Left Septal Pacing or Left Bundle Branch Pacing to Avoid Left Ventricle Systolic Dysfunction (STAY II)

Left Septal Pacing or Left Bundle Branch Pacing to Avoid Left Ventricle Systolic Dysfunction. A Multicenter Randomized Trial From the STAY Investigators

Right ventricular apical pacing (RVAP) can produce left ventricular dysfunction (LVD). Conduction system pacing (CSP) has been used successfully to reverse LVD in patients with left bundle branch block. A recent randomized controlled trial (RCT) has demonstrated that CSP, mostly performed with left bundle branch area pacing (LBBAP), can preserve normal ventricular function and heart failure admissions compared to RVAP in the setting of a high burden of ventricular pacing11 (Stay Trial).

Criteria to assess the LBBAP distinguishes those cases in which the LBB is captured (LBBP) from those in which only the muscular septum surrounding the LBB is captured (LVSP). To date, data regarding LVSP to preserve left ventricle ejection fraction (LVEF) is scarce and limited to non-randomized studies.

Study Overview

• Status: Recruiting
• Conditions: AV Block
• Intervention / Treatment: Device: Pacemaker and defibrillator

Detailed Description

Conventional right ventricular apical pacing (RVAP) can produce electrical and mechanical dysynchrony, which may lead to left ventricle dysfunction (LVD) in up to 12% of patients with normal left ventricle ejection fraction (LVEF). A high burden on RVAP is a major predictor of developing LVD, atrial fibrillation (AF), heart failure (HF), and mortality. CSP is able to preserve a more physiological pattern of cardiac electrical activation, utilizing the native conduction system network, or correcting a bundle branch block morphology in patients with disturbances at a proximal or intermediate level of the conduction system network.

The aim of the study is to demonstrate that LVSP can preserve ventricular function compared to LBBP in patients with preserved or mildly deteriorated LVEF and a high burden of expected ventricular pacing. A second hypothesis is to demonstrate than both LVSP and LBBP are both superior to RVAP.

Study design The STAY II trial is a multi-center, prospective, randomized, parallel, controlled study, comparing 12 months outcomes in a population undergoing pacemaker implantation due to a high degree atrio-ventricular block (AVB). All patients will sign informed consent and will be implanted with a pacemaker in a 1:2 randomized fashion to conventional RVAP vs LBBAP (LBBP or LVSP). Randomization to RVAP or LBBAP will be performed during the pre-procedural antibiotic infusion. Patients allocated in the LBBAP group will be evaluated after the procedure and classified as LBBP or LVSP upon the accomplishment of the accepted criteria for LBBAP (consensus).

Consecutive patients requiring permanent pacemaker implantation due to high degree AVB according to current guidelines will be evaluated for inclusion in the study. All patients need to fit all inclusion criteria and none of the exclusion criteria.

Location of the right ventricle pacing lead. Right ventricle apical pacing (RVAP): Capture of the RV by apex stimulation, generating a QRS with LBBB morphology and superior axis.

Left bundle branch pacing (LBBP): Capture of the LBB in one of its ramifications, generating a QRS with RBBB morphology and variable duration, which depends on the grade of impairment present in the more distal conduction system. The rapid activation of the LBB leads to a short left ventricle activation time (LVAT), less than 80 msec, or a long V6-V1 inter peak time (IPT), more than 44 msec. Several other criteria have been described in order to confirm the LBB capture21,22.

Left ventricle septal pacing (LVSP): Only left septal myocardium is captured, obtaining a variable QRS duration with a RBBB morphology in V1, which often are acceptable in terms of similarity with LBBP, but criteria for LBBP are not met.

Deep septal pacing (DSP): Only deep septal myocardium is captured, obtaining a variable QRS duration and morphology, without a RBBB morphology in V1.

Procedure work-flow

The study arm will be defined by randomization immediately before the implantation. Patients randomized to RVAP group will undergo a regular classical apex ventricular lead. Patients randomized to LBBAP will be implanted as follows:

An EP recording system displaying the 12-leads ECG and at least one channel with intracardiac signals will be used in all cases to allow appropriate measurements and to assess the LBBAP criteria accoding to the 2023 Consensus. The 3 required criteria will be: the QRS morphology in V1, the left ventricle activation time (LVAT) and the interpeak V6 to V1 time (IPT). Other measures will be taken at operators' discretion.

Of importance, LBBAP implantation procedure will be similar for all patients: the CSP lead will be implanted in the left bundle branch area with anatomical guidance. Unipolar stimulation aiming for a "W" pattern in V1 will be performed during septal maping. Operators then will screw the lead, aiming for a moderate drop in the impedance, representing a deep penetration into the septum, together with the conversion of the "W" pattern into a qR or rSR pattern in lead V1. The current of injury (COI) will be additionally used to guide the penetration of the lead.

The cornerstone of this study will be to accept the first location as the final location, as long as unipolar and bipolar thresholds are optimal, and the RBBB pattern in lead V1 remains. To ensure a balanced distribution between LBBP and LVSP, the first operator will not have access to any criteria measurement during the implant procedure, but the morphology in V1. In case of suboptimal thresholds or absence of a RBBB in V1, operator will proceed to implant de lead in a different position. After the procedure investigators will fulfill the Redcap database with all the banned EPRS measurements.

Data collection and data analyses Data will be loaded to an electronic CRF (Redcap) by a local authorized operator after the implantation procedure and during each control visit. Every participant center will have access only to their local patients. Only the PI will have access to all the patients. At the end of the recruitment, all the data will analyzed. Variables will be expressed as mean ± SD or number of cases and proportions according to the variable type (Continuous or discrete). Normality will be tested using the Shapiro-Wilk test. Paired T-test will be used to compare 12 months LVEF and LVEDD vs basal LVEF and LVEDD in each group, and for other continuous variables. Z-test will be used to compare discrete variables. KM analyses and Multivariate analyses searching for predictors will be performed. Statistical analysis will be performed using STATA® version 15.2 for windows (StataCorp LLC, Texas).

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ermengol Vallès, PhD; Phone Number: 0034666437038; Email: ermengolvalles@mac.com
• Study Contact Backup: Name: Jesus Jimenez, MD; Phone Number: 0034680714927; Email: jejilo78@gmail.com

Study Locations

• Spain
  • Barcelona, Spain, 08003
    • Recruiting
    • Hospital del Mar - IMIM
    • Contact: Ermengol Vallès, PhD; Phone Number: 0034666437038; Email: ermengolvalles@mac.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age of 18 years or more.
2. Preserved or mild deteriorated LVEF (Simpson >40%) assessed by a recent (<1 month before implantation) transthoracic echocardiography.
3. Indication for pacing based on the presence of a high degree AVB, and consequently with an anticipated high burden of ventricular pacing (>80%).
4. Life expectancy of more than 12 months and capability to understand the protocol, signing informed consent form, and complying with follow-up.

Exclusion Criteria:

1. Patients with indication for implantable cardioverter defibrillator device.
2. Patients with indication for a CRT device, with LVEF <40%.
3. Patients with previous severe LVD (Simpson LVEF <30%) and a recovered LVEF.
4. History of myocardial infarction/revascularization or cardiac surgery within 6 months before randomization.
5. Pregnancy, active cancer treatment, or participation in another clinical trial with active treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Right Ventricle Apical Pacing; Standard location for any pacing lead in the right ventricle	Device: Pacemaker and defibrillator; Pacemaker implantation, which can be a regular right ventricle apical lead or a LBBAP lead (LBBP or LVSP dependint on the criteria accomplished).
Experimental: Left bundle branch pacing; Stimulation in the Conduction System (righ ventricle) capturing the left budle branch	Device: Pacemaker and defibrillator; Pacemaker implantation, which can be a regular right ventricle apical lead or a LBBAP lead (LBBP or LVSP dependint on the criteria accomplished).
Experimental: Left septal pacing; Stimulation in the Conduction System (righ ventricle) without capturing the left budle branch	Device: Pacemaker and defibrillator; Pacemaker implantation, which can be a regular right ventricle apical lead or a LBBAP lead (LBBP or LVSP dependint on the criteria accomplished).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LVEF evolution	Change in the value (%) of LVEF at 12 months compared to basal	At 12 months after the pacemaker implantation
Admission due to HF	Hospital admission due to episode of heart failure (new onset HF or worsening from baseline NYHA)	From date of implantation until the date of first admission due to HF, whichever came first, assessed up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LVEED evolution	Change in left ventricle end dyastolic diametre from the baseline, at 12 months from pacemaker implantation	At 12 months after the pacemaker implantation
Admission due to AF	Hospital admission due to atrial fibrillation (new onset or relapse) after the pacemaker implantation	From date of implantation until the date of first admission due to AF, whichever came first, assessed up to 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ProBNP	Change in the value of pro-BNP at 12 months compared to baseline before pacemaker implantation	At 12 months after the pacemaker implantation
NYHA evolution	Change in the NYHA heart failure class at 12 months compared to baseline	At 12 months after the pacemaker implantation
MLWHFQ evolution	Change in the Minessota Living With Heart Failure Questionnare at 12 months compared to baseline (0-105 points, being 105 de worse situation)	At 12 months after the pacemaker implantation

Collaborators and Investigators

• Sponsor: Parc de Salut Mar

Publications and helpful links

General Publications

• Gonzalez-Matos CE, Rodriguez-Queralto O, Zaraket F, Jimenez J, Casteigt B, Valles E. Conduction System Stimulation to Avoid Left Ventricle Dysfunction. Circ Arrhythm Electrophysiol. 2024 Feb;17(2):e012473. doi: 10.1161/CIRCEP.123.012473. Epub 2024 Jan 29.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: November 19, 2024
• First Submitted That Met QC Criteria: November 23, 2024
• First Posted (Actual): November 27, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 10, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Heart failure; Left bundle branch area pacing; Conduction System Pacing; Right ventricle apical pacing; Left septum pacing; Left ventricle ejection fraction
• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Heart Block; Atrioventricular Block
• Other Study ID Numbers: 2024/11667/I

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All collected IPD can be shared
• IPD Sharing Time Frame: IPD can be available in January of 2027, until January of 2037
• IPD Sharing Access Criteria: IPD will be available to any investigator request if the proposal is satisfatory
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No