Physiological Ventricular Pacing Vs Managed Ventricular Pacing for Persistent AF Prevention in Prolonged AV Interval

Not Applicable

Recruiting

• Conditions: Sinus Node Disease; Atrioventricular; Block, Second Degree (Types I and II)
• Interventions: Device: PhysioVP; Device: DDD-VPA

• Registration Number: NCT05367037
• Lead Sponsor: Quovadis Associazione

Brief Summary

A multicenter, prospective, randomized study in a 1:1 ratio, single-blind with double-blind evaluation to evaluate the superiority of physiological ventricular pacing (proposed modality) vs. managed ventricular pacing (control) for prevention of persistent AF (PeAF) occurrence in patients with prolonged atrioventricular interval (PR≥180 ms) and indication for pacing: sinus node disease and/or paroxysmal type 1 or 2-second degree AV block.

Detailed Description

Study aim: Evaluate the superiority of physiological ventricular pacing (proposed modality) vs. managed ventricular pacing (control) for prevention of persistent AF (PeAF) occurrence in patients with prolonged atrioventricular interval (PR≥180 ms) and indication for pacing: sinus node disease and/or paroxysmal type 1 or 2-second degree AV block. If the efficacy superiority is confirmed, this pacing mode may be considered to reduce the occurrence of persistent atrial fibrillation in this group of patients.

Study design: Independent, multicenter, prospective, randomized study in a 1:1 ratio, single-blind with double-blind evaluation (the actual evaluator of the primary endpoint is the pacemaker device's internal diagnostic algorithm, without intervention by the Investigator). This study will use only CE-marked devices already part of clinical practice.

Groups:

* PhysioVP group: the Physiological Ventricular Pacing is achieved by delivering a pacing stimulus to a cardiac conduction structure, such as the bundle of His or left bundle branch of the His-Purkinje system, with a permanent lead. PhysioVP activates the heart through the native His-Purkinje conduction system, thus offering the most physiologic pacing approach to correct the PR interval and avoiding pacing-induced dyssynchrony.

* DDD-VPA group: In managed ventricular pacing, the right ventricular (RV) lead is implanted in the myocardial right ventricular (septum or apex). In this pacing mode, the ventricular pacing is minimized by using algorithms for right Ventricular Pacing Avoidance.

Devices used:

* PhysioVP group: a specialized delivery sheath for His-Purkinje system pacing with appropriate or standard leads will be used.

* DDD-VPA group: the RV leads will be implanted in the standard right ventricular myocardial sites (septum or apex) using standard bipolar active-fixation leads.

The atrial leads will be placed in the right atrial appendage in both groups. The 13 participating Italian Clinical Centers are proven experience in the PM implantation procedures used in the study.

Enrolled patients will be monitored by in-office clinical checks at 1, 12, 24, and 36 months and by home monitoring at 6, 18, and 30 months after implantation.

Study Timeline

• Study First Submitted: 2022-01-12
• Study First Submitted QC: 2022-05-04
• Study First Posted: 2022-05-10
• Study Start: 2022-07-27
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-06
• Last Update Posted: 2025-05-11
• Primary Completion: 2028-12
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 640

Inclusion Criteria

18 years older patients, able to express Informed Consent, with prolonged atrioventricular interval (PR>180 ms) and one of the following indications for PM implantation according to current guidelines:

• Sinus node disease.
• Paroxysmal type1or 2 second-degree AV-block.

Exclusion Criteria

• Candidacy for implantable cardioverter-defibrillator or cardiac resynchronization therapy device implantation.
• Severe grade mitral or aortic regurgitation/stenosis.
• Atrial fibrillation ablation (left pulmonary veins).
• Cardiac surgery < 3 months before PM implantation.
• History of long-standing persistent AF.
• Permanent third-degree AV block.
• Participation in another clinical trial in the past 3 months.
• Pregnancy or intention to become pregnant.
• Life expectancy of < 3 years.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PhysioVP group	PhysioVP	Physiological ventricular pacing
DDD-VPA group	DDD-VPA	Dual-chamber pacing with the addition of algorithms for ventricular pacing avoidance

Primary Outcome Measures

Name	Time	Method
PeAF Free	36 months	Freedom from persistent AF occurrences up to 36 months after the pacemaker (PM) implant.; The occurrence of PeAF is defined as the first AF / Atrial Flutter / Atrial Tachycardia episode lasting \> 7 days, detected by the PM after a 1-month post PM lead-stabilization period. A day of AF is satisfied with a device-detected daily AF burden of ≥ 23 hours. Device-detected AF may also be collected by remote monitoring tools, if available. The definition also includes the occurrence of episodes terminated by cardioversion, whatever its duration or undergoing AF ablation
Clinical composite outcome	36 months	Composite outcome based on the occurrence of one or more of the events: Death from cardiovascular disease, or heart failure, or pacing system upgrading to the conduction system pacing (CSP) or to the biventricular pacing (BVP).

Secondary Outcome Measures

Name	Time	Method
Clinical evaluations, MLHFQ	12, 24, and 36 months	Variation of Quality-of-Life assessment by Minnesota Living with Heart Failure questionnaire (MLHFQ).
Clinical evaluations	12, 24, and 36 months	Number of cardiovascular diseases related to health structure access.
Safety endpoints, PRAE	36 months	Rate of all procedure-related adverse events (PRAE).
Safety endpoints, Potentially harmful factor 1	36 months	Implantation/s procedure time (mm:ss).
Safety endpoints, Potentially harmful factor 2	36 months	Fluoroscopy time (mm:ss).
Safety endpoints, Incidence Rate of re-interventions	36 months	Rate of re-interventions for lead revision, replacement, or infection.
Hemodynamic performance, Diastolic function 4	12 months	Echocardiographic parameters: E/e' ratio.
Hemodynamic performance, Diastolic function 5	12 months	Echocardiographic parameters: Diastolic time (from onset E wave to end A wave) normalized for RR interval (ms).
Hemodynamic performance, Left atrial volume	12 months	Echocardiographic parameters: Left atrial volume (ml/m2).
Hemodynamic performance, Mitral regurgitation	12 months	Echocardiographic parameters: vena contracta (mm).
Clinical evaluations, NYHA	12, 24, and 36 months	NYHA class variation (I, II, III, IV).
Hemodynamic performance, LV remodeling 1	12 months	Echocardiographic parameters: Left Ventriculi end-systolic volume (ml/m2).
Hemodynamic performance, LV remodeling 2	12 months	Echocardiographic parameters: LVEF (%).
Hemodynamic performance, Diastolic function 2	12 months	Echocardiographic parameters: E wave deceleration time (ms).
Hemodynamic performance, Diastolic function 1	12 months	Echocardiographic parameters: E to A mitral wave amplitude ratio.
Hemodynamic performance, Diastolic function 3	12 months	Echocardiographic parameters: pulsed-wave tissue Doppler early diastolic septal mitral annular velocity (e') (cm/s).
Estimated battery longevity	36 months	Estimated residual battery longevity (time to end-of-life) by the implanted device every 6-months and/or when the primary endpoint is reached.

Trial Locations

Locations (1)

Elettrofisiologia, Cardiologia, Ospedale di Rovigo; 🇮🇹 Rovigo, Veneto, Italy