Evaluation of Left Bundle Branch Area Pacing As A Rescue Strategy for Cardiac Resynchronization Therapy Non-Response

Evaluation of Left Bundle Branch Area Pacing As A Rescue Strategy for Cardiac Resynchronization Therapy Non-response in Patients With Heart Failure: A Randomized Controlled Trial

This study aims to investigate whether the investigators can improve heart function in patients with heart failure who have undergone cardiac resynchronization therapy, but have not had an improvement in their heart function at least one year after the procedure. The investigators will evaluate whether placing a new pacing lead (electrode) in a different part of the heart may increase heart function and decrease heart failure symptoms.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure With Reduced Ejection Fraction; Systolic Heart Failure; Left Bundle Branch Area Pacing; CRT Non-Response
• Intervention / Treatment: Device: Left bundle branch area pacing; Diagnostic test: Cardiac MRI

Detailed Description

Heart failure is one of the leading causes of death, hospitalization and poor quality of life among Veterans. For many Veterans despite receiving maximal medical therapy for heart failure with reduced ejection fraction (HFrEF), their cardiac function and functional capacity markedly decreases and they develop delays and blocks in their intrinsic conduction system (i.e. left bundle branch block). These patients then meet criteria for cardiac resynchronization therapy (CRT), which has been shown to improve cardiac function. However, up to 40% of patients who undergo CRT do not experience the expected improvement in cardiac function or clinical improvement, and this is termed "non-response".

A critical limitation of traditional CRT is that the leads do not directly utilize the heart's intrinsic conduction tissue, called the His-Purkinje system. An extensive web of conduction tissue capable of transmitting the electrical signals all over the ventricles within milliseconds, the His-Purkinje system conducts electrical stimuli much faster than conduction through a usual myocardial cell. The left bundle branch is a component of the His-Purkinje system. As such, electrophysiologic therapies that directly activate the left bundle branch area (LBBAP) have emerged as possible solutions to the problem of non-response to CRT. Although data suggests that in patients with complete LBBB, LBBAP can better optimize electrical synchrony and improve cardiac function compared to traditional bi-ventricular CRT, the efficacy has not been studied in CRT non-responders.

Currently, the most frequently used technique for assessment of the left ventricle is echocardiography because it is widely available. However, several studies have demonstrated that cardiac MRI (CMR) is superior to echocardiography in measuring left ventricle ejection fraction, particularly in terms of interstudy reproducibility. Recent studies have also demonstrated CMR imaging to be safe even in patients with non-MRI-conditional pacemakers and defibrillators. Studies have also observed that patients undergoing MRI with non-MRI-conditional pacemakers or ICDs neither experienced device/lead failure nor were they at increased risk by undergoing MRI. Despite established safety of CMR in patients with cardiac devices, it is not being routinely performed because there are concerns that the devices will cause field inhomogeneity resulting in magnetic susceptibility artifacts and non-diagnostic image quality. However, these concerns are overcome by utilizing contemporary imaging protocols with gradient echo sequences as opposed to standard steady-state free precession. By using these new protocols for CMR in this study, the investigators aim to establish the feasibility of CMR to prospectively assess cardiac function at baseline and during follow-up in patients with cardiac devices (i.e. that the image quality in subjects with implantable devices is adequate and not undermined by image artifact).

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Selma D Carlson, MD; Phone Number: (612) 467-3662; Email: selma.carlson@va.gov

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55417-2309
      • Recruiting
      • Minneapolis VA Health Care System, Minneapolis, MN
      • Contact: Joshua P Nixon, PhD; Phone Number: 612-467-2804; Email: Joshua.Nixon@va.gov
      • Principal Investigator: Selma D Carlson, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

All Veterans in this study will have undergone CRT at least 12 months prior to enrollment and determined to have non-response by all the following criteria:

• Lack of improvement in New York Heart Association (NYHA) class
• Lack of LVEF increase by > 5%
• Lack of decrease in LVESV by > 15%

Exclusion Criteria:

• Unable to understand or provide informed consent
• Unable or unwilling to participate in the protocol or comply with any of its components
• Pregnant women
• Known cancer patients, actively receiving chemotherapy
• Patients unable to pass MRI safety screening (intra-orbital metallic foreign bodies, severe claustrophobia, etc)
• Patients with anatomical difficulties for implanting LBBAP
• Patients with high risk of procedure-related infection
• Immunocompromised patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LBBAP; This arm will investigate improvement in cardiac function following placement of the LBBA pacing electrode in half the patients.	Device: Left bundle branch area pacing; A cardiac pacing electrode is inserted into the left bundle branch area of the myocardium via a transvenous approach.; Other Names: LBBAP
Experimental: Cardiac MRI with devices; This arm will investigate the feasibility of cardiac MRI to be used to measure cardiac function in patients with cardiac devices.	Diagnostic test: Cardiac MRI; A diagnostic imaging test using magnetic resonance imaging to evaluate cardiac function.; Other Names: CMR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left ventricular ejection fraction by echocardiography	CRT non-response will be evaluated by echocardiography to assess left ventricular ejection fraction (LVEF). LVEF is reported as a percent.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left ventricular ejection fraction by cardiac MRI	Cardiac MRI (CMR) will also be used to assess left ventricular ejection fraction (LVEF). LVEF is reported as a percent.	6 months
Interventricular mechanical delay measurement by 2D speckle-tracking echocardiography	Left ventricular synchrony will be assessed by measuring the interventricular mechanical delay (measured in ms) using 2D speckle-tracking echocardiography.	6 months

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Selma D Carlson, MD, Minneapolis VA Health Care System, Minneapolis, MN

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2023
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2028

Study Registration Dates

• First Submitted: April 28, 2023
• First Submitted That Met QC Criteria: May 22, 2023
• First Posted (Actual): June 1, 2023

Study Record Updates

• Last Update Posted (Actual): June 1, 2023
• Last Update Submitted That Met QC Criteria: May 22, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Heart Failure; cardiac resynchronization therapy; Cardiac MRI; CMR; CRT; Left bundle branch area pacing; LBBAP; Non-response
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Heart Failure, Systolic
• Other Study ID Numbers: CARA-001-22F; CX002525 (Other Grant/Funding Number: VA CSR&D)

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: Yes
• product manufactured in and exported from the U.S.: Yes