MINERVA: MINimizE Right Ventricular Pacing to Prevent Atrial Fibrillation and Heart Failure

• Sponsor: Medtronic Bakken Research Center (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00262119
• Collaborator: (none)
• Enrollment: 1,300
• Location: 1
• Arms: 3
• Duration (Months): 85.9
• Patients Per Site Per Month: 15.1

Study Details

Study Description

Brief Summary

The aim of this study is to test the impact of the managed ventricular pacing (MVP) mode and atrial preventive and antitachycardia pacing therapies on the reduction of a composite clinical outcome composed of any death, permanent atrial fibrillation, and cardiovascular hospitalizations.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation; Heart Failure, Congestive	Device: Pacemaker Medtronic EnRhythm	Phase 4

Detailed Description

Kristensen et al. reported that AAIR pacing reduces atrial fibrillation (AF) development compared to DDDR pacing in sinus node disfunction patients.

Several authors have shown that, in patients with intact AV conduction, unnecessary chronic RV pacing can cause detrimental effects such as AF, left ventricular (LV) dysfunction and congestive heart failure. These findings arose the hypothesis that the non-physiologic nature of ventricular pacing may result in electrophysiological and LV remodeling changes that have potentially deleterious long-term effects.

The MVP mode, present in the Medtronic pacemaker EnRhythm, provides atrial based pacing with ventricular backup. It operates in true AAI(R) mode, it provides ventricular backup in case of a single conduction loss and converts to DDD(R) mode in case of persistent loss of AV conduction.

Aim of this study is to test the impact of the MVP pacing mode and atrial preventive and antitachycardia pacing therapies on the reduction of a composite clinical outcome composed by any death, permanent AF, cardiovascular hospitalizations.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Prevention
• Official Title: MINERVA: MINimizE Right Ventricular Pacing to Prevent Atrial Fibrillation and Heart Failure
• Study Start Date: Feb 1, 2006
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Apr 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Control Group PM programming according to actual clinical practice	Device: Pacemaker Medtronic EnRhythm; Pacemaker specific programming
Active Comparator: MVP Only PM programming according to actual clinical practice + MVP algorithm ON	Device: Pacemaker Medtronic EnRhythm; Pacemaker specific programming
Active Comparator: DDDRP PM programming according to actual clinical practice + MVP algorithm ON + Atrial fibrillation therapies ON	Device: Pacemaker Medtronic EnRhythm; Pacemaker specific programming

Outcome Measures

Primary Outcome Measures

1. Composite Endpoint Composed by Death for Any Cause, Cardiovascular Hospitalization or Permanent AF at 2 Years [2 years]

   The outcome measurement is the 2 years incidence, calculated by Kaplan Meier survival analysis, of the composite endpoint composed by death for any cause, cardiovascular hospitalization or permanent AF.

Secondary Outcome Measures

1. Death for All Causes at 2 Years [2 years]

   Incidence, estimated via Kaplan Meier survival analysis, of death for any cause at 2 years

2. Incidence of Permanent Atrial Fibrillation at 2 Years [2 years]

   Incidence, estimated via Kaplan Meier survival analysis, of permanent atrial fibrillation at 2 years

3. Incidence of Cardiovascular Hospitalizations at 2 Years [2 years]

   Incidence, estimated via Kaplan Meier survival analysis, of cardiovascular hospitalizations at 2 years

4. Burden of Composite Clinical Endpoint [2 years]

5. Subjects' Symptoms [2 years]

6. Heart Failure Medications [2 years]

7. Cumulative Percentage of Ventricular Pacing [2 years]

8. Cardiovascular Death [2 years]

9. Any Hospitalization [2 years]

10. Atrial Fibrillation Burden [2 years]

11. Persistent Atrial Fibrillation (AF) [2 years]

12. Adverse Events [2 years]

13. Development of Atrioventricular (AV) Block and Pacemaker Dependency [2 years]

14. Predictors of Stroke, Transient Ischemic Attack (TIA) and Arterial Embolism [2 years]

15. Echocardiogram Data About Left Ventricular Fractional Shortening and Ejection Fraction and Left Atrium Dilatation [2 years]

16. Clinical Outcome in All the Patients With MVP ON Between Patients With Optimized AV-delay and Patients Without Optimized AV-delay [2 years]

17. Time to Development of the Composite Endpoint Between All Randomized Subjects in the Three Arms in Subgroups of Patients [2 years]

18. Frequency, Type, and Associated Cost of Health Care Utilization and Utility [2 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Class I/Class II indications for dual chamber pacing

• Previous implant of an EnRhythm dual chamber implantable pulse generator (IPG) since maximum 2 weeks

• History of atrial arrhythmias (at least one electrocardiogram [ECG] or Holter documented episodes in the last 12 months)

Exclusion Criteria:

• Less than 18 years of age

• Pregnancy

• Unwilling or unable to give informed consent or to commit to follow-up schedule

• Medical conditions that preclude protocol required testing or limit study participation

• Enrolled or intend to participate in another clinical trial during the course of this study

• A life expectancy of less than 2 years

• Patient is a candidate for an implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT) device implant

• Anticipated major cardiac surgery within the course of this study

• Permanent III degree AV-block or history of AV node ablation

• History of permanent AF (as defined below)

• AF ablation (left pulmonary veins) or other cardiac surgery < 3 months

• Prior implant of defibrillator device or pacemaker (apart from EnRhythm IPG implanted within two weeks)

• Uncontrolled hyperthyroidism

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medtronic Italia S.p.A.	Rome		Italy	00193

Sponsors and Collaborators

• Medtronic Bakken Research Center

Investigators

• Principal Investigator: Luigi Padeletti, Prof., Ospedale Careggi - Firenze
• Principal Investigator: Giuseppe Boriani, Dr., Ospedale Sant'Orsola - Bologna
• Principal Investigator: Luis Mont, Dr., Hospital Clinic of Barcelona
• Principal Investigator: Reinhard C Funck, Dr., Philipps University Hospital - Marburg
• Principal Investigator: Carsten W Israel, Dr., J. W. Goethe University Hospital - Frankfurt
• Principal Investigator: Helmut Pürerfellner, Dr., Elisabethinen Hospital
• Principal Investigator: Antonis S Manolis, Prof., Evagelismos Hospital - Athens
• Principal Investigator: André Pisapia, Dr, Hôpital Saint-Joseph - Marseille
• Principal Investigator: Raymond Tukkie, Dr, Kennemer Gasthuis

Study Documents (Full-Text)

None provided.

More Information

Publications

• Andersen HR, Nielsen JC, Thomsen PE, Thuesen L, Mortensen PT, Vesterlund T, Pedersen AK. Long-term follow-up of patients from a randomised trial of atrial versus ventricular pacing for sick-sinus syndrome. Lancet. 1997 Oct 25;350(9086):1210-6.
• Connolly SJ, Kerr CR, Gent M, Roberts RS, Yusuf S, Gillis AM, Sami MH, Talajic M, Tang AS, Klein GJ, Lau C, Newman DM. Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes. Canadian Trial of Physiologic Pacing Investigators. N Engl J Med. 2000 May 11;342(19):1385-91.
• Kristensen L, Nielsen JC, Mortensen PT, Pedersen OL, Pedersen AK, Andersen HR. Incidence of atrial fibrillation and thromboembolism in a randomised trial of atrial versus dual chamber pacing in 177 patients with sick sinus syndrome. Heart. 2004 Jun;90(6):661-6.
• Lamas GA, Lee KL, Sweeney MO, Silverman R, Leon A, Yee R, Marinchak RA, Flaker G, Schron E, Orav EJ, Hellkamp AS, Greer S, McAnulty J, Ellenbogen K, Ehlert F, Freedman RA, Estes NA 3rd, Greenspon A, Goldman L; Mode Selection Trial in Sinus-Node Dysfunction. Ventricular pacing or dual-chamber pacing for sinus-node dysfunction. N Engl J Med. 2002 Jun 13;346(24):1854-62.
• Mattioli AV, Vivoli D, Mattioli G. Influence of pacing modalities on the incidence of atrial fibrillation in patients without prior atrial fibrillation. A prospective study. Eur Heart J. 1998 Feb;19(2):282-6.
• Nielsen JC, Andersen HR, Thomsen PE, Thuesen L, Mortensen PT, Vesterlund T, Pedersen AK. Heart failure and echocardiographic changes during long-term follow-up of patients with sick sinus syndrome randomized to single-chamber atrial or ventricular pacing. Circulation. 1998 Mar 17;97(10):987-95.
• Nielsen JC, Kristensen L, Andersen HR, Mortensen PT, Pedersen OL, Pedersen AK. A randomized comparison of atrial and dual-chamber pacing in 177 consecutive patients with sick sinus syndrome: echocardiographic and clinical outcome. J Am Coll Cardiol. 2003 Aug 20;42(4):614-23.

• Responsible Party: Medtronic Bakken Research Center
• ClinicalTrials.gov Identifier: NCT00262119
• Other Study ID Numbers: MNV-20-171005
• First Posted: Dec 6, 2005
• Last Update Posted: Apr 21, 2016
• Last Verified: Mar 1, 2016

• Keywords provided by Medtronic Bakken Research Center: Physiological pacing; Antitachycardia pacing therapies
• Additional relevant MeSH terms: Heart Failure; Atrial Fibrillation

Study Results

Participant Flow

Recruitment Details	The recruitment period was between February 2006 and April 2010. Patients were enrolled in cardiology departments.
Pre-assignment Detail	A total of 1300 patients were enrolled in the study. Enrollment was followed by a 1-month run-in period. Patients with ventricular pacing ≥ 95% on device check in the run-in period were excluded from the study. At the end of the run-in period, randomization was performed. In all, 1166 patients were randomized and followed up.

Arm/Group Title	Control Group	MVP Only	DDDRP
Arm/Group Description	PM programming according to actual clinical practice Pacemaker Medtronic EnRhythm: Pacemaker specific programming	PM programming according to actual clinical practice + MVP algorithm ON Pacemaker Medtronic EnRhythm: Pacemaker specific programming	PM programming according to actual clinical practice + MVP algorithm ON + Atrial fibrillation therapies ON Pacemaker Medtronic EnRhythm: Pacemaker specific programming
Period Title: Overall Study
STARTED	385	398	383
COMPLETED	327	328	325
NOT COMPLETED	58	70	58

Baseline Characteristics

Arm/Group Title	Control Group	MVP Only	DDDRP	Total
Arm/Group Description	PM programming according to actual clinical practice Pacemaker Medtronic EnRhythm: Pacemaker specific programming	PM programming according to actual clinical practice + MVP algorithm ON Pacemaker Medtronic EnRhythm: Pacemaker specific programming	PM programming according to actual clinical practice + MVP algorithm ON + Atrial fibrillation therapies ON Pacemaker Medtronic EnRhythm: Pacemaker specific programming	Total of all reporting groups
Overall Participants	385	398	383	1166
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	73 (9)	74 (9)	74 (9)	74 (9)
Sex: Female, Male (Count of Participants)
Female	180 46.8%	188 47.2%	210 54.8%	578 49.6%
Male	205 53.2%	210 52.8%	173 45.2%	588 50.4%
Region of Enrollment (participants) [Number]
Italy	203 52.7%	211 53%	202 52.7%	616 52.8%
Netherlands	41 10.6%	43 10.8%	39 10.2%	123 10.5%
Spain	16 4.2%	18 4.5%	17 4.4%	51 4.4%
Portugal	43 11.2%	44 11.1%	44 11.5%	131 11.2%
Austria	15 3.9%	14 3.5%	15 3.9%	44 3.8%
France	0 0%	1 0.3%	1 0.3%	2 0.2%
Germany	8 2.1%	5 1.3%	3 0.8%	16 1.4%
Greece	23 6%	25 6.3%	25 6.5%	73 6.3%
Hong Kong	1 0.3%	1 0.3%	1 0.3%	3 0.3%
Israel	7 1.8%	7 1.8%	8 2.1%	22 1.9%
Kuwait	2 0.5%	4 1%	3 0.8%	9 0.8%
Russian Federation	10 2.6%	11 2.8%	9 2.3%	30 2.6%
Slovakia	5 1.3%	5 1.3%	6 1.6%	16 1.4%
Switzerland	9 2.3%	7 1.8%	7 1.8%	23 2%
Taiwan	2 0.5%	2 0.5%	3 0.8%	7 0.6%

Outcome Measures

1. Secondary Outcome

Title	Death for All Causes at 2 Years
Description	Incidence, estimated via Kaplan Meier survival analysis, of death for any cause at 2 years
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

The analysis was intention to treat therefore all randomized patients were included in the analysis

Arm/Group Title	Control Group	MVP Only	DDDRP
Arm/Group Description	PM programming according to actual clinical practice Pacemaker Medtronic EnRhythm: Pacemaker specific programming	PM programming according to actual clinical practice + MVP algorithm ON Pacemaker Medtronic EnRhythm: Pacemaker specific programming	PM programming according to actual clinical practice + MVP algorithm ON + Atrial fibrillation therapies ON Pacemaker Medtronic EnRhythm: Pacemaker specific programming
Measure Participants	383	398	383
Number (95% Confidence Interval) [percentage of participants]	5.6 1.5%	5.1 1.3%	4.6 1.2%

2. Secondary Outcome

Title	Incidence of Permanent Atrial Fibrillation at 2 Years
Description	Incidence, estimated via Kaplan Meier survival analysis, of permanent atrial fibrillation at 2 years
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

The analysis was intention to treat therefore all randomized patients were analysed

Arm/Group Title	Control Group	MVP Only	DDDRP
Arm/Group Description	PM programming according to actual clinical practice Pacemaker Medtronic EnRhythm: Pacemaker specific programming	PM programming according to actual clinical practice + MVP algorithm ON Pacemaker Medtronic EnRhythm: Pacemaker specific programming	PM programming according to actual clinical practice + MVP algorithm ON + Atrial fibrillation therapies ON Pacemaker Medtronic EnRhythm: Pacemaker specific programming
Measure Participants	383	398	385
Number (95% Confidence Interval) [percentage of participants]	9.2 2.4%	7.7 1.9%	3.8 1%

3. Secondary Outcome

Title	Incidence of Cardiovascular Hospitalizations at 2 Years
Description	Incidence, estimated via Kaplan Meier survival analysis, of cardiovascular hospitalizations at 2 years
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Analysis was intention to treat therefore all randomized patients were analysed

Arm/Group Title	Control Group	MVP Only	DDDRP
Arm/Group Description	PM programming according to actual clinical practice Pacemaker Medtronic EnRhythm: Pacemaker specific programming	PM programming according to actual clinical practice + MVP algorithm ON Pacemaker Medtronic EnRhythm: Pacemaker specific programming	PM programming according to actual clinical practice + MVP algorithm ON + Atrial fibrillation therapies ON Pacemaker Medtronic EnRhythm: Pacemaker specific programming
Measure Participants	383	398	385
Number (95% Confidence Interval) [percentage of participants]	16.8 4.4%	13.7 3.4%	15.2 4%

4. Secondary Outcome

Title	Burden of Composite Clinical Endpoint
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Subjects' Symptoms
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Heart Failure Medications
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Cumulative Percentage of Ventricular Pacing
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Cardiovascular Death
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	Any Hospitalization
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Secondary Outcome

Title	Atrial Fibrillation Burden
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Secondary Outcome

Title	Persistent Atrial Fibrillation (AF)
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Secondary Outcome

Title	Adverse Events
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

13. Secondary Outcome

Title	Development of Atrioventricular (AV) Block and Pacemaker Dependency
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

14. Secondary Outcome

Title	Predictors of Stroke, Transient Ischemic Attack (TIA) and Arterial Embolism
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

15. Secondary Outcome

Title	Echocardiogram Data About Left Ventricular Fractional Shortening and Ejection Fraction and Left Atrium Dilatation
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

16. Secondary Outcome

Title	Clinical Outcome in All the Patients With MVP ON Between Patients With Optimized AV-delay and Patients Without Optimized AV-delay
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

17. Secondary Outcome

Title	Time to Development of the Composite Endpoint Between All Randomized Subjects in the Three Arms in Subgroups of Patients
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

18. Secondary Outcome

Title	Frequency, Type, and Associated Cost of Health Care Utilization and Utility
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

19. Primary Outcome

Title	Composite Endpoint Composed by Death for Any Cause, Cardiovascular Hospitalization or Permanent AF at 2 Years
Description	The outcome measurement is the 2 years incidence, calculated by Kaplan Meier survival analysis, of the composite endpoint composed by death for any cause, cardiovascular hospitalization or permanent AF.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Analysis was intention to treat therefore all randomized patients were considered in the analyses

Arm/Group Title	Control Group	MVP Only	DDDRP
Arm/Group Description	PM programming according to actual clinical practice Pacemaker Medtronic EnRhythm: Pacemaker specific programming	PM programming according to actual clinical practice + MVP algorithm ON Pacemaker Medtronic EnRhythm: Pacemaker specific programming	PM programming according to actual clinical practice + MVP algorithm ON + Atrial fibrillation therapies ON Pacemaker Medtronic EnRhythm: Pacemaker specific programming
Measure Participants	385	398	383
Number (95% Confidence Interval) [percentage of participants]	28.0 7.3%	23.1 5.8%	21.5 5.6%

Adverse Events

Arm/Group Title	Control Group		MVP Only		DDDRP
Arm/Group Description	PM programming according to actual clinical practice Pacemaker Medtronic EnRhythm: Pacemaker specific programming		PM programming according to actual clinical practice + MVP algorithm ON Pacemaker Medtronic EnRhythm: Pacemaker specific programming		PM programming according to actual clinical practice + MVP algorithm ON + Atrial fibrillation therapies ON Pacemaker Medtronic EnRhythm: Pacemaker specific programming
All Cause Mortality
	Control Group		MVP Only		DDDRP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Control Group		MVP Only		DDDRP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	180/385 (46.8%)		165/398 (41.5%)		169/383 (44.1%)
Blood and lymphatic system disorders
Anemia	0/385 (0%)	0	4/398 (1%)	4	0/383 (0%)	0
Coagulation problem	0/385 (0%)	0	1/398 (0.3%)	1	0/383 (0%)	0
Cardiac disorders
Acute Cornary Syndrome/Acute Myocardial Infarction	7/385 (1.8%)	8	5/398 (1.3%)	6	5/383 (1.3%)	5
Atrial Arrhythmia	42/385 (10.9%)	58	50/398 (12.6%)	71	38/383 (9.9%)	42
AV conduction disorders	0/385 (0%)	0	1/398 (0.3%)	1	0/383 (0%)	0
Cardiac death	7/385 (1.8%)	7	8/398 (2%)	8	8/383 (2.1%)	8
General cardiovascular disorders	2/385 (0.5%)	2	0/398 (0%)	0	2/383 (0.5%)	2
Heart Failure	13/385 (3.4%)	17	13/398 (3.3%)	16	13/383 (3.4%)	16
Sudden Cardiac Arrest	4/385 (1%)	4	6/398 (1.5%)	6	3/383 (0.8%)	3
Sympthoms of chest pain, angina, palpitation, dyspnea on exertion or cardiopalmo	13/385 (3.4%)	16	7/398 (1.8%)	9	8/383 (2.1%)	8
Ventricular Tachycardia or Fibrillation	1/385 (0.3%)	1	1/398 (0.3%)	1	6/383 (1.6%)	6
Endocrine disorders
Glucose metabolism disorders	3/385 (0.8%)	3	3/398 (0.8%)	3	2/383 (0.5%)	2
Hyperthyroidism	1/385 (0.3%)	1	0/398 (0%)	0	1/383 (0.3%)	1
Eye disorders
Eye disease	1/385 (0.3%)	1	0/398 (0%)	0	3/383 (0.8%)	3
Gastrointestinal disorders
Gastrointestinal disorders	10/385 (2.6%)	16	5/398 (1.3%)	6	7/383 (1.8%)	8
General disorders
Death for non cardiac reason	10/385 (2.6%)	10	15/398 (3.8%)	15	8/383 (2.1%)	8
Death for unknown causes	15/385 (3.9%)	15	13/398 (3.3%)	13	25/383 (6.5%)	25
Hemorrage	7/385 (1.8%)	10	6/398 (1.5%)	7	5/383 (1.3%)	5
Hypertension	3/385 (0.8%)	3	4/398 (1%)	4	1/383 (0.3%)	1
Other general disorders	20/385 (5.2%)	24	14/398 (3.5%)	14	14/383 (3.7%)	16
Syncope	4/385 (1%)	4	4/398 (1%)	4	8/383 (2.1%)	8
Hepatobiliary disorders
Gallbladdert disorder	4/385 (1%)	4	0/398 (0%)	0	1/383 (0.3%)	3
Hepatic disorder	1/385 (0.3%)	1	1/398 (0.3%)	1	1/383 (0.3%)	1
Infections and infestations
Infection and infestations	3/385 (0.8%)	4	4/398 (1%)	4	4/383 (1%)	5
Injury, poisoning and procedural complications
Consequences of drugs administration	4/385 (1%)	4	1/398 (0.3%)	1	3/383 (0.8%)	3
Lead dislodgement	17/385 (4.4%)	19	18/398 (4.5%)	19	15/383 (3.9%)	15
Pacemaker/Lead related complications	5/385 (1.3%)	5	3/398 (0.8%)	4	4/383 (1%)	4
Ureteral catheter dysfunction or dislodgement	1/385 (0.3%)	10	0/398 (0%)	0	0/383 (0%)	0
Investigations
Enteroscopy, colonoscopy or video capsule endoscopy procedure	2/385 (0.5%)	3	0/398 (0%)	0	0/383 (0%)	0
Musculoskeletal and connective tissue disorders
Muscoloskeletal disease	23/385 (6%)	33	5/398 (1.3%)	5	10/383 (2.6%)	11
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasia	8/385 (2.1%)	11	7/398 (1.8%)	7	4/383 (1%)	4
Renal and urinary disorders
Prostate disorder	3/385 (0.8%)	3	2/398 (0.5%)	2	0/383 (0%)	0
Renal or urinary disease	4/385 (1%)	4	7/398 (1.8%)	9	3/383 (0.8%)	4
Respiratory, thoracic and mediastinal disorders
Acute Pulmonary Edema	1/385 (0.3%)	1	2/398 (0.5%)	2	3/383 (0.8%)	3
Bronchitis	3/385 (0.8%)	6	1/398 (0.3%)	1	1/383 (0.3%)	1
Cronic Obstructive Pulmonary Disease	0/385 (0%)	0	2/398 (0.5%)	4	1/383 (0.3%)	2
Other respiratory, thoracic and mediastinal disorders	3/385 (0.8%)	3	8/398 (2%)	8	8/383 (2.1%)	8
Pneumonia	5/385 (1.3%)	6	7/398 (1.8%)	10	3/383 (0.8%)	3
Symptoms of dyspnea, shortness of breath, fatigue, cough and or tachypnea	3/385 (0.8%)	3	4/398 (1%)	7	4/383 (1%)	4
Surgical and medical procedures
Ablation	2/385 (0.5%)	2	2/398 (0.5%)	2	3/383 (0.8%)	3
Coronary Artery Bypass Graft	3/385 (0.8%)	3	1/398 (0.3%)	1	0/383 (0%)	0
Other cardiac surgical interventions	2/385 (0.5%)	3	3/398 (0.8%)	3	4/383 (1%)	4
Other surgical interventions	9/385 (2.3%)	11	21/398 (5.3%)	22	16/383 (4.2%)	16
Pacemaker replacement, explant or repositioning	17/385 (4.4%)	17	7/398 (1.8%)	7	17/383 (4.4%)	17
Stent implantation/Angiography	6/385 (1.6%)	6	3/398 (0.8%)	3	5/383 (1.3%)	5
Vascular disorders
Aneurysm	0/385 (0%)	0	2/398 (0.5%)	2	1/383 (0.3%)	1
Coronary Artery Disease	2/385 (0.5%)	2	1/398 (0.3%)	1	2/383 (0.5%)	2
Other cerebrovascular disorders	0/385 (0%)	0	0/398 (0%)	0	1/383 (0.3%)	1
Other vascular disorders	0/385 (0%)	0	3/398 (0.8%)	4	1/383 (0.3%)	1
Peripheral vascular disease	1/385 (0.3%)	1	0/398 (0%)	0	0/383 (0%)	0
Stroke	4/385 (1%)	4	3/398 (0.8%)	3	2/383 (0.5%)	2
Transient Ischemic Attack	4/385 (1%)	4	4/398 (1%)	4	4/383 (1%)	5
Other (Not Including Serious) Adverse Events
	Control Group		MVP Only		DDDRP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/385 (0%)		0/398 (0%)		0/383 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.