Trial Outcomes & Findings for Biopace Study: Biventricular Pacing for Atrioventricular Block to Prevent Cardiac Desynchronization (NCT NCT00187278)

NCT ID: NCT00187278

Last Updated: 2021-01-25

Results Overview

Number of deaths observed

Recruitment status

COMPLETED

Study phase

Target enrollment

1833 participants

Primary outcome timeframe

Study duration (5.7 years mean follow-up)

Results posted on

2021-01-25

Participant Flow

Patients were enrolled between May 2003 and September 2007.

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.

Participant milestones

Participant milestones
Measure	RV Pacing Standard Pacemaker implant RV Pacing: Standard Pacemaker implant	Biventricular Pacing Biventricular Pacemaker implant Biventricular Pacing: Biventricular Pacemaker implant
Overall Study STARTED	918	915
Overall Study COMPLETED	908	902
Overall Study NOT COMPLETED	10	13

Reasons for withdrawal

Reasons for withdrawal
Measure	RV Pacing Standard Pacemaker implant RV Pacing: Standard Pacemaker implant	Biventricular Pacing Biventricular Pacemaker implant Biventricular Pacing: Biventricular Pacemaker implant
Overall Study Protocol Violation	10	13

Baseline Characteristics

Biopace Study: Biventricular Pacing for Atrioventricular Block to Prevent Cardiac Desynchronization

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	RV Pacing n=908 Participants Standard Pacemaker implant RV Pacing: Standard Pacemaker implant	Biventricular Pacing n=902 Participants Biventricular Pacemaker implant Biventricular Pacing: Biventricular Pacemaker implant	Total n=1810 Participants Total of all reporting groups
Age, Continuous	73.3 years STANDARD_DEVIATION 9.0 • n=5 Participants	73.8 years STANDARD_DEVIATION 9.0 • n=7 Participants	73.5 years STANDARD_DEVIATION 9.2 • n=5 Participants
Sex: Female, Male Female	296 Participants n=5 Participants	278 Participants n=7 Participants	574 Participants n=5 Participants
Sex: Female, Male Male	612 Participants n=5 Participants	624 Participants n=7 Participants	1236 Participants n=5 Participants
Body mass index	27.5 kg/m^2 STANDARD_DEVIATION 4.7 • n=5 Participants	27.4 kg/m^2 STANDARD_DEVIATION 4.3 • n=7 Participants	27.4 kg/m^2 STANDARD_DEVIATION 4.5 • n=5 Participants
Ventricular pacing at 1 month	86.4 % n=5 Participants	90.2 % n=7 Participants	88.3 % n=5 Participants
Underlying cardiac diseases All	572 participants n=5 Participants	571 participants n=7 Participants	1143 participants n=5 Participants
Underlying cardiac diseases Ischaemic heart disease	274 participants n=5 Participants	274 participants n=7 Participants	548 participants n=5 Participants
Underlying cardiac diseases Hypertensive heart disease	281 participants n=5 Participants	262 participants n=7 Participants	543 participants n=5 Participants
Underlying cardiac diseases Dlated cardiomyopathy	43 participants n=5 Participants	51 participants n=7 Participants	94 participants n=5 Participants
Underlying cardiac diseases Valvulopathy	170 participants n=5 Participants	165 participants n=7 Participants	335 participants n=5 Participants
Underlying cardiac diseases Prior MI	162 participants n=5 Participants	141 participants n=7 Participants	308 participants n=5 Participants
Cardiovascular risk factor Hypertension	696 participants n=5 Participants	666 participants n=7 Participants	1362 participants n=5 Participants
Cardiovascular risk factor Diabetes mellitus	255 participants n=5 Participants	251 participants n=7 Participants	506 participants n=5 Participants
Left ventricular ejection fraction (LVEF)	55.5 % STANDARD_DEVIATION 12.4 • n=5 Participants	55.3 % STANDARD_DEVIATION 12.1 • n=7 Participants	55.4 % STANDARD_DEVIATION 12.2 • n=5 Participants
Left Ventricular Ejection Fraction (LVEF) range LVEF ≤ 35%	74 participants n=5 Participants	78 participants n=7 Participants	152 participants n=5 Participants
Left Ventricular Ejection Fraction (LVEF) range 35% < LVEF ≤ 50%	221 participants n=5 Participants	198 participants n=7 Participants	419 participants n=5 Participants
Left Ventricular Ejection Fraction (LVEF) range LVEF > 50%	613 participants n=5 Participants	626 participants n=7 Participants	1239 participants n=5 Participants
QRS duration	118.8 ms STANDARD_DEVIATION 30.3 • n=5 Participants	118.1 ms STANDARD_DEVIATION 30.8 • n=7 Participants	118.4 ms STANDARD_DEVIATION 30.5 • n=5 Participants
QRS range QRS ≤ 120ms	571 participants n=5 Participants	571 participants n=7 Participants	1142 participants n=5 Participants
QRS range 120ms < QRS ≤ 150ms	190 participants n=5 Participants	176 participants n=7 Participants	366 participants n=5 Participants
QRS range QRS > 150ms	147 participants n=5 Participants	155 participants n=7 Participants	302 participants n=5 Participants
Atrial arrhythmias Atrial arrhythmias	225 participants n=5 Participants	225 participants n=7 Participants	450 participants n=5 Participants
Atrial arrhythmias None	683 participants n=5 Participants	677 participants n=7 Participants	1360 participants n=5 Participants
Left bundle branch block (LBBB) LBBB	166 participants n=5 Participants	150 participants n=7 Participants	316 participants n=5 Participants
Left bundle branch block (LBBB) None	742 participants n=5 Participants	752 participants n=7 Participants	1494 participants n=5 Participants
Scheduled for ICD Scheduled for ICD	22 participants n=5 Participants	26 participants n=7 Participants	48 participants n=5 Participants
Scheduled for ICD Not scheduled for ICD	886 participants n=5 Participants	976 participants n=7 Participants	1762 participants n=5 Participants
Indications for device implantation Persistent bradycardia	538 participants n=5 Participants	540 participants n=7 Participants	1078 participants n=5 Participants
Indications for device implantation Intermittent bradycardia	368 participants n=5 Participants	362 participants n=7 Participants	730 participants n=5 Participants
Indications for device implantation Unknown	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants

PRIMARY outcome

Timeframe: Study duration (5.7 years mean follow-up)

Number of deaths observed

Outcome measures

Outcome measures
Measure	RV Pacing n=908 Participants Standard Pacemaker implant RV Pacing: Standard Pacemaker implant	Biventricular Pacing n=902 Participants Biventricular Pacemaker implant Biventricular Pacing: Biventricular Pacemaker implant
Total Mortality	307 Participants	305 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	RV Pacing n=908 Participants Standard Pacemaker implant RV Pacing: Standard Pacemaker implant	Biventricular Pacing n=902 Participants Biventricular Pacemaker implant Biventricular Pacing: Biventricular Pacemaker implant
Death or Heart Failure Hospitalization	346 Participants	363 Participants

SECONDARY outcome

Timeframe: 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)

Outcome measures

Outcome measures
Measure	RV Pacing n=908 Participants Standard Pacemaker implant RV Pacing: Standard Pacemaker implant	Biventricular Pacing n=902 Participants Biventricular Pacemaker implant Biventricular Pacing: Biventricular Pacemaker implant
Death Due to Cardiovascular Causes	106 Participants	107 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	RV Pacing n=672 Participants Standard Pacemaker implant RV Pacing: Standard Pacemaker implant	Biventricular Pacing n=675 Participants Biventricular Pacemaker implant Biventricular Pacing: Biventricular Pacemaker implant
Functional Capacity as Measured by the Distance Covered in the 6-minute Walk Test	371.3 meters Standard Deviation 128.8	371.2 meters Standard Deviation 129.1

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	RV Pacing n=724 Participants Standard Pacemaker implant RV Pacing: Standard Pacemaker implant	Biventricular Pacing n=715 Participants Biventricular Pacemaker implant Biventricular Pacing: Biventricular Pacemaker implant
Health Related Quality of Life Measured by the Minnesota Living With Heart Failure Questionnaire©	16.0 score on a scale Standard Deviation 15.4	15.3 score on a scale Standard Deviation 15.5

SECONDARY outcome

Timeframe: Study duration (5.7 years mean follow-up)

Outcome measures

Outcome measures
Measure	RV Pacing n=899 Participants Standard Pacemaker implant RV Pacing: Standard Pacemaker implant	Biventricular Pacing n=888 Participants Biventricular Pacemaker implant Biventricular Pacing: Biventricular Pacemaker implant
Incidence of Hospitalizations for Deterioration of Heart Failure	0.043 hospitalization per patient year	0.037 hospitalization per patient year

SECONDARY outcome

Timeframe: Study duration (5.7 years mean follow-up)

Outcome measures

Outcome measures
Measure	RV Pacing n=899 Participants Standard Pacemaker implant RV Pacing: Standard Pacemaker implant	Biventricular Pacing n=888 Participants Biventricular Pacemaker implant Biventricular Pacing: Biventricular Pacemaker implant
Incidence of Hospitalizations for Cardiovascular Events	0.162 hospitalizations per patient year	0.161 hospitalizations per patient year

SECONDARY outcome

Timeframe: Study duration (5.7 years mean follow-up)

Outcome measures

Outcome measures
Measure	RV Pacing n=899 Participants Standard Pacemaker implant RV Pacing: Standard Pacemaker implant	Biventricular Pacing n=888 Participants Biventricular Pacemaker implant Biventricular Pacing: Biventricular Pacemaker implant
Incidence of Hospitalizations for Any Reason	0.392 Hospitalization per patient year	0.432 Hospitalization per patient year

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Implantation

Population: There was an attempt of left ventricular lead implantation only for subjects from Biventricular Pacing group.

Outcome measures

Outcome measures
Measure	RV Pacing Standard Pacemaker implant RV Pacing: Standard Pacemaker implant	Biventricular Pacing n=883 Participants Biventricular Pacemaker implant Biventricular Pacing: Biventricular Pacemaker implant
Successful Implantation of the Left Ventricular Lead	—	760 participants

SECONDARY outcome

Timeframe: Study duration (5.7 years mean follow-up)

Chronic atrial fibrillation is defined as presence of atrial fibrillation in two subsequent ECG´s/visits.

Outcome measures

Outcome measures
Measure	RV Pacing n=908 Participants Standard Pacemaker implant RV Pacing: Standard Pacemaker implant	Biventricular Pacing n=902 Participants Biventricular Pacemaker implant Biventricular Pacing: Biventricular Pacemaker implant
Chronic Atrial Fibrillation (Defined as Presence of Atrial Fibrillation in Two Subsequent ECG´s/Visits)	91 participants	76 participants

SECONDARY outcome

Timeframe: 24 months post-implant

Outcome measures

Outcome measures
Measure	RV Pacing n=614 Participants Standard Pacemaker implant RV Pacing: Standard Pacemaker implant	Biventricular Pacing n=592 Participants Biventricular Pacemaker implant Biventricular Pacing: Biventricular Pacemaker implant
Functional Capacity as Measured by the Distance Covered in the 6-minute Walk Test	369.3 meters Standard Deviation 127.2	376.5 meters Standard Deviation 132.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	RV Pacing n=662 Participants Standard Pacemaker implant RV Pacing: Standard Pacemaker implant	Biventricular Pacing n=675 Participants Biventricular Pacemaker implant Biventricular Pacing: Biventricular Pacemaker implant
Health Related Quality of Life Measured by the Minnesota Living With Heart Failure Questionnaire©	17.5 score on a scale Standard Deviation 17.6	17.3 score on a scale Standard Deviation 16.6

SECONDARY outcome

Timeframe: Study Duration (5.7 years mean follow-up)

Outcome measures

Outcome measures
Measure	RV Pacing n=899 Participants Standard Pacemaker implant RV Pacing: Standard Pacemaker implant	Biventricular Pacing n=888 Participants Biventricular Pacemaker implant Biventricular Pacing: Biventricular Pacemaker implant
Duration of Hospitalizations for Deterioration of Heart Failure	0.40 days per patient year	0.39 days per patient year

SECONDARY outcome

Timeframe: Study Duration (5.7 years mean follow-up)

Outcome measures

Outcome measures
Measure	RV Pacing n=899 Participants Standard Pacemaker implant RV Pacing: Standard Pacemaker implant	Biventricular Pacing n=888 Participants Biventricular Pacemaker implant Biventricular Pacing: Biventricular Pacemaker implant
Duration of Hospitalizations for Cardiovascular Events	1.52 Days per patient year	1.50 Days per patient year

SECONDARY outcome

Timeframe: Study duration (5.7 years mean follow-up)

Outcome measures

Outcome measures
Measure	RV Pacing n=899 Participants Standard Pacemaker implant RV Pacing: Standard Pacemaker implant	Biventricular Pacing n=888 Participants Biventricular Pacemaker implant Biventricular Pacing: Biventricular Pacemaker implant
Duration of Hospitalizations for Any Reason	3.72 days per patient year	4.14 days per patient year

SECONDARY outcome

Timeframe: Study Duration (5.7 years mean follow-up)

Only serious adverse events related to the left ventricular lead are included.

Outcome measures

Outcome measures
Measure	RV Pacing n=908 Participants Standard Pacemaker implant RV Pacing: Standard Pacemaker implant	Biventricular Pacing n=902 Participants Biventricular Pacemaker implant Biventricular Pacing: Biventricular Pacemaker implant
Adverse Events Related to Left Ventricular Lead	1 participants	38 participants

Adverse Events

RV Pacing

Serious events: 641 serious events

Other events: 451 other events

Deaths: 307 deaths

Biventricular Pacing

Serious events: 698 serious events

Other events: 507 other events

Deaths: 305 deaths

Serious adverse events

Other adverse events

Additional Information

Pascale Ducloux, Clinical Manager

St Jude Medical

Phone: +3227746709

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	RV Pacing n=908 participants at risk Standard Pacemaker implant	Biventricular Pacing n=902 participants at risk Biventricular Pacemaker implant
Blood and lymphatic system disorders Anemia	1.5% 14/908 • Number of events 19 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	1.6% 14/902 • Number of events 16 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Blood and lymphatic system disorders Epistaxis	0.33% 3/908 • Number of events 3 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.22% 2/902 • Number of events 2 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Blood and lymphatic system disorders Haemoptysis	0.11% 1/908 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.00% 0/902 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Blood and lymphatic system disorders Hematochezia	0.11% 1/908 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.00% 0/902 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Blood and lymphatic system disorders Hypercalcemia	0.22% 2/908 • Number of events 2 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.00% 0/902 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Blood and lymphatic system disorders Hyperkalemia	0.11% 1/908 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.11% 1/902 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Blood and lymphatic system disorders Hyponatremia	0.00% 0/908 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.11% 1/902 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Blood and lymphatic system disorders Thromboemboli	0.22% 2/908 • Number of events 2 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.67% 6/902 • Number of events 6 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders AV Fistula	0.11% 1/908 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.33% 3/902 • Number of events 5 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Acute Coronary Syndrome	0.55% 5/908 • Number of events 7 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.11% 1/902 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Angina	0.11% 1/908 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.11% 1/902 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Arrhythmia	5.3% 48/908 • Number of events 56 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	6.0% 54/902 • Number of events 75 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Bradycardia	0.33% 3/908 • Number of events 3 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.00% 0/902 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Cardiac arrest	0.22% 2/908 • Number of events 2 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.22% 2/902 • Number of events 3 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Cardiomyopathy	0.11% 1/908 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.11% 1/902 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Chest Pain	5.5% 50/908 • Number of events 68 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	5.3% 48/902 • Number of events 63 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Dyspnea	5.1% 46/908 • Number of events 71 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	6.7% 60/902 • Number of events 74 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Endocarditis	0.22% 2/908 • Number of events 2 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.55% 5/902 • Number of events 7 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Exacerbation of heart failure	14.5% 132/908 • Number of events 179 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	11.4% 103/902 • Number of events 144 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Hypertension	1.4% 13/908 • Number of events 16 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	2.0% 18/902 • Number of events 20 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Hypertrophic obstructive cardiomyopathy	0.00% 0/908 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.11% 1/902 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Hypotension	0.55% 5/908 • Number of events 5 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.55% 5/902 • Number of events 5 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Mitral Regurgitation	0.11% 1/908 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.00% 0/902 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Myocardial infarction	3.2% 29/908 • Number of events 34 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	2.9% 26/902 • Number of events 26 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Palpitations	0.11% 1/908 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.33% 3/902 • Number of events 3 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Rise in threshold and exit block	1.3% 12/908 • Number of events 12 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	2.4% 22/902 • Number of events 24 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Shortness of Breath	0.44% 4/908 • Number of events 4 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.33% 3/902 • Number of events 3 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Valve damage	2.9% 26/908 • Number of events 36 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	2.0% 18/902 • Number of events 19 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Congenital, familial and genetic disorders Lowry Wood Syndrome	0.11% 1/908 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.00% 0/902 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Ear and labyrinth disorders Vertigo	0.00% 0/908 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.44% 4/902 • Number of events 4 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Endocrine disorders Diabetes	1.1% 10/908 • Number of events 13 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	1.3% 12/902 • Number of events 12 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Endocrine disorders Glycemia	0.00% 0/908 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.22% 2/902 • Number of events 2 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Endocrine disorders Hyperglycemia	0.22% 2/908 • Number of events 2 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.44% 4/902 • Number of events 4 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Endocrine disorders Hypoglycemia	0.33% 3/908 • Number of events 5 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.55% 5/902 • Number of events 6 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Eye disorders Cataract	0.22% 2/908 • Number of events 3 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.11% 1/902 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Eye disorders Galucoma	0.11% 1/908 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.11% 1/902 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Eye disorders Macular Degeneration	0.00% 0/908 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.11% 1/902 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Gastrointestinal disorders Cholangitis	0.00% 0/908 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.11% 1/902 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Gastrointestinal disorders Constipation	0.11% 1/908 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.22% 2/902 • Number of events 2 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Gastrointestinal disorders Diverticulitis	0.11% 1/908 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.00% 0/902 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.

Other adverse events
Measure	RV Pacing n=908 participants at risk Standard Pacemaker implant	Biventricular Pacing n=902 participants at risk Biventricular Pacemaker implant
Blood and lymphatic system disorders Anemia	0.55% 5/908 • Number of events 5 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.44% 4/902 • Number of events 4 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Blood and lymphatic system disorders Bicytopenia	0.00% 0/908 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.11% 1/902 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Blood and lymphatic system disorders Epistaxis	0.11% 1/908 • Number of events 2 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.33% 3/902 • Number of events 3 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Blood and lymphatic system disorders Hematochezia	0.11% 1/908 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.00% 0/902 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Blood and lymphatic system disorders Hypereosinophilia	0.00% 0/908 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.11% 1/902 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Blood and lymphatic system disorders Hyperkalemia	0.11% 1/908 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.00% 0/902 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Blood and lymphatic system disorders Thromboemboli	0.33% 3/908 • Number of events 3 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.55% 5/902 • Number of events 5 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Acute Coronary Syndrome	0.11% 1/908 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.11% 1/902 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Arrhythmia	10.6% 96/908 • Number of events 119 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	11.9% 107/902 • Number of events 135 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Arteritis	0.00% 0/908 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.11% 1/902 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Bigeminy	0.00% 0/908 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.11% 1/902 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Cardiac arrest	0.00% 0/908 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.11% 1/902 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Chest Pain	2.6% 24/908 • Number of events 29 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	3.4% 31/902 • Number of events 43 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Dyspnea	4.2% 38/908 • Number of events 47 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	5.2% 47/902 • Number of events 55 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Exacerbation of heart failure	2.5% 23/908 • Number of events 24 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	2.5% 23/902 • Number of events 23 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Heart block	0.11% 1/908 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.00% 0/902 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Hypertension	0.88% 8/908 • Number of events 9 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	1.4% 13/902 • Number of events 15 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Hypotension	0.77% 7/908 • Number of events 9 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.89% 8/902 • Number of events 8 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Mitral Regurgitation	0.00% 0/908 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.22% 2/902 • Number of events 2 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Myocardial infarction	0.99% 9/908 • Number of events 9 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.44% 4/902 • Number of events 4 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Palpitations	0.77% 7/908 • Number of events 8 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.44% 4/902 • Number of events 6 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Percutaneous Coronary Intervention	0.00% 0/908 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.11% 1/902 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Rise in threshold and exit block	1.3% 12/908 • Number of events 12 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	3.0% 27/902 • Number of events 31 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Shortness of Breath	1.2% 11/908 • Number of events 11 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.78% 7/902 • Number of events 9 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Cardiac disorders Valve damage	1.1% 10/908 • Number of events 14 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.44% 4/902 • Number of events 4 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Ear and labyrinth disorders Tinnitus	0.00% 0/908 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.11% 1/902 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Ear and labyrinth disorders Vertigo	0.33% 3/908 • Number of events 3 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.22% 2/902 • Number of events 3 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Endocrine disorders Diabetes	1.3% 12/908 • Number of events 12 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	1.4% 13/902 • Number of events 14 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Endocrine disorders Hyperlipidemia	0.22% 2/908 • Number of events 2 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.11% 1/902 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Endocrine disorders Hypoglycemia	0.11% 1/908 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.11% 1/902 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Endocrine disorders Toxic multinodular goitre	0.11% 1/908 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.00% 0/902 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Eye disorders Cataract	0.77% 7/908 • Number of events 7 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.55% 5/902 • Number of events 7 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Eye disorders Galucoma	0.00% 0/908 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.22% 2/902 • Number of events 2 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Eye disorders Macular Degeneration	0.00% 0/908 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.11% 1/902 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Gastrointestinal disorders Constipation	0.11% 1/908 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.33% 3/902 • Number of events 3 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Gastrointestinal disorders Diverticulitis	0.22% 2/908 • Number of events 2 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.00% 0/902 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Gastrointestinal disorders Nausea	0.11% 1/908 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.11% 1/902 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Gastrointestinal disorders Pancreatitis	0.22% 2/908 • Number of events 2 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.00% 0/902 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Gastrointestinal disorders Ulcer	0.33% 3/908 • Number of events 3 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.00% 0/902 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.
Gastrointestinal disorders Abdominal pain	0.11% 1/908 • Number of events 1 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.	0.00% 0/902 • Study duration (5.7 years mean follow-up) The sponsor assessed all events except the death cases without further information, duplicate events and uncomplicated device replacement due to end of life. 5628 events were reviewed and assessed by the sponsor. Subjects may experience more than one adverse event.