Safety and Efficacy of His Bundle Pacing Validated by Extracardiac Vagal Nerve Stimulation

Overview

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.

Full Title of Study: “Safety and Efficacy of HIs Bundle Pacing Validated by electrophySiological STudy, autonOmic Tests and extRacardiac Vagal Nerve Stimulation (HIS-STORY)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 2022

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.

Interventions

  • 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.

Arms, Groups and Cohorts

  • Active Comparator: ECANS started from the right vagus nerve
    • superior ECANS and ultrasonography guided inferior ECANS
  • Active Comparator: ECANS started from the left vagus nerve
    • superior ECANS and ultrasonography guided inferior ECANS

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 85 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • 4th Military Hospital
  • Collaborator
    • Subcarpathian Center for Cardiovascular Intervention
  • Provider of Information About this Clinical Study
    • Principal Investigator: Krystian Josiak, Krystian Josiak, MD, PhD – 4th Military Hospital
  • Overall Official(s)
    • Krystian Josiak, MD, PhD, Principal Investigator, 4th Military Hospital
  • Overall Contact(s)
    • Krystian Josiak, MD, PhD, +48 516625985, kjosiak@4wsk.pl

Citations Reporting on Results

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. Review.

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. Review.

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. Review.

Zyśko D, Gajek J, Koźluk 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, Sledź 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.

Stec S, Dobaj Ł, Śledź A, Stępień-Wałek AM, Ton V, Śledź 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.

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