Targeting Risk Interventions and Metformin for Atrial Fibrillation (TRIM-AF)

TRIM-AF Cohorts

Inclusion Criteria:

1. Permanent pacemaker or implantable cardioverter-defibrillator (ICD) (with or without
cardiac resynchronization therapy (CRT) with an implanted atrial lead capable of
providing AF diagnostics and remote monitoring.

2. Paroxysmal AF, or persistent AF with plans for conversion.

3. AF on cardiac implantable electrical device (CIED) over the past 3 months with at
least 1 episode lasting ≥5 minutes.

4. If on an antiarrhythmic drug, then on a stable regimen for the past 3 months.

Exclusion Criteria:

1. Permanent AF with no plans to convert to sinus rhythm.

2. If in persistent AF, current episode >12 months in duration (current long-standing
persistent AF)

3. New York Heart Association (NYHA) Functional Class IV heart failure

4. Diagnosed with diabetes mellitus

5. On metformin or other pharmacologic therapy for diabetes mellitus.

6. Use of anti-retroviral protease inhibitors (e.g. ombitasvir, paritaprevir, ritonavir,
dasabuvir) or topiramate.

7. Known sensitivity to metformin

8. Moderate renal disease (eGFR <45 ml/min/1.73 m2 or Cr >1.8)

9. Significant alcohol use (average >2 drinks/day)

10. Metabolic acidosis (serum bicarbonate <22 meq/L) or history of lactic acidosis

11. History of hepatic dysfunction - bilirubin >1.5x upper limits of normal, unless due to
Gilbert's syndrome

12. Planned antiarrhythmic (class I or III) drug change, AF ablation/PVI procedure or
cardiac surgery over the first 3 mos of the study

13. For patients on dofetilide, corrected QT interval (QTc) >460 ms if QRS duration is
100 ms, adjusted QTc >460 ms. Adjusted QTc = QTc - (QRS
duration - 100 ms).

14. Women who are pregnant, breast-feeding or of child-bearing potential and not willing
or able to use an acceptable form of contraception.

15. Participants considered by the investigator to be unsuitable for the study for any of
the following reasons: Not agreeable for treatment with metformin or anticipated to
have poor compliance on study drug treatment; inability to follow diet or exercise
instructions; unwilling to attend study follow-up visits

16. Life expectancy less than 2 years due to concomitant disease.

17. Age <18 years old.

TRIM - No AF Cohort

Inclusion Criteria:

1. Permanent pacemaker or ICD (with or without CRT) with an implanted atrial lead capable
of providing AF diagnostics and remote monitoring.

2. No AF on CIED over the past 6 months.

3. No history of AF.

4. Age >/=18 years old.

Exclusion Criteria:

1. History of AF.