Atrial Fibrillation, Mitral Valve Insufficiency, Mitral Valve Stenosis
Conditions
Keywords
Mitral Valve Regurgitation, Mitral Valve Surgery, Mitral Valve Disease, Ablation, Catheter, Catheter Ablation, Radiofrequency
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.
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).
Interventions
PROCEDUREMVS
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.
DEVICEAblation
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.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
National Institute of Neurological Disorders and Stroke (NINDS)
Canadian Institutes of Health Research (CIHR)
Annetine Gelijns
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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. * a) 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. * b) 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Freedom From Atrial Fibrillation | Measured at Month 12 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MVS Alone 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. | 127 |
| MVS + 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.
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. | 133 |
| Total | 260 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 13 | 10 |
| Overall Study | Lost to Follow-up | 6 | 8 |
| Overall Study | Withdrawal by Subject | 9 | 6 |
Baseline characteristics
| Characteristic | MVS + Ablation | MVS Alone | Total |
|---|---|---|---|
| Age, Continuous | 69.7 years STANDARD_DEVIATION 10.4 | 69.4 years STANDARD_DEVIATION 10 | 69.6 years STANDARD_DEVIATION 10.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 8 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 123 Participants | 119 Participants | 242 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Gender Female | 57 Participants | 63 Participants | 120 Participants |
| Gender Male | 76 Participants | 64 Participants | 140 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 12 Participants | 27 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 116 Participants | 112 Participants | 228 Participants |
| Region of Enrollment Canada | 22 participants | 21 participants | 43 participants |
| Region of Enrollment United States | 111 participants | 106 participants | 217 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 36 / 127 | 40 / 133 |
| serious Total, serious adverse events | 69 / 127 | 77 / 133 |
Outcome results
Primary
Freedom From Atrial Fibrillation
Time frame: Measured at Month 12
Population: Since the primary analysis is an intent-to-treat, outcomes were imputed for patients with missing data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MVS Alone | Freedom From Atrial Fibrillation | 31.1 percentage of patients |
| MVS + Ablation | Freedom From Atrial Fibrillation | 61.8 percentage of patients |
Secondary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MVS Alone | Composite of Death, Stroke, Serious Adverse Events (Cardiac and Non-cardiac), and Cardiac Re-hospitalizations Less Than 30 Days Post-procedure or Hospital Discharge | 22.8 percentage of patients |
| MVS + Ablation | Composite of Death, Stroke, Serious Adverse Events (Cardiac and Non-cardiac), and Cardiac Re-hospitalizations Less Than 30 Days Post-procedure or Hospital Discharge | 31.6 percentage of patients |