Impact of Atrio-ventricular Optimization With His Bundle Pacing on Treatment of Atrio-ventricular Dromotropathy

Atrioventricular Block Clinical Trial

Official title:

Impact of Atrio-ventricular Optimization With His Bundle Pacing on Treatment of Atrio-ventricular Dromotropathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04544345
• Other study ID #: UMCLj-AVdromHis
• Status: Completed
• Phase: N/A
• Start date: December 23, 2019
• Est. completion date: January 4, 2023

Study information

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

Clinical Trial Summary

This study aims to determine the clinical and hemodynamic benefit of atrio-ventricular (AV) resynchronization with His bundle pacing in patients with symptomatic first degree AV block.

Description:

The term AV dyssynchrony was introduced by Salden F. and coauthors in 2018. It stands for the adverse effects of AV dyssynchrony due to PR interval prolongation. According to the ESC and ACC guidelines, severe first degree AV block is an IIa indication for permanent pacemaker implantation, yet data on these patients' clinical outcomes are scarce. To independently determine the impact of AV resynchronization, His bundle pacing will be used to avoid intraventricular desynchronization. Symptomatic patients with severe first-degree AV block and echocardiographically proven AV dyssynchrony will be included in the study. All patients will receive a dual-chamber pacemaker with an atrial lead positioned in the right atrium and ventricular lead placed on the bundle of His. In a single-blind cross-over design, patients will be randomized to AV sequential His bundle pacing with echo-guided AV optimization or back-up VVI pacing mode. Each study period will last for three months. At the end of both periods, cardiopulmonary exercise testing, complete echocardiographic study, and clinical evaluation will be performed. Peak oxygen uptake and echocardiography-based hemodynamic parameters in both periods will be compared.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: January 4, 2023
• Est. primary completion date: September 13, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• First OR second degree Mobitz type 1 atrioventricular block with a PR interval > 250 ms
• left ventricular ejection fraction > 50%
• echocardiographic criteria of atrioventricular dyssynchrony (diastolic filling time/RR interval ratio < 0,4 OR fusion of E and A waves OR diastolic mitral regurgitation)
• symptoms on exertion (dyspnea, palpitations)
• insufficient shortening of PR interval during exercise (PR interval > 200 ms at heart rate of 100 beats per minute)

Exclusion Criteria:

• left ventricular ejection fraction < 50%
• third degree atrioventricular block
• atrial fibrillation
• sinus node disease
• left bundle branch block
• right bundle branch block
• ventricular arrhythmia that indicates implantation of cardioverter defibrillator
• consumption of drugs that influence atrioventricular conduction
• active bacterial infection
• inability to undergo cardiopulmonary exercise test
• anaemia (haemoglobin concentration < 100 g/L)
• pregnancy

Related Conditions & MeSH terms

• Atrioventricular Block
• Atrioventricular Dyssynchrony

Intervention

Device:
• His bundle pacing, AV optimized
A Select Secure 3830 (Medtronic, MN, USA) pacing lead will be placed on the bundle of His. In case of unsuccessful His capture, left bundle branch area pacing is going to be targeted. Pacemaker will be programmed to a low base rate and a high tracking rate to allow for intrinsic sinus rhythm. AV delay will be optimized with echocardiography to the shortest AV delay without truncation of the A wave on transmitral pulse wave doppler.
• Backup VVI pacing
Pacemaker will be programmed to VVI (ventricular only) mode with low base rate as to allow for intrinsic sinus rhythm without AV optimization.

Locations

Country	Name	City	State
Slovenia	UMC Ljubljana	Ljubljana

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Centre Ljubljana

Country where clinical trial is conducted

Slovenia, 

References & Publications (12)

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

Aro AL, Anttonen O, Kerola T, Junttila MJ, Tikkanen JT, Rissanen HA, Reunanen A, Huikuri HV. Prognostic significance of prolonged PR interval in the general population. Eur Heart J. 2014 Jan;35(2):123-9. doi: 10.1093/eurheartj/eht176. Epub 2013 May 14. — View Citation

European Society of Cardiology (ESC); European Heart Rhythm Association (EHRA); Brignole M, Auricchio A, Baron-Esquivias G, Bordachar P, Boriani G, Breithardt OA, Cleland J, Deharo JC, Delgado V, Elliott PM, Gorenek B, Israel CW, Leclercq C, Linde C, Mont L, Padeletti L, Sutton R, Vardas PE. 2013 ESC guidelines on cardiac pacing and cardiac resynchronization therapy: the task force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Europace. 2013 Aug;15(8):1070-118. doi: 10.1093/europace/eut206. Epub 2013 Jun 24. No abstract available. — View Citation

Iliev II, Yamachika S, Muta K, Hayano M, Ishimatsu T, Nakao K, Komiya N, Hirata T, Ueyama C, Yano K. Preserving normal ventricular activation versus atrioventricular delay optimization during pacing: the role of intrinsic atrioventricular conduction and pacing rate. Pacing Clin Electrophysiol. 2000 Jan;23(1):74-83. doi: 10.1111/j.1540-8159.2000.tb00652.x. — View Citation

Joshi NP, Stopper MM, Li J, Beshai JF, Pavri BB. Impact of baseline PR interval on cardiac resynchronization therapy outcomes in patients with narrow QRS complexes: an analysis of the ReThinQ Trial. J Interv Card Electrophysiol. 2015 Aug;43(2):145-9. doi: 10.1007/s10840-015-9999-y. Epub 2015 Apr 29. — View Citation

Kiehl EL, Makki T, Kumar R, Gumber D, Kwon DH, Rickard JW, Kanj M, Wazni OM, Saliba WI, Varma N, Wilkoff BL, Cantillon DJ. Incidence and predictors of right ventricular pacing-induced cardiomyopathy in patients with complete atrioventricular block and preserved left ventricular systolic function. Heart Rhythm. 2016 Dec;13(12):2272-2278. doi: 10.1016/j.hrthm.2016.09.027. — View Citation

Kutyifa V, Stockburger M, Daubert JP, Holmqvist F, Olshansky B, Schuger C, Klein H, Goldenberg I, Brenyo A, McNitt S, Merkely B, Zareba W, Moss AJ. PR interval identifies clinical response in patients with non-left bundle branch block: a Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy substudy. Circ Arrhythm Electrophysiol. 2014 Aug;7(4):645-51. doi: 10.1161/CIRCEP.113.001299. Epub 2014 Jun 24. — View Citation

Moss AJ, Hall WJ, Cannom DS, Klein H, Brown MW, Daubert JP, Estes NA 3rd, Foster E, Greenberg H, Higgins SL, Pfeffer MA, Solomon SD, Wilber D, Zareba W; MADIT-CRT Trial Investigators. Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med. 2009 Oct 1;361(14):1329-38. doi: 10.1056/NEJMoa0906431. Epub 2009 Sep 1. — View Citation

Salden FCWM, Kutyifa V, Stockburger M, Prinzen FW, Vernooy K. Atrioventricular dromotropathy: evidence for a distinctive entity in heart failure with prolonged PR interval? Europace. 2018 Jul 1;20(7):1067-1077. doi: 10.1093/europace/eux207. — View Citation

Sharma PS, Dandamudi G, Naperkowski A, Oren JW, Storm RH, Ellenbogen KA, Vijayaraman P. Permanent His-bundle pacing is feasible, safe, and superior to right ventricular pacing in routine clinical practice. Heart Rhythm. 2015 Feb;12(2):305-12. doi: 10.1016/j.hrthm.2014.10.021. Epub 2014 Oct 22. — View Citation

Wilkoff BL, Cook JR, Epstein AE, Greene HL, Hallstrom AP, Hsia H, Kutalek SP, Sharma A; Dual Chamber and VVI Implantable Defibrillator Trial Investigators. Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial. JAMA. 2002 Dec 25;288(24):3115-23. doi: 10.1001/jama.288.24.3115. — View Citation

Zhang J, Guo J, Hou X, Wang Y, Qian Z, Li K, Ge P, Zou J. Comparison of the effects of selective and non-selective His bundle pacing on cardiac electrical and mechanical synchrony. Europace. 2018 Jun 1;20(6):1010-1017. doi: 10.1093/europace/eux120. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in exercise capacity	Measured by peak oxygen consumption on cardiopulmonary exercise test	Baseline, 3 months, 6 months
Primary	Changes in left ventricular stroke volume	Measured by echocardiography	Baseline, 3 months, 6 months
Primary	Changes in quality of life using the 5 level EQ-5D questionnaire	EQ-5D is a standardized measure of health status consisting of 2 pages - the EQ-5D descriptive system (descriptive system with five levels) and the EQ visual analog scale ranging from 0 (worst state) to 100 (best state).	Baseline, 3 months, 6 months
Secondary	Changes in left ventricular volume	End diastolic volume measured echocardiographicaly with biplane Simpson method	Baseline, 3 months, 6 months
Secondary	Changes in left atrial volume	Left atrial volume indexed by body surface area measured by echocardiography	Baseline, 3 months, 6 months
Secondary	Changes in the measure of left ventricular mechanical dyssynchrony	Measured by mid-ventricular radial speckle-tracking strain with an anteroseptal to posterior wall delay (AS-P delay)	Baseline, 3 months, 6 months
Secondary	Changes in QRS complex width	Measured by electrocardiogram	Baseline, 3 months, 6 months
Secondary	Changes in pacing thresholds	Measured during device check	Baseline, 3 months, 6 months
Secondary	Changes in sensing of R wave	Measured during device check	Baseline, 3 months, 6 months
Secondary	Changes in lead impedance	Measured during device check	Baseline, 3 months, 6 months
Secondary	Fluoroscopy time	Time of fluoroscopy use during device implantation	Baseline
Secondary	Adverse events	Any of the following adverse events: pocket hematoma, pneumothorax, hemothorax, cardiac tamponade, lead dislocation, lead perforation, cardiac implantable device infection	through study completion, an average of one year