PReventive Effect Of Left Bundle Branch Area Pacing Versus righT vEntricular paCing on All Cause deaTh, Heart Failure Progression, and Ventricular dysSYNChrony in Patients With Substantial Ventricular Pacing (PROTECT-SYNC): Multicenter Prospective Randomized Controlled Trial

Study Overview
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Brief Summary
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PROTECT-SYNC study is a multicenter, randomized, controlled trial. A total of 7 medical centers across Republic of Korea will enroll 450 patients during 2 years of enrollment period, and followed for 2 years of follow-up period. The purpose of this study to compare the clinical outcomes of Left Bundle Branch Area Pacing (LBBAP) compared to Right Ventricular Pacing (RVP) in bradyarrhythmia patients who require high burden of ventricular pacing (>40%).

Detailed Description
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PROTECT-SYNC study is a multicenter, randomized, controlled trial that is designed to assess whether LBBAP may reduce the risk of composite primary endpoint including all cause mortalty, HF hospitalization and/or urgent HF related visit, occurrence of pacing induced CMP, and CRT-upgrade event, compared to RVP in patients who require substantial (>40%) ventricular pacing. Patients who require pacemaker and substantial (>40%) ventricular pacing will be randomized to LBBAP or RVP group, and a total of 7 medical centers across Republic of Korea will enroll 450 patients during 2 years of enrollment period, and followed for 2 years of follow-up period.

Official Title
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PReventive Effect Of Left Bundle Branch Area Pacing Versus righT vEntricular paCing on All Cause deaTh, Heart Failure Progression, and Ventricular dysSYNChrony in Patients With Substantial Ventricular Pacing (PROTECT-SYNC): Multicenter Prospective Randomized Controlled Trial

Conditions
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Bradyarrhythmia, Atrioventricular Block, Left Bundle Branch Area Pacing

Intervention / Treatment
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* Procedure: Left bundle branch area pacing
* Procedure: Right ventricular pacing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 19 years old and willing and capable to give informed consent Patients who is willing and able to comply with the prescribed follow-up tests and schedule of evaluations. 3 Scheduled to receive a pacemaker implant 4. Substantial percentage of V pacing rate (>40%) is anticipated Exclusion criteria: Incapacitated or unable to read or write Patient who is an indication of ICD or CRT History of prosthetic valve surgery on tricuspid valve Prior myocardial infarction including ventricular septum Life expectancy < 12 months due to any condition Unavailable for at least 24 months of follow-up visits Pregnant or breastfeeding at the time of signing consent Prior Heart transplant surgery Persistent Left Superior Vena Cava (PLSVC)

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LBBAP group<br>In this arm, a left bundle branch area pacing(LBBAP) lead will be attempted to be placed. | Procedure: Left bundle branch area pacing<br>* LBBAP success is defined if ventricular lead is successfully placed at interventricular septum and RBB configuration observed during unipolar tip pacing. LBB capture is defined if fulfilling criterion 1 and at least one in criteria 2. RBBB configuration observed during unipolar tip pacing One of the following should be met: Abrupt shortening of Stim-LVAT (stimulus to peak of the R wave in V6 [LV activation time]) of >10ms during increasing output Short and constant stim-LVAT and the shortest stim-LVAT <75ms in non-LBBB and <85ms in LBBB Programmed stimulation by pacing lead changes QRS morphology from nonselective LBB to LV septal capture LBB potential (LBB-V interval of 15 to 35ms) Transition from nonselective LBB capture to selective LBB capture at near threshold outputs If criterion 1 is fulfilled but none in criteria 2 is met, the procedure is considered to be deep septal pacing (DSP).<br>|
| Active Comparator: RVP group<br>In this arm, a Right ventricular pacing (RVP) lead will be attempted to be placed. | Procedure: Right ventricular pacing<br>* Right ventricular pacing is the traditional pacing modality for ventricular pacing. Implantation of a RV pacing lead (apex or septum of right ventricle) will be attempted using the standard-of-care technique first<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| composite of all-cause death, heart failure hospitalization, occurrence of pacing induced cardiomyopathy, and an upgrade to cardiac resynchronization therapy | All-cause death: including cardiovascular and non-cardiovascular deaths. Heart failure hospitalization: An unplanned outpatient or emergency department visit or inpatient hospitalization in which the patient presented with signs and symptoms consistent with heart failure and required intravenous therapy. Occurrence of Pacing induced cardiomyopathy : LVEF <50% and absolute LVEF decline ≥10% or increase in LVESV ≥15% Upgrade to cardiac resynchronization therapy (CRT): Upgrade from pacemaker to CRT-Pacemaker/CRT-Defibrillator due to impaired LV function (LVEF decrease to 40% or less). | during 2 years after pacemaker implantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| all cause mortality | All cause deaths including cardiovascular and non-cardiovascular deaths. | during 2 years after pacemaker implantation | 
| Cardiovascular mortality | Cardiovascular death | during 2 years after pacemaker implantation | 
| Heart failure hospitalization | An unplanned outpatient or emergency department visit or inpatient hospitalization in which the patient presented with signs and symptoms consistent with heart failure and required intravenous therapy. | during 2 years after pacemaker implantation | 
| success rate of LBBAP implantation | LBBAP success is defined if ventricular lead is successfully placed at interventricular septum and RBB configuration observed during unipolar tip pacing. | during 3days after pacemaker implantation | 
| LBBAP related complications | Loss of lead function or need for lead revision, extraction, replacement for any reason | during 2 years after pacemaker implantation | 
| LBB capture failure | failed LBB capture, confirmed by investigator | during 2 years after pacemaker implantation | 
| Short-term procedure and Device related complications | composite of device and procedure related complications until 7 days after procedure | during 1wk after pacemaker implantation | 
| Long-term procedure and Device related complications | composite of device and procedure related complications after 7 days after procedure | during 1wk after pacemaker implantation | 
| Rate of LV systolic dysfunction | LVEF <50% and absolute reduction in LVEF >10%, and/or an increase in LVESV ≥15%. | 6month and 2yr after pacemaker implantation | 
| Changes in cardiopulmonary exercise test parameters | (VO2 peak, Exercise intensity, Peak Respiratory Exchange Ratio (Peak RER), Exercise time, age predicted aerobic capacity, VE/VCO2 slope, Lactate threshold, Max predicted HR, Max HR / Max predicted HR, presence of ST change , AF at Baseline, Incident AF during exercise | 6month and 2yr after pacemaker implantation | 
| Incidental atrial fibrillation | Newly developed atrial fibrillation in patients without documented atrial fibrillation | during 2 years after pacemaker implantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Left Bundle Branch Area pacing, Right Ventricular Pacing, Heart Failure, Atrioventricular block