Pacemaker Implantation Versus Cardioneuroablation for Functional Atrioventricular Block

NCT05774262 | Recruiting DMC

• 1 other identifier: 2022/ABM/03/00035
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 2

Brief Summary

The TELE-SPACER study is a multicenter, noncommercial, physician-initiated, proof-of-concept, prospective, randomized, controlled, unblinded clinical trial and registry designed to compare two methods of treatment of patients with functional Atrio-Ventricular Block (AVB): the guidelines-recommended elective pacemaker (PM) therapy vs cardiovascular autonomic tests (CAT), electrophysiologic assessment (EPS) with referral to cardioneuroablation (CNA) and reevaluation of indications for PM therapy. The main questions TELE-SPACER aims to answer are:

• Can the investigators successfully treat functional AVB without implantable device (PM)?
• Can the investigators prove the feasibility and safety and demonstrate non-inferiority of CNA procedure in patients with functional AVB, avoiding long-term permanent pacing, its limitations, complications and costs ? The TELE-SPACER trial will validate the European Society of Cardiology (ESC) recommendations (level C of evidence: expert opinion) for elective PM implantation and will introduce CNA as effective treatment in the functional AVB patient population. Functional AVB - defined as a persistent or paroxysmal AVB with a positive results of atropine test

Conditions

Atrioventricular Block

Keywords

AVB; Pacemaker implantation; Cardioneuroablation; Cardiovascular autonomic testing (CAT); Telemedicine

Outcome Measures

Primary Outcomes (1)

• To determine the efficacy of CNA in the treatment of AVB in comparison to PM therapy within 12 months of PM implantation/CNA procedure.

  This is objective endpoint examining the onset of AVB episodes after PM/CNA. It will specify the number of pauses \> 3.0 s in the ECG external recorder for group B (occurrence of \> 1 pause or the need for earlier (0-12 months) PM implantation will be an indicator of the failure of the CNA procedure), assuming the presence of PM stimulation in group A at the level between 93-100% (equates to the continued duration of the AVB treated with PM).

  12 months

Secondary Outcomes (8)

• Occurrence of MACE (major advers cardiac events)

  at 0, 3, 6, 12 months

• Assessment of the effect of CNA and PM implantation on AVB symptoms based on based on VAS (Visual Analog Scale)

  0, 3, 6, 12 months

• Assessment of the effect of CNA and PM implantation on health-related quality of life (QOL) based on questionaire EQ-5D-5L

  0, 6, 12 months

• Assessment of the effect of CNA and PM implantation on health-related quality of life (QOL) based on questionaire SF-36

  0, 6, 12 months

• Assessment of the effect of CNA and PM implantation on fatique based on Modified Fatigue Impact Scale (MFIS)

  0, 6, 12 moths

Study Arms (2)

Group A - PACEMAKER

ACTIVE COMPARATOR

Group A, n=50 patients aged 18-75 years with indications for elective PM implantation according to the 2021 ESC guidelines for cardiac pacing due to paroxysmal or persistent AVB with a positive results of atropine test. Group A is early elective pacemaker implantation (PM) strategy in functional AVB.

Procedure: Pacemaker implantation

Group B - CARDIONEUROABLATION

ACTIVE COMPARATOR

Group B, n=50 patients aged 18-75 years with indications for elective PM implantation according to the 2021 ESC guidelines for cardiac pacing due to paroxysmal or persistent AVB with a positive results of atropine test. Group B will undergo strategy of postponed/deferred PM implantation in functional AVB. Patients wil be implanted and monitored with ILR (in case of severe symptomatic AVB always the emergency system will be called). After cardiovascular autonomic testing (CAT), electrophysiological study (EPS), extra cardiac vagal nerve stimulation (ECVS) and cardioneuroablation will be performed. If CNA is succesful, pacemaker implantation will be cancelled. If CNA is unsuccessful, second session of CNA will be planned. In case of inefficient second attempt, patients will be referred for PM implantation. They will cross-over to PACEMAKER arm.

Procedure: Cardioneuroablation (CNA)

Interventions

Pacemaker implantation PROCEDURE

Elective pacemaker implantation (DDDR) for functional AVB according to the 2021 ESC Guidelines for Cardiac Pacing

Group A - PACEMAKER

Cardioneuroablation (CNA) PROCEDURE

Experimental method; elective implantable loop recorder (ILR) and biatrial, binodal, atomically and electroanatomically guided CNA with extracardiac vagal nerve stimulation (ECVS) prior and after procedure monitoring (disappearance of ECVS-induced AVB with the goal of achieving post-procedure and maintaining a target heart rate \> 50 beats per minute). CNA procedure is performed with radio-frequency generators and irrigated catheters and with support of 3D-electroanatomic mapping system. CNA group will receive external ECG recorders. The major reason for external ECG recorders is to provide documentation of clinical AVB, as well as monitoring of patients before and after CNA (or PM implantation, if accepted). In case of severe AVB symptoms always the emergency system will be called.

Group B - CARDIONEUROABLATION

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent to participate in the study
• Age 18-75
• Indication (at least one) of the European Society of Cardiology (ESC) for elective pacemaker implantation due to isolated (without sinus node dysfunction and bundle branch block) paroxysmal, persistent or reflex atrioventricular block:
• Symptomatic first degree AVB (above 300 msec). Class IIaC
• Symptomatic Mobitz type I second degree AVB. Class IIaC
• AVB 2:1, even asymptomatic, but not during sleep. Class IIaC
• Mobitz II type advanced 2nd degree AVB or complete block (3rd degree AVB). Class IC
• Advanced AVB during AF regardless of symptoms, but not during sleep. Class IC
• Reflex syncope in patients over 40 years of age with documented pauses within the AVB mechanism, symptomatic (\>3 sec) or asymptomatic \>6 sec. Class IC
• Reflex syncope in patients over 40 years of age with documented pauses within AVB mechanism in the course of sick sinus syndrome (CSS). Class IC
• Reflex syncope in patients over 40 years of age with documented pauses within AVB mechanism during tilt test. Class IC

You may not qualify if:

• Implanted pacemaker/ICD/CRT
• Sinus node dysfunction with indication for pacemaker implantation
• Planned ablation of the atrioventricular junction
• Severe prolonged bradycardia in advanced AVB requiring intravenous drugs and temporary pacing
• Status post cardiac surgery
• Acute myocardial infarction and heart failure (not related to bradycardia)
• Status post percutaneous valvular intervention or ablation
• Acute infection or any other accompanying disease which is contraindication to percutaneous procedures and/or implantation of a pacemaker
• Pregnancy, nursing or planned pregnancy within 12 months
• Decompensated chronic diseases (endocrine disorders, electrolyte disorders, etc.)
• Advanced cardiomyopathies with indication for ICD implantation in primary or secondary prevention of sudden cardiac death (SCD)
• Advanced ventricular arrhythmias with indication for ICD implantation in primary or secondary prevention of SCD
• Persistent right or left bundle branch block
• Musculoskeletal diseases with separate indications for pacemaker implantation
• Contraindications to the procedures used in the study

Sponsors & Collaborators

• American Heart of Poland: lead

Study Sites (2)

American Heart of Poland

Dąbrowa Górnicza, 41-300, Poland

RECRUITING

American Heart of Poland

Mielec, 39-300, Poland

RECRUITING

Related Publications (21)

• Brignole M, Moya A, de Lange FJ, Deharo JC, Elliott PM, Fanciulli A, Fedorowski A, Furlan R, Kenny RA, Martin A, Probst V, Reed MJ, Rice CP, Sutton R, Ungar A, van Dijk JG; ESC Scientific Document Group. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J. 2018 Jun 1;39(21):1883-1948. doi: 10.1093/eurheartj/ehy037. No abstract available.

  PMID: 29562304 BACKGROUND

• Glikson M, Nielsen JC, Kronborg MB, Michowitz Y, Auricchio A, Barbash IM, Barrabes JA, Boriani G, Braunschweig F, Brignole M, Burri H, Coats AJS, Deharo JC, Delgado V, Diller GP, Israel CW, Keren A, Knops RE, Kotecha D, Leclercq C, Merkely B, Starck C, Thylen I, Tolosana JM; ESC Scientific Document Group. 2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy. Eur Heart J. 2021 Sep 14;42(35):3427-3520. doi: 10.1093/eurheartj/ehab364. No abstract available.

  PMID: 34455430 BACKGROUND

• Shen WK, Sheldon RS, Benditt DG, Cohen MI, Forman DE, Goldberger ZD, Grubb BP, Hamdan MH, Krahn AD, Link MS, Olshansky B, Raj SR, Sandhu RK, Sorajja D, Sun BC, Yancy CW. 2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation. 2017 Aug 1;136(5):e60-e122. doi: 10.1161/CIR.0000000000000499. Epub 2017 Mar 9. No abstract available.

  PMID: 28280231 BACKGROUND

• Klank-Szafran M, Stec S, Sledz J, Janion M. [Radiofrequency ablation and cardioneuroablation for AVNRT and atrioventricular block]. Kardiol Pol. 2010 Jun;68(6):720-4. Polish.

  PMID: 20806214 BACKGROUND

• Aksu T, Guler TE, Bozyel S, Ozcan KS, Yalin K, Mutluer FO. Cardioneuroablation in the treatment of neurally mediated reflex syncope: a review of the current literature. Turk Kardiyol Dern Ars. 2017 Dec;45(1):33-41. doi: 10.5543/tkda.2016.55250.

  PMID: 28106018 BACKGROUND

• Baysal E, Guler TE, Gopinathannair R, Bozyel S, Yalin K, Aksu T. Catheter Ablation of Atrioventricular Block: From Diagnosis to Selection of Proper Treatment. JACC Case Rep. 2020 Sep 15;2(11):1793-1801. doi: 10.1016/j.jaccas.2020.07.050. eCollection 2020 Sep.

  PMID: 34317058 BACKGROUND

• Aksu T, Gopinathannair R, Bozyel S, Yalin K, Gupta D. Cardioneuroablation for Treatment of Atrioventricular Block. Circ Arrhythm Electrophysiol. 2021 Sep;14(9):e010018. doi: 10.1161/CIRCEP.121.010018. Epub 2021 Sep 1.

  PMID: 34465122 BACKGROUND

• Wileczek A, Polewczyk A, Kluk M, Kutarski A, Stec S. Ultrasound-guided imaging for vagus nerve stimulation to facilitate cardioneuroablation for the treatment of functional advanced atrioventricular block. Indian Pacing Electrophysiol J. 2021 Nov-Dec;21(6):403-406. doi: 10.1016/j.ipej.2021.06.008. Epub 2021 Jun 26.

  PMID: 34186197 BACKGROUND

• Josiak K, Stec S, Zysko D, Skonieczny B, Kosior J, Sledz J, Wilczek A, Stodolkiewicz-Nowarska E, Biel B, Szymkiewicz P, Skoczynski P, Karbarz D, Ludwik B, Banasiak W, Jagielski D. Safety and efficacy of His bundle pacing validated by extracardiac vagal nerve stimulation (HIS-STORY). Cardiol J. 2022;29(4):698-701. doi: 10.5603/CJ.a2022.0053. Epub 2022 Jun 15. No abstract available.

  PMID: 35703044 BACKGROUND

• Reichert A, Wileczek A, Stec S. Cardioneuroablation for the effective treatment of recurrent vasovagal syncope to restore driving abilities. Kardiol Pol. 2022;80(11):1158-1160. doi: 10.33963/KP.a2022.0189. Epub 2022 Aug 10. No abstract available.

  PMID: 35946179 BACKGROUND

• Gajda R, Knechtle B, Gebska-Kuczerowska A, Gajda J, Stec S, Krych M, Kwasniewska M, Drygas W. Amateur Athlete with Sinus Arrest and Severe Bradycardia Diagnosed through a Heart Rate Monitor: A Six-Year Observation-The Necessity of Shared Decision-Making in Heart Rhythm Therapy Management. Int J Environ Res Public Health. 2022 Aug 19;19(16):10367. doi: 10.3390/ijerph191610367.

  PMID: 36012002 BACKGROUND

• Pachon JC, Pachon EI, Pachon JC, Lobo TJ, Pachon MZ, Vargas RN, Jatene AD. "Cardioneuroablation"--new treatment for neurocardiogenic syncope, functional AV block and sinus dysfunction using catheter RF-ablation. Europace. 2005 Jan;7(1):1-13. doi: 10.1016/j.eupc.2004.10.003.

  PMID: 15670960 RESULT

• 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.

  PMID: 21712276 RESULT

• Pachon M JC, Pachon M EI, Santillana P TG, Lobo TJ, Pachon CTC, Pachon M JC, Albornoz V RN, Zerpa A JC. Simplified Method for Vagal Effect Evaluation in Cardiac Ablation and Electrophysiological Procedures. JACC Clin Electrophysiol. 2015 Oct;1(5):451-460. doi: 10.1016/j.jacep.2015.06.008. Epub 2015 Aug 21.

  PMID: 29759475 RESULT

• Yao Y, Shi R, Wong T, Zheng L, Chen W, Yang L, Huang W, Bao J, Zhang S. Endocardial autonomic denervation of the left atrium to treat vasovagal syncope: an early experience in humans. Circ Arrhythm Electrophysiol. 2012 Apr;5(2):279-86. doi: 10.1161/CIRCEP.111.966465. Epub 2012 Jan 24.

  PMID: 22275485 RESULT

• 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.

  PMID: 31330187 RESULT

• Sun W, Zheng L, Qiao Y, Shi R, Hou B, Wu L, Guo J, Zhang S, Yao Y. Catheter Ablation as a Treatment for Vasovagal Syncope: Long-Term Outcome of Endocardial Autonomic Modification of the Left Atrium. J Am Heart Assoc. 2016 Jul 8;5(7):e003471. doi: 10.1161/JAHA.116.003471.

  PMID: 27402231 RESULT

• Aksu T, Golcuk E, Yalin K, Guler TE, Erden I. Simplified Cardioneuroablation in the Treatment of Reflex Syncope, Functional AV Block, and Sinus Node Dysfunction. Pacing Clin Electrophysiol. 2016 Jan;39(1):42-53. doi: 10.1111/pace.12756. Epub 2015 Oct 26.

  PMID: 26411271 RESULT

• Osorio TG, Paparella G, Stec S, Chierchia GB, de Asmundis C. Cardiac parasympathetic modulation in the setting of radiofrequency ablation for atrial fibrillation. Arch Med Sci. 2019 Apr 26;17(6):1716-1721. doi: 10.5114/aoms.2019.84717. eCollection 2021.

  PMID: 34900053 RESULT

• Piotrowski R, Baran J, Kulakowski P. Cardioneuroablation using an anatomical approach: a new and promising method for the treatment of cardioinhibitory neurocardiogenic syncope. Kardiol Pol. 2018;76(12):1736-1738. doi: 10.5603/KP.a2018.0200. Epub 2018 Oct 19. No abstract available.

  PMID: 30338504 RESULT

• Pachon-M EI, Pachon-Mateos JC, Higuti C, Santillana-P TG, Lobo T, Pachon C, Pachon-Mateos J, Zerpa J, Ortencio F, Amarante RC, Silva RF, Osorio TG. Relation of Fractionated Atrial Potentials With the Vagal Innervation Evaluated by Extracardiac Vagal Stimulation During Cardioneuroablation. Circ Arrhythm Electrophysiol. 2020 Apr;13(4):e007900. doi: 10.1161/CIRCEP.119.007900. Epub 2020 Mar 19.

  PMID: 32188285 RESULT

MeSH Terms

Conditions

Atrioventricular Block

Condition Hierarchy (Ancestors)

Heart Block; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Sebastian M Stec, MD, PhD

  American Heart of Poland

  PRINCIPAL INVESTIGATOR

• Edyta Stodolkiewicz-Nowarska, MD, PhD

  American Heart of Poland

  STUDY DIRECTOR

• Krzysztof Milewski, MD, PhD

  American Heart of Poland

  STUDY CHAIR

Central Study Contacts

Sebastian M Stec, MD, PhD

CONTACT

+48 600-298-022; smstec@wp.pl

Edyta Stodolkiewicz-Nowarska, MD PhD

CONTACT

+48 785-885-425; edytastod@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor, Principal Investigator

Model Details: multicenter, noncommercial, physician-initiated, proof-of-concept, prospective, randomized, controlled trial and registry

Study Record Dates

• First Submitted: February 17, 2023
• First Posted: March 17, 2023
• Study Start: September 1, 2023
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 18, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.
• Access Criteria: De-identified individual participant level data and measurements including tables, figures, and appendices or supplementary material that support the results presented in a manuscript. Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information or to submit a request, please contact PI smstec@wp.pl

Locations

PL (2)