Safety and Efficacy of His Bundle Pacing Validated by Extracardiac Vagal Nerve Stimulation (HIS-STORY)

Safety and Efficacy of HIs Bundle Pacing Validated by electrophySiological STudy, autonOmic Tests and extRacardiac Vagal Nerve Stimulation (HIS-STORY)

Different studies for extracardiac vagal nerve stimulation (ECANS) have been published and confirmed the influence of the vagus nerve on automaticity and conduction properties of the sinus node, atria, atrioventricular node, as well as the His-Purkinje system (HPS) and ventricles. However, there are limited data on the clinical value and impact of ECANS as well as vagus nerve activity on the parameters of permanent His-bundle (HB) or left bundle branch (LBB) pacing. Moreover, there have been no prospective studies evaluating the feasibility and efficacy of ECANS and the management of ECANS-induced scenarios, such as an exit block, increase in pacing threshold, as well as vagally mediated arrhythmias and conduction abnormalities in patients with physiological conduction system pacing (HB/LBB pacing).

The objective of the HIS-STORY study in humans is to evaluate the clinical value of ECANS in patients with HB/LBB pacing for further development of patient-centered management strategy.

Study Overview

• Status: Recruiting
• Conditions: Permanent His Bundle Pacing; Permanent Left Bundle Branch Pacing
• Intervention / Treatment: Diagnostic test: extracardiac vagal nerve stimulation (ECANS) + EPS

Detailed Description

This is a multicenter, prospective, open-label, randomized, interventional study enrolling patients with indications for permanent cardiac pacing according to the current European Society of Cardiology Guidelines on Cardiac Pacing. All participants will undergo permanent pacemaker implantation for HB or LBB pacing. Subsequently, an invasive electrophysiological study (EPS) and ECANS will be performed. The 2 x 2 randomisation will be performed, i.e. right vs left side superior ECANS and blinded for operator ultrasonography guided effective vs ineffective inferior vagal nerve stimulation). The randomisation will prove the feasibility and efficacy of superior ECANS and feasibility, efficacy, and reproducibility of ultrasonography guided inferior ECANS. All the measured parameters as well as demographic and clinical data will be recorded in the study database. Patients with an exit block or an increase in a pacing threshold of an HB/LBB electrode will be further managed by electrophysiologists from the research group. The management will be based on clinical assessment and patient's decision and may involve pacemaker reprogramming, pacemaker upgrade with a back-up pacing electrode implantation, or cardio-neuro-ablation.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Krystian Josiak, MD, PhD; Phone Number: +48 516625985; Email: kjosiak@4wsk.pl

Study Locations

• Poland
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland, 50-981
      • Recruiting
      • 4th Military Hospital, Cardiology Department
      • Contact: Krystian Josiak, MD, PhD; Phone Number: +48 261660223; Email: kjosiak@4wsk.pl
      • Sub-Investigator: Dorota Zyśko, prof, MD
      • Sub-Investigator: Dariusz Jagielski, MD, PhD
      • Sub-Investigator: Paweł Szymkiewicz, MD, PhD
      • Sub-Investigator: Piotrowska Katarzyna, MD, PhD
      • Sub-Investigator: Bartosz Biel, MD
      • Sub-Investigator: Przemysław Skoczyński, MD, PhD
      • Sub-Investigator: Joanna Relewicz, MD, PhD
  • Mazowieckie
    • Radom, Mazowieckie, Poland, 26-617
      • Recruiting
      • Mazovian Speciality Hospital, Cardiology Department
      • Contact: Jarosław Kosior, MD, PhD; Phone Number: +48 3613676; Email: jaroslaw.kosior@icloud.com
      • Principal Investigator: Jarosław Kosior, MD, PhD
      • Sub-Investigator: Janusz Śledź, MD, PhD
  • Podkarpackie
    • Sanok, Podkarpackie, Poland, 38-500
      • Recruiting
      • Subcarpathian Center for Cardiovascular Intervention
      • Contact: Sebastion Stec, prof, MD; Phone Number: +48 600298022; Email: smstec@wp.pl
      • Principal Investigator: Sebastian Stec, prof, MD
      • Sub-Investigator: Antoni Wilczek, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• signed informed consent form
• effective and stable HB or LBB pacing
• sinus rhythm during the intervention procedure

Exclusion Criteria:

• contraindications to invasive EPS
• contraindications to general anesthesia
• contraindications to atropine administration (e.g., glaucoma)
• persistent atrial fibrillation or atrial flutter
• pregnancy
• diseases that may cause autonomic system neuropathy
• use of medications that may affect the parasympathetic system
• a history of cardiac surgery
• a history of ablation due to arrhythmia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ECANS started from the right vagus nerve; superior ECANS and ultrasonography guided inferior ECANS	Diagnostic test: extracardiac vagal nerve stimulation (ECANS) + EPS; The study intervention will consist of 3 steps, all of which will be performed under general anesthesia: EPS with the measurement of parameters of atrioventricular conduction and programmed atrial and ventricular pacing.; ECANS of the right and the left vagus nerve (from the right and left internal jugular vein, respectively; patients will be randomized to start from the right or the left side) performed during: 1) the patient's spontaneous heart rhythm (if present); 2) HB/LBB pacing with permanently programmed impulse parameters; 3) HB/LBB pacing at a pacing threshold of +0.1 V; and 4) 5 minutes after intravenous injection of atropine (0.02-0.04 mg/kg).; EPS with the measurement of parameters of atrioventricular conduction and programmed atrial and ventricular pacing.
Active Comparator: ECANS started from the left vagus nerve; superior ECANS and ultrasonography guided inferior ECANS	Diagnostic test: extracardiac vagal nerve stimulation (ECANS) + EPS; The study intervention will consist of 3 steps, all of which will be performed under general anesthesia: EPS with the measurement of parameters of atrioventricular conduction and programmed atrial and ventricular pacing.; ECANS of the right and the left vagus nerve (from the right and left internal jugular vein, respectively; patients will be randomized to start from the right or the left side) performed during: 1) the patient's spontaneous heart rhythm (if present); 2) HB/LBB pacing with permanently programmed impulse parameters; 3) HB/LBB pacing at a pacing threshold of +0.1 V; and 4) 5 minutes after intravenous injection of atropine (0.02-0.04 mg/kg).; EPS with the measurement of parameters of atrioventricular conduction and programmed atrial and ventricular pacing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Loss of HB/LBB capture or significant increase in pacing threshold	significant increase in pacing threshold = above the permanently programmed impulse amplitude of HB/LBB electrode induced by ECANS	0-12 months after HB/LBB pacemaker implantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A nonsignificant increase in pacing threshold	below the permanently programmed impulse amplitude of HB/LBB electrode induced by ECANS	0-12 months after HB/LBB pacemaker implantation
Prolongation of the stimulus-QRS interval during HB/LBB pacing induced by ECANS		0-12 months after HB/LBB pacemaker implantation

Other Outcome Measures

Outcome Measure	Time Frame
Any arrhythmia induced by ECANS	0-12 months after HB/LBB pacemaker implantation

Collaborators and Investigators

• Sponsor: 4th Military Hospital
• Collaborators: Wroclaw Medical University; Subcarpathian Center for Cardiovascular Intervention; Mazovian Speciality Hospital
• Investigators: Principal Investigator: Krystian Josiak, MD, PhD, 4th Military Hospital

Publications and helpful links

General Publications

• Abdelrahman M, Subzposh FA, Beer D, Durr B, Naperkowski A, Sun H, Oren JW, Dandamudi G, Vijayaraman P. Clinical Outcomes of His Bundle Pacing Compared to Right Ventricular Pacing. J Am Coll Cardiol. 2018 May 22;71(20):2319-2330. doi: 10.1016/j.jacc.2018.02.048. Epub 2018 Mar 10.
• Kronborg MB, Mortensen PT, Poulsen SH, Gerdes JC, Jensen HK, Nielsen JC. His or para-His pacing preserves left ventricular function in atrioventricular block: a double-blind, randomized, crossover study. Europace. 2014 Aug;16(8):1189-96. doi: 10.1093/europace/euu011. Epub 2014 Feb 7.
• Dandamudi G, Vijayaraman P. How to perform permanent His bundle pacing in routine clinical practice. Heart Rhythm. 2016 Jun;13(6):1362-6. doi: 10.1016/j.hrthm.2016.03.040. Epub 2016 Mar 22. No abstract available.
• Josiak K, Nowak K, Fuglewicz A, Jagielski D, Banasiak W, Ponikowski P. Does right ventricular pacing increase the risk of ventricular arrhythmias in patients with an implantable cardioverter-defibrillator? Kardiol Pol. 2014;72(4):381-4. doi: 10.5603/KP.2014.0073. No abstract available.
• Sharma PS, Dandamudi G, Naperkowski A, Oren JW, Storm RH, Ellenbogen KA, Vijayaraman P. Permanent His-bundle pacing is feasible, safe, and superior to right ventricular pacing in routine clinical practice. Heart Rhythm. 2015 Feb;12(2):305-12. doi: 10.1016/j.hrthm.2014.10.021. Epub 2014 Oct 22.
• Burri H, Jastrzebski M, Vijayaraman P. Electrocardiographic Analysis for His Bundle Pacing at Implantation and Follow-Up. JACC Clin Electrophysiol. 2020 Jul;6(7):883-900. doi: 10.1016/j.jacep.2020.03.005.
• Zysko D, Gajek J, Kozluk E, Mazurek W. Electrocardiographic characteristics of atrioventricular block induced by tilt testing. Europace. 2009 Feb;11(2):225-30. doi: 10.1093/europace/eun299. Epub 2008 Nov 5.
• 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.
• 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.
• Stec S, Dobaj L, Sledz A, Stepien-Walek AM, Ton V, Sledz J. Cardioneuroablation for management of cardioinhibitory vasovagal syncope and pacemaker complications. HeartRhythm Case Rep. 2020 May 11;6(8):531-534. doi: 10.1016/j.hrcr.2020.04.021. eCollection 2020 Aug. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2021
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: March 21, 2021
• First Submitted That Met QC Criteria: March 24, 2021
• First Posted (Actual): March 25, 2021

Study Record Updates

• Last Update Posted (Actual): December 20, 2022
• Last Update Submitted That Met QC Criteria: December 19, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: His bundle pacing; extracardiac vagal nerve stimulation; left bundle branch pacing
• Other Study ID Numbers: 4thMilitaryH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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