Conduction System Pacing Versus Biventricular Pacing for Cardiac resYNChronization

Heart Failure Clinical Trial

— CSP-SYNC  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05155865
• Other study ID #: CSP-SYNC
• Status: Active, not recruiting
• Phase: N/A
• Start date: January 10, 2022
• Est. completion date: November 28, 2024

Study information

• Verified date: January 2023
• Source: University Medical Centre Ljubljana
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 62
• Est. completion date: November 28, 2024
• Est. primary completion date: November 28, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bundle-Branch Block
• Cardiac Remodeling, Ventricular
• Cardiomyopathies
• Cardiomyopathy, Dilated
• Heart Failure
• Left Bundle-Branch Block
• Resynchronization Therapy
• Ventricular Remodeling

Intervention

Device:
• Resynchronization with conduction system pacing
Implantation of permanent pacemaker with conduction system pacing (preferably left bundle branch) with or without defibrillator lead placement
• Cardiac resynchronization therapy with biventricular stimulation
Implantation of cardiac resynchronization therapy with biventricular stimulation with or without defibrillator lead placement

Locations

Country	Name	City	State
Slovenia	University medical centre Ljubljana	Ljubljana

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Centre Ljubljana

Country where clinical trial is conducted

Slovenia, 

References & Publications (11)

Abdelrahman M, Subzposh FA, Beer D, Durr B, Naperkowski A, Sun H, Oren JW, Dandamudi G, Vijayaraman P. Clinical Outcomes of His Bundle Pacing Compared to Right Ventricular Pacing. J Am Coll Cardiol. 2018 May 22;71(20):2319-2330. doi: 10.1016/j.jacc.2018.02.048. Epub 2018 Mar 10. — View Citation

Brugada J, Katritsis DG, Arbelo E, Arribas F, Bax JJ, Blomstrom-Lundqvist C, Calkins H, Corrado D, Deftereos SG, Diller GP, Gomez-Doblas JJ, Gorenek B, Grace A, Ho SY, Kaski JC, Kuck KH, Lambiase PD, Sacher F, Sarquella-Brugada G, Suwalski P, Zaza A; ESC Scientific Document Group. 2019 ESC Guidelines for the management of patients with supraventricular tachycardiaThe Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC). Eur Heart J. 2020 Feb 1;41(5):655-720. doi: 10.1093/eurheartj/ehz467. No abstract available. Erratum In: Eur Heart J. 2020 Nov 21;41(44):4258. — View Citation

Cvijic M, Duchenne J, Unlu S, Michalski B, Aarones M, Winter S, Aakhus S, Fehske W, Stankovic I, Voigt JU. Timing of myocardial shortening determines left ventricular regional myocardial work and regional remodelling in hearts with conduction delays. Eur Heart J Cardiovasc Imaging. 2018 Aug 1;19(8):941-949. doi: 10.1093/ehjci/jex325. — View Citation

Dandamudi G, Vijayaraman P. History of His bundle pacing. J Electrocardiol. 2017 Jan-Feb;50(1):156-160. doi: 10.1016/j.jelectrocard.2016.09.011. Epub 2016 Sep 24. — View Citation

Deif B, Ballantyne B, Almehmadi F, Mikhail M, McIntyre WF, Manlucu J, Yee R, Sapp JL, Roberts JD, Healey JS, Leong-Sit P, Tang AS. Cardiac resynchronization is pro-arrhythmic in the absence of reverse ventricular remodelling: a systematic review and meta-analysis. Cardiovasc Res. 2018 Sep 1;114(11):1435-1444. doi: 10.1093/cvr/cvy182. — View Citation

Duchenne J, Aalen JM, Cvijic M, Larsen CK, Galli E, Bezy S, Beela AS, Unlu S, Pagourelias ED, Winter S, Hopp E, Kongsgard E, Donal E, Fehske W, Smiseth OA, Voigt JU. Acute redistribution of regional left ventricular work by cardiac resynchronization therapy determines long-term remodelling. Eur Heart J Cardiovasc Imaging. 2020 Jun 1;21(6):619-628. doi: 10.1093/ehjci/jeaa003. — View Citation

Galand V, Singh JP, Leclercq C. Alternative left ventricular pacing approaches for optimal cardiac resynchronization therapy. Heart Rhythm. 2019 Aug;16(8):1281-1289. doi: 10.1016/j.hrthm.2019.03.011. Epub 2019 Mar 16. — View Citation

Herweg B, Welter-Frost A, Vijayaraman P. The evolution of cardiac resynchronization therapy and an introduction to conduction system pacing: a conceptual review. Europace. 2021 Apr 6;23(4):496-510. doi: 10.1093/europace/euaa264. — View Citation

Sharma PS, Vijayaraman P. Conduction System Pacing for Cardiac Resynchronisation. Arrhythm Electrophysiol Rev. 2021 Apr;10(1):51-58. doi: 10.15420/aer.2020.45. — View Citation

Vinther M, Risum N, Svendsen JH, Mogelvang R, Philbert BT. A Randomized Trial of His Pacing Versus Biventricular Pacing in Symptomatic HF Patients With Left Bundle Branch Block (His-Alternative). JACC Clin Electrophysiol. 2021 Nov;7(11):1422-1432. doi: 10.1016/j.jacep.2021.04.003. Epub 2021 Apr 25. — View Citation

Wu S, Su L, Vijayaraman P, Zheng R, Cai M, Xu L, Shi R, Huang Z, Whinnett ZI, Huang W. Left Bundle Branch Pacing for Cardiac Resynchronization Therapy: Nonrandomized On-Treatment Comparison With His Bundle Pacing and Biventricular Pacing. Can J Cardiol. 2021 Feb;37(2):319-328. doi: 10.1016/j.cjca.2020.04.037. Epub 2020 May 7. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Difference in Heart Failure Class	From class 1 to 4	6 months
Primary	Difference in pro-BNP value	pg/mL	6 months
Primary	Difference in 6-minute walk test distance	meters	6 months
Primary	Difference in the EQ-5D index	score	6 months
Secondary	Difference in myocardial work redistribution	Echo measurement	acute after the procedure, 1 month, 6 months, 12 months
Secondary	Difference in QRS complex width	ms	acute after the procedure, 1 month, 6 months, 12 months
Secondary	Difference in filtered QRS duration on high-resolution electrocardiogram	ms	acute after procedure, 1 month, 6 months, 12 months
Secondary	Difference in sum absolute QRST integral	ms	acute after the procedure, 1 month, 6 months, 12 months
Secondary	Difference in arrhythmia occurrence	Descriptive	at least 12 months after enrollment
Secondary	Rate of procedural complications	Descriptive	at least 12 months after enrollment
Secondary	Tpeak-end duration	ms	acute after the procedure, 1 month, 6 months, 12 months