REstoration of SYNChronous Cardiac Function Due to Physiologic cArdiac Pacing Modalities With Clinical Endpoints

NCT07684547 | Not Yet Recruiting FDA Device

• 2 other identifiers: FF107 RESYNC-PACE ver1.0Biotronik Research Grant FF107
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational study is to evaluate the long-term clinical outcomes of physiologic cardiac resynchronization therapy (CRT) using conduction system pacing strategies compared with conventional biventricular CRT in patients with heart failure with reduced ejection fraction (HFrEF) and electrical dyssynchrony. The main questions it aims to answer are:

• Does physiologic CRT (including left bundle branch area pacing \[LBBAP\] and LBBAP-optimized CRT) reduce the combined risk of all-cause mortality and heart failure hospitalization compared with conventional biventricular CRT?
• Does physiologic CRT improve cardiac function and reverse ventricular remodeling more effectively than conventional CRT? Participants receiving physiologic CRT as part of routine clinical care will undergo standard follow-up evaluations, including electrocardiography, echocardiography, laboratory testing, and device interrogation. Clinical outcomes will be collected prospectively for 24 months and compared with a historical cohort of patients treated with conventional biventricular CRT. The study will assess clinical outcomes, echocardiographic response, electrical resynchronization parameters, and device-related safety in a real-world heart failure population.

Conditions

Heart Failure - NYHA II - IV; Left Bundle Branch Area Pacing; Left Bundle Branch Block; Resynchronization Therapy; Intraventricular Conduction Delay

Keywords

carrdiac resynchornization therapy; Physiologic Pacing; Conduction System Pacing; Electrical Resynchronization; Physiologic CRT

Outcome Measures

Primary Outcomes (1)

• Composite of All-Cause Mortality and Heart Failure Hospitalization

  Time to first occurrence of the composite endpoint of all-cause mortality or hospitalization due to worsening heart failure during the 24-month follow-up period.

  24 months

Secondary Outcomes (4)

• Change in Left Ventricular Ejection Fraction (LVEF)

  Baseline to 24 months

• Change in Left Ventricular End-Systolic Volume ( LV ESV)

  Baseline to 24 months

• Change in paced QRS Duration

  Baseline to 24 months

• New York Heart Association Heart Failure Functional Status

  Baseline to 24 months

Other Outcomes (1)

• Device-Related and Procedure-Related Complications

  24 months

Study Arms (2)

Left bundle branch block patients

LBBB Cohort (qLV-guided Cardiac Resynchronization Therapy) Patients in this cohort have symptomatic heart failure with reduced left ventricular ejection fraction and complete left bundle branch block (LBBB) according to contemporary guideline criteria. Cardiac resynchronization therapy is performed using a personalized implantation strategy guided by the qLV ratio, defined as the interval between QRS onset and local left ventricular activation divided by the intrinsic QRS duration. The left ventricular lead is positioned at the site with the longest achievable electrical delay to maximize resynchronization benefit. Patients receive either conventional biventricular CRT or LOT- CRT according to clinical decision-making and anatomical feasibility. The cohort is followed longitudinally to evaluate the relationship between qLV-guided lead placement, electrical resynchronization, reverse ventricular remodeling, heart failure hospitalization, and all-cause mortality.

Device: Physiologic cardiac resynchronization using conduction system pacing and selective LV lead optimization.

Intraventricular conduction delay patients

IVCD Cohort (Conduction System Pacing-Guided Resynchronization Strategy) Patients in this cohort have symptomatic heart failure with reduced left ventricular ejection fraction and intraventricular conduction delay (IVCD) without typical left bundle branch block morphology. The resynchronization strategy is guided by the degree of electrical correction achieved with conduction system pacing. During implantation, left bundle branch area pacing (LBBAP) is attempted and paced QRS duration is assessed. If conduction system pacing alone results in a paced QRS duration greater than 130 ms, a Left Bundle Branch Area Pacing Optimized Cardiac Resynchronization Therapy (LOT-CRT) system is implanted by adding a left ventricular lead to further improve ventricular synchrony. The cohort is followed longitudinally to evaluate the association between electrical resynchronization, reverse ventricular remodeling, heart failure hospitalization, and all-cause mortality.

Device: Physiologic cardiac resynchronization using conduction system pacing and selective LV lead optimization.

Interventions

Physiologic cardiac resynchronization using conduction system pacing and selective LV lead optimization. DEVICE

Conduction System Pacing-Guided Cardiac Resynchronization Therapy is an individualized resynchronization strategy used in patients with heart failure, reduced left ventricular ejection fraction, and electrical dyssynchrony. The intervention is based on direct recruitment of the native cardiac conduction system through left bundle branch area pacing (LBBAP). During implantation, electrical resynchronization is assessed using electrocardiographic and device-derived parameters. In patients with intraventricular conduction delay or incomplete electrical correction, additional left ventricular pacing may be provided using a coronary sinus lead, resulting in Left Bundle Branch Area Pacing Optimized Cardiac Resynchronization Therapy (LOT-CRT). The intervention aims to achieve more physiological ventricular activation than conventional biventricular pacing, improve electrical synchrony, promote reverse ventricular remodeling, and reduce heart failure-related adverse events.

Also known as: Cardiac resynchronization therapy using left bundle branch area pacing with or without LV lead optimization., Cardiac resynchronization guided by conduction system pacing to improve ventricular synchrony.

Intraventricular conduction delay patients; Left bundle branch block patients

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population consists of adult patients with heart failure with reduced ejection fraction (HFrEF) who are treated at the University of Pécs Clinical Centre Heart Institute and meet contemporary guideline indications for cardiac resynchronization therapy (CRT). Eligible participants have symptomatic heart failure despite guideline-directed medical therapy, left ventricular systolic dysfunction, and evidence of electrical dyssynchrony manifested by left bundle branch block (LBBB) or intraventricular conduction delay (IVCD). The prospective cohort includes patients undergoing conduction system pacing-based CRT as part of routine clinical care, while the historical control cohort includes patients previously treated with conventional biventricular CRT at the same institution. The study population represents a real-world heart failure population routinely referred for CRT implantation in tertiary cardiovascular care.

You may qualify if:

• Age ≥18 years.
• Symptomatic heart failure despite guideline-directed medical therapy.
• Left ventricular ejection fraction (LVEF) ≤40%.
• Indication for cardiac resynchronization therapy according to contemporary ESC guideline recommendations.
• QRS duration ≥150 ms with either:
• Left bundle branch block (LBBB), or Intraventricular conduction delay (IVCD).
• Planned implantation of a CRT system
• Ability to provide written informed consent
• Expected survival greater than 24 months.

You may not qualify if:

• Age \<18 years and Age 100 \< years
• Pregnancy or breastfeeding.
• Inability or unwillingness to provide informed consent.
• Life expectancy \<12 months due to non-cardiac comorbidities.
• Active systemic infection or infection involving a cardiac implantable electronic device.
• Reversible causes of heart failure expected to improve without CRT.
• Participation in another interventional clinical trial that may affect study outcomes.
• Inability to comply with follow-up requirements.
• Missing essential baseline or follow-up data (retrospective cohort).
• Any condition that, in the opinion of the investigators, would make participation inappropriate or interfere with study assessments.

Sponsors & Collaborators

• University of Pecs: lead
• Medical University of Pecs: collaborator

Study Sites (1)

Heart Institute , University of Pécs

Pécs, Baranya, 7621, Hungary

Location

Related Publications (4)

• Guo J, Luo W, Zhao S, Cui H, Wang X, Li X. Conduction system pacing compared with biventricular pacing for cardiac resynchronization therapy: a systematic review and meta-analysis. Front Cardiovasc Med. 2026 Jun 5;13:1776637. doi: 10.3389/fcvm.2026.1776637. eCollection 2026.

  PMID: 42325689 BACKGROUND

• Jastrzebski M, Moskal P, Huybrechts W, Curila K, Sreekumar P, Rademakers LM, Ponnusamy SS, Herweg B, Sharma PS, Bednarek A, Rajzer M, Vijayaraman P. Left bundle branch-optimized cardiac resynchronization therapy (LOT-CRT): Results from an international LBBAP collaborative study group. Heart Rhythm. 2022 Jan;19(1):13-21. doi: 10.1016/j.hrthm.2021.07.057. Epub 2021 Jul 30.

  PMID: 34339851 BACKGROUND

• Leventopoulos G, Nastouli KM, Bozika M, Papastavrou E, Apostolos A, Koros R, Perperis A, Koniari I, Vlassopoulou N, Chronopoulos P, Travlos CK, Moulias A, Davlouros P. Understanding LOT-CRT: Current Insights, Limitations, and Our Center's Experience. J Clin Med. 2025 Apr 27;14(9):3025. doi: 10.3390/jcm14093025.

  PMID: 40364057 BACKGROUND

• Ezer P, Szucs K, Lukacs R, Bisztray T, Vilmanyi G, Szokodi I, Komocsi A, Konyi A. The Suboptimal QLV Ratio May Indicate the Need for a Left Bundle Branch Area Pacing-Optimized Cardiac Resynchronization Therapy Upgrade. J Clin Med. 2024 Sep 26;13(19):5742. doi: 10.3390/jcm13195742.

  PMID: 39407802 BACKGROUND

MeSH Terms

Conditions

Bundle-Branch Block

Condition Hierarchy (Ancestors)

Heart Block; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Peter Ezer MD PhD, assistant professor

CONTACT

+36305468840; ezerpeti@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 24 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD Assistant professor of Cardiology

Study Record Dates

• First Submitted: June 28, 2026
• First Posted: July 6, 2026
• Study Start: June 29, 2026
• Primary Completion (Estimated): June 29, 2030
• Study Completion (Estimated): June 29, 2031
• Last Updated: July 10, 2026

Record last verified: 2026-07

Locations

HU (1)