Clinical trial NCT05155865: Conduction System Pacing Versus Biventricular Pacing for Cardiac ResYNChronization
Official title: Conduction System Pacing Versus Biventricular Pacing for Cardiac ResYNChronization (CSP-SYNC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Dilated Cardiomyopathy with Conduction Defect
Left Bundle-Branch Block
Heart Failure
Resynchronization Therapy
Cardiac Remodeling, Ventricular
Keywords: left bundle branch block
dilated cardiomyopathy
resynchronization therapy
myocardial work
arrhythmia
Lead sponsor: University Medical Centre Ljubljana
Sponsor class: OTHER
First posted: 2021-12-14
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

The proposed inclusion criteria represent the minimum recommendations for CRT implantation according to the ESC 2021 guidelines. In addition:

1. Sinus rhythm and complete left bundle branch block according to Strauss criteria
2. LVEF ≤35%
3. NYHA class II-III
4. Optimal medical heart failure therapy for at least 3 months before enrollment
5. The patient is able to understand and willing to provide a written informed consent
6. 18 years of age or older

Exclusion Criteria:

1. Mechanical tricuspid valve replacement
2. More than moderate valvular disease
3. Unstable angina, acute MI, CABG, or PCI within the past 6 months
4. Persistent or permanent atrial fibrillation
5. Ventricular arrhythmias (frequent PVC) which do not allow to acquire consecutive regular beats during echocardiography and electrocardiography
6. Higher degree AV block
7. Life expectancy of less than 12 months
8. Pregnancy and breastfeeding
9. Acute illness or active systemic infection

Primary outcomes:
measure: Change in left ventricular volume
timeFrame: acute after the procedure, 1 month, 6 months, 12 months
measure: Change in left ventricular ejection fraction
timeFrame: acute procedure, 1 month, 6 months, 12 months
measure: Difference in Heart Failure Class
timeFrame: 6 months
measure: Difference in pro-BNP value
timeFrame: 6 months
measure: Difference in 6-minute walk test distance
timeFrame: 6 months
measure: Difference in the EQ-5D index
timeFrame: 6 months
Secondary outcomes:
measure: Difference in myocardial work redistribution
timeFrame: acute after the procedure, 1 month, 6 months, 12 months
measure: Difference in QRS complex width
timeFrame: acute after the procedure, 1 month, 6 months, 12 months
measure: Difference in filtered QRS duration on high-resolution electrocardiogram
timeFrame: acute after procedure, 1 month, 6 months, 12 months
measure: Difference in sum absolute QRST integral
timeFrame: acute after the procedure, 1 month, 6 months, 12 months
measure: Difference in arrhythmia occurrence
timeFrame: at least 12 months after enrollment
measure: Rate of procedural complications
timeFrame: at least 12 months after enrollment
measure: Tpeak-end duration
timeFrame: acute after the procedure, 1 month, 6 months, 12 months
Other outcomes:
Locations:
city: Ljubljana
country: Slovenia
facility: University medical centre Ljubljana
Study officials:
affiliation: University Medical Centre Ljubljana (Slovenia)
name: Marta Cvijc, MD
role: STUDY_CHAIR
affiliation: University Medical Centre Ljubljana (Slovenia)
name: Anja Zupan Meznar, MD
role: STUDY_CHAIR
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