Biopace Study: Biventricular Pacing for Atrioventricular Block to Prevent Cardiac Desynchronization

Study Overview
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Brief Summary
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The primary purpose of the study is to evaluate if patients with a standard indication for permanent ventricular pacing, left ventricular ejection fraction without limit, or any QRS duration will profit from the prevention of ventricular desynchronisation.

Detailed Description
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The study will be performed as a controlled, single-blind, international, multicenter, prospective, randomized, parallel group design. In order to pragmatically examine the effectiveness of biventricular pacing in patients with an indication for ventricular pacing, the study group with biventricular pacing is compared to a control group with standard pacemakers which only allow univentricular (right ventricular) stimulation, as it has been the standard outside of clinical studies until so far.

Official Title
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Biventricular Pacing for Atrioventricular Block in Left Ventricular Dysfunction to Prevent Cardiac Desynchronization

Conditions
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Atrioventricular Block, Ventricular Dysfunction

Intervention / Treatment
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* Device: Biventricular Pacing
* Device: RV Pacing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presence of an indication for ventricular pacing according to the actual guidelines for the implantation of cardiac pacemakers and a need for frequent (or even permanent) ventricular pacing for: Permanent 3rd degree atrioventricular (AV)-block or Intermittent 3rd degree AV-block in combination with 1st degree AV-block with a pQ-interval ≥ 220 ms or 2nd degree AV-block type Mobitz II in combination with 1st degree AV-block with a pQ-interval ≥ 220 ms or 2nd degree AV-block type Mobitz I (if indicated) in combination with 1st degree AV-block with a pQ-interval ≥ 220 ms or 1st degree AV-block with a pQ-interval ≥ 220 ms and indication for ventricular pacing (includes indication for ventricular pacing based on long HV interval measured during invasive electrophysiological testing) or Sick-sinus-syndrome with symptomatic sinus bradycardia or sinus arrest as primary indication for device implantation in combination with long 1st degree AV-block with a pQ-interval ≥ 220 ms or Chronic (permanent) atrial fibrillation (flutter or tachycardia) with a spontaneous heart (ventricular) rate at rest ≤ 60/min or Chronic (permanent) atrial fibrillation (flutter or tachycardia) with a spontaneous heart (ventricular) rate at rest ≤ 75/min, if initiation or increase of pharmacological treatment with a relevant heart rate lowering effect (negative chronotropic effect) is planned for the time after pacemaker implantation (i.e. ß-blockers for heart failure and rate control) Patients scheduled for AV node ablation Any QRS duration and morphology Left ventricular ejection fraction (LVEF) without limit as measured by echocardiography (in at least one plane, either 4- or 2-chamber or apical long axis view) Signed written informed consent of the patient or a first-degree relative for study participation after informing the patient/relative about the risks and the aim of the study Willingness and ability to comply with the prescribed follow-up tests and schedule of evaluations. Absence of an implanted ventricular pacing device (patients with atrial pacemakers and new need for ventricular pacing may be included) Exclusion Criteria: Implanted Cardioverter Defibrillator or consideration for implantation of an ICD due to arrhythmia indication. However, ICD implant for primary prevention of sudden cardiac death in patients with LVEF ≤ 35 % (in accordance with the actual guidelines for the implantation of arrhythmia devices[LVEF < 30%] and in accordance with the results of the SCD-Heft study [LVEF < 35%) will be allowed. Implanted ventricular pacing device Status 1 for cardiac transplantation and likelihood to receive transplantation within 2 years (these patients would not be expected to fulfill the follow-up requirements as outlined in this protocol) Evidence of acute left ventricular dysfunction and high probability for its reversibility (e.g. acute myocarditis, tachycardiomyopathy) Implanted prosthetic tricuspid valve Severe musculoskeletal disorder(s) Age below 18 years Current or planned pregnancy in the next 6 months Current or recent (within the past 30 days) participation in any other clinical investigation Life expectancy of less than 6 months Patient's inability to independently comprehend and complete the Quality of Life (QoL) questionnaire

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: RV Pacing<br>Standard Pacemaker implant | Device: RV Pacing<br>* Standard Pacemaker implant<br>|
| Experimental: Biventricular Pacing<br>Biventricular Pacemaker implant | Device: Biventricular Pacing<br>* Biventricular Pacemaker implant<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Mortality | Number of deaths observed | Study duration (5.7 years mean follow-up) | 
| Death or Heart Failure Hospitalization | Number of subjects who experienced death or hospitalization where heart failure is a primary cause of hospitalization | Study duration (5.7 years mean follow-up) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death Due to Cardiovascular Causes | Number of subjects who died due to cardiovascular causes, as classified by the independent Event Adjudication Committee (IEAC) | Study duration (5.7 years mean follow-up) | 
| Functional Capacity as Measured by the Distance Covered in the 6-minute Walk Test |  | 12 months post-implant | 
| Health Related Quality of Life Measured by the Minnesota Living With Heart Failure Questionnaire© | Minnesota Living with Heart Failure (MLWHF) questionnaire score at 12 months MLWHF score: the total scale is from 0 to 105, with higher scores indicating worse health status. | 12 months post-implant | 
| Incidence of Hospitalizations for Deterioration of Heart Failure |  | Study duration (5.7 years mean follow-up) | 
| Incidence of Hospitalizations for Cardiovascular Events |  | Study duration (5.7 years mean follow-up) | 
| Incidence of Hospitalizations for Any Reason |  | Study duration (5.7 years mean follow-up) | 
| Cardiac Structure and Function |  | 12 & 24 months | 
| Successful Implantation of the Left Ventricular Lead |  | Implantation | 
| Chronic Atrial Fibrillation (Defined as Presence of Atrial Fibrillation in Two Subsequent ECG´s/Visits) | Chronic atrial fibrillation is defined as presence of atrial fibrillation in two subsequent ECG´s/visits. | Study duration (5.7 years mean follow-up) | 
| Functional Capacity as Measured by the Distance Covered in the 6-minute Walk Test |  | 24 months post-implant | 
| Health Related Quality of Life Measured by the Minnesota Living With Heart Failure Questionnaire© | Minnesota Living with Heart Failure (MLWHF) questionnaire score at 24 months. MLWHF score: the total scale is from 0 to 105, with higher scores indicating worse health status. | 24 months post-implant | 
| Duration of Hospitalizations for Deterioration of Heart Failure |  | Study Duration (5.7 years mean follow-up) | 
| Duration of Hospitalizations for Cardiovascular Events |  | Study Duration (5.7 years mean follow-up) | 
| Duration of Hospitalizations for Any Reason |  | Study duration (5.7 years mean follow-up) | 
| Adverse Events Related to Left Ventricular Lead | Only serious adverse events related to the left ventricular lead are included. | Study Duration (5.7 years mean follow-up) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Standard pacing indication