Trial Outcomes & Findings for BIO monitorinG in Patients With Preserved Left ventricUlar Function AfteR Diagnosed Myocardial Infarction (NCT NCT02341534)

Last Updated: 2023-04-13

Results Overview

The primary endpoint is defined as death for cardiovascular reasons or unplanned hospitalization for cardiovascular reasons as per study protocol. The time period with regards to the Time-to-Event Outcome Measures starts with the randomization of the patient. All patients will be assessed for Time-to-Event Outcome Measures until formal study termination is announced or until the individual patient meets a drop out criterion in accordance with the study protocol. The study period is estimated 6 years.

Recruitment status

COMPLETED

Study phase

Target enrollment

802 participants

Primary outcome timeframe

2 years

Results posted on

2023-04-13

Participant Flow

802 patients were enrolled, 12 exited the study before randomization.

Participant milestones

Participant milestones
Measure	BioMonitor Arm Patients are implanted with investigational device. Device transfers daily arrhythmia information. Investigators react on information if required. If no arrhythmias are detected, patients are followed by standard post-MI routine.	Control Arm Patients do not receive investigational device, i.e. no additional arrhythmia monitoring. Patients are followed by standard post-MI routine.
Overall Study STARTED	398	392
Overall Study COMPLETED	322	325
Overall Study NOT COMPLETED	76	67

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BioMonitor Arm n=398 Participants BioMonitor group (implantation with investigational device + transfer of information via Home Monitoring) BioMonitor: Patients will be implanted with the BioMonitor + Home Monitoring feature	Control Arm n=392 Participants Control group (standard of care)	Total n=790 Participants Total of all reporting groups
Age, Continuous	71.5 years STANDARD_DEVIATION 7.7 • n=398 Participants	70.8 years STANDARD_DEVIATION 8.5 • n=392 Participants	71.2 years STANDARD_DEVIATION 8.1 • n=790 Participants
Sex: Female, Male Female	107 Participants n=398 Participants	115 Participants n=392 Participants	222 Participants n=790 Participants
Sex: Female, Male Male	291 Participants n=398 Participants	277 Participants n=392 Participants	568 Participants n=790 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: 2 years

Outcome measures

Outcome measures
Measure	BioMonitor Arm n=398 Participants BioMonitor group (implantation with investigational device + transfer of information via Home Monitoring) BioMonitor: Patients will be implanted with the BioMonitor + Home Monitoring feature	Control Arm n=392 Participants Control group (standard of care)
Kaplan-Meier Estimate of Percentage of Participants With Major Adverse Cardiac Event (MACE)	21.6 percentage of patients with event Interval 17.7 to 26.2	24.3 percentage of patients with event Interval 20.3 to 29.0

SECONDARY outcome

Timeframe: 2 years

The occurrence of death due to any cause will be recorded and analyzed.

Outcome measures

Outcome measures
Measure	BioMonitor Arm n=398 Participants BioMonitor group (implantation with investigational device + transfer of information via Home Monitoring) BioMonitor: Patients will be implanted with the BioMonitor + Home Monitoring feature	Control Arm n=392 Participants Control group (standard of care)
Kaplan-Meier Estimate of Percentage of Participants With Outcome of Death Due to Any Cause	6.7 percentage of patients with event Interval 4.6 to 9.8	7.1 percentage of patients with event Interval 4.9 to 10.3

SECONDARY outcome

Timeframe: 2 years

Assessment of the time from randomization to death for any reason or heart transplantation during the clinical investigation.

Outcome measures

Outcome measures
Measure	BioMonitor Arm n=398 Participants BioMonitor group (implantation with investigational device + transfer of information via Home Monitoring) BioMonitor: Patients will be implanted with the BioMonitor + Home Monitoring feature	Control Arm n=392 Participants Control group (standard of care)
Kaplan-Meier Estimate of Percentage of Participants With Outcome of Death Due to Any Cause or Heart Transplantation	6.7 percentage of patients with event Interval 4.6 to 9.8	7.1 percentage of patients with event Interval 4.9 to 10.3

SECONDARY outcome

Timeframe: 2 years

Assessment of the time from randomization to cardiovascular death or heart transplantation during the clinical investigation. A specified endpoint definition will be given by the members of the EAEC and documented in the charter agreement.

Outcome measures

Outcome measures
Measure	BioMonitor Arm n=398 Participants BioMonitor group (implantation with investigational device + transfer of information via Home Monitoring) BioMonitor: Patients will be implanted with the BioMonitor + Home Monitoring feature	Control Arm n=392 Participants Control group (standard of care)
Kaplan-Meier Estimate of Percentage of Participants With Outcome of Cardiovascular Death or Heart Transplantation	3.5 percentage of patients with event Interval 2.1 to 6.0	4.7 percentage of patients with event Interval 2.9 to 7.4

SECONDARY outcome

Timeframe: 2 years

Assessment of the time from randomization to first hospitalization or urgent visit for worsening of the patient status due to heart failure, or death due to heart failure. A specified endpoint definition will be given by the members of the EAEC and documented in the charter agreement.

Outcome measures

Outcome measures
Measure	BioMonitor Arm n=398 Participants BioMonitor group (implantation with investigational device + transfer of information via Home Monitoring) BioMonitor: Patients will be implanted with the BioMonitor + Home Monitoring feature	Control Arm n=392 Participants Control group (standard of care)
Kaplan-Meier Estimate of Percentage of Participants With Worsening of Heart Failure Requiring Hospitalization or Urgent Visit	6.0 percentage of patients with event Interval 4.0 to 9.0	5.9 percentage of patients with event Interval 3.9 to 8.9

SECONDARY outcome

Timeframe: 2 years

Assessment of the time from randomization to the first hospitalization resulting from an arrhythmia or death resulting from arrhythmia. A specified endpoint definition will be given by the members of the EAEC and documented in the charter agreement.

Outcome measures

Outcome measures
Measure	BioMonitor Arm n=398 Participants BioMonitor group (implantation with investigational device + transfer of information via Home Monitoring) BioMonitor: Patients will be implanted with the BioMonitor + Home Monitoring feature	Control Arm n=392 Participants Control group (standard of care)
Kaplan-Meier Estimate of Percentage of Participants With an Arrhythmia Resulting in Hospitalization	3.3 percentage of patients with event Interval 1.8 to 5.9	3.4 percentage of patients with event Interval 2.0 to 5.9

SECONDARY outcome

Timeframe: 2 years

Assessment of the time from randomization to the first hospitalization resulting from acute coronary syndrome or death resulting from acute coronary syndrome. A specified endpoint definition will be given by the members of the EAEC and documented in the charter agreement.

Outcome measures

Outcome measures
Measure	BioMonitor Arm n=398 Participants BioMonitor group (implantation with investigational device + transfer of information via Home Monitoring) BioMonitor: Patients will be implanted with the BioMonitor + Home Monitoring feature	Control Arm n=392 Participants Control group (standard of care)
Kaplan-Meier Estimate of Percentage of Participants With Acute Coronary Syndrome Resulting in Hospitalization	10.6 percentage of patients with event Interval 7.8 to 14.3	15.1 percentage of patients with event Interval 11.8 to 19.2

SECONDARY outcome

Timeframe: 2 years

Assessment of the time from randomization to the first hospitalization resulting from stroke or death resulting from stroke. A specified endpoint definition will be given by the members of the EAEC and documented in the charter agreement.

Outcome measures

Outcome measures
Measure	BioMonitor Arm n=398 Participants BioMonitor group (implantation with investigational device + transfer of information via Home Monitoring) BioMonitor: Patients will be implanted with the BioMonitor + Home Monitoring feature	Control Arm n=392 Participants Control group (standard of care)
Kaplan-Meier Estimate of Percentage of Participants With Stroke Resulting in Hospitalization	3.6 percentage of patients with event Interval 2.1 to 6.1	3.0 percentage of patients with event Interval 1.6 to 5.3

SECONDARY outcome

Timeframe: 2 years

Assessment of the time from randomization to the first hospitalization resulting from major bleeding or death resulting from major bleeding. A specified endpoint definition will be given by the members of the EAEC and documented in the charter agreement.

Outcome measures

Outcome measures
Measure	BioMonitor Arm n=398 Participants BioMonitor group (implantation with investigational device + transfer of information via Home Monitoring) BioMonitor: Patients will be implanted with the BioMonitor + Home Monitoring feature	Control Arm n=392 Participants Control group (standard of care)
Kaplan-Meier Estimate of Percentage of Participants With Major Bleeding Resulting in Hospitalization	0.6 percentage of patients with event Interval 0.2 to 2.4	1.1 percentage of patients with event Interval 0.4 to 2.9

SECONDARY outcome

Timeframe: 2 years

Assessment of the time from randomization to the first hospitalization resulting from systemic embolism or death resulting from systemic embolism. A specified endpoint definition will be given by the members of the EAEC and documented in the charter agreement.

Outcome measures

Outcome measures
Measure	BioMonitor Arm n=398 Participants BioMonitor group (implantation with investigational device + transfer of information via Home Monitoring) BioMonitor: Patients will be implanted with the BioMonitor + Home Monitoring feature	Control Arm n=392 Participants Control group (standard of care)
Kaplan-Meier Estimate of Percentage of Participants With Systemic Embolism Resulting in Hospitalization	0.3 percentage of patients with event Interval 0.0 to 2.0	0.7 percentage of patients with event Interval 0.2 to 2.7

SECONDARY outcome

Timeframe: 2 years

Assessment of the time from randomization to first arrhythmia.

Outcome measures

Outcome measures
Measure	BioMonitor Arm n=398 Participants BioMonitor group (implantation with investigational device + transfer of information via Home Monitoring) BioMonitor: Patients will be implanted with the BioMonitor + Home Monitoring feature	Control Arm n=392 Participants Control group (standard of care)
Kaplan-Meier Estimate of Percentage of Participants With an Arrhythmia	53.6 percentage of patients with event Interval 48.5 to 58.8	10 percentage of patients with event Interval 7.3 to 13.5

SECONDARY outcome

Timeframe: All data are collected for the period from randomization until official study end or drop-out, for all enrolled patients, up to 6 years.

Post-hoc categorical summary of most frequent therapies initiated after detection of arrhythmias.

Outcome measures

Outcome measures
Measure	BioMonitor Arm n=195 Participants BioMonitor group (implantation with investigational device + transfer of information via Home Monitoring) BioMonitor: Patients will be implanted with the BioMonitor + Home Monitoring feature	Control Arm n=44 Participants Control group (standard of care)
Type of Initiated Therapies Pacemaker implantation	45 Participants	6 Participants
Type of Initiated Therapies Reduction of heart-rate lowering drugs	43 Participants	5 Participants
Type of Initiated Therapies Oral anticoagulation treatment	84 Participants	18 Participants
Type of Initiated Therapies Betablocker treatment	13 Participants	6 Participants
Type of Initiated Therapies Antiarrhythmics	10 Participants	9 Participants

SECONDARY outcome

Timeframe: 2 years

Assessment of the time from randomization to first therapy. In this context therapy is the attempted remediation of the patient's regular heartbeat.

Outcome measures

Outcome measures
Measure	BioMonitor Arm n=398 Participants BioMonitor group (implantation with investigational device + transfer of information via Home Monitoring) BioMonitor: Patients will be implanted with the BioMonitor + Home Monitoring feature	Control Arm n=392 Participants Control group (standard of care)
Kaplan-Meier Estimate of Percentage of Participants Receiving Therapy After Arrhythmia Diagnosis	53.6 percentage of patients with event Interval 48.5 to 58.8	10.0 percentage of patients with event Interval 7.3 to 13.5

SECONDARY outcome

Timeframe: We report the intraindividual change from 6-months to 24-months. All data are collected for the period from randomization until official study end or drop-out, for all enrolled patients.

A further secondary endpoint is the assessment of the patient's well-being. The patient's well-being will be recorded during the regular telephone contacts using the WHO-5 Well-being Index. The scale reaches from 0 (worst status) to 100 (best possible status).

Outcome measures

Outcome measures
Measure	BioMonitor Arm n=398 Participants BioMonitor group (implantation with investigational device + transfer of information via Home Monitoring) BioMonitor: Patients will be implanted with the BioMonitor + Home Monitoring feature	Control Arm n=392 Participants Control group (standard of care)
Change in World Health Organization Five Well-being Index (WHO-5) From 6 Months to 24 Months.	0.1 Change in units on the WHO-5 scale Standard Deviation 17.6	0.7 Change in units on the WHO-5 scale Standard Deviation 21.2

OTHER_PRE_SPECIFIED outcome

Timeframe: From Baseline measurement to 60 months. All data are collected for the period from randomization until official study end or drop-out, for all enrolled patients.

Population: Not all patients contributed to this endpoint. The EQ-5D-5L was only introduced later in the trial via an amendment in 2019.

The EQ-5D-5L questionnaire was administered during the telephone contacts to estimate utility values at different time points for an economic evaluation. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. The scale reaches from 0 (worst status) to 100 (best possible status).

Outcome measures

Outcome measures
Measure	BioMonitor Arm n=353 Participants BioMonitor group (implantation with investigational device + transfer of information via Home Monitoring) BioMonitor: Patients will be implanted with the BioMonitor + Home Monitoring feature	Control Arm n=351 Participants Control group (standard of care)
Mean Value of EQ-5D-5L Baseline	74.9 Units on the EQ-5D-5L scale Standard Deviation 16.4	75.0 Units on the EQ-5D-5L scale Standard Deviation 18.8
Mean Value of EQ-5D-5L 12-months	72.5 Units on the EQ-5D-5L scale Standard Deviation 17.7	73.2 Units on the EQ-5D-5L scale Standard Deviation 16.9
Mean Value of EQ-5D-5L 24-months	71.6 Units on the EQ-5D-5L scale Standard Deviation 18.2	71.3 Units on the EQ-5D-5L scale Standard Deviation 18.1
Mean Value of EQ-5D-5L 36-months	71.2 Units on the EQ-5D-5L scale Standard Deviation 19.2	69.5 Units on the EQ-5D-5L scale Standard Deviation 18.4
Mean Value of EQ-5D-5L 48-months	69.9 Units on the EQ-5D-5L scale Standard Deviation 17.3	69.8 Units on the EQ-5D-5L scale Standard Deviation 19.2
Mean Value of EQ-5D-5L 60-months	74.8 Units on the EQ-5D-5L scale Standard Deviation 20.8	64.4 Units on the EQ-5D-5L scale Standard Deviation 21.2

Adverse Events

BioMonitor Arm

Serious events: 300 serious events

Other events: 259 other events

Deaths: 43 deaths

Control Arm

Serious events: 267 serious events

Other events: 173 other events

Deaths: 42 deaths

Serious adverse events

Other adverse events

Additional Information

Sascha Mrosk, Senior Clinical Project Manager

BIOTRONIK SE & Co. KG

Phone: 15168901308

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	BioMonitor Arm n=398 participants at risk BioMonitor group (implantation with investigational device + transfer of information via Home Monitoring) BioMonitor: Patients will be implanted with the BioMonitor + Home Monitoring feature	Control Arm n=392 participants at risk Control group (standard of care)
Infections and infestations Abdominal abscess	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.51% 2/392 • Number of events 2 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Gastrointestinal disorders Abdominal discomfort	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Infections and infestations Abdominal infection	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Gastrointestinal disorders Abdominal pain	0.75% 3/398 • Number of events 3 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	1.0% 4/392 • Number of events 5 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Gastrointestinal disorders Abdominal pain upper	0.50% 2/398 • Number of events 2 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.77% 3/392 • Number of events 3 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Metabolism and nutrition disorders Abnormal loss of weight	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Infections and infestations Abscess limb	0.75% 3/398 • Number of events 3 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.51% 2/392 • Number of events 2 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Infections and infestations Abscess rupture	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Injury, poisoning and procedural complications Accident	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.51% 2/392 • Number of events 2 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Metabolism and nutrition disorders Acidosis	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Gastrointestinal disorders Acquired oesophageal web	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Skin and subcutaneous tissue disorders Actinic keratosis	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Cardiac disorders Acute coronary syndrome	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Renal and urinary disorders Acute kidney injury	2.3% 9/398 • Number of events 9 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	2.6% 10/392 • Number of events 12 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Cardiac disorders Acute myocardial infarction	6.8% 27/398 • Number of events 30 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	8.9% 35/392 • Number of events 44 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Ear and labyrinth disorders Acute vestibular syndrome	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma pancreas	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenoma benign	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adrenocortical carcinoma	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
General disorders Adverse drug reaction	6.0% 24/398 • Number of events 30 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	3.8% 15/392 • Number of events 20 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Psychiatric disorders Alcohol abuse	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
General disorders Alcohol interaction	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Immune system disorders Allergy to animal	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Eye disorders Amaurosis fugax	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Investigations Ammonia increased	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Nervous system disorders Amnesia	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.51% 2/392 • Number of events 2 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Blood and lymphatic system disorders Anaemia	2.0% 8/398 • Number of events 8 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	2.0% 8/392 • Number of events 10 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Blood and lymphatic system disorders Anaemia of chronic disease	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Injury, poisoning and procedural complications Anaemia postoperative	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.51% 2/392 • Number of events 2 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Gastrointestinal disorders Anal fissure	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Gastrointestinal disorders Anal skin tags	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Cardiac disorders Angina pectoris	4.5% 18/398 • Number of events 20 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	6.9% 27/392 • Number of events 36 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Cardiac disorders Angina unstable	0.75% 3/398 • Number of events 3 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	3.8% 15/392 • Number of events 17 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Vascular disorders Angiodysplasia	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Skin and subcutaneous tissue disorders Angioedema	0.50% 2/398 • Number of events 2 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Vascular disorders Angiopathy	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Injury, poisoning and procedural complications Animal bite	0.50% 2/398 • Number of events 2 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Injury, poisoning and procedural complications Ankle fracture	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.

Other adverse events
Measure	BioMonitor Arm n=398 participants at risk BioMonitor group (implantation with investigational device + transfer of information via Home Monitoring) BioMonitor: Patients will be implanted with the BioMonitor + Home Monitoring feature	Control Arm n=392 participants at risk Control group (standard of care)
Musculoskeletal and connective tissue disorders Trigger finger	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Ear and labyrinth disorders Tympanosclerosis	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Cardiac disorders Sinoatrial block	0.75% 3/398 • Number of events 3 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Cardiac disorders Sinus arrest	3.5% 14/398 • Number of events 15 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Cardiac disorders Sinus bradycardia	9.0% 36/398 • Number of events 43 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Cardiac disorders Sinus node dysfunction	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.51% 2/392 • Number of events 2 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Cardiac disorders Sinus tachycardia	1.0% 4/398 • Number of events 4 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Infections and infestations Skin candida	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Skin and subcutaneous tissue disorders Skin disorder	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Skin and subcutaneous tissue disorders Skin exfoliation	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Skin and subcutaneous tissue disorders Skin haemorrhage	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Infections and infestations Skin infection	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.51% 2/392 • Number of events 2 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Skin and subcutaneous tissue disorders Skin irritation	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Injury, poisoning and procedural complications Skin laceration	0.50% 2/398 • Number of events 2 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.51% 2/392 • Number of events 2 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Skin and subcutaneous tissue disorders Skin mass	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Skin and subcutaneous tissue disorders Skin ulcer	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.51% 2/392 • Number of events 2 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.75% 3/398 • Number of events 3 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Psychiatric disorders Sleep disorder	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Nervous system disorders Somnolence	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Nervous system disorders Speech disorder	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Reproductive system and breast disorders Spermatocele	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Nervous system disorders Spinal claudication	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Musculoskeletal and connective tissue disorders Spinal disorder	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.75% 3/398 • Number of events 3 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Musculoskeletal and connective tissue disorders Spinal pain	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Musculoskeletal and connective tissue disorders Spinal stenosis	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Musculoskeletal and connective tissue disorders Spondylolisthesis	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Blood and lymphatic system disorders Spontaneous haematoma	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Vascular disorders Steal syndrome	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Injury, poisoning and procedural complications Stoma site haemorrhage	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Injury, poisoning and procedural complications Stoma site hypergranulation	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Gastrointestinal disorders Stomatitis	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Psychiatric disorders Stress	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Renal and urinary disorders Stress urinary incontinence	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Cardiac disorders Supraventricular extrasystoles	2.3% 9/398 • Number of events 9 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Cardiac disorders Supraventricular tachycardia	3.0% 12/398 • Number of events 13 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Nervous system disorders Syncope	1.0% 4/398 • Number of events 5 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.77% 3/392 • Number of events 3 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Vascular disorders Temporal arteritis	0.00% 0/398 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.26% 1/392 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.
Musculoskeletal and connective tissue disorders Tendon pain	0.25% 1/398 • Number of events 1 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.	0.00% 0/392 • 2 years and 9 months mean follow-up duration Adverse event definitions in this trial are based on ISO14155.