His-bundle Pacing vs. Right Ventricular Apical Pacing in Patients With Reduced Ejection Fraction

Study Overview
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Brief Summary
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The study compares standard right ventricle apical pacing with so called His-bundle pacing, for patients with slightly or moderately reduced ejection fraction and atrioventricular block requiring pacemaker therapy. The primary outcome is left ventricular ejection fraction measured after 6 months.

Detailed Description
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Patients with reduced systolic ejection fraction (40≤ ejection fraction ≤55%) and pacemaker indication due to high degree AV block are included. The study has a randomized double blinded crossover design. Patients are implanted with a standard right ventricle lead and right atrial lead (if indicated), and in addition a His-bundle lead. Randomization is performed as to which pacing modality is used during the first 6 months. After 6 months the pacing modality is changed. Patients are blinded and endpoint adjudicators, including echocardiography staff, are blinded. Device nurse and physician are not blinded. Primary endpoint is difference in left ventricular ejection fraction after 6 months, paired comparisons are used and each patient is their own control. Secondary endpoints include complications and safety of the device/electrode, and quality of life.

Official Title
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His-bundle Pacing vs. Right Ventricular Apical Pacing in Patients With Reduced Ejection

Conditions
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His Bundle Pacing, Heart Failure, Systolic

Intervention / Treatment
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* Device: His-bundle pacing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: AV block II or III with high expected pacing need Left ventricular ejection fraction between 40% and 55% (inclusive) Willing to participate and sign informed consent Exclusion Criteria: Under 18 years old Pregnant Hypertrophic cardiomyopathy Cardiac sarcoidosis Cardiac amyloidosis Previous myocardial infarction within last 3 months Ventricular septum defect or other other left ventricular corrective surgery Congenital heart disease surgically corrected Atrial fibrillation with uncontrolled rate (if not planned for AV node ablation)

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: Crossover Assignment
Interventional Model Description: Randomized double blinded crossover design.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: His-bundle pacing first<br>Patients are allocated to receive His-bundle pacing for a period of 6 months. Then the patients will cross over to traditional right ventricular (RV) apical pacing for 6 months. | Device: His-bundle pacing<br>* A standard pacing electrode (Medtronic 4076) will be placed in RV apex (or RV septum as a secondary option) and in the right atrial appendage (if indicated). A dedicated His-bundle pacemaker electrode (Medtronic 3830) will be placed in the region of His bundle, using a dedicated introducer sheath (Medtronic C304 or Medtronic C315). His-bundle potentials will be identified and His-bundle capture (non-selective or selective) will be ascertained using an electrophysiology recording system. Device programming will focus on providing physiological atrioventricular delay and safety RV pacing as backup.<br>|
| Experimental: RV apical pacing first<br>Patients are allocated to receive traditional RV apical pacing for a period of 6 months. Then the patients will cross over to His-bundle pacing for 6 months. | Device: His-bundle pacing<br>* A standard pacing electrode (Medtronic 4076) will be placed in RV apex (or RV septum as a secondary option) and in the right atrial appendage (if indicated). A dedicated His-bundle pacemaker electrode (Medtronic 3830) will be placed in the region of His bundle, using a dedicated introducer sheath (Medtronic C304 or Medtronic C315). His-bundle potentials will be identified and His-bundle capture (non-selective or selective) will be ascertained using an electrophysiology recording system. Device programming will focus on providing physiological atrioventricular delay and safety RV pacing as backup.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ejection Fraction | Absolute difference in left ventricular systolic ejection fraction (absolute percent) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Percentage of device-related adverse events. Events will be classified as general, associated with His-bundle lead or associated with RV lead | 12 months | 
| Left ventricular activation time | Total left ventricular mechanical activation time (measured with tissue doppler echocardiography) | 6 months | 
| NT-ProBNP | Difference in NT-ProBNP levels | 6 months | 
| QRS duration | Difference in total QRS duration on ECG | 6 months | 
| Left Ventricular Activation Time (LVAT) | Maximum unipolar spike-to-peak-T-wave in V5-V6 | 6 months | 
| 6 minute walk test | Difference in six minute hall walk test (meters) | 6 months | 
| Change in quality of life measured by the Short Form Health Survey (SF-36) mean score | Difference in health related quality of life, measured by the SF-36 questionnaire, calculated as difference in mean from baseline to follow-up (calculated using the official scoring algorithm, where each sub scale is assigned a score between 0-100, higher score represents better health) | 6 months | 
| Change in quality of life measured by the EuroQol EQ-5D-5L Questionnaire | Difference in health related quality of life, measured by the mean score of the EQ-5D (version 5L) questionnaire (totalt score ranging from 5-25 points, higher score represents more health related problems/disability) | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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His bundle pacing, Conduction system pacing, Heart failure, systolic, Quality of life, Left ventricular ejection fraction