Atrial Fibrillation, Heart Failure, Congestive
Conditions
Keywords
Physiological pacing, Antitachycardia pacing therapies
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.
Interventions
DEVICEPacemaker Medtronic EnRhythm
Pacemaker specific programming
Sponsors
Medtronic Cardiac Rhythm and Heart Failure
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite Endpoint Composed by Death for Any Cause, Cardiovascular Hospitalization or Permanent AF at 2 Years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Subjects' Symptoms | 2 years | — |
| Heart Failure Medications | 2 years | — |
| Cumulative Percentage of Ventricular Pacing | 2 years | — |
| Cardiovascular Death | 2 years | — |
| Any Hospitalization | 2 years | — |
| Adverse Events | 2 years | — |
| Death for All Causes at 2 Years | 2 years | Incidence, estimated via Kaplan Meier survival analysis, of death for any cause at 2 years |
| Incidence of Permanent Atrial Fibrillation at 2 Years | 2 years | Incidence, estimated via Kaplan Meier survival analysis, of permanent atrial fibrillation at 2 years |
| Incidence of Cardiovascular Hospitalizations at 2 Years | 2 years | Incidence, estimated via Kaplan Meier survival analysis, of cardiovascular hospitalizations at 2 years |
| Burden of Composite Clinical Endpoint | 2 years | — |
| Persistent Atrial Fibrillation (AF) | 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 | — |
| Atrial Fibrillation Burden | 2 years | — |
Countries
Italy
Participant flow
Recruitment details
The recruitment period was between February 2006 and April 2010. Patients were enrolled in cardiology departments.
Pre-assignment details
A total of 1300 patients were enrolled in the study. Enrollment was followed by a 1-month run-in period. Patients with ventricular pacing ≥ 95% on device check in the run-in period were excluded from the study. At the end of the run-in period, randomization was performed. In all, 1166 patients were randomized and followed up.
Participants by arm
| Arm | Count |
|---|---|
| Control Group PM programming according to actual clinical practice
Pacemaker Medtronic EnRhythm: Pacemaker specific programming | 385 |
| MVP Only PM programming according to actual clinical practice + MVP algorithm ON
Pacemaker Medtronic EnRhythm: Pacemaker specific programming | 398 |
| DDDRP PM programming according to actual clinical practice + MVP algorithm ON + Atrial fibrillation therapies ON
Pacemaker Medtronic EnRhythm: Pacemaker specific programming | 383 |
| Total | 1,166 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 20 | 19 | 16 |
| Overall Study | Lost to Follow-up | 38 | 51 | 42 |
Baseline characteristics
| Characteristic | MVP Only | Total | Control Group | DDDRP |
|---|---|---|---|---|
| Age, Continuous | 74 years STANDARD_DEVIATION 9 | 74 years STANDARD_DEVIATION 9 | 73 years STANDARD_DEVIATION 9 | 74 years STANDARD_DEVIATION 9 |
| Region of Enrollment Austria | 14 participants | 44 participants | 15 participants | 15 participants |
| Region of Enrollment France | 1 participants | 2 participants | 0 participants | 1 participants |
| Region of Enrollment Germany | 5 participants | 16 participants | 8 participants | 3 participants |
| Region of Enrollment Greece | 25 participants | 73 participants | 23 participants | 25 participants |
| Region of Enrollment Hong Kong | 1 participants | 3 participants | 1 participants | 1 participants |
| Region of Enrollment Israel | 7 participants | 22 participants | 7 participants | 8 participants |
| Region of Enrollment Italy | 211 participants | 616 participants | 203 participants | 202 participants |
| Region of Enrollment Kuwait | 4 participants | 9 participants | 2 participants | 3 participants |
| Region of Enrollment Netherlands | 43 participants | 123 participants | 41 participants | 39 participants |
| Region of Enrollment Portugal | 44 participants | 131 participants | 43 participants | 44 participants |
| Region of Enrollment Russian Federation | 11 participants | 30 participants | 10 participants | 9 participants |
| Region of Enrollment Slovakia | 5 participants | 16 participants | 5 participants | 6 participants |
| Region of Enrollment Spain | 18 participants | 51 participants | 16 participants | 17 participants |
| Region of Enrollment Switzerland | 7 participants | 23 participants | 9 participants | 7 participants |
| Region of Enrollment Taiwan | 2 participants | 7 participants | 2 participants | 3 participants |
| Sex: Female, Male Female | 188 Participants | 578 Participants | 180 Participants | 210 Participants |
| Sex: Female, Male Male | 210 Participants | 588 Participants | 205 Participants | 173 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 385 | 0 / 398 | 0 / 383 |
| serious Total, serious adverse events | 180 / 385 | 165 / 398 | 169 / 383 |
Outcome results
Primary
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.
Time frame: 2 years
Population: Analysis was intention to treat therefore all randomized patients were considered in the analyses
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Group | Composite Endpoint Composed by Death for Any Cause, Cardiovascular Hospitalization or Permanent AF at 2 Years | 28.0 percentage of participants |
| MVP Only | Composite Endpoint Composed by Death for Any Cause, Cardiovascular Hospitalization or Permanent AF at 2 Years | 23.1 percentage of participants |
| DDDRP | Composite Endpoint Composed by Death for Any Cause, Cardiovascular Hospitalization or Permanent AF at 2 Years | 21.5 percentage of participants |
Secondary
Adverse Events
Time frame: 2 years
Secondary
Any Hospitalization
Time frame: 2 years
Secondary
Atrial Fibrillation Burden
Time frame: 2 years
Secondary
Burden of Composite Clinical Endpoint
Time frame: 2 years
Secondary
Cardiovascular Death
Time frame: 2 years
Secondary
Clinical Outcome in All the Patients With MVP ON Between Patients With Optimized AV-delay and Patients Without Optimized AV-delay
Time frame: 2 years
Secondary
Cumulative Percentage of Ventricular Pacing
Time frame: 2 years
Secondary
Death for All Causes at 2 Years
Incidence, estimated via Kaplan Meier survival analysis, of death for any cause at 2 years
Time frame: 2 years
Population: The analysis was intention to treat therefore all randomized patients were included in the analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Group | Death for All Causes at 2 Years | 5.6 percentage of participants |
| MVP Only | Death for All Causes at 2 Years | 5.1 percentage of participants |
| DDDRP | Death for All Causes at 2 Years | 4.6 percentage of participants |
Secondary
Development of Atrioventricular (AV) Block and Pacemaker Dependency
Time frame: 2 years
Secondary
Echocardiogram Data About Left Ventricular Fractional Shortening and Ejection Fraction and Left Atrium Dilatation
Time frame: 2 years
Secondary
Frequency, Type, and Associated Cost of Health Care Utilization and Utility
Time frame: 2 years
Secondary
Heart Failure Medications
Time frame: 2 years
Secondary
Incidence of Cardiovascular Hospitalizations at 2 Years
Incidence, estimated via Kaplan Meier survival analysis, of cardiovascular hospitalizations at 2 years
Time frame: 2 years
Population: Analysis was intention to treat therefore all randomized patients were analysed
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Group | Incidence of Cardiovascular Hospitalizations at 2 Years | 16.8 percentage of participants |
| MVP Only | Incidence of Cardiovascular Hospitalizations at 2 Years | 13.7 percentage of participants |
| DDDRP | Incidence of Cardiovascular Hospitalizations at 2 Years | 15.2 percentage of participants |
Secondary
Incidence of Permanent Atrial Fibrillation at 2 Years
Incidence, estimated via Kaplan Meier survival analysis, of permanent atrial fibrillation at 2 years
Time frame: 2 years
Population: The analysis was intention to treat therefore all randomized patients were analysed
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Group | Incidence of Permanent Atrial Fibrillation at 2 Years | 9.2 percentage of participants |
| MVP Only | Incidence of Permanent Atrial Fibrillation at 2 Years | 7.7 percentage of participants |
| DDDRP | Incidence of Permanent Atrial Fibrillation at 2 Years | 3.8 percentage of participants |
Secondary
Persistent Atrial Fibrillation (AF)
Time frame: 2 years
Secondary
Predictors of Stroke, Transient Ischemic Attack (TIA) and Arterial Embolism
Time frame: 2 years
Secondary
Subjects' Symptoms
Time frame: 2 years
Secondary
Time to Development of the Composite Endpoint Between All Randomized Subjects in the Three Arms in Subgroups of Patients
Time frame: 2 years