Efficacy and Safety of Catheter abLation in patiEnts With seVere mitrAl regurgiTation and pErsistent Atrial Fibrillation: a Randomized Controlled Trial (ELEVATE-AF)

Efficacy and Safety of Catheter abLation in patiEnts With seVere mitrAl regurgiTation and pErsistent Atrial Fibrillation: a Randomized Controlled Trial(ELEVATE-AF)

Atrial fibrillation (AF) leads to atrial functional mitral regurgitation (MR) through mechanisms including mitral annular dilatation, systolic leaflet motion distance alteration, and contractility decrease. Compared with primary MR, atrial functional MR due to AF and other diseases tends to have a worse prognosis, with a higher risk of death and heart failure hospitalization. MR and AF co-exist and exacerbate left atrial dysfunction, further causing worse cardiac dysfunction, valvular regurgitation, and aggravating prognosis.

The best therapy for secondary MR is unclear because MR is only one component of the disease, and restoration of mitral valve competence is not curative. Catheter ablation improves symptoms and cardiac function in patients with AF, reduces risks of AF recurrence and hospitalization, as well as increases quality of life. For patients with AF combined with functional moderate-to-severe MR, previous observational studies have found that the severity of MR significantly reduced after taking catheter ablation to restore sinus rhythm. We hypothesized that catheter ablation would significantly improve the severity of MR in patients with severe atrial functional MR combined with persistent AF compared with drug therapy alone.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation (AF); Catheter Ablation; Atrial Functional Mitral Regurgitation
• Intervention / Treatment: Procedure: Catheter ablation plus medication; Procedure: (ELEVATE-AF X) experimental group; Drug: Medication; Procedure: (ELEVATE-AF X) control group

Detailed Description

The ELEVATE-AF is a multi-center, open-label, parallel design, randomized controlled trial. Eligible subjects will be randomized in a 1:1 ratio to the catheter ablation combined with drug group or to the drug-alone group. A total of 146 patients with persistent atrial fibrillation and severe atrial functional mitral regurgitation (MR) (severity of moderate-to-severe [3+] or severe [4+]) will be enrolled at up to 17 investigational sites in China. The enrollment period is estimated to last approximately 18 months. The primary endpoint is the proportion of patients with residual MR of moderate [2+] or less assessed by transthoracic echocardiography at 3 months. MR severity is confirmed by the Echocardiography Core Lab according to the American Society of Cardiac Ultrasound criteria (mitral effective regurgitant orifice area [EROA)]≤20 mm2). The secondary endpoints evaluate: (i)all-cause mortality; (ii)cardiovascular hospitalization; (iii)undergoing interventional or surgical treatment of mitral valve; (iv)heart failure hospitalization or emergency room visit; (v)change in scores on the Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) Questionnaire, and the 5-level EQ-5D version (EQ-5D-5L); (vi) freedom from any documented atrial arrhythmias lasting more than 30 seconds and atrial fibrillation burden. The safety endpoints include: (i)perioperative surgical complications (within 30 days after catheter ablation procedure); (ii)major bleeding (ISTH definition); (iii)stroke and systemic embolism.

As an extension of the ELEVATE-AF trial, ELEVATE-AF X study will conducted after 3-month follow-up of ELEVATE-AF. The ELEVATE-AF X study is designed as a prospective, multi-center, continued access registry study. The objective of the this study is to validate the long-term outcomes of catheter ablation procedure in patients with persistent AF and severe atrial functional MR. All patients will receive catheter ablation if the procedure is needed, and the medical therapy for ELEVATE-AF X is identical to that of ELEVATE-AF trial. Active follow-up of patients will be performed through 12 months.

• Study Type: Interventional
• Enrollment (Estimated): 146
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Caihua Sang, MD
• Study Contact Backup: Name: Liu HE, MD; Phone Number: +86 13810720787; Email: theliu@139.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230022
      • Recruiting
      • The First Affiliated Hospital of Anhui Medical University
      • Principal Investigator: Ronghui Yu, MD
      • Contact: Ronghui Yu, MD; Phone Number: +86 13901080383; Email: ronghuiyu@vip.sina.com
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100029
      • Recruiting
      • Beijing Anzhen Hospital, Capital Medical University
      • Contact: Liu HE, MD; Phone Number: +86 13810720787; Email: theliu@139.com
      • Contact: Caihua Sang, MD; Phone Number: +86 010-81992281; Email: sch9613070@sina.com
      • Principal Investigator: Caihua Sang, MD
      • Principal Investigator: Changsheng Ma, MD
    • Beijing, Beijing Municipality, China, 100191
      • Recruiting
      • Peking University Third Hospital
      • Contact: Yida Tang, MD; Phone Number: +86 13901010211; Email: tang_yida@163.com
      • Principal Investigator: Yida Tang, MD
  • Fujian
    • Xiamen, Fujian, China, 361006
      • Not yet recruiting
      • Xiamen University Affiliated Cardiovascular Hospital
      • Principal Investigator: Yan Wang, MD
      • Contact: Yan Wang, MD; Phone Number: +86 13860488088; Email: wy@medmail.com.cn
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Not yet recruiting
      • Guangdong Provincial People's Hospital
      • Principal Investigator: Wei Wei, MD
      • Contact: Wei Wei, MD; Phone Number: +86 13724893386; Email: weiwei@gdph.org.cn
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • Recruiting
      • The Second Hospital of Hebeimedical University
      • Contact: Jingzhao Lu, MD; Phone Number: +86 13230177989; Email: ljchb2h@hebmu.edu.cn
      • Principal Investigator: Jingzhao Lu, MD
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150001
      • Recruiting
      • The First Affiliated Hospital of Harbin Medical University
      • Principal Investigator: Yue Li, MD
      • Contact: Yue Li, MD; Phone Number: +86 13945057313; Email: ly99ly@vip.163.com
    • Harbin, Heilongjiang, China, 450052
      • Recruiting
      • The Second Affiliated Hospital of Harbin Medical University
      • Principal Investigator: Bo Yu, MD
      • Contact: Bo Yu, MD; Phone Number: +86 13804585601; Email: yubodr@163.com
  • Henan
    • Zhengzhou, Henan, China, 450052
      • Not yet recruiting
      • The first affiliated hospital of Zhengzhou university
      • Contact: Yingwei Chen, MD; Phone Number: +86 18639001891; Email: zzchenyingwei@126.com
      • Principal Investigator: Yingwei Chen, MD
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Recruiting
      • Wuhan Asia Heart Hospital
      • Contact: Hua Yan, MD; Phone Number: +86 13100659066; Email: yanhua0807@aliyun.com
      • Principal Investigator: Hua Yan, MD
    • Wuhan, Hubei, China, 430030
      • Recruiting
      • Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology
      • Principal Investigator: Yan Wang, MD
      • Contact: Yan Wang, MD; Phone Number: +86 13697326307; Email: newswangyan@126.com
  • Jilin
    • Changchun, Jilin, China, 130000
      • Not yet recruiting
      • The First Hospital of Jilin University
      • Contact: Yang Yu, MD; Email: fredyy@163.com
      • Principal Investigator: Yang Yu, MD
  • Ningxia
    • Yinchuan, Ningxia, China, 750002
      • Recruiting
      • People's Hospital of Ningxia Hui Autonomous Region
      • Contact: Shaojing Xi, MD; Phone Number: +86 18295107706; Email: xishaojing0318@163.com
      • Principal Investigator: Shaojing Xi, MD
  • Shandong
    • Jinan, Shandong, China, 250000
      • Recruiting
      • Shandong Provincial Qianfoshan Hospital
      • Contact: Hesheng Hu, MD; Phone Number: +86 13589112300; Email: hyperhhs@163.com
      • Principal Investigator: Hesheng Hu, MD
  • Shanxi
    • Xi’an, Shanxi, China, 710061
      • Not yet recruiting
      • The First Affiliated Hospital of Xi'an Jiaotong University
      • Principal Investigator: Zuyi Yuan, MD
      • Contact: Zuyi Yuan, MD; Phone Number: +86 13571828319; Email: zuyiyuan@xjtu.edu.cn
    • Xi’an, Shanxi, China, 710000
      • Recruiting
      • Tangdu Hospital-Air Force Medical University
      • Contact: Yan Li, MD; Phone Number: +86 13892890227; Email: profleeyan@163.com
      • Principal Investigator: Yan Li, MD
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Recruiting
      • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
      • Contact: Chenyang Jiang, MD; Phone Number: +86 13857190051; Email: jiangchenyangmail@163.com
      • Principal Investigator: Chenyang Jiang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients were required to have moderate-to-severe or greater (≥3+) atrial functional mitral regurgitation assessed by transthoracic echocardiography within 14 days before randomization. Mitral regurgitation severity was graded by an echocardiography core-lab based on the American Society of Echocardiography criteria, specifically an effective regurgitant orifice area (EROA) ≥30 mm²
2. Age 18-80 years
3. Persistent atrial fibrillation diagnosed by electrocardiogram
4. Left ventricular ejection fraction ≥50% assessed by transthoracic echocardiography within 14 days before randomization(confirmed by the echocardiography core-lab)
5. Left ventricular end-diastolic internal diameter ≤60 mm and left atrial anterior- posterior diameter ≤60 mm in echocardiographic parasternal long-axis view within 14 days before randomization(confirmed by the echocardiography core-lab)
6. Agree to undergo catheter ablation and be able to undergo follow-up as required.

Exclusion Criteria:

1. paroxysmal atrial fibrillation, atrial fibrillation secondary to an apparently reversible cause, or with history of previous ablation;
2. primary mitral valve pathology, including calcification, sclerosis, prolapse, flail, tendon cable rupture, valve degeneration, infective endocarditis, rheumatic lesions, or ischemic lesions;
3. history of previous mitral valve surgery or transcatheter manipulation;
4. mitral valve orifice area <4 cm2;
5. aortic valve disease requiring surgical or transcatheter intervention;
6. untreated clinically significant coronary artery disease requiring revascularization;
7. history of previous myocardial infarction;
8. previous definitive diagnosis of cardiomyopathies such as dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, arrhythmogenic cardiomyopathy, and infiltrative cardiomyopathies (e.g., amyloidosis, hemochromatosis, and nodular disease)
9. echocardiographic evidence of intracardiac mass or thrombus;
10. implant of cardiac device (pacemaker, implantable cardioverter defibrillator, cardiac resynchronization therapy device, or left atria appendage closure);
11. hemodynamic instability requiring cardiac assist devices, intra-aortic balloon pump (IABP), or other hemodynamic support;
12. any percutaneous cardiac intervention (percutaneous coronary intervention, transcatheter aortic valve replacement, etc.) within the 30 days prior to randomization,
13. any cardiac surgery within the 6 months prior to randomization;
14. active infections requiring current antibiotic therapy;
15. a known hypersensitivity or contradiction to procedure medications which cannot be adequately managed medically;
16. contraindication to appropriate anti-coagulation therapy;
17. chronic obstructive pulmonary disease (COPD) requiring continuous home oxygen therapy or chronic oral steroid therapy;
18. acute cerebrovascular accident within 30 days prior to randomization or Modified Rankin Score ≥ 4;
19. symptomatic severe carotid stenosis (>70% by ultrasound);
20. other planned surgical or interventional procedures within the next 3 months;
21. liver failure;
22. renal failure or dialysis status;
23. pregnant or planning pregnancy within the next 3 months;
24. life expectancy < 12 months (e.g., advanced malignant tumors);
25. currently participating in other interventional studies;
26. circumstances that, in the judgment of the researcher, make participation in this study unsuitable.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Catheter ablation plus medication group; All patients assigned to the catheter ablation group will receive AF catheter ablation and receive the same medical therapy as the control group.	Procedure: Catheter ablation plus medication; All patients will receive atrial fibrillation catheter ablation. They also should receive guideline-directed medical therapy, anticoagulation, and rate control with medications according to the guidelines.; Procedure: (ELEVATE-AF X) experimental group; Subsequent ablations may be considered for patients with recurrence，and the medical therapy for ELEVATE-AF X is identical to that of the ELEVATE-AF trial.
Active Comparator: Medication group; All patients should receive guideline-directed medical therapy, anticoagulation, and rate control with medications according to the guidelines.	Drug: Medication; Patients will receive guideline-directed medical therapy, anticoagulation, and rate control according to the guidelines for the management of AF and heart failure.; Procedure: (ELEVATE-AF X) control group; All patients could receive catheter ablation if the procedure is needed, and the medical therapy for ELEVATE-AF X is identical to that of the ELEVATE-AF trial.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary endpoint is the proportion of patients with residual MR of moderate [2+] or less assessed by transthoracic echocardiography at 3 months.	The primary endpoint is the proportion of patients with residual MR of moderate [2+] or less assessed by transthoracic echocardiography at 3 months. MR severity is confirmed by the Echocardiography Core Lab according to the American Society of Cardiac Ultrasound criteria (mitral effective regurgitant orifice area [EROA)]≤20 mm2).	3 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
all-cause mortality		3 month
cardiovascular hospitalization		3 month
undergoing interventional or surgical treatment of mitral valve		3 month
heart failure hospitalization or emergency room visit		3 month
Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) score change between baseline and 3 month	Quality of life assessed by AFEQT questionaire	3 month
EuroQoL 5-Dimension 5-Level (EQ-5D-5L) score change between baseline and 3 month	Quality of life assessed by EQ-5D-5L scale	3 month
freedom from any documented atrial arrhythmias lasting more than 30 seconds and atrial fibrillation burden		3 month
(ELEVATE-AF X) the proportion of patients with residual MR of moderate [2+] or less assessed by transthoracic echocardiography		12 month
(ELEVATE-AF X) all-cause mortality		12 month
(ELEVATE-AF X) cardiovascular hospitalization		12 month
(ELEVATE-AF X) undergoing interventional or surgical treatment of mitral valve		12 month
(ELEVATE-AF X) heart failure hospitalization or emergency room visit		12 month
(ELEVATE-AF X) Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) score change between baseline and 12 month	Quality of life assessed by AFEQT questionaire	12 month
(ELEVATE-AF X) EuroQoL 5-Dimension 5-Level (EQ-5D-5L) score change between baseline and 12 month	Quality of life assessed by EQ-5D-5L scale	12 month
(ELEVATE-AF X) freedom from any documented atrial arrhythmias lasting more than 30 seconds and atrial fibrillation burden		12 month
Change from baseline to 3 months in the 6-minute walk distance		3 months
(ELEVATE-X) Change from baseline to 12 months in the 6-minute walk distance		12 months

Other Outcome Measures

Outcome Measure	Time Frame
perioperative procedural complications	3 months
major bleeding (ISTH definition)	3 months
stroke and systemic embolism	3 months
(ELEVATE-AF X) major bleeding (ISTH definition)	12 month
(ELEVATE-AF X) stroke and systemic embolism	12 month

Collaborators and Investigators

• Sponsor: Beijing Anzhen Hospital
• Collaborators: Abbott
• Investigators: Principal Investigator: Caihua Sang, MD, Beijing Anzhen Hospital; Principal Investigator: Changsheng Ma, MD, Beijing Anzhen Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: March 11, 2025
• First Submitted That Met QC Criteria: March 16, 2025
• First Posted (Actual): March 19, 2025

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 11, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: atrial fibrillation; mitral regurgitation; catheter ablation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Heart Valve Diseases; Pathological Conditions, Signs and Symptoms; Atrial Fibrillation; Mitral Valve Insufficiency; Pharmaceutical Preparations; Investigative Techniques; Epidemiologic Research Design; Epidemiologic Methods; Research Design; Methods; Therapeutics; Surgical Procedures, Operative; Technology, Pharmaceutical; Ablation Techniques; Radiofrequency Ablation; Radiofrequency Therapy; Control Groups; Dosage Forms; Catheter Ablation
• Other Study ID Numbers: 2025KLS10; 2022YFC3601303 (Other Grant/Funding Number: the National Key Research and Development Program of China)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No