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

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.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation; Heart Failure, Congestive
• Intervention / Treatment: Device: Pacemaker Medtronic EnRhythm

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.

• Study Type: Interventional
• Enrollment (Actual): 1300
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 00193
    • Medtronic Italia S.p.A.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Control Group; PM programming according to actual clinical practice	Device: Pacemaker Medtronic EnRhythm; Pacemaker specific programming
ACTIVE_COMPARATOR: MVP Only; PM programming according to actual clinical practice + MVP algorithm ON	Device: Pacemaker Medtronic EnRhythm; Pacemaker specific programming
ACTIVE_COMPARATOR: DDDRP; PM programming according to actual clinical practice + MVP algorithm ON + Atrial fibrillation therapies ON	Device: Pacemaker Medtronic EnRhythm; Pacemaker specific programming

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

Collaborators and Investigators

• Sponsor: Medtronic Bakken Research Center
• Investigators: Principal Investigator: Luigi Padeletti, Prof., Ospedale Careggi - Firenze; Principal Investigator: Giuseppe Boriani, Dr., Ospedale Sant'Orsola - Bologna; Principal Investigator: Luis Mont, Dr., Hospital Clinic of Barcelona; Principal Investigator: Reinhard C Funck, Dr., Philipps University Hospital - Marburg; Principal Investigator: Carsten W Israel, Dr., J. W. Goethe University Hospital - Frankfurt; Principal Investigator: Helmut Pürerfellner, Dr., Elisabethinen Hospital; Principal Investigator: Antonis S Manolis, Prof., Evagelismos Hospital - Athens; Principal Investigator: André Pisapia, Dr, Hôpital Saint-Joseph - Marseille; Principal Investigator: Raymond Tukkie, Dr, Kennemer Gasthuis

Publications and helpful links

General Publications

• Andersen HR, Nielsen JC, Thomsen PE, Thuesen L, Mortensen PT, Vesterlund T, Pedersen AK. Long-term follow-up of patients from a randomised trial of atrial versus ventricular pacing for sick-sinus syndrome. Lancet. 1997 Oct 25;350(9086):1210-6. doi: 10.1016/S0140-6736(97)03425-9.
• Lamas GA, Lee KL, Sweeney MO, Silverman R, Leon A, Yee R, Marinchak RA, Flaker G, Schron E, Orav EJ, Hellkamp AS, Greer S, McAnulty J, Ellenbogen K, Ehlert F, Freedman RA, Estes NA 3rd, Greenspon A, Goldman L; Mode Selection Trial in Sinus-Node Dysfunction. Ventricular pacing or dual-chamber pacing for sinus-node dysfunction. N Engl J Med. 2002 Jun 13;346(24):1854-62. doi: 10.1056/NEJMoa013040.
• Connolly SJ, Kerr CR, Gent M, Roberts RS, Yusuf S, Gillis AM, Sami MH, Talajic M, Tang AS, Klein GJ, Lau C, Newman DM. Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes. Canadian Trial of Physiologic Pacing Investigators. N Engl J Med. 2000 May 11;342(19):1385-91. doi: 10.1056/NEJM200005113421902.
• Mattioli AV, Vivoli D, Mattioli G. Influence of pacing modalities on the incidence of atrial fibrillation in patients without prior atrial fibrillation. A prospective study. Eur Heart J. 1998 Feb;19(2):282-6. doi: 10.1053/euhj.1997.0616.
• Kristensen L, Nielsen JC, Mortensen PT, Pedersen OL, Pedersen AK, Andersen HR. Incidence of atrial fibrillation and thromboembolism in a randomised trial of atrial versus dual chamber pacing in 177 patients with sick sinus syndrome. Heart. 2004 Jun;90(6):661-6. doi: 10.1136/hrt.2003.016063.
• Nielsen JC, Andersen HR, Thomsen PE, Thuesen L, Mortensen PT, Vesterlund T, Pedersen AK. Heart failure and echocardiographic changes during long-term follow-up of patients with sick sinus syndrome randomized to single-chamber atrial or ventricular pacing. Circulation. 1998 Mar 17;97(10):987-95. doi: 10.1161/01.cir.97.10.987.
• Nielsen JC, Kristensen L, Andersen HR, Mortensen PT, Pedersen OL, Pedersen AK. A randomized comparison of atrial and dual-chamber pacing in 177 consecutive patients with sick sinus syndrome: echocardiographic and clinical outcome. J Am Coll Cardiol. 2003 Aug 20;42(4):614-23. doi: 10.1016/s0735-1097(03)00757-5.
• Boriani G, Tukkie R, Manolis AS, Mont L, Purerfellner H, Santini M, Inama G, Serra P, de Sousa J, Botto GL, Mangoni L, Grammatico A, Padeletti L; MINERVA Investigators. Atrial antitachycardia pacing and managed ventricular pacing in bradycardia patients with paroxysmal or persistent atrial tachyarrhythmias: the MINERVA randomized multicentre international trial. Eur Heart J. 2014 Sep 14;35(35):2352-62. doi: 10.1093/eurheartj/ehu165. Epub 2014 Apr 25.
• Funck RC, Boriani G, Manolis AS, Puererfellner H, Mont L, Tukkie R, Pisapia A, Israel CW, Grovale N, Grammatico A, Padeletti L; MINERVA Study Group. The MINERVA study design and rationale: a controlled randomized trial to assess the clinical benefit of minimizing ventricular pacing in pacemaker patients with atrial tachyarrhythmias. Am Heart J. 2008 Sep;156(3):445-51. doi: 10.1016/j.ahj.2008.05.004.

Study record dates

Study Major Dates

• Study Start: February 1, 2006
• Primary Completion (ACTUAL): April 1, 2012
• Study Completion (ACTUAL): April 1, 2013

Study Registration Dates

• First Submitted: December 4, 2005
• First Submitted That Met QC Criteria: December 4, 2005
• First Posted (ESTIMATE): December 6, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): April 21, 2016
• Last Update Submitted That Met QC Criteria: March 23, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Physiological pacing; Antitachycardia pacing therapies
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Heart Failure; Atrial Fibrillation
• Other Study ID Numbers: MNV-20-171005