AV Block, Heart Failure, Heart Failure With Reduced Ejection Fraction, Intraventricular Conduction Delay, LBBB, Pacing-Induced Cardiomyopathy, RBBB
Conditions
Brief summary
The investigators aim to prospectively test the comparative effectiveness of His or Left bundle branch pacing in relation to patient centered outcomes (quality of life, physical activity, heart failure hospitalization, mortality) and comparative safety in relation to device-related complications and re-interventions (e.g., lead dislodgement, infection) relative to standard of care biventricular pacing in patients with heart failure due to left ventricular systolic dysfunction (LVEF≤50%) and with either a wide QRS (≥130 ms) or with/anticipated \>40% pacing who are already receiving current standard heart failure pharmacological therapy.
Detailed description
In this prospective, randomized, multi-center clinical trial, the investigators aim to prospectively evaluate the comparative effectiveness His or Left bundle branch pacing (His/LBBP) vs. biventricular pacing (BiVP) in patients with heart failure due to left ventricular systolic dysfunction (LVEF≤50%) and with either a wide QRS (≥130 ms) or with/anticipated \>40% pacing who are already receiving current standard heart failure pharmacological therapy by assessing all cause death and heart failure hospitalization at the end of the study. Additional formal secondary objectives include evaluation disease-specific quality and psychological adjustment changes at 1 year after device implant and evaluation of a composite of death of any cause or heart failure hospitalization or more \>15% increase in the left ventricular end-systolic volume index at the end of the study.
Interventions
DEVICEBiVP
Biventricular pacing has been shown to improve outcomes by delivering synchronized electrical stimuli to the right and left ventricles utilizing an an endocardial right atrial lead, an endocardial right ventricular lead, and an epicardial left ventricular lead implanted in a branch of the coronary sinus. For LVEF≤35% a biventricular pacemaker-defibrillator will be implanted while for LVEF 36-50% a biventricular pacemaker will be implanted.
DEVICEHis/LBBP
Pacing at the level His-Bundle or left bundle branch is used to correct the underlying conduction abnormality, resulting in a faster and more homogeneous activation of the heart pacing directly via the intrinsic conduction system of the heart accompanied by a right atrial endocardial lead and a right ventricular defibrillator endocardial lead for LVEF≤35% and by a right atrial endocardial lead for LVEF 36-50%.
Sponsors
Patient-Centered Outcomes Research Institute
University of Utah
Virginia Commonwealth University
Cleveland Clinic Florida
East Carolina University
Baylor College of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men and women 18 years of age or older. * A LVEF ≤ 50% within 6 months prior to enrollment. * Resting QRS duration ≥130 ms as evidenced by a historical 12-lead ECG prior to enrollment OR anticipated right ventricular pacing \>40% OR device in place with right ventricular pacing \> 40%. * Are optimized on HF guideline directed medical therapy according to current HF published guidelines OR patient's physician will make an effort to start all guideline-directed medical therapy and titrate doses up as permitted by the participant clinical status and co-morbidities prior to implantation procedure.
Exclusion criteria
* Women who are pregnant, lactating, or plan to become pregnant during the course of the trial. * Participants with angiographic evidence of coronary disease who are candidates for coronary revascularization and are likely to undergo coronary artery bypass graft surgery or percutaneous coronary, intervention in the next three (3) months. * Enzyme-positive myocardial infarction within the past three (3) months prior to enrollment. * Coronary artery bypass graft surgery or percutaneous coronary intervention (balloon and/or stent angioplasty) within the past three (3) months prior to enrollment. * Reversible non-ischemic cardiomyopathy (e.g., acute viral myocarditis). * Participants with Chagas disease, cardiac sarcoidosis or amyloidosis. * Expected to receive left ventricular assist device or heart transplantation within 6 months. * Participants with primary severe valvular disease (e.g., aortic stenosis). * Have a life expectancy of less than 12 months. * Participants with irreversible brain damage from preexisting cerebral disease. * Participants with a contrast dye allergy unable or unwilling to undergo pretreatment with steroids and/or diphenhydramine. * Participants participating in any other interventional cardiovascular clinical trial. * Participants who would be unable to comply with the study's follow-up visit schedule; or * Participants who had any prior unsuccessful attempt at implantation of biventricular pacing (BiVP), His Bundle Pacing (HBP), or Left Bundle Branch Pacing (LBBP) device.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| A combined clinical endpoint of all-cause mortality and hospitalization for heart failure | 5.5 years | The primary efficacy outcome will be described using Kaplan-Meier freedom from event curves over time, with event-free survival compared between assigned treatment arms using a logrank test, stratified by levels of the two factors (LVEF (≤35% vs. 36 to 50%) and conduction abnormality (LBBB vs non-LBBB)) used for randomization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cardiovascular hospitalization at 5.5 years | 5.5 years | Secondary endpoint measured from first hospitalization for cardiovascular disease |
| Change in Six Minute Walk Test performance at 12 months | 12 months | Secondary endpoint measured from Six Minute Walk Test |
| Patient activity measured through cardiovascular implantable electronic devices (CIED) at 12 months | 12 months | Measurement Patient activity measured through cardiovascular implantable electronic devices (CIED) |
| Change in NT-proBNP at 12 months | 12 months | Measurement of heart failure serum biomarker NT-proBNP |
| Assess change in Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) at 12 months | 12 months | Assess change in Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) item score measured before and at 12 months after implant. |
| Change in composite endpoint comprised of death, first hospitalization for worsening HF and left ventricular end systolic volume index (LVESVi) at 5.5 years | 5.5 years | Secondary endpoint measured from all cause death, first hospitalization for heart failure and echocardiography on left ventricular end-systolic volume index (LVESVi) in the His/LBBP vs. BIV-BiVP arm |
| Composite of cardiovascular death or heart transplant or durable left ventricular assist device or more > 15% increase in the LVESVi or change in KCCQ-12 at the end of the study using win ratio | 5.5 years | Secondary endpoint measured from cardiovascular death or heart transplant or durable left ventricular assist device or more \> 15% increase in the LVESVi or change in KCCQ-12 at the end of the study using win ratio |
| Death from any cause at 5.5 years | 5.5 years | Secondary endpoint measured from all cause death |
| Death from any cardiovascular cause at 5.5 years | 5.5 years | Secondary endpoint measured from death due to cardiovascular causes |
| Hospitalization for heart failure at 5.5 years | 5.5 years | Secondary endpoint measured from first hospitalization for heart failure |
| Total HF hospitalizations | 5.5 years | Total number of HF hospitalizations |
| Composite of cardiovascular death or first HF hospitalization | 5.5 years | Secondary endpoint measured from cardiovascular death, first hospitalization for heart failure |
| Composite cardiovascular death or HF hospitalization or heart transplant or durable left ventricular assist device | 5.5 years | Secondary endpoint measured from cardiovascular death, heart transplant or durable left ventricular assist device |
| Change in NYHA Classification at 12 months | 12 months | Secondary endpoint measured from New York Heart Association class |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Left Ventricular Ejection Fraction (LVEF) at 12 months | 12 months | Measurement of LVEF before and at 12 months after implant using echocardiography |
| Appropriate ICD therapy for ventricular arrhythmias | 5.5 years | Antitachycardia pacing or ICD shocks |
| Incidence of atrial tachyarrhythmia events | 5.5 years | Atrial arrhythmia event measured through cIED |
Countries
Canada, United States
Contacts
Primary ContactMihail G Chelu, MD, PhD
Backup ContactMerin Thomas
Outcome results
None listed