HIS Alternative II - UK Site

Direct HIS/LBB Pacing as an Alternative to Biventricular Pacing in Patients With Symptomatic Heart Failure Despite Optimal Medical Treatment and ECG With Typical Left Bundle Branch Block

The study will investigate the feasibility of using direct HIS pacing or left bundle branch pacing (LBB pacing) as an alternative to biventricular pacing in patients with symptomatic heart failure and an ECG with a typical left bundle branch block pattern.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Left Bundle-Branch Block
• Intervention / Treatment: Device: HIS/LBB pacing; Device: LV pacing

Detailed Description

Biventricular pacing has for more than a decade been standard of care for patients with HFrEF, LVEF < 35%, NYHA II-IV despite optimal medical treatment and an ECG with left bundle branch block (LBBB). However, it is not always ideal because of several drawbacks such as phrenic nerve capture, inability to reach late activated areas and many more. Direct HIS pacing can in many cases capture the left bundle and provide normal electrical activation of the left ventricle but sometimes with high pacing thresholds. Recently direct left bundle branch pacing has shown promise with synchronous activation of the left ventricle at low pacing thresholds.

In the present study the investigators randomize 125 patients in one center to either conventional CRT (45 patients) or HIS/LBB pacing (80 patients). In the HIS/LBB arm, direct HIS-pacing is attempted first but if its not possible or the pacing threshold for capturing the left bundle branch is > 2.5 V at 1 ms the investigators switch to placing a LBB-lead.

Power calculation for non-inferiority: With the 50 patients in the first His Alternative study (25 Biv-CRT og 25 His-CRT) the investigators observed a fall in systolic volumes of 34% and 46% with a standard deviation of 13-16%. Using these numbers it would take at least 108 patients to be 90% sure that the lower limit of a one-sided 97.5% confidence interval (equal to a 95% two-sided confidence interval) would be over the non-inferiority limit of -10%.

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

Contacts and Locations

• Study Contact: Name: Daniel Keene, MBChB; Phone Number: 020 3313 1000; Email: daniel.keene@nhs.net
• Study Contact Backup: Name: mohamed zuhair, MBBS; Phone Number: 020 3313 1000; Email: m.zuhair@nhs.net

Study Locations

• United Kingdom
  • London, United Kingdom
    • Recruiting
    • Hammersmith Hospital
    • Contact: Daniel Keene

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients over 18 years of age, ischemic or non-ischemic cardiomyopathy with LVEF ≤ 35% assessed by echocardiography, NYHA class II-IV heart failure symptoms despite optimal medical treatment and

  • Either planned new implantation of a biventricular pacing system (CRT-P or CRT-D), where the ECG is with sinus rhythm and a typical left bundle branch block (see definition below)
  • Or planned upgrade of an existing pacemaker or ICD to a biventricular pacing system (CRT-P or CRT-D), where the ECG is with sinus rhythm and a typical left bundle branch block or there has been> 90% right ventricular pacing from an existing pacemaker for at least 2 months prior to enrollment
• Signed informed consent

• Typical left bundle branch block:

  • QRS width > 130 msec for women and > 140 msec for men QS or rS pattern in leads V1 and V2, and mid-QRS plateau phase with or without extras in at least 2 of leads V1, V2, V5, V6, I, and aVL

Exclusion Criteria:

• Existing biventricular pacing system
• Permanent atrial fibrillation
• Severe renal failure with eGFR < 30 ml/min
• AMI or CABG within the last three months
• The patient does not want to participate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HIS/LBB pacing; In this arm a right ventricular (RV) lead or implantable cardioverter defibrillator (ICD) lead is placed first and then implantation of a HIS-pacing lead is attempted. If it is not possible to find and pace HIS, to correct the LBBB or the threshold for correcting the LBBB is > 2.5 V at 1 ms, implantation of a LBB-pacing lead is attempted instead. If that is not possible either, a left ventricular (LV) lead is implanted. Intervention: Device: HIS/LBB pacing	Device: HIS/LBB pacing; 3830 lead to HIS or LBB
Active Comparator: LV pacing; In this arm an RV-lead or ICD-lead is placed first and then implantation of a LV-pacing lead is attempted. If this is not possible due to anatomical difficulties (no coronary sinus (CS) access, no available branches other than v cordis anterior or v cordis media) or electrical difficulties (no capture below 4 V at 1.0 msec or phrenic nerve stimulation < 2x pacing threshold), implantation of a HIS-pacing lead is attempted instead. If that is not possible or the threshold for correcting the LBBB is > 2.5 V at 1 ms, implantation of a LBB-pacing lead is attempted instead. Intervention: Device: LV pacing	Device: LV pacing; LV lead in a CS branch

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Left ventricular end-systolic volume	Echocardiographic response after 6 months defined as decrease in left ventricular systolic volume of ≥ 15% of baseline	6 months
Success rate of implanting a HIS-bundle lead with capture of the left bundle branch or a LBB-lead with narrowing of QRS	The success rate of implanting a pacing lead to the HIS-bundle with capture of the left bundle at a threshold < 2.5 V at 1 ms or implantation of a LBB lead with narrowing of the QRS duration and maintaining this effect at 6 month follow-up	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in LVEF and left ventricular chamber dimensions	Echocardiographic response assessed by chamber dimensions and LVEF on a continuous scale	6 months
Change in 6-min hall-walk test	Functional response after 6 months defined as an increase in 6-min walking distance of ≥ 20% of the initial value	6 months
Change in NYHA class	Symptomatic response after 6 months defined as a fall in NYHA class of ≥ 1	6 months
Change in Minnesota Living with Heart Failure score	Change in well-being after 6 months defined as a decrease in Minnesota Living With Heart Failure score of ≥ 15% of baseline	6 months
Shortening of QRS duration	Shortening the duration of the QRS complex defined as the widest paced QRS complex rated at 12-lead ECG after 6 months	6 months
Change in NT-pro BNP value	Change in NT-pro BNP value	6 months
Complications	Device-related complications (periprocedural: electrode reoperation, pneumothorax, hemothorax, pericardial bleeding/tamponade and later (after 30 days post implantation): LV/HIS electrode reoperation, change of device due to battery depletion and infection requiring extraction).	6 months

Collaborators and Investigators

• Sponsor: Imperial College Healthcare NHS Trust
• Collaborators: Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2023
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: March 16, 2023
• First Submitted That Met QC Criteria: April 13, 2023
• First Posted (Actual): April 14, 2023

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Heart Block; Heart Failure; Bundle-Branch Block
• Other Study ID Numbers: 22HH7978

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Will share data with international arm of the project NCT04409119
• IPD Sharing Time Frame: 6 months following final recruitment
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

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