CSP Versus BiVP for Heart Failure Patients With RVP Upgraded to Cardiac Resynchronization Therapy (CSP-UPGRADE)

Conduction System Pacing Versus Biventricular Pacing for Heart Failure Patients With Right Ventricular Pacing Upgraded to Cardiac Resynchronization Therapy: a Prospective Multicenter Non-inferiority Randomized Controlled Study

The present study is a prospective, multicenter, non-inferiority, randomized controlled trail. It aims to investigate whether the efficacy of conduction system pacing (CSP) is non-inferior to biventricular pacing (BiVP) in patients with heart failure and right ventricular pacing (RVP) requiring upgrading to cardiac resynchronization therapy (CRT).

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Cardiac Resynchronization Therapy; Right Ventricular Pacing; Biventricular Pacing; Conduction System Pacing
• Intervention / Treatment: Device: Conduction system pacing; Device: Biventricular pacing

Detailed Description

RVP is a standardized treatment strategy for severe bradyarrhythmia. However, RVP can result in electrical and mechanical dyssynchrony of the heart, which will adversely affect cardiac function. Until now, many studies have shown that RVP can promote the progression of heart failure, especially in patients with high ventricular pacing percentage. For these heart failure patients, upgrading to CRT is a feasible and effective therapy.

BiVP is a traditional method to achieve CRT, which can improve cardiac synchrony and provide great clinical outcomes for heart failure patients upgraded from RVP. CSP contains left bundle branch pacing (LBBP) and His bundle pacing (HBP), which is able to activate native His-Purkinje conduction system and solve the problems caused by RVP. Although HBP has high technical requirements, lower sense value and higher threshold, it is the pacing modality closest to physiological conditions so far. Since first reported by Huang et al. in 2017, LBBP has been carried out boomingly all over the world. LBBP has been reported to offer higher success rate with higher sense value and lower pacing thresholds compared with HBP, which can also achieve similar electrical and mechanical resynchronization as well as HBP.

However, no randomized controlled studies have been reported to compare the efficacy of CSP and BiVP in patients with heart failure and RVP requiring upgrading to CRT. CSP-UPGRADE is a non-inferiority study, and the purpose of which is to investigate whether the efficacy of CSP is not inferior to BiVP in such patients. Eligible patients will be 1:1 randomized to two groups. The primary outcome is change in LVEF between baseline and six months after device implantation assessed by echocardiography. According to BUDAPEST-CRT Upgrade trial, half of lower limit of the 95% confidence interval for difference in mean ΔLVEF between the CRTD and ICD group is about 3.8%, which is used as non-inferiority margin in the present study. Based on previous studies and cases, it is assumed that the mean ΔLVEF values in patients upgraded to CSP and BiVP are equal and the standard deviations are both 5%. With power as 80%, alpha as 0.025, rate of lost-of-follow-up as 10%, the final sample size was estimated as 66 by using PASS Version 21.0.3 (33 patients for each group). If the non-inferiority test reaches positive results, then we will further verify whether CSP is superior to BiVP in such patients.

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jiangang Zou; Phone Number: 86-13605191407; Email: jgzou@njmu.edu.cn

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Recruiting
      • The First Affiliated Hospital with Nanjing Medical University
      • Contact: Jiangang Zou; Phone Number: 86-13605191407; Email: jgzou@njmu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients with symptomatic heart failure (LVEF <50%) after right ventricular pacing for at least 3 months;
2. NYHA class II-IV;
3. NT-proBNP >125pg/mL in patients with sinus rhythm, NT-proBNP >250pg/mL in patients with atrial fibrillation;
4. Right ventricular pacing percentage >40%;
5. Adult patients aged 18-80;
6. With informed consent signed.

Exclusion Criteria:

1. History of acute myocardial infarction within 3 months before enrollment;
2. Frequent premature ventricular contraction (>15%) or malignant ventricular arrhythmia which is difficult to control;
3. History of valvular heart disease intervention within 3 months before enrollment;
4. After mechanical tricuspid valve replacement;
5. Ventricular septal hypertrophy (≥15mm during diastole);
6. Complex congenital heart disease;
7. History of heart transplantation;
8. Enrollment in any other study;
9. Pregnant or with child-bearing plan;
10. A life expectancy of less than 12 months.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CSP group; In this group, CSP lead is attempted to be placed, including LBBP and HBP.	Device: Conduction system pacing; Firstly, we will attempt LBBP if the patient is allocated to the experimental group. If we can not achieve LBBP successfully, then we will turn to attempt HBP.
Active Comparator: BiVP group; In this group, traditional RA lead , RV lead and LV lead are attempted to be placed.	Device: Biventricular pacing; Implantation of RA lead, RV lead and LV lead are attempted using the standard-of-care technique.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ΔLVEF	Change in LVEF between baseline and six months after device implantation	Baseline; 6-month follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ΔLVEDD	Change in LVEDD between baseline and follow-up	Baseline; 3-month follow-up; 6-month follow-up
ΔLVEDV	Change in LVEDV between baseline and follow-up	Baseline; 3-month follow-up; 6-month follow-up
ΔLVESV	Change in LVESV between baseline and follow-up	Baseline; 3-month follow-up; 6-month follow-up
Paced QRS duration	Paced QRS duration is evaluated before discharge and follow-up	1 day before discharge; 1-month follow-up; 3-month follow-up; 6-month follow-up
Echocardiographic response rate	The percentage of patients responding to CRT upgrade assessed by echocardiography	Baseline; 6-month follow-up
Changes in NT-proBNP	The changes of NT-proBNP between baseline and follow-up	Baseline; 3-month follow-up; 6-month follow-up
Changes in New York Heart Association Heart Function Classification	The higher the classification, the more severe the heart failure symptoms (four levels: I, II, III and IV)	Baseline; 1-month follow-up; 3-month follow-up; 6-month follow-up
Changes in 6-minute Walk Distance	Distance that a participant walk within 6 minutes	Baseline; 3-month, 6-month follow-up
Change in Quality Of Life Questionnaire score	Reflect the effect of heart failure on quality of life, and higher scores represent a worse outcome	Baseline; 3-month follow-up; 6-month follow-up
Incidence of clinical adverse events	Including all-cause mortality, cardiovascular mortality, heart failure hospitalization and malignant ventricular arrhythmia	1 day before discharge; 1-month follow-up; 3-month follow-up; 6-month follow-up
Procedure-related costs	Costs related to device implantation	1 day before discharge
Estimated longevity of the device	The longevity of the device will be estimated during pacemaker test	1 day before discharge; 1-month follow-up; 3-month follow-up; 6-month follow-up
Pacing parameters	Number of atrial fibrillation and NSVT/VT	1 day before discharge; 1-month follow-up; 3-month follow-up; 6-month follow-up
Pacemaker related complications	Including but not limited to hemorrhage, pneumothorax, pericardial effusion, device-related infection and lead displacement	1 day before discharge; 1-month follow-up; 3-month follow-up; 6-month follow-up

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Collaborators: First Affiliated Hospital, Sun Yat-Sen University; Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University; The First Affiliated Hospital of Soochow University; Third Affiliated Hospital, Sun Yat-Sen University; Shantou Central Hospital; The Affiliated Hospital of Xuzhou Medical University; Huizhou Third People's Hospital, Guangzhou Medical University; Meizhou People's Hospital; The Third Affiliated Hospital of Soochow University; Rugao People's Hospital; Nanfang Hospital, Southern Medical University; The Affiliated Changzhou Second People's Hospital of Nanjing Medical University; The Affiliated Zhangjiagang Hospital of Soochow University

Publications and helpful links

General Publications

• Tops LF, Schalij MJ, Bax JJ. The effects of right ventricular apical pacing on ventricular function and dyssynchrony implications for therapy. J Am Coll Cardiol. 2009 Aug 25;54(9):764-76. doi: 10.1016/j.jacc.2009.06.006.
• Glikson M, Nielsen JC, Kronborg MB, Michowitz Y, Auricchio A, Barbash IM, Barrabes JA, Boriani G, Braunschweig F, Brignole M, Burri H, Coats AJS, Deharo JC, Delgado V, Diller GP, Israel CW, Keren A, Knops RE, Kotecha D, Leclercq C, Merkely B, Starck C, Thylen I, Tolosana JM; ESC Scientific Document Group. 2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy. Eur Heart J. 2021 Sep 14;42(35):3427-3520. doi: 10.1093/eurheartj/ehab364. No abstract available. Erratum In: Eur Heart J. 2022 May 1;43(17):1651.
• Chung MK, Patton KK, Lau CP, Dal Forno ARJ, Al-Khatib SM, Arora V, Birgersdotter-Green UM, Cha YM, Chung EH, Cronin EM, Curtis AB, Cygankiewicz I, Dandamudi G, Dubin AM, Ensch DP, Glotzer TV, Gold MR, Goldberger ZD, Gopinathannair R, Gorodeski EZ, Gutierrez A, Guzman JC, Huang W, Imrey PB, Indik JH, Karim S, Karpawich PP, Khaykin Y, Kiehl EL, Kron J, Kutyifa V, Link MS, Marine JE, Mullens W, Park SJ, Parkash R, Patete MF, Pathak RK, Perona CA, Rickard J, Schoenfeld MH, Seow SC, Shen WK, Shoda M, Singh JP, Slotwiner DJ, Sridhar ARM, Srivatsa UN, Stecker EC, Tanawuttiwat T, Tang WHW, Tapias CA, Tracy CM, Upadhyay GA, Varma N, Vernooy K, Vijayaraman P, Worsnick SA, Zareba W, Zeitler EP. 2023 HRS/APHRS/LAHRS guideline on cardiac physiologic pacing for the avoidance and mitigation of heart failure. Heart Rhythm. 2023 Sep;20(9):e17-e91. doi: 10.1016/j.hrthm.2023.03.1538. Epub 2023 May 20.
• Kaye GC, Linker NJ, Marwick TH, Pollock L, Graham L, Pouliot E, Poloniecki J, Gammage M; Protect-Pace trial investigators. Effect of right ventricular pacing lead site on left ventricular function in patients with high-grade atrioventricular block: results of the Protect-Pace study. Eur Heart J. 2015 Apr 7;36(14):856-62. doi: 10.1093/eurheartj/ehu304. Epub 2014 Sep 4.
• Khurshid S, Obeng-Gyimah E, Supple GE, Schaller R, Lin D, Owens AT, Epstein AE, Dixit S, Marchlinski FE, Frankel DS. Reversal of Pacing-Induced Cardiomyopathy Following Cardiac Resynchronization Therapy. JACC Clin Electrophysiol. 2018 Feb;4(2):168-177. doi: 10.1016/j.jacep.2017.10.002. Epub 2017 Nov 15.
• Shan P, Su L, Zhou X, Wu S, Xu L, Xiao F, Zhou X, Ellenbogen KA, Huang W. Beneficial effects of upgrading to His bundle pacing in chronically paced patients with left ventricular ejection fraction <50. Heart Rhythm. 2018 Mar;15(3):405-412. doi: 10.1016/j.hrthm.2017.10.031. Epub 2017 Nov 16.
• Qian Z, Wang Y, Hou X, Qiu Y, Wu H, Zhou W, Zou J. Efficacy of upgrading to left bundle branch pacing in patients with heart failure after right ventricular pacing. Pacing Clin Electrophysiol. 2021 Mar;44(3):472-480. doi: 10.1111/pace.14147. Epub 2021 Jan 31.
• Merkely B, Hatala R, Wranicz JK, Duray G, Foldesi C, Som Z, Nemeth M, Goscinska-Bis K, Geller L, Zima E, Osztheimer I, Molnar L, Karady J, Hindricks G, Goldenberg I, Klein H, Szigeti M, Solomon SD, Kutyifa V, Kovacs A, Kosztin A. Upgrade of right ventricular pacing to cardiac resynchronization therapy in heart failure: a randomized trial. Eur Heart J. 2023 Oct 21;44(40):4259-4269. doi: 10.1093/eurheartj/ehad591.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: January 19, 2024
• First Submitted That Met QC Criteria: January 27, 2024
• First Posted (Estimated): February 5, 2024

Study Record Updates

• Last Update Posted (Estimated): February 5, 2024
• Last Update Submitted That Met QC Criteria: January 27, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: 2023-SR-811

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No