Arrhythmia, Atrial Fibrillation, Bradycardia, Tachycardia, Supraventricular
Conditions
Keywords
Atrial Fibrillation, Atrial Tachyarrhythmia, Arrhythmia, Bradycardia, Cardiac Pacemaker, IPG Indication, Pacing
Brief summary
The purpose of this study is to find out if specialized programs in the AT500 and EnRhythm pacemakers will reduce the number of irregular heartbeat in the upper chamber of the heart and reduce symptoms (such as shortness of breath, dizziness, and others).
Detailed description
The purpose of the study was to confirm the AT500 intervention pacing effectiveness data previously seen in the ASPECT clinical trial and to gather additional data to understand the effectiveness of the intervention pacing features. Specifically, the goal of the trial is to demonstrate a reduction in frequency in symptomatic atrial tachycardia/atrial fibrillation recurrence with the intervention pacing features in patients with a pacing indication and a history of atrial tachyarrhythmias with atrial pacing leads located in the region of Bachmann's Bundle.
Interventions
DEVICEIntervention Pacing Features
Intervention pacing features (atrial rate stabilization algorithm, atrial preference pacing algorithm, post mode switch overdrive pacing algorithm) in the pacemaker.
Sponsors
Medtronic Cardiac Rhythm and Heart Failure
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Subjects with fast and/or slow heartbeats who are in need of dual chamber pacing (pacing in both the atria and ventricles) as determined by their doctor. * Subjects who have a history of occasional fast heartbeats originating from the upper heart chambers. * Subjects who have experienced at least two symptomatic episodes of fast heartbeats three months prior to enrollment. * Subjects that are expected to stay on the same heart medications during the length study.
Exclusion criteria
* Subjects who have permanent (chronic) or persistent (not self-terminating) atrial fibrillation (fast heartbeats originating from the upper heart chambers). * Subjects who have atrial fibrillation due to a reversible cause, i.e. electrolyte imbalance. * Subjects who are current or immediate implantable cardioverter defibrillator (ICD) recipients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Symptomatic Atrial Tachycardia/Atrial Fibrillation Episodes Per Subject Per Month | 6-months (per Intervention) | The frequency of symptomatic atrial tachycardia/atrial fibrillation (AT/AF) episodes as measured by the Patient Assistant and retrieved from save-to-disk information. For each subject and programming period (3-9 month period and 9-15 month period), the rate of symptomatic AT/AF episodes was computed by summing the total number of Patient Assistant activations during device recorded AT/AF episodes divided by months of device follow-up in each study period. Within each subject, the ON minus OFF difference in rate of symptomatic AT/AF was computed |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate Subject Symptoms With the Atrial Fibrillation (AF) Symptom Checklist | 6 months (per Intervention) | The AF symptom checklist (SCL) is a 16 item questionnaire measuring the frequency of 16 arrhythmia related symptoms such as tiredness/lack of energy, heart fluttering/skipping, heart racing, lightheadedness, etc. Symptom frequency is rated as never (scored as 0), rarely (scored as 1), sometimes (scored as 2), often (scored as 3), and always (scored as 4). Scores are summed across each subject and timepoint and range from 0 (no symptoms) to 64 (always symptoms). For each subject the 9 month and 15 months scores were summed respectively and ON minus OFF differences computed. |
| Time to First Cardioversion (Changing an Abnormal Heart Rhythm Into a Normal One by Using Either Medication or Electrical Shock) | 6 months (per Intervention) | The dates of cardioversions attempted for atrial fibrillation (AF) since the previous study visit were collected at the 3, 9, and 15 month follow-up visits. For each randomized subject, the months to first attempted cardioversion during each randomized study period (3-9 months and 9-15 months) was determined. A repeated measures Cox proportional hazards model was used to compare the attempted cardioversion rate during periods of time where the pacing features were programmed ON versus OFF. |
| Atrial Tachycardia/Atrial Fibrillation (AT/AF) Burden | 6 months (per Intervention) | AT/AF burden is defined as the sum of the duration of all atrial arrhythmias as recorded by the device divided by the device follow-up time during the programming period expressed as hours of atrial arrhythmia per day. |
Countries
Canada, United States
Participant flow
Recruitment details
The first study implant occurred on 13 February 2004 and the last study visit occurred on 10 November 2010
Pre-assignment details
At the 3-month post-implant follow-up visit, all implanted subjects with documented Atrial tachycardia/Atrial fibrillation episode(s) during the 3-month observation period were eligible for randomization. Subjects with no documented Atrial tachycardia/Atrial fibrillation episodes were followed as part of the non-randomized group.
Participants by arm
| Arm | Count |
|---|---|
| On-Off Subjects have intervention pacing features turned On according to randomization assignment in the first crossover period then Off in the second period. | 132 |
| Off-On Subjects have intervention pacing features turned Off according to the randomization assignment for the first crossover period and then On in the second period. | 124 |
| Non-Randomized Group Subjects exiting prior to the 3-month randomization visit or subjects with no AT/AF burden during the 3-month observation period | 144 |
| Total | 400 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 4 | 2 | 5 |
| Overall Study | Did not meet inclusion/exclusion | 0 | 0 | 6 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 |
| Overall Study | No implant attempted | 0 | 0 | 1 |
| Overall Study | Non-study device implanted | 2 | 1 | 3 |
| Overall Study | Other Exit Reason | 6 | 4 | 12 |
| Overall Study | Physician Decision | 1 | 0 | 6 |
| Overall Study | Withdrawal by Subject | 5 | 3 | 15 |
Baseline characteristics
| Characteristic | On-Off | Off-On | Non-Randomized Group | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 107 Participants | 94 Participants | 117 Participants | 318 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 30 Participants | 27 Participants | 82 Participants |
| Age Continuous | 73.0 years STANDARD_DEVIATION 9.9 | 70.6 years STANDARD_DEVIATION 9.3 | 72.4 years STANDARD_DEVIATION 9.2 | 72.0 years STANDARD_DEVIATION 9.5 |
| Region of Enrollment Canada | 7 participants | 6 participants | 5 participants | 18 participants |
| Region of Enrollment United States | 125 participants | 118 participants | 139 participants | 382 participants |
| Sex: Female, Male Female | 82 Participants | 60 Participants | 80 Participants | 222 Participants |
| Sex: Female, Male Male | 50 Participants | 64 Participants | 64 Participants | 178 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 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 7 / 132 | 8 / 124 | 4 / 144 |
Outcome results
Primary
Rate of Symptomatic Atrial Tachycardia/Atrial Fibrillation Episodes Per Subject Per Month
The frequency of symptomatic atrial tachycardia/atrial fibrillation (AT/AF) episodes as measured by the Patient Assistant and retrieved from save-to-disk information. For each subject and programming period (3-9 month period and 9-15 month period), the rate of symptomatic AT/AF episodes was computed by summing the total number of Patient Assistant activations during device recorded AT/AF episodes divided by months of device follow-up in each study period. Within each subject, the ON minus OFF difference in rate of symptomatic AT/AF was computed
Time frame: 6-months (per Intervention)
Population: Patient Assistant data which contained markers for symptomatic atrial tachycardia or atrial fibrillation episodes obtained from save-to-disk data was required from both randomized follow-up periods (3-9 months and 9-15 months) for the subject to be included in the primary ITT analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Pacing Features Programmed ON | Rate of Symptomatic Atrial Tachycardia/Atrial Fibrillation Episodes Per Subject Per Month | 2.0 Episodes per subject per month | Standard Deviation 4.8 |
| Intervention Pacing Features Programmed OFF | Rate of Symptomatic Atrial Tachycardia/Atrial Fibrillation Episodes Per Subject Per Month | 1.8 Episodes per subject per month | Standard Deviation 5.2 |
Comparison: Null Hypothesis: rate of symptomatic atrial tachycardia/atrial fibrillation episodes during periods when intervention pacing features ON is greater to or equal to the rate of symptomatic atrial tachycardia/atrial fibrillation episodes during periods where intervention pacing features were programmed OFF Alternative Hypothesis: rate of symptomatic AT/AF during periods of ON programming is less than the rate of symptomatic AT/AF during OFF programmingp-value: 0.629t-test, 1 sided
Secondary
Atrial Tachycardia/Atrial Fibrillation (AT/AF) Burden
AT/AF burden is defined as the sum of the duration of all atrial arrhythmias as recorded by the device divided by the device follow-up time during the programming period expressed as hours of atrial arrhythmia per day.
Time frame: 6 months (per Intervention)
Population: Of the 256 randomized to ON-OFF or OFF-ON programming, 225 had device data necessary for computing AT/AF burden in both randomized study periods.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Pacing Features Programmed ON | Atrial Tachycardia/Atrial Fibrillation (AT/AF) Burden | 4.0 hours per day | Standard Deviation 6.8 |
| Intervention Pacing Features Programmed OFF | Atrial Tachycardia/Atrial Fibrillation (AT/AF) Burden | 4.1 hours per day | Standard Deviation 7.2 |
Comparison: Null Hypothesis: There is no difference in AT/AF burden during periods on ON and OFF programming Alternative Hypothesis: AT/AF burden is lower during periods of ON programming compared to periods of OFF programmingp-value: 0.394Wilcoxon (Mann-Whitney)
Secondary
Evaluate Subject Symptoms With the Atrial Fibrillation (AF) Symptom Checklist
The AF symptom checklist (SCL) is a 16 item questionnaire measuring the frequency of 16 arrhythmia related symptoms such as tiredness/lack of energy, heart fluttering/skipping, heart racing, lightheadedness, etc. Symptom frequency is rated as never (scored as 0), rarely (scored as 1), sometimes (scored as 2), often (scored as 3), and always (scored as 4). Scores are summed across each subject and timepoint and range from 0 (no symptoms) to 64 (always symptoms). For each subject the 9 month and 15 months scores were summed respectively and ON minus OFF differences computed.
Time frame: 6 months (per Intervention)
Population: Of the 256 randomized subjects only 211 completed the AF symptom checklist at both the 9-month and 15-month visit. Since this was a crossover study, data from both visits was required for the subject to be included in the analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intervention Pacing Features Programmed ON | Evaluate Subject Symptoms With the Atrial Fibrillation (AF) Symptom Checklist | 12.0 Scores on a scale |
| Intervention Pacing Features Programmed OFF | Evaluate Subject Symptoms With the Atrial Fibrillation (AF) Symptom Checklist | 13.0 Scores on a scale |
Comparison: The null hypothesis is that the symptom frequency score does not differ between while intervention pacing features were programmed ON versus OFF.~This secondary objective was not powered.p-value: 0.165Wilcoxon (Mann-Whitney)
Secondary
Time to First Cardioversion (Changing an Abnormal Heart Rhythm Into a Normal One by Using Either Medication or Electrical Shock)
The dates of cardioversions attempted for atrial fibrillation (AF) since the previous study visit were collected at the 3, 9, and 15 month follow-up visits. For each randomized subject, the months to first attempted cardioversion during each randomized study period (3-9 months and 9-15 months) was determined. A repeated measures Cox proportional hazards model was used to compare the attempted cardioversion rate during periods of time where the pacing features were programmed ON versus OFF.
Time frame: 6 months (per Intervention)
Population: All randomized subjects with follow-up during intervention pacing feature programming period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Pacing Features Programmed ON | Time to First Cardioversion (Changing an Abnormal Heart Rhythm Into a Normal One by Using Either Medication or Electrical Shock) | 2.1 Months | Standard Deviation 1.7 |
| Intervention Pacing Features Programmed OFF | Time to First Cardioversion (Changing an Abnormal Heart Rhythm Into a Normal One by Using Either Medication or Electrical Shock) | 3.3 Months | Standard Deviation 1.6 |
Comparison: Null Hypothesis: AF Cardioversion attempt rate is the same during periods of ON and OFF programming~Alternative Hypothesis: AF Cardioversion attempt rate is different during periods of ON and OFF programmingp-value: 0.60395% CI: [0.39, 1.73]Regression, Cox