Conduction System Pacing Versus Biventricular Pacing for Cardiac resYNChronization

Study Overview
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Brief Summary
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Cardiac resynchronization therapy (CRT) with biventricular pacing (BiV) is the cornerstone treatment for heart failure patients with ventricular dyssynchrony. Recently, a new concept, conduction system pacing (CSP) with permanent pacing, including His bundle pacing and left bundle branch pacing, has been proposed as a potential alternative to conventional BiV-CRT. The prospective, randomized trial will compare echocardiographic, electrocardiographic, and clinical effects of CSP versus conventional BiV pacing in heart failure patients with reduced ejection fraction (LVEF ≤ 35%), sinus rhythm, and left bundle branch block. Patients will be randomized to either CSP or biventricular pacing study group and followed up for at least 6 months. The study will explore whether CSP is non-inferior to BiV pacing in echocardiographic, electrocardiographic, and clinical outcomes.

Detailed Description
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Cardiac resynchronization therapy (CRT) with biventricular pacing is an integral part of heart failure therapy in patients with reduced ejection fraction and wide QRS. Previous studies have demonstrated improved quality of life, reduced heart failure hospitalization, and decreased all-cause mortality. However, approx. 30% of patients still do not benefit from this therapy. High pacing thresholds and phrenic nerve stimulation are also common problems with BiV stimulation. Newer CRT systems with improved programmability and algorithms in conjunction with quadripolar left ventricular leads have solved some challenges of BiV pacing. However, BiV stimulation with non-physiological epicardial activation has shown a possible pro-arrhythmic effect which is more pronounced in the non-responder population. On the other hand, CSP provides synchronous physiological ventricular activation with possible superior electrical and mechanical resynchronization compared to BiV pacing. Electrical activation maps obtained during CSP showed normalization of left bundle branch block with more homogeneous electrical resynchronization than in biventricular pacing. Additionally, BiV CRT effectively corrects mechanical dyssnchrony, demonstrated with homogenization of myocardial work. This has already been proven as the underlying pathophysiological mechanism for successful CRT response. However, the effect of CSP on echocardiographic parameters of mechanical dyssynchrony is not known. Previous studies of CSP focused on feasibility and its benefits over right ventricular pacing in patients with refractory atrial fibrillation who underwent atrioventricular node ablation and pacemaker implantation. Promising results were followed by the acknowledgment of this physiological mode of pacing by the recent guidelines of European Society of Cardiology. However, studies evaluating the value of CSP as an alternative approach to BiV CRT in heart failure patients are limited. The purpose of this study is to compare the effects of CSP and conventional BiV pacing on electrocardiographic and echocardiographic parameters as well as on clinical outcomes in patients with heart failure with reduced ejection fraction (LVEF ≤35%), sinus rhythm, and left bundle branch block. In this single-center study, 60 patients will be randomized into one of two arms: a BiV pacing arm with BiV CRT implantation based on clinical guidelines or an experimental CSP arm with the implantation of a CSP device. Device with a defibrillator (ICD) will be selected at the discretion of the implanting physician. Baseline and follow up assessments will include clinical evaluation (New York Heart Association class, 6-minute walking distance), evaluation of quality of life (EQ-5D index), laboratory tests (N-terminal pro-B-type natriuretic peptide), electrocardiographic recordings (standard 12-leads ECG and high-resolution-ECG), and echocardiographic evaluation (standard echocardiographic parameters of LV reverse remodeling and non-invasive myocardial work assessment). Intra-operative and procedural parameters will also be recorded. Investigators hypothesize that CSP could represent a feasible and safe alternative to conventional BiV pacing in terms of clinical, electrocardiographic, and echocardiographic outcomes.

Official Title
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Conduction System Pacing Versus Biventricular Pacing for Cardiac resYNChronization (CSP-SYNC)

Conditions
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Dilated Cardiomyopathy With Conduction Defect, Left Bundle-Branch Block, Heart Failure, Resynchronization Therapy, Cardiac Remodeling, Ventricular

Intervention / Treatment
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* Device: Resynchronization with conduction system pacing
* Device: Cardiac resynchronization therapy with biventricular stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The proposed inclusion criteria represent the minimum recommendations for CRT implantation according to the ESC 2021 guidelines. In addition: Sinus rhythm and complete left bundle branch block according to Strauss criteria LVEF ≤35% NYHA class II-III Optimal medical heart failure therapy for at least 3 months before enrollment The patient is able to understand and willing to provide a written informed consent 18 years of age or older Exclusion Criteria: Mechanical tricuspid valve replacement More than moderate valvular disease Unstable angina, acute MI, CABG, or PCI within the past 6 months Persistent or permanent atrial fibrillation Ventricular arrhythmias (frequent PVC) which do not allow to acquire consecutive regular beats during echocardiography and electrocardiography Higher degree AV block Life expectancy of less than 12 months Pregnancy and breastfeeding Acute illness or active systemic infection

Ages Eligible for Study
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Minimum Age: 18 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Resynchronization with conduction system pacing<br>Implantation of permanent pacemaker with conduction system pacing (preferably left bundle branch) with or without defibrillator lead placement. Optimal guidelines-based heart failure treatment and antiarrhythmic drugs. | Device: Resynchronization with conduction system pacing<br>* Implantation of permanent pacemaker with conduction system pacing (preferably left bundle branch) with or without defibrillator lead placement<br>|
| Active Comparator: Cardiac resynchronization therapy with biventricular stimulation<br>Implantation of cardiac resynchronization therapy with biventricular stimulation with or without defibrillator lead placement. Optimal guidelines-based heart failure treatment and antiarrhythmic drugs. | Device: Cardiac resynchronization therapy with biventricular stimulation<br>* Implantation of cardiac resynchronization therapy with biventricular stimulation with or without defibrillator lead placement<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in left ventricular volume | Effect on reverse left ventricular remodeling measured as changes in left ventricular volume in both arms | acute after the procedure, 1 month, 6 months, 12 months | 
| Change in left ventricular ejection fraction | Effect on reverse left ventricular remodeling measured as changes in left ventricular ejection fraction in both arms | acute procedure, 1 month, 6 months, 12 months | 
| Difference in Heart Failure Class | From class 1 to 4 | 6 months | 
| Difference in pro-BNP value | pg/mL | 6 months | 
| Difference in 6-minute walk test distance | meters | 6 months | 
| Difference in the EQ-5D index | score | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in myocardial work redistribution | Echo measurement | acute after the procedure, 1 month, 6 months, 12 months | 
| Difference in QRS complex width | ms | acute after the procedure, 1 month, 6 months, 12 months | 
| Difference in filtered QRS duration on high-resolution electrocardiogram | ms | acute after procedure, 1 month, 6 months, 12 months | 
| Difference in sum absolute QRST integral | ms | acute after the procedure, 1 month, 6 months, 12 months | 
| Difference in arrhythmia occurrence | Descriptive | at least 12 months after enrollment | 
| Rate of procedural complications | Descriptive | at least 12 months after enrollment | 
| Tpeak-end duration | ms | acute after the procedure, 1 month, 6 months, 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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left bundle branch block, dilated cardiomyopathy, resynchronization therapy, myocardial work, arrhythmia