Ablate and Pace HIS Study

Study Overview
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Brief Summary
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Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and estimates suggest its prevalence is increasing. Despite the advances in AF ablation strategies, the outcome of ablation procedures in persistent AF is still unsatisfactory. In addition, many patients are not candidates for ablation due to advanced age, comorbidities and previous failed ablation procedures. It is well known that there is no mortality benefit from rhythm versus rate control strategy in AF, therefore the increased number of AV node ablation and pacemaker insertion for patients with symptomatic AF with uncontrolled heart rate. Following AV node ablation, it is understandable that these patients will be paced 100% of the time where the value of physiological pacing will be at its most. The current standard practice is to pace the right ventricle for this cohort of patients unless they have severe LV systolic dysfunction when a biventricular pacing might be recommended. Previous data showed that RV pacing only can lead to deterioration of LV function, worsening of heart failure symptoms and increased mortality. HIS bundle pacing is a novel technique of pacing through placing the pacemaker lead on the junction box between the top and bottom chamber of the heart. This will allow the utilisation of the normal/intrinsic HIS Purkinjie (eclectic cables) to stimulate the ventricles. This can offer a physiological pacing modality and reduce pacing induced cardiomyopathy specially in pacing dependent pacing. The Ablate and Pace HIS Study proposes that the new method of HIS pacing is safe, effective and superior to the existing method of RV pacing in patients with atrial fibrillation who demonstrate signs of heart failure.

Detailed Description
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The Ablate and Pace HIS Study is a single-centre, prospective randomised single-blinded study, recruiting a sub-population of patients with AF who are deemed not fit for rhythm control strategy. These patients have been referred for a pacemaker implant and AVN node ablation as a symptomatic rate control option. The study aims to randomise a total of 100 participants into either the RV only pacing arm or the HBP arm. All patients will be implanted with a pacemaker device with one lead positioned in the right ventricle, and only in the HBP arm will an additional lead be positioned on the distal HIS bundle in order to obtain direct HIS-bundle capture. The RV lead will be only be used as a back-up option for the HBP arm if needed. Participants will undergo AVN ablation either at the same setting or 4-6 weeks later according to clinical indication and operator preference. A double-blinded design will then be employed to investigate the effect of HIS pacing. Endpoint measurements will be taken at Baseline, 4 weeks, 6 months and 12 months post randomisation. Treatment allocation will be blinded to the patients and endpoint assessor. All participants will be informed of their allocated treatment arm at the end of their 12 month follow up visit. Funding has been provided by Medtronic. The study Sponsor is University Hospitals of Leicester.

Official Title
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Safety and Efficacy of Distal His Bundle Pacing Compared to Right Ventricular Pacing in Patients With Symptomatic Atrial Fibrillation Undergoing AV Node Ablation With Evidence of Heart Failure, a Randomised Control Study

Conditions
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HIS Bundle Pacing, Atrial Fibrillation

Intervention / Treatment
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* Procedure: Ablation and Pacemaker Implantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 or above Symptomatic AF, New York Heart Association (NYHA) class II-IV Willing to consent for the study AF regardless type, deemed not suitable for rhythm control strategy that has been referred for AVN ablation with one of the following: Impaired LV function, EF <50 %. And or Raised N-Terminal Pro B-type Natriuretic Peptide ( NT-ProBNP) >365 ng/L Exclusion Criteria: Patient who has already got a pacemaker in situ Known severe LVSD when biventricular device is the thought to be the preferred pacing modality Females in child bearing period Lack of capacity to consent Other serious medical condition with life expectancy of less than 1 year Less than 18 years Unwilling to consent for the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Right Ventricular Only Pacing<br>All study participants will have an RV lead inserted, but this arm will have an RV lead only. | Procedure: Ablation and Pacemaker Implantation<br>* All patients will be implanted with a pacemaker device with one lead positioned in right ventricle (control arm only) and an additional lead will be positioned on the distal (ventricular) HIS bundle if in intervention arm. All patients will undergo ablation.<br>|
| Other: HIS Bundle Pacing<br>Participants in this group will have HIS bundle pacing, but in addition will have an RV lead inserted that will serve as a backup alternative in the event HIS bundle pacing is not effective. | Procedure: Ablation and Pacemaker Implantation<br>* All patients will be implanted with a pacemaker device with one lead positioned in right ventricle (control arm only) and an additional lead will be positioned on the distal (ventricular) HIS bundle if in intervention arm. All patients will undergo ablation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with 20% improvement in 6 minutes-walk distance, AFEQT questionnaire score, and number of steps and distance walked per day assessed by a Fitbit smart watch | 20% improvement in all 3 areas | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of LV function, LVESV assessed by echocardiogram | Improvement of LV function, LVESV assessed by echocardiogram | 12 months | 
| Change in NT-ProBNP level | Change in NT-ProBNP level | 12 months | 
| Incidence of hospitalisation for heart failure, need for device upgrade to biventricular pacemaker or mortality | Incidence of hospitalisation for heart failure, need for device upgrade to biventricular pacemaker or mortality | 12 months | 
| Pacing parameters | RV threshold/HIS bundle lead will be checked, and this will be documented if it has changed. | 12 months | 
| Fluoroscopy time during the device insertion | Fluoroscopy time during the device insertion | During device insertion | 
| Safety consideration: rate of infection, lead failure, displacement or the need for a repeat procedure | Safety consideration: rate of infection, lead failure, displacement or the need for a repeat procedure | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIS Bundle Pacing, Atrial Fibrillation