Atrial Fibrillation
Conditions
Brief summary
This study is to determine, through continuous monitoring with the Reveal implantable cardiac monitor (ICM), the incidence of atrial fibrillation (AF) in patients suspected to be at high risk for having AF and to understand how physicians manage these patients after AF has been detected. This study will also seek to identify what patient characteristics are most predictive of developing AF.
Interventions
DEVICEREVEAL Implantable Cardiac Monitor
Sponsors
Medtronic Cardiac Rhythm and Heart Failure
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SCREENING
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient meets the approved indications to receive the Reveal ICM * Patient is suspected, based on symptomatology and/or demographics, of having atrial fibrillation or at high risk of having AF, as determined by the clinical investigator * Patient has a Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, prior Stroke or transient ischemic attack (TIA) or thromboembolism (doubled) (CHADS2) score ≥ 3 OR has a CHADS2 score = 2 with at least one of the following documented: renal impairment (GFR 30-60 ml/min), sleep apnea, coronary artery disease, or chronic obstructive pulmonary disease. Note: stroke/TIA criterion as part of the CHADS2 score for this trial is limited to either an ischemic stroke or TIA, which occurred more than one year prior to enrollment. * Patient is 18 years of age or older * Patient has a life expectancy of 18 months or more * Patient, or legally authorized representative, is willing to sign and date the consent form * Patient is willing and able to be remotely monitored (i.e., eligible for enrollment into the Medtronic CareLink Network)
Exclusion criteria
* Patient has a documented history of AF or atrial flutter * Patient had an ischemic stroke or TIA within past year prior to enrollment * Patient has a history of a hemorrhagic stroke * Patient is currently implanted with an implantable pulse generator (IPG), implantable cardioverter defibrillator (ICD), cardiac resynchronization therapy pacemaker (CRT-P), or cardiac resynchronization therapy defibrillator (CRT-D) device * New York Heart Association (NYHA) Class IV Heart Failure patient * Patient had heart surgery within previous 90 days prior to enrollment * Patient had a myocardial infarction (MI) within the previous 90 days prior to enrollment * Patient is taking chronic immuno-suppressant therapy * Patient is taking an anti-arrhythmic drug * Patient is contraindicated for long term anticoagulation medication * Patient is taking a long-term anticoagulation medication * Any concomitant condition which, in the opinion of the investigator, would not allow safe participation in the study (e.g., drug addiction, alcohol abuse, emotional / psychological diagnosis) * Patient is enrolled in another study that could confound the results of this study, without documented pre-approval from Medtronic study manager * Patient has a creatinine clearance \<30 ml/min or is on dialysis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 18 Month Incidence Rate of Atrial Fibrillation (AF) Lasting Six or More Minutes | Implant to 18 months post device insertion | Incidence of adjudicated AF lasting six or more minutes at 18 months. Each arrhythmic episode detected by the patient's Reveal device will be reviewed to determine if it is 1) an actual atrial fibrillation episode, and (2) is at least 6 minutes in duration. The first such episode per patient occurring within 18 months will be utilized to determine the 18 month incidence rate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Predictors of the Incidence of AF | Time from implant to date of last stored available device data (maximum of 30 months) | AF will be defined as in the primary outcome. Baseline characteristics including demographics, medical history, and biomarkers at enrollment will be tested for their association with a patient's risk of developing AF. |
| Actions Taken in Response to Awareness of AF | Time from first identified episode of AF to study exit (maximum of 30 months) | Clinical actions taken in response to clinician awareness of a patient's AF onset or progression will be summarized |
Countries
Austria, Germany, Italy, Netherlands, Slovenia, Spain, United States
Participant flow
Pre-assignment details
Patients in the 'No Reveal Implantable Cardiac Monitor Implant Attempt' arm were exited from the study prior to an implant attempt. Therefore, no outcome data are available. Baseline data are not presented due to variable data collection before the time of exit. Adverse event data were collected for this cohort, and are reported below.
Participants by arm
| Arm | Count |
|---|---|
| Reveal Implantable Cardiac Monitor Implant Attempted Enrolled subjects who had a Reveal Implantable Cardiac Monitor implant attempt (i.e. underwent the procedure to have a Reveal device implanted) | 395 |
| Total | 395 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | Death | 13 | 0 |
| Overall Study | Lost to Follow-up | 11 | 0 |
| Overall Study | Other (e.g. AF detection pre-implant) | 29 | 8 |
| Overall Study | Physician Decision | 19 | 5 |
| Overall Study | Protocol Violation | 1 | 10 |
| Overall Study | Withdrawal by Subject | 26 | 27 |
Baseline characteristics
| Characteristic | Reveal Implantable Cardiac Monitor Implant Attempted |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 307 Participants |
| Age, Categorical Between 18 and 65 years | 88 Participants |
| Age, Continuous | 71.6 years STANDARD_DEVIATION 9.8 |
| Region of Enrollment Austria | 18 participants |
| Region of Enrollment Germany | 39 participants |
| Region of Enrollment Italy | 19 participants |
| Region of Enrollment Netherlands | 6 participants |
| Region of Enrollment Slovenia | 4 participants |
| Region of Enrollment Spain | 7 participants |
| Region of Enrollment United States | 302 participants |
| Sex: Female, Male Female | 188 Participants |
| Sex: Female, Male Male | 207 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 13 / 395 | 0 / 51 |
| other Total, other adverse events | 34 / 395 | 1 / 51 |
| serious Total, serious adverse events | 153 / 395 | 1 / 51 |
Outcome results
Primary
18 Month Incidence Rate of Atrial Fibrillation (AF) Lasting Six or More Minutes
Incidence of adjudicated AF lasting six or more minutes at 18 months. Each arrhythmic episode detected by the patient's Reveal device will be reviewed to determine if it is 1) an actual atrial fibrillation episode, and (2) is at least 6 minutes in duration. The first such episode per patient occurring within 18 months will be utilized to determine the 18 month incidence rate.
Time frame: Implant to 18 months post device insertion
Population: This analysis only included patients who received an implantable cardiac monitor, met all inclusion/exclusion criteria, and had device data available. Of the 395 participants who underwent an implant attempt, 1 attempt was unsuccessful, 7 subjects did not meet all inclusion/exclusion criteria, and 2 subjects had no post-implant device data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primary Objective Analysis Cohort | 18 Month Incidence Rate of Atrial Fibrillation (AF) Lasting Six or More Minutes | 29.3 percent of participants |
Secondary
Actions Taken in Response to Awareness of AF
Clinical actions taken in response to clinician awareness of a patient's AF onset or progression will be summarized
Time frame: Time from first identified episode of AF to study exit (maximum of 30 months)
Population: Each visit represents the number of subjects who had a 1st, 2nd, 3rd visit, etc. in which AF was identified by the physician. Subjects in the Sixth Visit with AF Detected column had 6 visits in which AF was detected by the physician, and the column reflects the actions taken at that sixth visit.
| Arm | Measure | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Primary Objective Analysis Cohort | Actions Taken in Response to Awareness of AF | Ablation | 0 Actions at Visits |
| Primary Objective Analysis Cohort | Actions Taken in Response to Awareness of AF | Referral to Another Physician | 5 Actions at Visits |
| Primary Objective Analysis Cohort | Actions Taken in Response to Awareness of AF | Cardioversion | 2 Actions at Visits |
| Primary Objective Analysis Cohort | Actions Taken in Response to Awareness of AF | Rate Control Medication Initiated | 4 Actions at Visits |
| Primary Objective Analysis Cohort | Actions Taken in Response to Awareness of AF | Oral Anticoagulation Initiated | 61 Actions at Visits |
| Primary Objective Analysis Cohort | Actions Taken in Response to Awareness of AF | Rhythm Control Medication Initiated | 13 Actions at Visits |
| AF Predictors Analysis Cohort: No AF Episodes | Actions Taken in Response to Awareness of AF | Ablation | 2 Actions at Visits |
| AF Predictors Analysis Cohort: No AF Episodes | Actions Taken in Response to Awareness of AF | Cardioversion | 2 Actions at Visits |
| AF Predictors Analysis Cohort: No AF Episodes | Actions Taken in Response to Awareness of AF | Referral to Another Physician | 0 Actions at Visits |
| AF Predictors Analysis Cohort: No AF Episodes | Actions Taken in Response to Awareness of AF | Rate Control Medication Initiated | 3 Actions at Visits |
| AF Predictors Analysis Cohort: No AF Episodes | Actions Taken in Response to Awareness of AF | Oral Anticoagulation Initiated | 5 Actions at Visits |
| AF Predictors Analysis Cohort: No AF Episodes | Actions Taken in Response to Awareness of AF | Rhythm Control Medication Initiated | 2 Actions at Visits |
| Third Visit With AF Detected | Actions Taken in Response to Awareness of AF | Cardioversion | 1 Actions at Visits |
| Third Visit With AF Detected | Actions Taken in Response to Awareness of AF | Rhythm Control Medication Initiated | 0 Actions at Visits |
| Third Visit With AF Detected | Actions Taken in Response to Awareness of AF | Rate Control Medication Initiated | 2 Actions at Visits |
| Third Visit With AF Detected | Actions Taken in Response to Awareness of AF | Ablation | 3 Actions at Visits |
| Third Visit With AF Detected | Actions Taken in Response to Awareness of AF | Referral to Another Physician | 0 Actions at Visits |
| Third Visit With AF Detected | Actions Taken in Response to Awareness of AF | Oral Anticoagulation Initiated | 0 Actions at Visits |
| Fourth Visit With AF Detected | Actions Taken in Response to Awareness of AF | Rate Control Medication Initiated | 1 Actions at Visits |
| Fourth Visit With AF Detected | Actions Taken in Response to Awareness of AF | Oral Anticoagulation Initiated | 1 Actions at Visits |
| Fourth Visit With AF Detected | Actions Taken in Response to Awareness of AF | Rhythm Control Medication Initiated | 1 Actions at Visits |
| Fourth Visit With AF Detected | Actions Taken in Response to Awareness of AF | Cardioversion | 0 Actions at Visits |
| Fourth Visit With AF Detected | Actions Taken in Response to Awareness of AF | Ablation | 1 Actions at Visits |
| Fourth Visit With AF Detected | Actions Taken in Response to Awareness of AF | Referral to Another Physician | 0 Actions at Visits |
| Fifth Visit With AF Detected | Actions Taken in Response to Awareness of AF | Ablation | 0 Actions at Visits |
| Fifth Visit With AF Detected | Actions Taken in Response to Awareness of AF | Referral to Another Physician | 0 Actions at Visits |
| Fifth Visit With AF Detected | Actions Taken in Response to Awareness of AF | Cardioversion | 0 Actions at Visits |
| Fifth Visit With AF Detected | Actions Taken in Response to Awareness of AF | Oral Anticoagulation Initiated | 2 Actions at Visits |
| Fifth Visit With AF Detected | Actions Taken in Response to Awareness of AF | Rate Control Medication Initiated | 0 Actions at Visits |
| Fifth Visit With AF Detected | Actions Taken in Response to Awareness of AF | Rhythm Control Medication Initiated | 0 Actions at Visits |
| Sixth Visit With AF Detected | Actions Taken in Response to Awareness of AF | Cardioversion | 0 Actions at Visits |
| Sixth Visit With AF Detected | Actions Taken in Response to Awareness of AF | Ablation | 0 Actions at Visits |
| Sixth Visit With AF Detected | Actions Taken in Response to Awareness of AF | Rate Control Medication Initiated | 0 Actions at Visits |
| Sixth Visit With AF Detected | Actions Taken in Response to Awareness of AF | Referral to Another Physician | 0 Actions at Visits |
| Sixth Visit With AF Detected | Actions Taken in Response to Awareness of AF | Oral Anticoagulation Initiated | 0 Actions at Visits |
| Sixth Visit With AF Detected | Actions Taken in Response to Awareness of AF | Rhythm Control Medication Initiated | 0 Actions at Visits |
Secondary
Predictors of the Incidence of AF
AF will be defined as in the primary outcome. Baseline characteristics including demographics, medical history, and biomarkers at enrollment will be tested for their association with a patient's risk of developing AF.
Time frame: Time from implant to date of last stored available device data (maximum of 30 months)
Population: This analysis only included patients who received an implantable cardiac monitor, were not on antiarrhythmic medications at baseline, and had device data available. Of the 395 participants who underwent an implant attempt, 1 attempt was unsuccessful, 1 subject was on antiarrhythmic medication, and 2 subjects had no post-implant device data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Primary Objective Analysis Cohort | Predictors of the Incidence of AF | Family history of AF | 5 Participants |
| Primary Objective Analysis Cohort | Predictors of the Incidence of AF | Heart failure | 31 Participants |
| Primary Objective Analysis Cohort | Predictors of the Incidence of AF | Hypertension | 122 Participants |
| Primary Objective Analysis Cohort | Predictors of the Incidence of AF | Prior stroke > 1 year ago | 23 Participants |
| Primary Objective Analysis Cohort | Predictors of the Incidence of AF | Coronary artery disease | 75 Participants |
| Primary Objective Analysis Cohort | Predictors of the Incidence of AF | Sleep apnea | 28 Participants |
| Primary Objective Analysis Cohort | Predictors of the Incidence of AF | Vascular disease | 25 Participants |
| Primary Objective Analysis Cohort | Predictors of the Incidence of AF | Gender (Male) | 67 Participants |
| Primary Objective Analysis Cohort | Predictors of the Incidence of AF | Diabetes | 80 Participants |
| Primary Objective Analysis Cohort | Predictors of the Incidence of AF | Renal impairment | 60 Participants |
| Primary Objective Analysis Cohort | Predictors of the Incidence of AF | Chronic obstructive pulmonary disorder | 19 Participants |
| AF Predictors Analysis Cohort: No AF Episodes | Predictors of the Incidence of AF | Sleep apnea | 75 Participants |
| AF Predictors Analysis Cohort: No AF Episodes | Predictors of the Incidence of AF | Vascular disease | 54 Participants |
| AF Predictors Analysis Cohort: No AF Episodes | Predictors of the Incidence of AF | Heart failure | 50 Participants |
| AF Predictors Analysis Cohort: No AF Episodes | Predictors of the Incidence of AF | Chronic obstructive pulmonary disorder | 57 Participants |
| AF Predictors Analysis Cohort: No AF Episodes | Predictors of the Incidence of AF | Hypertension | 244 Participants |
| AF Predictors Analysis Cohort: No AF Episodes | Predictors of the Incidence of AF | Renal impairment | 106 Participants |
| AF Predictors Analysis Cohort: No AF Episodes | Predictors of the Incidence of AF | Prior stroke > 1 year ago | 56 Participants |
| AF Predictors Analysis Cohort: No AF Episodes | Predictors of the Incidence of AF | Gender (Male) | 138 Participants |
| AF Predictors Analysis Cohort: No AF Episodes | Predictors of the Incidence of AF | Coronary artery disease | 157 Participants |
| AF Predictors Analysis Cohort: No AF Episodes | Predictors of the Incidence of AF | Diabetes | 168 Participants |
| AF Predictors Analysis Cohort: No AF Episodes | Predictors of the Incidence of AF | Family history of AF | 3 Participants |
Comparison: The null hypothesis was that age did not influence a patient's risk of experiencing AF (it's coefficient in a Cox proportional hazards model was 0).p-value: <0.00195% CI: [1.05, 1.11]Regression, Cox
Comparison: The null hypothesis was that body mass index (BMI) did not influence a patient's risk of experiencing AF (it's coefficient in a Cox proportional hazards model was 0).p-value: 0.0295% CI: [1.01, 1.08]Regression, Cox
Comparison: The null hypothesis was that gender did not influence a patient's risk of experiencing AF (it's coefficient for being male in a Cox proportional hazards model was 0).p-value: 0.5695% CI: [0.77, 1.61]Regression, Cox
Comparison: The null hypothesis was that diabetes did not influence a patient's risk of experiencing AF (it's coefficient in a Cox proportional hazards model was 0).p-value: 0.6695% CI: [0.74, 1.59]Regression, Cox
Comparison: The null hypothesis was that heart failure did not influence a patient's risk of experiencing AF (it's coefficient in a Cox proportional hazards model was 0).p-value: 0.7395% CI: [0.69, 1.69]Regression, Cox
Comparison: The null hypothesis was that hypertension did not influence a patient's risk of experiencing AF (it's coefficient in a Cox proportional hazards model was 0).p-value: 0.5895% CI: [0.58, 2.6]Regression, Cox
Comparison: The null hypothesis was that renal impairment did not influence a patient's risk of experiencing AF (it's coefficient in a Cox proportional hazards model was 0).p-value: 0.6595% CI: [0.64, 1.32]Regression, Cox
Comparison: The null hypothesis was that Chronic obstructive pulmonary disease (COPD) did not influence a patient's risk of experiencing AF (it's coefficient in a Cox proportional hazards model was 0).p-value: 0.2295% CI: [0.45, 1.2]Regression, Cox
Comparison: The null hypothesis was that prior stroke more than one year pre-device implant did not influence a patient's risk of experiencing AF (it's coefficient in a Cox proportional hazards model was 0).p-value: 0.5395% CI: [0.54, 1.38]Regression, Cox
Comparison: The null hypothesis was that coronary artery disease did not influence a patient's risk of experiencing AF (it's coefficient in a Cox proportional hazards model was 0).p-value: 0.2195% CI: [0.53, 1.15]Regression, Cox
Comparison: The null hypothesis was that sleep apnea did not influence a patient's risk of experiencing AF (it's coefficient in a Cox proportional hazards model was 0).p-value: 0.1995% CI: [0.45, 1.17]Regression, Cox
Comparison: The null hypothesis was that family history of AF did not influence a patient's risk of experiencing AF (it's coefficient in a Cox proportional hazards model was 0).p-value: 0.1695% CI: [0.76, 5.14]Regression, Cox
Comparison: The null hypothesis was that vascular disease did not influence a patient's risk of experiencing AF (it's coefficient in a Cox proportional hazards model was 0).p-value: 0.6395% CI: [0.56, 1.43]Regression, Cox