Atrial Fibrillation (AF), Cardiomyopathies, Heart Failure
Conditions
Keywords
LBBAP, Left Bundle Branch Area Pacing, CRT, Cardiac Resynchronization Therapy, Permanent Atrial Fibrillation, Conduction System Pacing, AVJ Ablation, Heart Failure
Brief summary
This is a prospective, multicenter, randomized controlled trial comparing Left Bundle Branch Area Pacing (LBBAP)-based cardiac resynchronization therapy (CRT) with conventional coronary sinus (CS) lead-based CRT in patients with permanent atrial fibrillation (AF) and heart failure (HF) who meet indications for CRT device implantation. Atrial fibrillation and heart failure frequently coexist, and both rapid heart rate and its irregularity contribute to worsening cardiac function. Atrioventricular junction (AVJ) ablation combined with CRT (biventricular pacing) has been established as an effective strategy for rate control and cardiac resynchronization in this population, supported by Class I recommendation in the 2021 ESC guidelines. However, conventional biventricular CRT via the CS lead can induce artificial electrical dyssynchrony, particularly in patients with a narrow QRS complex, potentially limiting its benefit. Conduction system pacing (CSP), including LBBAP, has emerged as a physiologic alternative that directly stimulates the native conduction system, preserving synchronous ventricular activation. Recent evidence (ALTERNATIVE-AF trial) suggests CSP may be superior to biventricular CRT in permanent AF patients undergoing AVJ ablation. However, no randomized controlled trial has directly compared LBBAP-based CRT with CS lead-based CRT in this specific population. The SYNC-AF trial will randomize 44 patients (22 per arm) to either LBBAP or CS pacing for CRT. The primary endpoint is change in left ventricular ejection fraction (LVEF) at 12 months as assessed by echocardiography in a blinded core laboratory. Secondary endpoints include changes in QRS duration, major adverse clinical events, device/procedure-related complications, and ventricular arrhythmia burden.
Detailed description
ECHOCARDIOGRAPHIC CORE LAB: All echocardiographic assessments (LVEF, LVESV, LVEDV, etc.) are performed and interpreted by a blinded independent core laboratory at Severance Hospital to ensure objective and consistent measurement. FOLLOW-UP SCHEDULE: Screening (implant day) → Visit 1 (2 weeks-1 month) → Visit 2 (3 months ±3 months) → Visit 3 (6 months ±3 months) → Visit 4 (12 months ±3 months). STATISTICAL ANALYSIS: Primary analysis follows the Intention-To-Treat (ITT) principle. Per-Protocol (PP) analysis will be performed as sensitivity analysis. The primary endpoint (LVEF change at 12 months) will be compared using Student's t-test or Wilcoxon rank-sum test. Time-to-event analyses will use Kaplan-Meier survival curves with log-rank test and Cox proportional hazards model. SAMPLE SIZE: 44 patients total (22 per arm). Based on the assumption of an absolute 10% greater improvement in LVEF with LBBAP-CRT vs. BiV-CRT, with 80% power and 5% two-sided alpha, with 10% dropout allowance. PARTICIPATING CENTERS: Multiple centers in the Republic of Korea (at least 4 centers), led by Severance Hospital, Yonsei University College of Medicine.
Interventions
DEVICELeft Bundle Branch Area Pacing (LBBAP) for CRT
CRT device (CRT-P or CRT-D) implantation using LBBAP as the left ventricular pacing lead. A pacing lead is advanced through the interventricular septum to achieve left bundle branch area capture, confirmed by pacing parameters and electrocardiographic criteria (RBBB-like pattern with short R-peak latency in V5/V6). RV lead is implanted in standard fashion. AVJ ablation may be performed per clinical indication.
DEVICECoronary Sinus (CS) Lead-Based Biventricular CRT
CRT device (CRT-P or CRT-D) implantation using a conventional coronary sinus (CS) lead as the left ventricular pacing lead. The CS lead is advanced via the coronary sinus into a lateral or posterolateral cardiac vein to achieve biventricular pacing. RV lead is implanted in standard fashion. AVJ ablation may be performed per clinical indication.
Sponsors
Yonsei University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Open-label study. Participants, care providers, and investigators are not masked to treatment allocation. However, echocardiographic outcome assessors at the blinded central core laboratory are masked to treatment assignment.
Intervention model description
Two parallel arms: LBBAP group (experimental) vs. CS pacing group (active comparator). 1:1 randomization. Open-label design with blinded echocardiographic core lab assessment.
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥19 years 2. Indication for CRT (CRT-P or CRT-D) device implantation per current guidelines 3. Permanent atrial fibrillation (with or without planned AVJ ablation) 4. Ability to understand the purpose of the study and provide written informed consent
Exclusion criteria
1. Prosthetic tricuspid valve 2. Prior myocardial infarction involving the interventricular septal area 3. Life expectancy less than 12 months 4. Unable to comply with planned 12-month follow-up for any reason 5. Pregnancy 6. History of heart transplantation 7. Persistent left superior vena cava (PLSVC)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline Left Ventricular Ejection Fraction (LVEF) at 12 Months | Baseline (at the time of device implantation) and 12 months post-implantation | Change in left ventricular ejection fraction (LVEF) from baseline to 12 months post-implantation, as measured by transthoracic echocardiography performed and interpreted by a blinded independent central core laboratory. LVEF is assessed using the biplane Simpson method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with absolute LVEF increase ≥5% at 12 months | 12 months post-implantation | Echocardiographic CRT response defined as absolute improvement in LVEF of ≥5% or ≥10% from baseline at 12 months, assessed by blinded core lab. |
| Proportion of patients with absolute LVEF increase ≥10% at 12 months | 12 months post-implantation | Echocardiographic CRT response defined as absolute improvement in LVEF of ≥5% or ≥10% from baseline at 12 months, assessed by blinded core lab. |
| Change in QRS Duration From Baseline | Immediately post-implant and at 12 months | QRS duration measured from surface ECG in milliseconds. |
| Time to First Treated Ventricular Arrhythmia | Up to 12 months | Time from randomization to first detection of treated ventricular arrhythmia (VT/VF) recorded by the implanted device within 12 months. |
| Composite of All-Cause Death and Heart Failure Hospitalization | Up to 12 months (first occurrence) | Clinical events adjudicated by an independent committee. Heart failure hospitalization defined as unplanned outpatient/ED visit or inpatient admission with HF signs/symptoms requiring intravenous therapy. |
| All-cause mortality | Up to 12 months (first occurrence) | Clinical events adjudicated by an independent committee. Heart failure hospitalization defined as unplanned outpatient/ED visit or inpatient admission with HF signs/symptoms requiring intravenous therapy. |
| Heart failure hospitalization | Up to 12 months (first occurrence) | Clinical events adjudicated by an independent committee. Heart failure hospitalization defined as unplanned outpatient/ED visit or inpatient admission with HF signs/symptoms requiring intravenous therapy. |
| Cardiovascular death | Up to 12 months (first occurrence) | Clinical events adjudicated by an independent committee. Heart failure hospitalization defined as unplanned outpatient/ED visit or inpatient admission with HF signs/symptoms requiring intravenous therapy. |
| Immediate procedural success rate of LBBAP lead implantation | Immediately after the implantation procedure | Successful LBBAP lead placement defined by achievement of left bundle branch capture with acceptable pacing threshold (≤1.5V/0.5ms), impedance (300-1200Ω), and electrocardiographic criteria (RBBB pattern, short R-peak latency in V5/V6). |
| Lead capture loss rate at 12 months | 12 months post-implantation | Loss of left bundle branch capture or inability to maintain pacing threshold \<2.5V/0.5ms at 12 months. |
| Composite Rate of Worsening Heart Failure by Echocardiographic Criteria | Up to 12 months | Composite endpoint defined as ≥5% absolute decrease in LVEF from baseline or ≥15% increase in LVESV from baseline during follow-up. |
| Device and Procedure-Related Complications | Up to 12 months (device/procedure-related complications within 7 days for acute; up to 12 months for chronic) | All device/procedure-related complications and reinterventions occurring up to 12 months, adjudicated by an independent events committee. |
| Reintervention Rate | Up to 12 months | All device/procedure-related complications and reinterventions occurring up to 12 months, adjudicated by an independent events committee. |
Contacts
CONTACTTae-Hoon Kim, Professor
Outcome results
None listed