Surgical Ablation Versus No Surgical Ablation for Patients With Atrial Fibrillation Undergoing Mitral Valve Surgery

• Sponsor: Annetine Gelijns (Other)
• Overall Status: Completed
• CT.gov ID: NCT00903370
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH), National Institute of Neurological Disorders and Stroke (NINDS) (NIH), Canadian Institutes of Health Research (CIHR) (Other)
• Enrollment: 260
• Locations: 21
• Arms: 2
• Duration (Months): 68
• Patients Per Site: 12.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of the research is to determine whether treating atrial fibrillation with surgical ablation during scheduled mitral valve surgery is better than mitral valve surgery by itself without the surgical ablation. Surgical ablation of atrial fibrillation is a technique used by surgeons to deaden atrial heart tissue and block electrical signals that may be causing your heart to beat irregularly. There are no new procedures being tested in this study; both mitral valve surgery and surgical ablation are used regularly in patients who have mitral valve problems and atrial fibrillation, although no surgical ablation devices have been approved by the Food and Drug Administration for the treatment of atrial fibrillation. What is not known with certainty, is whether patients with atrial fibrillation who are having planned mitral valve surgery would do better if they also had surgical ablation rather than medication alone to treat their atrial fibrillation.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation; Mitral Valve Insufficiency; Mitral Valve Stenosis	Procedure: MVS; Device: Ablation	Phase 2

Detailed Description

The purpose of this study is to determine whether the addition of surgical ablation to planned mitral valve surgery for patients with persistent or longstanding persistent AF (within 6 months prior to randomization) reduces the incidence of postoperative heart arrhythmia compared to mitral valve repair with medication therapy alone. This is a randomized, multi-center trial which will enroll 260 subjects who will be randomized in a 1:1 fashion to: (a) mitral valve surgery plus surgical ablation or (b) mitral valve surgery without ablation (control group). All patients will undergo ligation or excision of the left atrial appendage. Patients assigned to the ablation group will be further randomized (1:1) to one of two lesion sets: (1) pulmonary vein isolation only or (2) biatrial Maze lesions. The target population for this trial consists of adult patients with mitral valve disease requiring surgical intervention and persistent or longstanding persistent atrial fibrillation. All patients who meet the eligibility criteria may be included in the study regardless of gender, race or ethnicity. The primary efficacy endpoint is freedom from AF, which will be measured by 3-day continuous monitoring at 6 months and 12 months post-ablation. The primary safety endpoint is a composite of death, stroke, serious cardiac events (heart failure, myocardial infarction), cardiac re-hospitalizations, transient ischemic attack, pulmonary embolism, peripheral embolism, excessive bleeding, deep sternal wound infection/mediastinitis, damage to specialized conduction system requiring permanent pacemaker, damage to peripheral structures, such as the esophagus, within 30 days post-procedure or hospital discharge (whichever is later).

Study Design

• Study Type: Interventional
• Actual Enrollment: 260 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Surgical Ablation Versus No Surgical Ablation for Patients With Persistent or Longstanding Persistent Atrial Fibrillation (AF) Undergoing Mitral Valve Surgery
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: MVS All participants will undergo mitral valve surgery with ligation/excision of left atrial appendage.	Procedure: MVS; All participants will have their left atrial appendage excised or excluded. For mitral regurgitation, the procedures will be a valve repair in the majority of cases. For valves that are not amenable to repair, and for most cases of mitral stenosis, a valve replacement will be performed.; Other Names: Mitral Valve Repair Mitral Valve Replacement
Experimental: Ablation Participants will undergo mitral valve surgery with ligation/excision of left atrial appendage plus surgical ablation with pulmonary vein isolation or biatrial lesion set.	Procedure: MVS; All participants will have their left atrial appendage excised or excluded. For mitral regurgitation, the procedures will be a valve repair in the majority of cases. For valves that are not amenable to repair, and for most cases of mitral stenosis, a valve replacement will be performed.; Other Names: Mitral Valve Repair Mitral Valve Replacement ; Device: Ablation; For participants treated by pulmonary vein isolation, two separate encircling lesions will be made around the left and right pulmonary veins. For participants treated with biatrial maze lesion set, the left atrial lesions will include, the two encircling lesions, as well as connecting lesions between to the pulmonary veins, from the pulmonary veins to the mitral valve annulus, and from the pulmonary veins to the left atrial appendage. The right pulmonary veins will be isolated first. Isolation will be confirmed by pacing the pulmonary veins at the previously identified threshold for capture. If no atrial capture is noted, it will be inferred that the right pulmonary veins were isolated. If atrial capture is noted, additional ablations on the atrial cuff will be performed until isolation is confirmed. This will be repeated on the left pulmonary veins.; Other Names: Surgical Ablation

Outcome Measures

Primary Outcome Measures

1. Freedom From Atrial Fibrillation [Measured at Month 12]

Secondary Outcome Measures

1. Composite of Death, Stroke, Serious Adverse Events (Cardiac and Non-cardiac), and Cardiac Re-hospitalizations Less Than 30 Days Post-procedure or Hospital Discharge [Less than 30 days post-procedure or hospital discharge]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Able to sign Informed Consent and Release of Medical Information forms

• Age ≥ 18 years

• Clinical indications for mitral valve surgery for the following:

1. Organic mitral valve disease; or

2. Functional non-ischemic mitral regurgitation; or

3. Ischemic mitral regurgitation with evidence of concomitant structural mitral valve disease

Note: May include need for surgical management of functional tricuspid regurgitation or patent foramen ovale. May also include concomitant CABG, aortic arch or aortic valve procedure. Surgical intervention may be performed via sternotomy or minimally invasive procedure.

• 1. Persistent AF within 6 months prior to randomization, defined as non self-terminating AF lasting greater than 7 days but no more than one year, or lasting less than 7 days but necessitating pharmacologic or electrical cardioversion.

• Duration of AF must be documented by medical history and

• Presence of AF must be documented by a direct electrocardiographic assessment within 6 months prior to randomization.

• 1. Longstanding persistent AF is defined as continuous AF of greater than one year duration.

• Duration of AF must be documented by medical history and

• Presence of AF must be documented by a direct electrocardiographic assessment upon arrival in the OR.

• Able to use heart rhythm monitor

Exclusion Criteria:

• 1. AF without indication for mitral valve surgery 2. AF is paroxysmal 3. Evidence of left atrial thrombus by intra-operative TEE 4. Evidence of active infection 5. Mental impairment or other conditions that may not allow subject to understand the nature, significance, and scope of study 6. Surgical management of hypertrophic obstructive cardiomyopathy 7. Previous catheter ablation for AF 8. Life expectancy of less than one year 9. Absolute contraindications for anticoagulation therapy 10. Enrollment in concomitant drug or device trials 11. Uncontrolled hypo- or hyperthyroidism 12. FEV1 < 30% of predicted value and/or need for home oxygen therapy 13. Women who are pregnant as evidenced by positive pregnancy test 14. Women of childbearing age who do not agree to be on adequate birth control throughout the period of the trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale New Haven Hospital	New Haven	Connecticut	United States	06510
2	Christiana Care Health Services	Newark	Delaware	United States	19701
3	Emory University	Atlanta	Georgia	United States	30383
4	University of Maryland	Baltimore	Maryland	United States	21201
5	NIH Heart Center at Suburban Hospital	Bethesda	Maryland	United States	20892
6	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
7	Baystate Medical Center	Springfield	Massachusetts	United States	01199
8	University of Michigan	Ann Arbor	Michigan	United States	48109
9	Montefiore Einstein Heart Center	Bronx	New York	United States	10467
10	Mount Sinai School of Medicine	New York	New York	United States	10029
11	Columbia University Medical Center	New York	New York	United States	10032
12	Duke University	Durham	North Carolina	United States	27710
13	East Carolina Heart Institute	Greenville	North Carolina	United States	27834
14	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
15	Ohio State University	Columbus	Ohio	United States	43210
16	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
17	Baylor Research Institute	Plano	Texas	United States	75093
18	University of Virginia	Charlottesville	Virginia	United States	22908
19	University of Alberta Hospital	Edmonton	Alberta	Canada	T6G2B7
20	Montreal Heart Institute	Montreal	Quebec	Canada	H1T 1C8
21	Quebec Heart Institute/Laval Hopital	Quebec		Canada	H7M 3L9

Sponsors and Collaborators

• Annetine Gelijns
• National Heart, Lung, and Blood Institute (NHLBI)
• National Institute of Neurological Disorders and Stroke (NINDS)
• Canadian Institutes of Health Research (CIHR)

Investigators

• Study Chair: Timothy Gardner, MD, Christiana Care Health Services
• Study Chair: Patrick O'Gara, MD, Brigham and Women's Hospital
• Principal Investigator: Annetine C. Gelijns, Ph.D., Icahn School of Medicine at Mount Sinai

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Click here for the Cardiothoracic Surgical Trials Network Web site

Publications

None provided.

• Responsible Party: Annetine Gelijns, Professor of Health Policy, Chair Department of Health Evidence & Policy, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT00903370
• Other Study ID Numbers: GCO 08-1078-0004; U01HL088942; U01HL088942-03; 656
• First Posted: May 18, 2009
• Last Update Posted: Feb 6, 2017
• Last Verified: Dec 1, 2016

• Keywords provided by Annetine Gelijns, Professor of Health Policy, Chair Department of Health Evidence & Policy, Icahn School of Medicine at Mount Sinai: Mitral Valve Regurgitation; Mitral Valve Surgery; Mitral Valve Disease; Ablation, Catheter; Catheter Ablation, Radiofrequency
• Additional relevant MeSH terms: Atrial Fibrillation; Mitral Valve Insufficiency; Mitral Valve Stenosis

Study Results

Participant Flow

Arm/Group Title	MVS Alone	MVS + Ablation
Arm/Group Description	Participants will undergo mitral valve surgery with ligation/excision of left atrial appendage. MVS alone: All participants will have their left atrial appendage excised or excluded. For mitral regurgitation, the procedures will be a valve repair in the majority of cases. For valves that are not amenable to repair, and for most cases of mitral stenosis, a valve replacement will be performed.	Participants will undergo mitral valve surgery with ligation/excision of left atrial appendage plus surgical ablation with pulmonary vein isolation or biatrial lesion set. MVS + ablation: For participants treated by pulmonary vein isolation, two separate encircling lesions will be made around the left and right pulmonary veins. For participants treated with biatrial maze lesion set, the left atrial lesions will include the two encircling lesions, as well as connecting lesions between to the pulmonary veins, from the pulmonary veins to the mitral valve annulus, and from the pulmonary veins to the left atrial appendage. The right pulmonary veins will be isolated first. Isolation will be confirmed by pacing the pulmonary veins at the previously identified threshold for capture. If no atrial capture noted, it will be inferred that the right pulmonary veins were isolated. If atrial capture noted, additional ablations on the atrial cuff will be performed until isolation is confirmed.
Period Title: Overall Study
STARTED	127	133
COMPLETED	99	109
NOT COMPLETED	28	24

Baseline Characteristics

Arm/Group Title	MVS Alone	MVS + Ablation	Total
Arm/Group Description	Participants will undergo mitral valve surgery with ligation/excision of left atrial appendage. MVS alone: All participants will have their left atrial appendage excised or excluded. For mitral regurgitation, the procedures will be a valve repair in the majority of cases. For valves that are not amenable to repair, and for most cases of mitral stenosis, a valve replacement will be performed.	Participants will undergo mitral valve surgery with ligation/excision of left atrial appendage plus surgical ablation with pulmonary vein isolation or biatrial lesion set. MVS + ablation: For participants treated by pulmonary vein isolation, two separate encircling lesions will be made around the left and right pulmonary veins. For participants treated with biatrial maze lesion set, the left atrial lesions will include the two encircling lesions, as well as connecting lesions between to the pulmonary veins, from the pulmonary veins to the mitral valve annulus, and from the pulmonary veins to the left atrial appendage. The right pulmonary veins will be isolated first. Isolation will be confirmed by pacing the pulmonary veins at the previously identified threshold for capture. If no atrial capture noted, it will be inferred that the right pulmonary veins were isolated. If atrial capture noted, additional ablations on the atrial cuff will be performed until isolation is confirmed.	Total of all reporting groups
Overall Participants	127	133	260
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.4 (10)	69.7 (10.4)	69.6 (10.2)
Gender (Count of Participants)
Female	63 49.6%	57 42.9%	120 46.2%
Male	64 50.4%	76 57.1%	140 53.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	8 6.3%	10 7.5%	18 6.9%
Not Hispanic or Latino	119 93.7%	123 92.5%	242 93.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	3 2.4%	2 1.5%	5 1.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	12 9.4%	15 11.3%	27 10.4%
White	112 88.2%	116 87.2%	228 87.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Canada	21 16.5%	22 16.5%	43 16.5%
United States	106 83.5%	111 83.5%	217 83.5%

Outcome Measures

1. Primary Outcome

Title	Freedom From Atrial Fibrillation
Time Frame	Measured at Month 12

Outcome Measure Data

Analysis Population Description

Since the primary analysis is an intent-to-treat, outcomes were imputed for patients with missing data.

Arm/Group Title	MVS Alone	MVS + Ablation
Arm/Group Description	Participants will undergo mitral valve surgery with ligation/excision of left atrial appendage. MVS alone: All participants will have their left atrial appendage excised or excluded. For mitral regurgitation, the procedures will be a valve repair in the majority of cases. For valves that are not amenable to repair, and for most cases of mitral stenosis, a valve replacement will be performed.	Participants will undergo mitral valve surgery with ligation/excision of left atrial appendage plus surgical ablation with pulmonary vein isolation or biatrial lesion set. MVS + ablation: For participants treated by pulmonary vein isolation, two separate encircling lesions will be made around the left and right pulmonary veins. For participants treated with biatrial maze lesion set, the left atrial lesions will include the two encircling lesions, as well as connecting lesions between to the pulmonary veins, from the pulmonary veins to the mitral valve annulus, and from the pulmonary veins to the left atrial appendage. The right pulmonary veins will be isolated first. Isolation will be confirmed by pacing the pulmonary veins at the previously identified threshold for capture. If no atrial capture noted, it will be inferred that the right pulmonary veins were isolated. If atrial capture noted, additional ablations on the atrial cuff will be performed until isolation is confirmed.
Measure Participants	127	133
Number (95% Confidence Interval) [percentage of patients]	31.1	61.8

2. Secondary Outcome

Title	Composite of Death, Stroke, Serious Adverse Events (Cardiac and Non-cardiac), and Cardiac Re-hospitalizations Less Than 30 Days Post-procedure or Hospital Discharge
Time Frame	Less than 30 days post-procedure or hospital discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MVS Alone	MVS + Ablation
Arm/Group Description	Participants will undergo mitral valve surgery with ligation/excision of left atrial appendage. MVS alone: All participants will have their left atrial appendage excised or excluded. For mitral regurgitation, the procedures will be a valve repair in the majority of cases. For valves that are not amenable to repair, and for most cases of mitral stenosis, a valve replacement will be performed.	Participants will undergo mitral valve surgery with ligation/excision of left atrial appendage plus surgical ablation with pulmonary vein isolation or biatrial lesion set. MVS + ablation: For participants treated by pulmonary vein isolation, two separate encircling lesions will be made around the left and right pulmonary veins. For participants treated with biatrial maze lesion set, the left atrial lesions will include the two encircling lesions, as well as connecting lesions between to the pulmonary veins, from the pulmonary veins to the mitral valve annulus, and from the pulmonary veins to the left atrial appendage. The right pulmonary veins will be isolated first. Isolation will be confirmed by pacing the pulmonary veins at the previously identified threshold for capture. If no atrial capture noted, it will be inferred that the right pulmonary veins were isolated. If atrial capture noted, additional ablations on the atrial cuff will be performed until isolation is confirmed.
Measure Participants	127	133
Number (95% Confidence Interval) [percentage of patients]	22.8	31.6

Adverse Events

Arm/Group Title	MVS Alone		MVS + Ablation
Arm/Group Description	Participants will undergo mitral valve surgery with ligation/excision of left atrial appendage. MVS alone: All participants will have their left atrial appendage excised or excluded. For mitral regurgitation, the procedures will be a valve repair in the majority of cases. For valves that are not amenable to repair, and for most cases of mitral stenosis, a valve replacement will be performed.		Participants will undergo mitral valve surgery with ligation/excision of left atrial appendage plus surgical ablation with pulmonary vein isolation or biatrial lesion set. MVS + ablation: For participants treated by pulmonary vein isolation, two separate encircling lesions will be made around the left and right pulmonary veins. For participants treated with biatrial maze lesion set, the left atrial lesions will include the two encircling lesions, as well as connecting lesions between to the pulmonary veins, from the pulmonary veins to the mitral valve annulus, and from the pulmonary veins to the left atrial appendage. The right pulmonary veins will be isolated first. Isolation will be confirmed by pacing the pulmonary veins at the previously identified threshold for capture. If no atrial capture noted, it will be inferred that the right pulmonary veins were isolated. If atrial capture noted, additional ablations on the atrial cuff will be performed until isolation is confirmed.
All Cause Mortality
	MVS Alone		MVS + Ablation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	MVS Alone		MVS + Ablation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	69/127 (54.3%)		77/133 (57.9%)
Cardiac disorders
Arrhythmias-Sustained ventricular arrhythmia	6/127 (4.7%)	6	4/133 (3%)	4
Arrhythmias-Sustained supraventricular arrhythmia	16/127 (12.6%)	21	19/133 (14.3%)	30
Cardiac conduction abnormalities requiring PPM	9/127 (7.1%)	9	25/133 (18.8%)	25
Pericardial Fluid Collection	5/127 (3.9%)	5	4/133 (3%)	4
Non-infectious Pericarditis	0/127 (0%)	0	1/133 (0.8%)	1
Heart Failure	11/127 (8.7%)	13	14/133 (10.5%)	19
Myocardial Infarction	2/127 (1.6%)	2	2/133 (1.5%)	2
Right Heart Failure	0/127 (0%)	0	1/133 (0.8%)	1
General disorders
Bleeding	6/127 (4.7%)	6	7/133 (5.3%)	7
Hepatobiliary disorders
Hepatic Dysfunction	3/127 (2.4%)	3	3/133 (2.3%)	3
Infections and infestations
Major Infection - Localized - Pneumonia	10/127 (7.9%)	11	3/133 (2.3%)	3
Major Infection - Localized - Other	7/127 (5.5%)	7	8/133 (6%)	10
Major Infection - Endocarditis	1/127 (0.8%)	1	1/133 (0.8%)	1
Major Infection - Sepsis	4/127 (3.1%)	4	8/133 (6%)	8
Nervous system disorders
Neurological Dysfunction - CVA-Ischemic	3/127 (2.4%)	3	3/133 (2.3%)	4
Neurological Dysfunction - CVA-Hemorrhagic	0/127 (0%)	0	1/133 (0.8%)	1
Neurological Dysfunction - Toxic Metabolic Encephalopathy	0/127 (0%)	0	1/133 (0.8%)	1
Neurological Dysfunction - Other (not stroke, TIA, Toxic Metabolic Encephalopathy)	1/127 (0.8%)	1	3/133 (2.3%)	3
Renal and urinary disorders
Renal Dysfunction (no dialysis)	4/127 (3.1%)	4	1/133 (0.8%)	1
Renal Failure (dialysis)	2/127 (1.6%)	2	4/133 (3%)	4
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	4/127 (3.1%)	4	11/133 (8.3%)	11
Pneumothorax	2/127 (1.6%)	2	1/133 (0.8%)	1
Respiratory Failure	14/127 (11%)	16	6/133 (4.5%)	6
Vascular disorders
Venous Thromboembolism Event	3/127 (2.4%)	4	3/133 (2.3%)	3
Other (Not Including Serious) Adverse Events
	MVS Alone		MVS + Ablation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/127 (28.3%)		40/133 (30.1%)
Cardiac disorders
Arrhythmias-Sustained supraventricular arrhythmia	15/127 (11.8%)	19	11/133 (8.3%)	12
Cardiac conduction abnormalities requiring PPM	3/127 (2.4%)	3	1/133 (0.8%)	1
General disorders
Bleeding	0/127 (0%)	0	2/133 (1.5%)	2
Injury, poisoning and procedural complications
Major Infection - Localized - Other	5/127 (3.9%)	5	7/133 (5.3%)	7
Nervous system disorders
Neurological Dysfunction - Toxic Metabolic Encephalopathy	0/127 (0%)	0	2/133 (1.5%)	2
Neurological Dysfunction - Other (not stroke, TIA, Toxic Metabolic Encephalopathy)	2/127 (1.6%)	2	2/133 (1.5%)	2
Renal and urinary disorders
Renal Dysfunction (no dialysis)	2/127 (1.6%)	2	3/133 (2.3%)	3
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	9/127 (7.1%)	9	9/133 (6.8%)	9
Pneumothorax	0/127 (0%)	0	4/133 (3%)	4
Vascular disorders
Venous Thromboembolism Event	2/127 (1.6%)	2	1/133 (0.8%)	1

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.