His-bundle Pacing vs. Right Ventricular Apical Pacing in Patients With Reduced Ejection Fraction (HIS-PrEF)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure, Systolic; His Bundle Pacing
• Intervention / Treatment: Device: His-bundle pacing

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Maiwand Farouq, MD, PhD; Phone Number: + 46 40 336415‬; Email: maiwand.farouq@skane.se
• Study Contact Backup: Name: Rasmus Borgquist, MD; Phone Number: +46 46 171010; Email: rasmus.borgquist@med.lu.se

Study Locations

• Sweden
  • Lund, Sweden
    • Recruiting
    • Skane University Hospital
    • Contact: Rasmus Borgquist; Phone Number: +4646171000; Email: rasmus.borgquist@med.lu.se
  • Umeå, Sweden
    • Recruiting
    • Norrland University Hospital
    • Contact: Steen Jensen, MD PhD; Email: steen.jensen@medicin.umu.se
  • Varberg, Sweden
    • Recruiting
    • Region Hallands Sjukhus Varberg
    • Contact: Cecilia Rorsman; Email: Cecilia.Rorsman@regionhalland.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: His-bundle pacing first; 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; 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.
Experimental: RV apical pacing first; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Region Skane
• Investigators: Principal Investigator: Rasmus Borgquist, MD PhD, Lund University, Skane University Hospital, Arrhythmia Section, Lund, Sweden

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: August 24, 2020
• First Submitted That Met QC Criteria: August 24, 2020
• First Posted (Actual): August 27, 2020

Study Record Updates

• Last Update Posted (Actual): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Quality of life; His bundle pacing; Left ventricular ejection fraction; Conduction system pacing; Heart failure, systolic
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Murmurs; Heart Failure; Systolic Murmurs; Heart Failure, Systolic
• Other Study ID Numbers: HIS-PrEF_study

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