The goal of this pilot study is to explore the efficacy of chloroquine in terminating persistent AF and assess its potential role as a pharmacological cardioversion agent for the management of AF.

This is an open-label, pilot study to explore the efficacy of chloroquine in terminating persistent AF within 2 weeks of drug administration and assess its potential role as a pharmacological cardioversion agent for the management of AF. Subjects will be followed for 2 weeks from the start of drug administration to study drug termination.

Inclusion Criteria:

1. Age 18 years and older
2. History of symptomatic persistent AF Persistent AF - defined as continuous AF that is sustained more than 7 days but less than 12 months. Episodes of AF of ≥ 48 hours duration in which a decision is made to terminate with electrical or pharmacological cardioversion prior to 7 days will also be classified as persistent AF
3. AF must be documented at least once either by ECG, event monitoring, loop recorder, telemetry, trans-telephonic monitoring, pacemaker or cardiac defibrillator readouts within 24 months prior to enrollment
4. Currently on anticoagulation therapy as indicated per local guidelines, which is considered optimal for stroke prevention in the opinion of the investigator
5. Implanted dual chamber pacemaker/ICD capable of monitoring atrial arrhythmias or willingness to wear a 2 weeks event monitor if patient does not have a device capable of monitoring atrial arrhythmias
6. Signed informed consent

Exclusion Criteria:

1. Age < 18 years

2. AF felt to be secondary to an obvious reversible cause such as, but not limited to, acute myocardial infarction, pulmonary embolism, recent surgery, pericarditis, alcohol intoxication, hypoxemia, or thyrotoxicosis

3. Structural heart disease including patients with artificial heart valves or valvular AF

4. Obstructive coronary artery disease or history of any myocardial infarction

5. Ejection fraction < 50% within 1 year of consent

6. Severe or moderate to severe aortic stenosis, mitral stenosis, aortic regurgitation, or mitral regurgitation per PI discretion

7. Prolonged QTc of >460 msec on baseline ECG

8. Contraindications to quinolines

9. Known allergy or hypersensitivity to Chloroquine

10. Use of amiodarone 12 months prior to enrollment

11. History of AF ablation within 30 days prior to enrollment

12. Renal impairment (eGFR < 30 mL/min/1.73 m2 or Serum Creatinine > 1.25 mg/dL) for subjects over the age of 65

13. Hepatic disease (ALT/AST 2X the upper normal limit)

14. History of alcohol abuse and/or drug abuse per PI discretion

15. Pre-existing auditory damage

16. History of epilepsy

17. Women of child-bearing potential (those who have had a menstrual period in the previous 12 months) who:

    • are pregnant or breast-feeding or plan to become pregnant during study or
    • who are not surgically sterile and are not practicing two acceptable methods of birth control, or do not plan to continue practicing two acceptable methods of birth control throughout the study (highly effective methods are listed under section 6.0 Pregnancy)

18. Current participation in another clinical study

19. Serious or active medical or psychiatric condition which, in the opinion of the investigator, may interfere with treatment, assessment, or compliance with the protocol

20. Not able to discontinue medications known to have significant interactions with chloroquine