Clinical trial NCT03347695: A New Operation for the Treatment for Long-standing Atrial Fibrillation
Official title: A New Operation (Left Atrial Geometric Volume Reduction, Pulmonary Vein Island Isolation and Left Appendage Base Closure) for the Treatment of Long Standing Persistent Atrial Fibrillation (AF) During Mitral Valve Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiovascular Disease
Keywords: atrial fibrillation
surgery
Lead sponsor: Fujian Medical University
Sponsor class: OTHER
First posted: 2017-11-20
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Atrial fibrillation(AF) often occurs in patients with mitral valve disease. Both mitral replacement and mitral valve plasty are the effective methods to the mitral valve disease. How to cure atrial fibrillation is the key to full recovery. Radiofrequency ablation (RFA) in surgery is an effective treatment for those patients. But there are some recurrence rate after RFA, particularly in patients with enlarged left atrium. So the investigators design a new procedure(Left Atrial Geometric Volume Reduction, Pulmonary Vein Island Isolation and Left Appendage Base Closure) during mitral surgery and study the outcomes to evaluate this new operation.

Detailed description: From September 2017, 20 selective patients, and then 120 consecutive patients with valvular atrial fibrillation were treated with our new operation. If the clinical results from the first 20 patients with restrict selection criteria are unsatisfied, that is, the restoration rate of the sinus rhythm was less than 50% at 1-year follow up, the study will be stopped. Otherwise, another single arm with 120 consecutive patients with valvular AF will be recruited for next phase.

Procedure details: All patients will have their left atrial geometric volume reduced, pulmonary vein island isolated and left appendage ligated or suture closed. After the superior vena cava was transected, two circular incisions were usually made in the left atrial wall between the pulmonary veins and the mitral annulus for circumferential atrial strip resection and pulmonary vein island isolation. The first circular incision was performed around the pulmonary veins. With this incision, pulmonary vein island was isolated and the left atrium was opened. The second one was performed in the interatrial groove and extended around the mitral annulus, leaving a 2 cm inferior wall margin from the annulus and the appendage in situ. With those two incisions, a circumferential strip of the left atrium was excised. Then the base of the left atrial appendage was ligated or excised and sutured. After the mitral manipulations, the center of the pulmonary vein island was longitudinally reef-imbricated with a 3-0 polypropylene continuous running suture to exclude toward the outside of the left atrial cavity. This plicated pulmonary vein island was directly anastomosed to the resected margin around the mitral annulus and the intraatrial septum instead of the interatrial groove. Finally, caval continuity was restored after aortic cross-clamp removal using a running 4-0 polypropylene suture.

Telephone contact was maintained with the patients after discharge.The use of antiarrhythmic medications will be allowed during the first 3 months(blanking period). Transthoracic 2-dimensional echocardiography and Holter monitoring will be obtained at baseline and at 3, 6, and 12 months after the initial operation. Whenever the participants have symptoms such as palpitation, dizziness, or shortness of breath, they could telephone the doctors.

The primary efficacy endpoint is freedom from AF at both 6 months and 12 months after surgery, assessed by 7-days continuous Holter monitoring. The primary safety are cardiopulmonary bypass time; and a composite of death, stroke, serious cardiac events (heart failure, myocardial infarction), cardiac re-hospitalizations, transient ischemic attack, pulmonary embolism, peripheral embolism, coronary artery injury, anatomical excessive bleeding, deep sternal wound infection/mediastinitis, damage to specialized conduction system requiring permanent pacemaker, and superior vena cava stenosis, within 30 days after the procedure or hospital discharge (whichever was later) The secondary efficacy endpoint are the left atrial linear dimensions and A wave reappearance measured by transthoracic echocardiography at 3 time points (before surgery, 6 and 12 months after surgery). The secondary safety endpoint are Major adverse cardiac events, which were defined as a non-weighted composite score of: death, stroke, worsening heart failure (+1 NYHA Class), hospitalization for heart failure, and mitral valve re-intervention within 12 months after surgery; and incidence of protocol-defined serious adverse events (especially thromboembolic and hemorrhagic events) within 12 months after surgery. Statistical analysis were performed with statistic package for social science( SPSS) 11.5 software. A value of P \< 0.05 was considered statistically significant.

Eligibility criteria: Phase I Inclusion Criteria

1. Able to sign Informed Consent and Release of Medical Information forms
2. Age ≥ 18 years and ≤ 60 years old
3. Clinical indications for only mitral valve surgery for the following:

   Organic mitral valve disease without other cardiac disorders (functional or structural).
4. 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 clinic.
5. Able to use heart rhythm monitor
6. Anteroposterior diameter of left atrial between 45mm and 60mm
7. Without history of stroke. Exclusion Criteria

1. AF without indication for mitral valve surgery; or 2. Ischemic mitral regurgitation with evidence of concomitant structural mitral valve disease; or 3. Functional tricuspid regurgitation; or 4. AF is only or paroxysmal persistent; or 5. Evidence of active infection; or 6. Mental impairment or other conditions that may not allow patient to understand the nature, significance, and scope of study; or 7. Surgical management of hypertrophic obstructive cardiomyopathy; or 8. Previous catheter ablation for AF; or 9. Life expectancy of less than one year; or 10. Absolute contraindications for anticoagulation therapy; or 11. Enrollment in concomitant drug or device trials; or 12. Uncontrolled hypo- or hyperthyroidism; or 13. FEV1 \< 30% of predicted value; or 14. Women who are pregnant as evidenced by positive pregnancy test; or 15. Women of childbearing age who do not agree to be on adequate birth control throughout the period of the trial; or 16. Diagnosed with infective endocarditis; or 17. Need emergency surgery. Phase II Inclusion Criteria

1. Able to sign Informed Consent and Release of Medical Information forms
2. Age ≥ 18 years
3. Clinical indications for mitral valve surgery for the following:

   Organic mitral valve disease; or Functional non-ischemic mitral regurgitation; or 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.
4. 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 clinic.
5. Able to use heart rhythm monitor

Exclusion Criteria

1. AF without indication for mitral valve surgery; or
2. AF is only or paroxysmal persistent; or
3. Evidence of active infection; or
4. Mental impairment or other conditions that may not allow patient to understand the nature, significance, and scope of study; or
5. Surgical management of hypertrophic obstructive cardiomyopathy; or
6. Previous catheter ablation for AF; or
7. Life expectancy of less than one year; or
8. Absolute contraindications for anticoagulation therapy; or
9. Enrollment in concomitant drug or device trials; or
10. Uncontrolled hypo- or hyperthyroidism; or
11. Women who are pregnant as evidenced by positive pregnancy test; or
12. Women of childbearing age who do not agree to be on adequate birth control throughout the period of the trial; or
13. Diagnosed with infective endocarditis; or
14. Need emergency surgery.

Primary outcomes:
measure: Numbers of Participants Free From AF
timeFrame: 3, 6, and 12 months after the operation
measure: Intraoperative Cardiopulmonary Bypass Duration
timeFrame: 1 hour after operation
measure: The Adverse Events Within 30 Days After Surgery
timeFrame: Within 30 days after surgery
Secondary outcomes:
measure: Change in Left Atrial Anteroposterior Diameter
timeFrame: 6 months and 12 months post-surgery
measure: Change in Left Atrial Transversal Diameter
timeFrame: 6 months and 12 months post-surgery
measure: Change in Left Atrial Superoinferior Diameter
timeFrame: 6 months and 12 months post-surgery
measure: The Number of Participants Who Will be Detected the Peak Late Trans-mitral Flow Velocity (A Wave) Reappearance
timeFrame: 6 months and 12 months post-surgery
measure: MACEs Within 12 Months After Surgery
timeFrame: Within 12 months
Other outcomes:
Locations:
city: FuZhou
country: China
facility: Department of Cardiovascular Surgery,Union Hospital
state: Fujian
Study officials:
affiliation: Union Hospital
name: Liangwan Chen, M.D
role: STUDY_DIRECTOR
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