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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Sick Sinus Syndrome; Sinus Node Dysfunction
• Intervention / Treatment: Procedure: Cardioneuroablation; Device: Permanent dual chamber pacemaker implantation

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Carlos Minguito Carazo, MD; Phone Number: 981 95 07 93; Email: carlosminguito@hotmail.es

Study Locations

• Spain
  • A Coruña
    • Santiago de Compostela, A Coruña, Spain, 15706
      • Recruiting
      • Hospital Clinico Universitario de Santiago
      • Contact: Carlos Carazo, MD; Email: carlosminguito@hotmail.es
      • Principal Investigator: Carlos Minguito Carazo, MD
      • Principal Investigator: Moisés Rodríguez Mañero, PhD
      • Principal Investigator: Jose Luis Martínez Sande, PhD
      • Sub-Investigator: Javier García Seara, PhD
      • Sub-Investigator: Xesus Alberte Fernández López, MD
      • Sub-Investigator: Laila González Melchor, MD
      • Sub-Investigator: Teba González Ferrero, MD
      • Sub-Investigator: Jose Ramón González Juanatey, PhD
      • Principal Investigator: Juliana Elices Teja, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cardioneuroablation; After 3D mapping of the surface of the left and right atrium and the superior vena cava (Ensite Navx or Carto system), 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.	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.; Other Names: Endocardial ganglion plexus ablation
Active Comparator: Permanent pacemaker implantation; A dual chamber pacemaker implantation will be performed. The device will be programmed in a AAI-DDDR mode to avoid unnecessary ventricular pacing.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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

Collaborators and Investigators

• Sponsor: Hospital Clinico Universitario de Santiago
• Collaborators: Spanish Society of Cardiology; Hospital Universitario Lucus Augusti
• Investigators: Principal Investigator: Carlos Minguito Carazo, MD, Hospital Clinico Universitario de Santiago; Study Director: Moises Rodríguez Mañero, PhD, Hospital Clinico Universitario de Santiago; Study Chair: Jose Ramón González Juanatey, PhD, Hospital Clinico Universitario de Santiago

Publications and helpful links

General Publications

• 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.
• 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.
• 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/europace/eur163. Epub 2011 Jun 28.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2021
• Primary Completion (Anticipated): November 1, 2023
• Study Completion (Anticipated): November 1, 2023

Study Registration Dates

• First Submitted: December 16, 2021
• First Submitted That Met QC Criteria: January 6, 2022
• First Posted (Actual): January 11, 2022

Study Record Updates

• Last Update Posted (Actual): January 11, 2022
• Last Update Submitted That Met QC Criteria: January 6, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: cardioneuroablation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Arrhythmia, Sinus; Heart Block; Sick Sinus Syndrome
• Other Study ID Numbers: 2021/307

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Study protocol, statistical analysis plan and informed consent form will be available for any who requires.
• IPD Sharing Time Frame: Baseline to 2 years
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No