Heart Failure and Reduced Ejection Fraction
Conditions
Keywords
heart failure and reduced ejection fraction, Bachmann bundle area pacing, interatrial block
Brief summary
To evaluate the effect of accelerated atrial resynchronization achieved through Bachmann bundle pacing at the time of implantable cardioverter-defibrillator implantation in patients with heart failure with reduced ejection fraction and interatrial block
Detailed description
Interatrial block (IAB) is a distinct electrocardiographic finding resulting from delayed conduction between the right and left atria through Bachmann's bundle (BB). In a prevalence study of non-hospitalized individuals aged 65 years or older in sinus rhythm, IAB was observed in 59% of participants. With population aging and improved survival among patients with cardiovascular comorbidities, the prevalence of IAB is expected to increase further. Importantly, IAB leads to delayed left atrial contraction and impaired left ventricular diastolic filling, pathophysiological features commonly observed in heart failure (HF) that contribute to worsening HF symptoms. Bachmann bundle area pacing (BBAP) has emerged as an attractive alternative to conventional right atrial appendage (RAA) pacing. Recent studies have demonstrated that BBAP, when guided by intracardiac electrograms and implemented using sheath-assisted atrial lead implantation techniques, is a safe and feasible approach for effectively correcting IAB. Echocardiographic data have shown that BBAP induces biatrial resynchronization. In clinical studies involving patients with heart failure with preserved ejection fraction (HFpEF), BBAP has been associated with significant clinical benefits, including improvements in quality of life, increased physical activity, and reductions in NT-proBNP levels. In these HFpEF studies, the clinical effects of BBAP were evaluated using physiologically accelerated pacing (approximately 70 beats per minute or individualized fine-tuned accelerated pacing based on body size and left ventricular ejection fraction), with particularly notable benefits observed in the improvement of diastolic function. Despite these promising findings, the role of BBAP and BBAP-mediated accelerated pacing in patients with heart failure with reduced ejection fraction (HFrEF) has not yet been clearly established. In animal (porcine) models, improvement in atrial synchrony achieved through BBAP has been shown to significantly increase left ventricular stroke volume compared with conventional RAA pacing, as confirmed by comprehensive hemodynamic analyses. However, despite the potential advantages of this more physiological pacing strategy, human data evaluating BBAP in patients with HFrEF remain limited. Accordingly, the present study aims to evaluate the clinical effects of atrial resynchronization achieved through accelerated BBAP in patients with HFrEF accompanied by interatrial block who meet indications for implantable cardioverter-defibrillator implantation.
Interventions
DEVICEBBAP on
ICD programmed for 6 weeks with LRL 70 beats/min, DDDR, and APP enabled.
DEVICEBBAP off
ICD programmed for 6 weeks with an LRL 30 beats/min in VVI mode
DRUGRAAP
ICD programmed for 6 weeks with LRL 70 beats/min, DDDR, and APP enabled.
Sponsors
Seoul National University Hospital
Medtronic
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The primary hypothesis will be evaluated through randomized allocation. For secondary analyses, a comparative assessment of effectiveness and safety versus the commonly used approach of accelerated atrial resynchronization via right atrial appendage pacing is deemed necessary; therefore, patients treated with right atrial appendage pacing will be prospectively enrolled as a separate cohort at institutions distinct from those recruiting for Bachmann bundle pacing
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years at the time of screening. 2. A documented diagnosis of chronic heart failure with New York Heart Association (NYHA) class II-IV. 3. Left ventricular ejection fraction (LVEF) ≤40%, documented by an imaging study performed within 12 months prior to screening. 4. Receiving optimized guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF), unless contraindicated or not tolerated: * Participants receiving ongoing treatment must be on a stable regimen for at least 1 month prior to screening (except for diuretics). * Most patients with heart failure require diuretics for volume control, and dose adjustments may be made based on clinical status, including symptoms, signs, and body weight. Each participant should receive individualized diuretic therapy to maintain optimal volume status. 5. Presence of interatrial block (IAB), defined as a P-wave duration ≥120 ms on a 12-lead electrocardiogram or ECG recording device. 6. An indication for dual-chamber implantable cardioverter-defibrillator (ICD) implantation for primary or secondary prevention. 7. NT-proBNP measured within 3 months prior to randomization meeting one of the following criteria: * NT-proBNP \>300 pg/mL
Exclusion criteria
1. Non-paroxysmal AF. 2. Uncontrolled tachyarrhythmia. 3. Sinus bradycardia requiring continuous atrial pacing or atrioventricular block requiring ventricular pacing. 4. Acute decompensated heart failure at the time of screening or hospitalization for worsening heart failure within 4 weeks prior to enrollment. 5. Moderate to severe primary valvular heart disease (functional mitral regurgitation or tricuspid regurgitation is not an exclusion criterion). 6. Prior mechanical tricuspid valve replacement. 7. Coronary revascularization (PCI or CABG) or valve surgery/repair performed within 12 weeks prior to enrollment, or planned after randomization. 8. Obstructive hypertrophic cardiomyopathy. 9. Infiltrative cardiomyopathy, including but not limited to amyloidosis, sarcoidosis, or Fabry disease. 10. An indication for cardiac resynchronization therapy (CRT). 11. Chronic kidney disease, defined as an estimated glomerular filtration rate (eGFR) \<15 mL/min/1.73 m² calculated using the CKD-EPI equation. 12. Chronic liver disease, defined as alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase \>3 times the upper limit of normal at screening. 13. Severe pulmonary disease, such as cor pulmonale or irreversible lung disease requiring inhaled therapy or long-term oxygen therapy. 14. Uncontrolled hypertension, defined as a mean blood pressure \>140/90 mmHg based on outpatient clinic measurements or home blood pressure recordings within the previous 30 days, or ongoing up-titration of antihypertensive medications. 15. Pregnant or breastfeeding women, or women planning pregnancy or breastfeeding during the study period. 16. Active malignancy requiring treatment at the time of screening. 17. Life expectancy \<12 months.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Relative change in NT-proBNP at 6 weeks (accelerated Bachmann bundle area pacing ON) compared with baseline (accelerated Bachmann bundle area pacing OFF). | up to 6 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score at 6 weeks, 16 weeks, and 12 months compared with baseline. | up to 12 months | — |
| Changes in E and A wave velocity (m/s) on echocardiography at 6 weeks, 16 weeks, and 12 months compared with baseline. | up to 12 months | — |
| Changes in E/A and E/E' ratios on echocardiography at 6 weeks, 16 weeks, and 12 months compared with baseline. | up to 12 months | — |
| Change in left atrial diameter (mm) on echocardiography at 6 weeks, 16 weeks, and 12 months compared with baseline. | up to 12 months | — |
| Change in left atrial strain (%) on echocardiography at 6 weeks, 16 weeks, and 12 months compared with baseline | up to 12 months | — |
| Change in left atrial volume index (LAVI, ml/m2) on echocardiography at 6 weeks, 16 weeks, and 12 months compared with baseline. | up to 12 months | — |
| Change in left ventricular ejection fraction (LVEF) at 6 weeks, 16 weeks, and 12 months compared with baseline. | up to 12 months | — |
| Change in NYHA functional class at 6 weeks, 16 weeks, and 12 months. | up to 12 months | — |
| Change in peak oxygen consumption (VO₂ max) at 6 weeks, 16 weeks, and 12 months compared with baseline. | up to 12 months | — |
| Incidence of newly detected atrial fibrillation (AF). | up to 12 months | — |
| Atrial fibrillation (AF) burden (%) | up to 12 months | — |
| Change in 6-minute walk distance (6MWD) compared with baseline. | up to 12 months | — |
| The occurence of clinical outcomes at 12 months, including: a) All-cause mortality, b) Worsening heart failure, regardless of hospitalization*, and c) Composite outcome of (a) and (b) | up to 12 months | \* Worsening heart failure is defined as deterioration in symptoms, signs, imaging, or laboratory findings requiring unplanned medical intervention, including up-titration of oral diuretics or administration of intravenous diuretics. |
Contacts
CONTACTEue-Keun Choi, M.D. Ph.D.
PRINCIPAL_INVESTIGATOREue-Keun Choi, M.D. Ph.D.
Seoul National University Hospital
Outcome results
None listed