A New Operation for the Treatment for Long-standing Atrial Fibrillation (ANOLAF)

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

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.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Disease
• Intervention / Treatment: Procedure: Left Atrial Geometric Volume Reduction, Pulmonary Vein Island Isolation and Left Appendage Base Closure(selected patients); Procedure: Left Atrial Geometric Volume Reduction, Pulmonary Vein Island Isolation and Left Appendage Base Closure

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.

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Fujian
    • FuZhou, Fujian, China, 350001
      • Department of Cardiovascular Surgery,Union Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A new operation; Left Atrial Geometric Volume Reduction, Pulmonary Vein Island Isolation and Left Appendage Base Closure	Procedure: Left Atrial Geometric Volume Reduction, Pulmonary Vein Island Isolation and Left Appendage Base Closure(selected patients); Left Atrial Geometric Volume Reduction, Pulmonary Vein Island Isolation and Left Appendage Base Closure
Other: A new operation (Selected pilot study); Left Atrial Geometric Volume Reduction, Pulmonary Vein Island Isolation and Left Appendage Base Closure	Procedure: Left Atrial Geometric Volume Reduction, Pulmonary Vein Island Isolation and Left Appendage Base Closure; Left Atrial Geometric Volume Reduction, Pulmonary Vein Island Isolation and Left Appendage Base Closure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Numbers of Participants Free From AF	Freedom from AF in patients with longstanding persistent AF undergoing MVS at 6 months and 12 months. AF will be measured by 7 days continuous Holter monitoring at 6 months and 12 months post-surgery; and freedom of AF will be defined by absence of AF lasting > 30 seconds at 12 months	3, 6, and 12 months after the operation
Intraoperative Cardiopulmonary Bypass Duration	Cardiopulmonary bypass (CPB) technology is used in most cardiovascular surgeries. These surgeries utilize CPB, which has been associated with some adverse effects. This is most likely due to exposure of blood to abnormal surfaces and conditions leading to systemic inflammatory responses. Prolonged CPB duration is associated with worse clinical outcomes.	1 hour after operation
The Adverse Events Within 30 Days After Surgery	The adverse events within 30 days after surgery, including: 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 surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Left Atrial Anteroposterior Diameter	echocardiographic change in left atrial anteroposterior diameter	6 months and 12 months post-surgery
Change in Left Atrial Transversal Diameter	echocardiographic change in left atrial transversal diameter	6 months and 12 months post-surgery
Change in Left Atrial Superoinferior Diameter	echocardiographic change in left atrial superoinferior diameter	6 months and 12 months post-surgery
The Number of Participants Who Will be Detected the Peak Late Trans-mitral Flow Velocity (A Wave) Reappearance	The peak late trans-mitral flow velocity (A wave) reappearance means recover of efficient left atrial contraction which indicates lower rate of thrombosis. Usually these is no A wave for AF patients. The peak late trans-mitral flow velocity 6 months and 12 months post-surgery, which will be measured by transthoracic echocardiography.	6 months and 12 months post-surgery
MACEs Within 12 Months After Surgery	MACEs within 12 months after surgery: defined as a non-weighted composite score of: death, stroke, worsening heart failure (+1 NYHA Class), CHF hospitalization, and mitral valve [MV] re-intervention.	Within 12 months

Collaborators and Investigators

• Sponsor: Fujian Medical University
• Investigators: Study Director: Liangwan Chen, M.D, Union Hospital

Publications and helpful links

General Publications

• Kuck KH, Brugada J, Furnkranz A, Metzner A, Ouyang F, Chun KR, Elvan A, Arentz T, Bestehorn K, Pocock SJ, Albenque JP, Tondo C; FIRE AND ICE Investigators. Cryoballoon or Radiofrequency Ablation for Paroxysmal Atrial Fibrillation. N Engl J Med. 2016 Jun 9;374(23):2235-45. doi: 10.1056/NEJMoa1602014. Epub 2016 Apr 4.
• Verma A, Jiang CY, Betts TR, Chen J, Deisenhofer I, Mantovan R, Macle L, Morillo CA, Haverkamp W, Weerasooriya R, Albenque JP, Nardi S, Menardi E, Novak P, Sanders P; STAR AF II Investigators. Approaches to catheter ablation for persistent atrial fibrillation. N Engl J Med. 2015 May 7;372(19):1812-22. doi: 10.1056/NEJMoa1408288.
• Kim JH, Na CY, Lee SJ, Oh SS. Circumferential left atrium resection for treating a giant left atrium. J Card Surg. 2013 Mar;28(2):102-8. doi: 10.1111/jocs.12061. Epub 2013 Jan 29.
• Shi J, Bai ZX, Zhang BG, Ren WJ, Guo YQ. A modified Cox maze IV procedure: a simpler technique for the surgical treatment of atrial fibrillation. Interact Cardiovasc Thorac Surg. 2016 Dec;23(6):856-860. doi: 10.1093/icvts/ivw256. Epub 2016 Aug 11.
• Zheng S, Zhang H, Li Y, Han J, Jia Y, Meng X. Comparison of Left Atrial and Biatrial Maze Procedure in the Treatment of Atrial Fibrillation: A Meta-Analysis of Clinical Studies. Thorac Cardiovasc Surg. 2016 Dec;64(8):661-671. doi: 10.1055/s-0035-1554941. Epub 2015 Jul 28.
• Kong MH, Lopes RD, Piccini JP, Hasselblad V, Bahnson TD, Al-Khatib SM. Surgical Maze procedure as a treatment for atrial fibrillation: a meta-analysis of randomized controlled trials. Cardiovasc Ther. 2010 Oct;28(5):311-26. doi: 10.1111/j.1755-5922.2010.00139.x.
• Baek MJ, Na CY, Oh SS, Lee CH, Kim JH, Seo HJ, Park SW, Kim WS. Surgical treatment of chronic atrial fibrillation combined with rheumatic mitral valve disease: Effects of the cryo-maze procedure and predictors for late recurrence. Eur J Cardiothorac Surg. 2006 Nov;30(5):728-36. doi: 10.1016/j.ejcts.2006.08.016. Epub 2006 Sep 26.
• Kumar P, Athanasiou T, De L Stanbridge R. Treatment of long-duration atrial fibrillation by modified maze procedure. J R Soc Med. 2002 Nov;95(11):552-3. doi: 10.1258/jrsm.95.11.552. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2017
• Primary Completion (Actual): March 1, 2021
• Study Completion (Actual): March 1, 2021

Study Registration Dates

• First Submitted: November 11, 2017
• First Submitted That Met QC Criteria: November 15, 2017
• First Posted (Actual): November 20, 2017

Study Record Updates

• Last Update Posted (Actual): October 29, 2021
• Last Update Submitted That Met QC Criteria: October 17, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: surgery; atrial fibrillation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Cardiovascular Diseases; Atrial Fibrillation
• Other Study ID Numbers: CLW2017AF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: plan to share study protocol, SAP and ICF with other researchers.
• IPD Sharing Time Frame: Data will become available after the study ends.
• IPD Sharing Access Criteria: cardiovascular researchers
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No