Atrioventricular Block, Ventricular Dysfunction
Conditions
Keywords
Standard pacing indication
Brief summary
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
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.
Interventions
DEVICEBiventricular Pacing
Biventricular Pacemaker implant
DEVICERV Pacing
Standard Pacemaker implant
Sponsors
Abbott Medical Devices
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 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: 1. Permanent 3rd degree atrioventricular (AV)-block or 2. Intermittent 3rd degree AV-block in combination with 1st degree AV-block with a pQ-interval ≥ 220 ms or 3. 2nd degree AV-block type Mobitz II in combination with 1st degree AV-block with a pQ-interval ≥ 220 ms or 4. 2nd degree AV-block type Mobitz I (if indicated) in combination with 1st degree AV-block with a pQ-interval ≥ 220 ms or 5. 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 6. 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 7. Chronic (permanent) atrial fibrillation (flutter or tachycardia) with a spontaneous heart (ventricular) rate at rest ≤ 60/min or 8. 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) 9. Patients scheduled for AV node ablation 2. Any QRS duration and morphology 3. 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) 4. 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 5. Willingness and ability to comply with the prescribed follow-up tests and schedule of evaluations. 6. Absence of an implanted ventricular pacing device (patients with atrial pacemakers and new need for ventricular pacing may be included)
Exclusion criteria
1. 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. 2. Implanted ventricular pacing device 3. 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) 4. Evidence of acute left ventricular dysfunction and high probability for its reversibility (e.g. acute myocarditis, tachycardiomyopathy) 5. Implanted prosthetic tricuspid valve 6. Severe musculoskeletal disorder(s) 7. Age below 18 years 8. Current or planned pregnancy in the next 6 months 9. Current or recent (within the past 30 days) participation in any other clinical investigation 10. Life expectancy of less than 6 months 11. Patient's inability to independently comprehend and complete the Quality of Life (QoL) questionnaire
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Mortality | Study duration (5.7 years mean follow-up) | Number of deaths observed |
| Death or Heart Failure Hospitalization | Study duration (5.7 years mean follow-up) | Number of subjects who experienced death or hospitalization where heart failure is a primary cause of hospitalization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Death Due to Cardiovascular Causes | Study duration (5.7 years mean follow-up) | Number of subjects who died due to cardiovascular causes, as classified by the independent Event Adjudication Committee (IEAC) |
| 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© | 12 months post-implant | 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. |
| 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) | Study duration (5.7 years mean follow-up) | Chronic atrial fibrillation is defined as presence of atrial fibrillation in two subsequent ECG´s/visits. |
| 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 | Study Duration (5.7 years mean follow-up) | Only serious adverse events related to the left ventricular lead are included. |
Countries
Germany
Participant flow
Recruitment details
Patients were enrolled between May 2003 and September 2007.
Pre-assignment details
1834 patients have been scheduled for randomization, while 1833 have been randomized to RV Pacing or Biventricular group. One patient could not be randomized due to organizational reasons.
Participants by arm
| Arm | Count |
|---|---|
| RV Pacing Standard Pacemaker implant
RV Pacing: Standard Pacemaker implant | 908 |
| Biventricular Pacing Biventricular Pacemaker implant
Biventricular Pacing: Biventricular Pacemaker implant | 902 |
| Total | 1,810 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 10 | 13 |
Baseline characteristics
| Characteristic | RV Pacing | Biventricular Pacing | Total |
|---|---|---|---|
| Age, Continuous | 73.3 years STANDARD_DEVIATION 9 | 73.8 years STANDARD_DEVIATION 9 | 73.5 years STANDARD_DEVIATION 9.2 |
| Atrial arrhythmias Atrial arrhythmias | 225 participants | 225 participants | 450 participants |
| Atrial arrhythmias None | 683 participants | 677 participants | 1360 participants |
| Body mass index | 27.5 kg/m^2 STANDARD_DEVIATION 4.7 | 27.4 kg/m^2 STANDARD_DEVIATION 4.3 | 27.4 kg/m^2 STANDARD_DEVIATION 4.5 |
| Cardiovascular risk factor Diabetes mellitus | 255 participants | 251 participants | 506 participants |
| Cardiovascular risk factor Hypertension | 696 participants | 666 participants | 1362 participants |
| Indications for device implantation Intermittent bradycardia | 368 participants | 362 participants | 730 participants |
| Indications for device implantation Persistent bradycardia | 538 participants | 540 participants | 1078 participants |
| Indications for device implantation Unknown | 2 participants | 0 participants | 2 participants |
| Left bundle branch block (LBBB) LBBB | 166 participants | 150 participants | 316 participants |
| Left bundle branch block (LBBB) None | 742 participants | 752 participants | 1494 participants |
| Left ventricular ejection fraction (LVEF) | 55.5 % STANDARD_DEVIATION 12.4 | 55.3 % STANDARD_DEVIATION 12.1 | 55.4 % STANDARD_DEVIATION 12.2 |
| Left Ventricular Ejection Fraction (LVEF) range 35% < LVEF ≤ 50% | 221 participants | 198 participants | 419 participants |
| Left Ventricular Ejection Fraction (LVEF) range LVEF ≤ 35% | 74 participants | 78 participants | 152 participants |
| Left Ventricular Ejection Fraction (LVEF) range LVEF > 50% | 613 participants | 626 participants | 1239 participants |
| QRS duration | 118.8 ms STANDARD_DEVIATION 30.3 | 118.1 ms STANDARD_DEVIATION 30.8 | 118.4 ms STANDARD_DEVIATION 30.5 |
| QRS range 120ms < QRS ≤ 150ms | 190 participants | 176 participants | 366 participants |
| QRS range QRS ≤ 120ms | 571 participants | 571 participants | 1142 participants |
| QRS range QRS > 150ms | 147 participants | 155 participants | 302 participants |
| Scheduled for ICD Not scheduled for ICD | 886 participants | 976 participants | 1762 participants |
| Scheduled for ICD Scheduled for ICD | 22 participants | 26 participants | 48 participants |
| Sex: Female, Male Female | 296 Participants | 278 Participants | 574 Participants |
| Sex: Female, Male Male | 612 Participants | 624 Participants | 1236 Participants |
| Underlying cardiac diseases All | 572 participants | 571 participants | 1143 participants |
| Underlying cardiac diseases Dlated cardiomyopathy | 43 participants | 51 participants | 94 participants |
| Underlying cardiac diseases Hypertensive heart disease | 281 participants | 262 participants | 543 participants |
| Underlying cardiac diseases Ischaemic heart disease | 274 participants | 274 participants | 548 participants |
| Underlying cardiac diseases Prior MI | 162 participants | 141 participants | 308 participants |
| Underlying cardiac diseases Valvulopathy | 170 participants | 165 participants | 335 participants |
| Ventricular pacing at 1 month | 86.4 % | 90.2 % | 88.3 % |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 307 / 908 | 305 / 902 |
| other Total, other adverse events | 451 / 908 | 507 / 902 |
| serious Total, serious adverse events | 641 / 908 | 698 / 902 |
Outcome results
Primary
Death or Heart Failure Hospitalization
Number of subjects who experienced death or hospitalization where heart failure is a primary cause of hospitalization
Time frame: Study duration (5.7 years mean follow-up)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RV Pacing | Death or Heart Failure Hospitalization | 346 Participants |
| Biventricular Pacing | Death or Heart Failure Hospitalization | 363 Participants |
p-value: 0.088295% CI: [0.756, 1.02]Regression, Cox
Primary
Total Mortality
Number of deaths observed
Time frame: Study duration (5.7 years mean follow-up)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RV Pacing | Total Mortality | 307 Participants |
| Biventricular Pacing | Total Mortality | 305 Participants |
p-value: 0.349295% CI: [0.789, 1.0088]Regression, Cox
Secondary
Adverse Events Related to Left Ventricular Lead
Only serious adverse events related to the left ventricular lead are included.
Time frame: Study Duration (5.7 years mean follow-up)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RV Pacing | Adverse Events Related to Left Ventricular Lead | 1 participants |
| Biventricular Pacing | Adverse Events Related to Left Ventricular Lead | 38 participants |
Secondary
Cardiac Structure and Function
Time frame: 12 & 24 months
Population: Data related to cardiac structure and function can not be presented as the data was not collected and analysis provided by the core lab.
Secondary
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.
Time frame: Study duration (5.7 years mean follow-up)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RV Pacing | Chronic Atrial Fibrillation (Defined as Presence of Atrial Fibrillation in Two Subsequent ECG´s/Visits) | 91 participants |
| Biventricular Pacing | Chronic Atrial Fibrillation (Defined as Presence of Atrial Fibrillation in Two Subsequent ECG´s/Visits) | 76 participants |
Secondary
Death Due to Cardiovascular Causes
Number of subjects who died due to cardiovascular causes, as classified by the independent Event Adjudication Committee (IEAC)
Time frame: Study duration (5.7 years mean follow-up)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RV Pacing | Death Due to Cardiovascular Causes | 106 Participants |
| Biventricular Pacing | Death Due to Cardiovascular Causes | 107 Participants |
p-value: 0.821595% CI: [0.74, 1.27]Regression, Cox
Secondary
Duration of Hospitalizations for Any Reason
Time frame: Study duration (5.7 years mean follow-up)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RV Pacing | Duration of Hospitalizations for Any Reason | 3.72 days per patient year |
| Biventricular Pacing | Duration of Hospitalizations for Any Reason | 4.14 days per patient year |
Secondary
Duration of Hospitalizations for Cardiovascular Events
Time frame: Study Duration (5.7 years mean follow-up)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RV Pacing | Duration of Hospitalizations for Cardiovascular Events | 1.52 Days per patient year |
| Biventricular Pacing | Duration of Hospitalizations for Cardiovascular Events | 1.50 Days per patient year |
Secondary
Duration of Hospitalizations for Deterioration of Heart Failure
Time frame: Study Duration (5.7 years mean follow-up)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RV Pacing | Duration of Hospitalizations for Deterioration of Heart Failure | 0.40 days per patient year |
| Biventricular Pacing | Duration of Hospitalizations for Deterioration of Heart Failure | 0.39 days per patient year |
Secondary
Functional Capacity as Measured by the Distance Covered in the 6-minute Walk Test
Time frame: 12 months post-implant
Population: This analysis includes all enrolled patients who completed the 6-minute walk test both at the baseline and 12-month visits. Due to that reason, the overall number of participants analyzed is different from the participant module.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RV Pacing | Functional Capacity as Measured by the Distance Covered in the 6-minute Walk Test | 371.3 meters | Standard Deviation 128.8 |
| Biventricular Pacing | Functional Capacity as Measured by the Distance Covered in the 6-minute Walk Test | 371.2 meters | Standard Deviation 129.1 |
Secondary
Functional Capacity as Measured by the Distance Covered in the 6-minute Walk Test
Time frame: 24 months post-implant
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RV Pacing | Functional Capacity as Measured by the Distance Covered in the 6-minute Walk Test | 369.3 meters | Standard Deviation 127.2 |
| Biventricular Pacing | Functional Capacity as Measured by the Distance Covered in the 6-minute Walk Test | 376.5 meters | Standard Deviation 132 |
Secondary
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.
Time frame: 12 months post-implant
Population: This analysis includes all enrolled patients who completed the Minnesota Living With Heart Failure questionnaire both at the baseline and 12-month visits. Due to that reason, the overall number of participants analyzed is different from the participant module.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RV Pacing | Health Related Quality of Life Measured by the Minnesota Living With Heart Failure Questionnaire© | 16.0 score on a scale | Standard Deviation 15.4 |
| Biventricular Pacing | Health Related Quality of Life Measured by the Minnesota Living With Heart Failure Questionnaire© | 15.3 score on a scale | Standard Deviation 15.5 |
Secondary
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.
Time frame: 24 months post-implant
Population: This analysis includes all enrolled patients who completed the Minnesota Living With Heart Failure questionnaire both at the baseline and 24-month visits. Due to that reason, the overall number of participants analyzed is different from the participant module.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RV Pacing | Health Related Quality of Life Measured by the Minnesota Living With Heart Failure Questionnaire© | 17.5 score on a scale | Standard Deviation 17.6 |
| Biventricular Pacing | Health Related Quality of Life Measured by the Minnesota Living With Heart Failure Questionnaire© | 17.3 score on a scale | Standard Deviation 16.6 |
Secondary
Incidence of Hospitalizations for Any Reason
Time frame: Study duration (5.7 years mean follow-up)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RV Pacing | Incidence of Hospitalizations for Any Reason | 0.392 Hospitalization per patient year |
| Biventricular Pacing | Incidence of Hospitalizations for Any Reason | 0.432 Hospitalization per patient year |
Secondary
Incidence of Hospitalizations for Cardiovascular Events
Time frame: Study duration (5.7 years mean follow-up)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RV Pacing | Incidence of Hospitalizations for Cardiovascular Events | 0.162 hospitalizations per patient year |
| Biventricular Pacing | Incidence of Hospitalizations for Cardiovascular Events | 0.161 hospitalizations per patient year |
Secondary
Incidence of Hospitalizations for Deterioration of Heart Failure
Time frame: Study duration (5.7 years mean follow-up)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RV Pacing | Incidence of Hospitalizations for Deterioration of Heart Failure | 0.043 hospitalization per patient year |
| Biventricular Pacing | Incidence of Hospitalizations for Deterioration of Heart Failure | 0.037 hospitalization per patient year |
Secondary
Successful Implantation of the Left Ventricular Lead
Time frame: Implantation
Population: There was an attempt of left ventricular lead implantation only for subjects from Biventricular Pacing group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Biventricular Pacing | Successful Implantation of the Left Ventricular Lead | 760 participants |