Efficacy of Cardiometabolic Risk Factor Control Through Metabolic Surgery on Management and Severity of Atrial Fibrillation: METSAFE Randomized Clinical Trial

Official Summary

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. It is estimated that between 3 and 6 million Americans are currently living with AF, while 12 million people in the United States will have AF in 2030. Obesity and its comorbidities such as type 2 diabetes (T2DM), hypertension, and obstructive sleep apnea (OSA) are major risk factors for development and progression of AF. Metabolic and Bariatric Surgery (MBS) is the most effective currently available treatment for obesity. Patients typically lose 20 to 35 percent of body weight after surgery which is often sustained for many years. MBS can improve all 5 major risk factors of AF including obesity, hypertension, T2DM, OSA, and systemic inflammation. The purpose of the study is to understand if MBS can affect the severity of AF and the toll AF's symptoms take on patients.

Eligibility Requirements

• Minimum Age: 18 Years
• Maximum Age: 80 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 100 participants

Study Arms

• Metabolic Surgery (ACTIVE_COMPARATOR)
  Roux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG)
• Control group (nonsurgical standard of care for obesity) (OTHER)
  In the Control group, the subjects will be receiving standard of care for nonsurgical management of obesity, including possible AOMs that are not contraindicated in patients with AF at the discretion of obesity medicine specialists.

Interventions

• PROCEDURE: Roux-en-Y Gastric Bypass or Sleeve Gastrectomy — Patients receive either RYGB or SG. The surgical risk, differential impact of each procedure on body weight and other obesity-related diseases, presence of other medical and mental problems, patient's behavioral factors (e.g., postoperative compliance, active smoking), medications, and goals will be considered when the patient and local medical team make a shared decision about the most appropriate surgical procedure.
• DRUG: Anti-Obesity Medication (AOM) treatment — Implementation of obesity pharmacotherapy in the nonsurgical group includes initial assessment of side effects and response, followed by achieving a clinically meaningful weight loss (5% weight loss) after three months. Once this goal is reached, AOMs will be continued throughout the study. If a weight plateau is reached within the first AOM, then another AOM may be added in combination in a stepwise fashion. The choice of AOMs considered may include metformin, topiramate, liraglutide, dulagluti

Primary Outcomes

• Relative change in total duration of being in atrial fibrillation (AF) (First 52 weeks of the study)

Secondary Outcomes

• Presence of at least 1 AF episode (First 52 weeks of the study)
• Change in number of AF episodes (≥30 seconds) (First 52 weeks of the study)
• Change in number of AF espisodes longer than 6 minutes (First 52 weeks of the study)
• Change in the longest AF duration (First 52 weeks of the study)
• Change in the second longest AF duration (First 52 weeks of the study)

Eligibility Criteria

INCLUSION CRITERIA

Entry into the study would require that the patient:

1. Is a candidate for general anesthesia
2. Is eligible for metabolic surgery (RYGB or SG)
3. Is ≥18 and ≤80 years old
4. has a BMI ≥35 and ≤65 kg/m2
5. has AF criteria, which:

   1. Must be documented by EKG or cardiac monitor or Zio XT Patch
   2. Must have symptomatic AF
   3. In terms of types of AF, either paroxysmal AF with at least one episode lasting ≥5 minutes in the last 3 months prior to screening, or persistent AF, or longstanding AF.
   4. Must have a minimum burden of 1% during a 2-week screening time with an ambulatory noninvasive cardiac monitor.
   5. Must be assessed and confirmed by an expert cardiologist (e.g., cardiac electrophysiologist) to meet eligibility.
6. Patients without history of prior AF ablation/PVI procedure or with history of prior failed AF ablation/PVI procedure are eligible for the study.
7. Patients with and without T2DM are eligible for the study. Patients with T2DM should have been on a stable dose of anti-diabetic medication (including insulin) for at least 3 months prior to entry, with HbA1c ≤12%.
8. Have the ability and willingness to participate in the study and agree to any of the arms involved in the study.
9. Able to understand the options and to comply with the requirements of each arm.
10. Have a negative urine pregnancy test at screening and randomization visits for women of childbearing potential.
11. Women, of childbearing age, must agree to use reliable method of contraception for 2 years.

EXCLUSION CRITERIA

1. Significant cardiac valvular disease (planned to undergo cardiac valve intervention/surgery in the next 12 months)
2. Significant atherosclerotic disease (planned to undergo coronary, carotid, or peripheral artery revascularization procedures in the next 12 months)
3. Severe uncompensated cardiopulmonary disease leading to American Society of Anesthesiologists Class IV or V
4. Classified as New York Heart Association Class IV
5. Left ventricular ejection fraction \<20% at the time of screening
6. Hospitalization for myocardial infarction, unstable angina, stroke, transient ischemic attack, heart surgery, coronary stent placement in the past 6 months
7. Prior bariatric and metabolic surgery of any kind (patients who had a gastric balloon or gastric band that were removed more than one year prior to enrollment are allowed to participate)
8. History of solid organ transplant
9. Type 1 diabetes or autoimmune diabetes
10. eGFR \< 30 mL/min/1.73 m2 at screening or being on dialysis
11. Decompensated cirrhosis characterized by ascites, hepatic encephalopathy, portal hypertension, or esophageal varices.
12. Anemia defined as hemoglobin less than 9 g/dL
13. Use of investigational therapy
14. Liver transaminase level \>300 U/L
15. Significant alcohol use (average \>2 drinks/day)
16. Presence of active malignancy (except non-melanoma skin cancer)
17. Life expectancy less than 3 years due to concomitant diseases
18. Major mental health, psychological disorders, or substance abuse disorders that in the opinion of the investigators could disqualify the patient from metabolic surgery
19. Any condition or major illness that, in the investigator's judgment, places the subject at undue risk by participating in the study
20. Unable to understand the risks, benefits and compliance requirements of study
21. Lack capacity to give informed consent
22. Plans to move outside the primary location of study (Northeast Ohio) within the next 12 months
23. Pregnant, breast-feeding or the intention of becoming pregnant or not using adequate contraceptive measures
24. Known adhesive allergies

Trial Locations

• The Cleveland Clinic, Cleveland, Ohio, United States

Contact Information

• Chytaine Hall — CONTACT
  Phone: 216-445-3983
  Email: hallc1@ccf.org
• Ali Aminian — CONTACT
  Phone: 2164450045
  Email: aminiaa@ccf.org

Study Officials

• Ali Aminani — PRINCIPAL_INVESTIGATOR
  Bariatric Research Medical Director

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