoid unnecessary ventricular pacing.

Locations

Country	Name	City	State
Spain	Hospital Clinico Universitario de Santiago	Santiago de Compostela	A Coruña

Sponsors (3)

Lead Sponsor	Collaborator
Hospital Clinico Universitario de Santiago	Hospital Universitario Lucus Augusti, Spanish Society of Cardiology

Country where clinical trial is conducted

Spain, 

References & Publications (3)

Hu F, Zheng L, Liang E, Ding L, Wu L, Chen G, Fan X, Yao Y. Right anterior ganglionated plexus: The primary target of cardioneuroablation? Heart Rhythm. 2019 Oct;16(10):1545-1551. doi: 10.1016/j.hrthm.2019.07.018. Epub 2019 Jul 19. — View Citation

Pachon JC, Pachon EI, Cunha Pachon MZ, Lobo TJ, Pachon JC, Santillana TG. Catheter ablation of severe neurally meditated reflex (neurocardiogenic or vasovagal) syncope: cardioneuroablation long-term results. Europace. 2011 Sep;13(9):1231-42. doi: 10.1093/ — View Citation

Pachon-M JC, Pachon-M EI, Pachon CTC, Santillana-P TG, Lobo TJ, Pachon-M JC, Zerpa-A JC, Cunha-P MZ, Higuti C, Ortencio FA, Amarante RC, Silva RF, Osorio TG. Long-Term Evaluation of the Vagal Denervation by Cardioneuroablation Using Holter and Heart Rate Variability. Circ Arrhythm Electrophysiol. 2020 Dec;13(12):e008703. doi: 10.1161/CIRCEP.120.008703. Epub 2020 Nov 16. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in the SF-36 Health Survey of quality of life	The SF-36 Health Survey is a validated, well known generic test for assessment of the health-related quality of life of patients.	Baseline and 6 months
Secondary	6 month free survival from permanent pacemaker implantation in the interventional group (cardioneuroablation)	Percentage of patients free from pacemaker at one year in the cardioneuroablation group	Baseline and 6 months
Secondary	Change in maximal heart rate and chronotropic incompetence in the exercise test	All patients will perform a baseline exercise test and after 6 months. Maximal heart rate and chronotropic response will be recorded.	Baseline and 6 months
Secondary	Differences in complications rates between both gropus	Most common complications regarding the procedure. In the cardioneuroablation group; complications regarding vascular access and pericardial tamponade. In the pacemaker group, pneumothorax, device infection and vascular access.	Baseline and 6 months
Secondary	Differences in 6 month free survival from syncope between both groups	Syncope will be defined as any spontaneous loss of conscious with posterior recovery.	Baseline and 6 months