MINERVA: MINimizE Right Ventricular Pacing to Prevent Atrial Fibrillation and Heart Failure

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to test the impact of the managed ventricular pacing (MVP) mode and atrial preventive and antitachycardia pacing therapies on the reduction of a composite clinical outcome composed of any death, permanent atrial fibrillation, and cardiovascular hospitalizations.

Detailed Description
-----------------
Kristensen et al. reported that AAIR pacing reduces atrial fibrillation (AF) development compared to DDDR pacing in sinus node disfunction patients. Several authors have shown that, in patients with intact AV conduction, unnecessary chronic RV pacing can cause detrimental effects such as AF, left ventricular (LV) dysfunction and congestive heart failure. These findings arose the hypothesis that the non-physiologic nature of ventricular pacing may result in electrophysiological and LV remodeling changes that have potentially deleterious long-term effects. The MVP mode, present in the Medtronic pacemaker EnRhythm, provides atrial based pacing with ventricular backup. It operates in true AAI(R) mode, it provides ventricular backup in case of a single conduction loss and converts to DDD(R) mode in case of persistent loss of AV conduction. Aim of this study is to test the impact of the MVP pacing mode and atrial preventive and antitachycardia pacing therapies on the reduction of a composite clinical outcome composed by any death, permanent AF, cardiovascular hospitalizations.

Official Title
-----------------
MINERVA: MINimizE Right Ventricular Pacing to Prevent Atrial Fibrillation and Heart Failure

Conditions
-----------------
Atrial Fibrillation, Heart Failure, Congestive

Intervention / Treatment
-----------------
* Device: Pacemaker Medtronic EnRhythm


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Class I/Class II indications for dual chamber pacing Previous implant of an EnRhythm dual chamber implantable pulse generator (IPG) since maximum 2 weeks History of atrial arrhythmias (at least one electrocardiogram [ECG] or Holter documented episodes in the last 12 months) Exclusion Criteria: Less than 18 years of age Pregnancy Unwilling or unable to give informed consent or to commit to follow-up schedule Medical conditions that preclude protocol required testing or limit study participation Enrolled or intend to participate in another clinical trial during the course of this study A life expectancy of less than 2 years Patient is a candidate for an implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT) device implant Anticipated major cardiac surgery within the course of this study Permanent III degree AV-block or history of AV node ablation History of permanent AF (as defined below) AF ablation (left pulmonary veins) or other cardiac surgery < 3 months Prior implant of defibrillator device or pacemaker (apart from EnRhythm IPG implanted within two weeks) Uncontrolled hyperthyroidism

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control Group<br>PM programming according to actual clinical practice | Device: Pacemaker Medtronic EnRhythm<br>* Pacemaker specific programming<br>|
| Active Comparator: MVP Only<br>PM programming according to actual clinical practice + MVP algorithm ON | Device: Pacemaker Medtronic EnRhythm<br>* Pacemaker specific programming<br>|
| Active Comparator: DDDRP<br>PM programming according to actual clinical practice + MVP algorithm ON + Atrial fibrillation therapies ON | Device: Pacemaker Medtronic EnRhythm<br>* Pacemaker specific programming<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Endpoint Composed by Death for Any Cause, Cardiovascular Hospitalization or Permanent AF at 2 Years | The outcome measurement is the 2 years incidence, calculated by Kaplan Meier survival analysis, of the composite endpoint composed by death for any cause, cardiovascular hospitalization or permanent AF. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death for All Causes at 2 Years | Incidence, estimated via Kaplan Meier survival analysis, of death for any cause at 2 years | 2 years | 
| Incidence of Permanent Atrial Fibrillation at 2 Years | Incidence, estimated via Kaplan Meier survival analysis, of permanent atrial fibrillation at 2 years | 2 years | 
| Incidence of Cardiovascular Hospitalizations at 2 Years | Incidence, estimated via Kaplan Meier survival analysis, of cardiovascular hospitalizations at 2 years | 2 years | 
| Burden of Composite Clinical Endpoint |  | 2 years | 
| Subjects' Symptoms |  | 2 years | 
| Heart Failure Medications |  | 2 years | 
| Cumulative Percentage of Ventricular Pacing |  | 2 years | 
| Cardiovascular Death |  | 2 years | 
| Any Hospitalization |  | 2 years | 
| Atrial Fibrillation Burden |  | 2 years | 
| Persistent Atrial Fibrillation (AF) |  | 2 years | 
| Adverse Events |  | 2 years | 
| Development of Atrioventricular (AV) Block and Pacemaker Dependency |  | 2 years | 
| Predictors of Stroke, Transient Ischemic Attack (TIA) and Arterial Embolism |  | 2 years | 
| Echocardiogram Data About Left Ventricular Fractional Shortening and Ejection Fraction and Left Atrium Dilatation |  | 2 years | 
| Clinical Outcome in All the Patients With MVP ON Between Patients With Optimized AV-delay and Patients Without Optimized AV-delay |  | 2 years | 
| Time to Development of the Composite Endpoint Between All Randomized Subjects in the Three Arms in Subgroups of Patients |  | 2 years | 
| Frequency, Type, and Associated Cost of Health Care Utilization and Utility |  | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Physiological pacing, Antitachycardia pacing therapies