Clinical trial NCT04544345: Impact of Atrio-ventricular Optimization With His Bundle Pacing on Treatment of Atrio-ventricular Dromotropathy
Official title: Impact of Atrio-ventricular Optimization With His Bundle Pacing on Treatment of Atrio-ventricular Dromotropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Atrioventricular Block
Atrioventricular Dyssynchrony
Keywords: AV block
His bundle pacing
AV dyssynchrony
AV optimization
AV dromotropathy
First degree AV block
Peak oxygen uptake
Lead sponsor: University Medical Centre Ljubljana
Sponsor class: OTHER
First posted: 2020-09-10
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Changes in exercise capacity
timeFrame: Baseline, 3 months, 6 months
measure: Changes in left ventricular stroke volume
timeFrame: Baseline, 3 months, 6 months
measure: Changes in quality of life using the 5 level EQ-5D questionnaire
timeFrame: Baseline, 3 months, 6 months
Secondary outcomes:
measure: Changes in left ventricular volume
timeFrame: Baseline, 3 months, 6 months
measure: Changes in left atrial volume
timeFrame: Baseline, 3 months, 6 months
measure: Changes in the measure of left ventricular mechanical dyssynchrony
timeFrame: Baseline, 3 months, 6 months
measure: Changes in QRS complex width
timeFrame: Baseline, 3 months, 6 months
measure: Changes in pacing thresholds
timeFrame: Baseline, 3 months, 6 months
measure: Changes in sensing of R wave
timeFrame: Baseline, 3 months, 6 months
measure: Changes in lead impedance
timeFrame: Baseline, 3 months, 6 months
measure: Fluoroscopy time
timeFrame: Baseline
measure: Adverse events
timeFrame: through study completion, an average of one year
Other outcomes:
Locations:
city: Ljubljana
country: Slovenia
facility: UMC Ljubljana
Study officials:
References:
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.
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.
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.
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.
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.
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.
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.
citation: 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.
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.
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.
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.
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.