Systolic Heart FailureNCT05884411
Evaluation of Left Bundle Branch Area Pacing As A Rescue Strategy for Cardiac Resynchronization Therapy Non-Response
A study testing Left bundle branch area pacing and Cardiac MRI in people with Systolic Heart Failure and Heart Failure With Reduced Ejection Fraction, run by VA Office of Research and Development at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Systolic Heart Failure, Heart Failure With Reduced Ejection Fraction, CRT Non-Response
- What is being tested?
- Left bundle branch area pacing and Cardiac MRI
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Apr 2023to 5 Aug 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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%
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Minneapolis VA Health Care System, Minneapolis, MN
Minneapolis, Minnesota, 55417-2309
About this study
Official title: 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.
Read the 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).
- Conditions
- Systolic Heart Failure, Heart Failure With Reduced Ejection Fraction, CRT Non-Response, Left Bundle Branch Area Pacing
- Being tested
- Left bundle branch area pacing, Cardiac MRI
- Keywords
- Heart Failure, CRT, LBBAP, Non-response, Cardiac MRI, CMR, Left bundle branch area pacing, cardiac resynchronization therapy
- Medical subject headings
- Heart Failure, Systolic, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Left bundle branch area pacingDevice
Also called LBBAP
A cardiac pacing electrode is inserted into the left bundle branch area of the myocardium via a transvenous approach.
Cardiac MRIDiagnostic test
Also called CMR
A diagnostic imaging test using magnetic resonance imaging to evaluate cardiac function.
| Study group | Role | What they receive |
|---|---|---|
| LBBAP | Experimental | This arm will investigate improvement in cardiac function following placement of the LBBA pacing electrode in half the patients. Receives: Device: Left bundle branch area pacing |
| Cardiac MRI with devices | Experimental | This arm will investigate the feasibility of cardiac MRI to be used to measure cardiac function in patients with cardiac devices. Receives: Diagnostic Test: Cardiac MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Secondary outcomes (2)
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.
Measured: 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.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2023
- Study start30 Apr 2023
- Primary completion5 Aug 2025
- Study completion5 Aug 2025
Why it stopped: unsuccessful recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Systolic Heart FailureStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be randomized to either receive the new pacing lead in the left bundle branch area or continue current cardiac therapy (CRT) with biventricular CRT
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Selma D Carlson, MD, Principal investigator, Minneapolis VA Health Care System, Minneapolis, MN
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05884411
- Sponsor's protocol ID
- CARA-001-22F
- Other IDs
- CX002525
- Status last verified
- Aug 2025
- First submitted
- 28 Apr 2023
- Last updated
- 11 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05884411
- Acronym / sponsor ID
- CARA-001-22F
- Conditions
- Systolic Heart Failure, Heart Failure With Reduced Ejection Fraction, CRT Non-Response, Left Bundle Branch Area Pacing
- Keywords
- Heart Failure, CRT, LBBAP, Non-response, Cardiac MRI, CMR, Left bundle branch area pacing, cardiac resynchronization therapy
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: unsuccessful recruitment
- Enrolment
- 0 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 30 Apr 2023 (actual)
- Primary completion
- 5 Aug 2025 (actual)
- Study completion
- 5 Aug 2025 (actual)
- First posted
- 1 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Patients will be randomized to either receive the new pacing lead in the left bundle branch area or continue current cardiac therapy (CRT) with biventricular CRT
| Arm | Type | Receives |
|---|---|---|
| LBBAP | Experimental | Device: Left bundle branch area pacingThis arm will investigate improvement in cardiac function following placement of the LBBA pacing electrode in half the patients. |
| Cardiac MRI with devices | Experimental | Diagnostic Test: Cardiac MRIThis arm will investigate the feasibility of cardiac MRI to be used to measure cardiac function in patients with cardiac devices. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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%
Key exclusion criteria (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Left bundle branch area pacingAlso: LBBAPA cardiac pacing electrode is inserted into the left bundle branch area of the myocardium via a transvenous approach. | Device | LBBAP |
| Cardiac MRIAlso: CMRA diagnostic imaging test using magnetic resonance imaging to evaluate cardiac function. | Diagnostic test | Cardiac MRI with devices |
Primary outcome
Left ventricular ejection fraction by echocardiography
Time frame: 6 months
CRT non-response will be evaluated by echocardiography to assess left ventricular ejection fraction (LVEF). LVEF is reported as a percent.
2 secondary outcomes
Left ventricular ejection fraction by cardiac MRI
Time frame: 6 months
Interventricular mechanical delay measurement by 2D speckle-tracking echocardiography
Time frame: 6 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Selma D Carlson, MD principal investigator
Minneapolis VA Health Care System, Minneapolis, MN
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Left bundle branch area pacing and Cardiac MRI in people with Systolic Heart Failure and Heart Failure With Reduced Ejection Fraction, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 11 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Left ventricular ejection fraction by echocardiography (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2025.