From February 2018 to February 2020, the investigators enroll consecutive patients with drug-refractory persistent atrial fibrillation who were scheduled for an initial catheter ablation.Patients are divided in to two group: persistent AF in radiofrequency ablation group, cryoballoon ablation group.

1. Radiofrequency ablation group: Each patient randomly allocated into the radiofrequency ablation group receives circumferential pulmonary vein isolation(CPVI), if atrial flutter is diagnosed before and during operation,then a radiofrequency is used to ablate cavo-tricuspid isthmus. Under the 3D electro-anatomical mapping system (Carto 3, Biosense Webster), after passing through the transseptal sheath, the ablation catheter is infused under pressure to enter into the left atrium to carry out radiofrequency ablation.The default strategy is to create a circle surrounding the two ipsilateral pulmonary veins. The cardioversion is performed if spontaneous conversion is not observed after CPVI. Observation is carried out for 20-30 minutes after the entrance and exit block of pulmonary vein potentials,in the meantime investigators will mapping the left atrial substrate. If mapping system detect a poor substrate,the investigators should continue to ablate for left atrial roof and posterior line.The situation of pulmonary vein potential conduction will be detected again. If there is a recovery, ablation will be continuously carried out.
2. Cryoballoon ablation group: Cryoablation is performed using a single cryoballoon. The diameter of the cryoballoon (Arctic Front Advance™ Cardiac CryoAblation Catheter; Medtronic, Minneapolis, MN) is determined as 28 mm or 23 mm according to pulmonary venography results. After passing through the transseptal sheath, the cryoballoon catheter enters into the left atrium and is continuously infused with heparin saline through a 15F oriented sheath. The balloon is inflated at the entrance of the pulmonary vein. The mapping confirms that the balloon blocks the entrance of the pulmonary vein. After blocking of the entrance of the pulmonary vein is enhanced, liquid nitrogen is injected for cryoablation. Before performing right pulmonary vein ablation, a secondary catheter is placed into the superior vena cava during the cryoablation. A cycle length of 999 ms is taken to continuously make the right phrenic nerve pulsate. If diaphragm movement is weakened or disappears, the cryoablation will be immediately stopped. In general, the cryoablation of each pulmonary vein is carried out twice. According to the objective condition, the operator determine whether or not to carry out an additional cryoablation. The cardioversion is performed if spontaneous conversion is not observed after CPVI. Then investigators will applicate electrophysiological substrate mapping for guiding ablation of atrial fibrillation,If mapping system detect a poor substrate, investigators should continue to ablate for left atrial roof and posterior line. By testing the entrance and exit block of pulmonary vein potentials，the investigators observe the duration of potentials.
3. All patients fill the follow-up form before operation. After catheter ablation therapy, all patients invited to come back to the outpatient clinic every week in the first month, and then at 2, 3, 6, 9, and 12 month to follow up. Patients received electrocardiogram and Holter monitor examination if with symptoms of palpitations. Those patients with no symptoms received electrocardiogram every month and Holter monitor examination every 6 months. Recurrence of atrial fibrillation was defined as atrial fibrillation/flutter or atrial tachycardia lasting ≥ 30 seconds 3 months after ablation therapy. Atrial electrical activity including atrial effective refractory period, atrial conduction time, electromechanical conduction time, P wave dispersion and spatial dispersion of atrial refractory will be measured before and after the operation.Blood samples (routine blood, high sensitivity c-reactive protein,B-type natriuretic peptide (BNP), cystatin C,homocysteine,β2-microglobulin) and transthoracic echocardiography indexes (left atrial anterior to posterior diameter, left atrial length-diameter,left atrial transverse-diameter,left atrial volume index, mitral e', E peak, A peak, E/A,velocity time integral (VTI), left atrial ejection fraction, left atrial strain, strain rate and atrial electrical - mechanical conduction time) are recorded in all patients at each follow-up. Patients with AF recurrence must have an electrocardiogram or a 24 hour holter monitor evidence.