Block, Heart, Heart Failure, Pacing-Induced Cardiomyopathy
Conditions
Keywords
pacing, cardiac resynchronization therapy, left bundle branch area pacing, conduction system pacing, heart failure, heart block
Brief summary
It is unknown whether left bundle branch area pacing (LBBAP) or biventricular pacing best prevents or reverses left ventricular (LV) adverse remodelling in patients with atrial fibrillation (AF) who require ventricular pacing or CRT. This randomized non-inferiority cross-over trial will compare left ventricular end-systolic volume change and secondary endpoints between LBBAP and biventricular pacing in patients with AF and LV dysfunction.
Detailed description
Rationale: Patients with atrial fibrillation (AF) and left ventricular (LV) dysfunction may require ventricular pacing because of bradycardia, AV junction ablation, or for cardiac resynchronization therapy. Right ventricular (RV) pacing is associated with the risk of adverse LV remodelling and heart failure, in particular in those with pre-existing LV dysfunction. Both LBBAP and biventricular pacing can prevent LV dyssynchrony. It is unknown which pacing mode best prevents or reverses LV adverse remodelling in patients with AF who require ventricular pacing or CRT. Primary objectives: 1. To compare LVESV change between LBBAP and biventricular pacing in patients with AF and LV dysfunction. Secondary objectives: 2. To compare change in quality of life, New York Heart Association functional class, 6-minute walking distance, QRS duration, vectorcardiographic QRS area, left ventricular ejection fraction (LVEF), global longitudinal strain and NT-proBNP between LBBAP and biventricular pacing in patients with AF and LV dysfunction. Study design: Randomized patient and assessor blinded non-inferiority cross-over trial. Study population: Patients with permanent AF and LVEF < 50% who require ventricular pacing because of bradycardia, AV junction ablation, or CRT. Intervention: Patients will be randomized according to a crossover design to first 6 months of LBBAP and then 6 months of biventricular pacing, or vice versa. After finishing the randomization phase of the study at 12 months, patients will be followed according to routine clinical practice. Clinical follow-up, an ECG, device interrogation and echocardiography will be performed at 36 months (2 years after finishing the randomization phase) in all patients. Main study parameters/endpoints: New York Heart Association (NYHA) functional class, Minnesota Living with Heart Failure Questionnaire (MLHFQ), 6-minute walking distance, ECG (vectorcardiographic QRS area, QRS duration), echocardiography (LVESV, LVEF, global longitudinal strain), NT-proBNP, lead and device performance (sensing, pacing, expected battery life), complications and costs will be evaluated for each pacing mode. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: For the purpose of this randomized controlled trial, patients will also receive a LBBAP lead. The additional risk of serious adverse events is \ 1.5% (lead dislodgement 1.1%, 0.4% acute coronary syndrome \[all managed conservatively without further sequelae in prior studies\]).(1) Patients who participate in the trial will have 3 extra follow-up visits, 4 extra questionnaires, 3 extra ECGs, 3 extra device interrogations, 3 extra echocardiograms and 4 extra blood samples (5 mL each).
Interventions
DEVICEBiventricular pacing
Pacing of the right and left ventricle using transvenous pacemaker leads
DEVICELeft bundle branch area pacing
Pacing of the left bundle branch area using a transvenous pacemaker lead
Sponsors
Aarhus University Hospital
srdpiers
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
The patient will be blinded to the treatment allocation. The assessor of the ECG endpoints and echocardiographic endpoints will be blinded to the treatment allocation.
Intervention model description
Randomized patient and assessor blinded non-inferiority cross-over trial.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all of the following criteria: * Adults ≥18 years with permanent AF and LVEF < 50% who either require ventricular pacing because of bradycardia including patients undergoing AV junction ablation, or have an indication for cardiac resynchronization therapy. * Expected percentage of ventricular pacing > 40% * ≥ 3 months of heart failure medication optimization Of note, patients who already have a device, but require an upgrade to a CRT device, can also be included
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded from participation in this study: * Age < 18 years * Pregnancy or active pregnancy wish * Not eligible for implantation of an RV lead, LBBAP lead, or LV lead in the coronary sinus * Recent valve intervention/surgery or acute myocardial infarction (< 6 months) * NYHA functional class IV heart failure, left ventricular assist device or cardiac transplant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Left ventricular end-systolic volume (LVESV) change | 6 months | Left ventricular end-systolic volume change measured by echocardiography |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in New York Heart Association functional class | 6 months | Change in New York Heart Association functional class (NYHA) |
| Change in Minnesota living with heart failure questionnaire | 6 months | The Minnesota living with heart failure questionnaire (MLHFQ) is a self-administered disease-specific questionnaire for patients with heart failure, comprising 21 items rated on six-point Likert scales, representing different degrees of impact of heart failure on quality of life, from 0 (none) to 5 (very much). It provides a total score (range 0-105, from best to worst quality of life). |
| Change in 6-minute walking distance | 6 months | Change in 6-minute walking distance |
| Change in QRS duration | 6 months | Change in QRS duration on the 12-lead ECG |
| Change in vectorcardiographic QRS area | 6 months | Change in vectorcardiographic QRS area on the vectorcardiogram reconstructed from a regular 12-lead ECG |
| Change in NT-proBNP | 6 months | Change in NT-proBNP as a heart failure biomarker |
| Complications | 6 months | Complications related to device and leads |
| Lead pacing thresholds | 6 months | Lead pacing thresholds, expressed as volts at pulse width (e.g. 0.4 V @ 0.4 ms). A lower pacing threshold is better. |
| Costs | 6 months | Costs related to the device and leads |
| Change in left ventricular function | 6 months | Change in left ventricular function ejection fraction and global longitudinal strain on echocardiography |
Countries
Denmark, Netherlands
Contacts
Primary ContactSebastiaan RD Piers, MD, PhD
Outcome results
None listed