Catheter ablation has become as the first-line treatment for patients with symptomatic atrial fibrillation (AF). As the cornerstone of catheter ablation for AF, the safety and efficacy of circumferential pulmonary vein isolation (CPVI) have been confirmed. However, for persistent AF, especially for long-standing persistent AF (LSPAF), the recurrence rate is still high. Whether the ethanol infusion (EI) into the vein of Marshall (EI-VOM) and linear ablation could improve the success rate remains controversial.

The SINUS study is a prospective, multicenter, randomized trial, which is designed to compare the efficacy and safety between CPVI with modified linear ablation (CPVI-MLA) and CPVI only for the treatment of LSPAF.

The SINUS study will include 320 patients with LSPAF undergoing catheter ablation for the first time. All patients will be randomized to either the CPVI-MLA group or CPVI only group in a 1:1 ratio. The CPVI-MLA strategy is a fixed ablation approach consisting of EI-VOM, CPVI, left atrial posterior wall isolation (PWI), linear ablation of mitral isthmus (MI), left atrial intima adjoining CS (LAI-CS) and cavo-tricuspid isthmus (CTI), and superior vena cava isolation (SVCI). The follow-up is for a minimum of 12 months with rhythm monitoring. The primary endpoint is freedom from any documented atrial arrhythmia including atrial fibrillation (AF), atrial tachycardia (AT), or atrial flutter (AFL) > 30 seconds after the initial 3 months blanking period without the use of antiarrhythmic drugs (AADs), at 12 months after the index ablation procedure.

Inclusion Criteria:

1. 1. Patients with symptomatic LSPAF refractory to at least one antiarrhythmic drug; LSPAF will be defined as a sustained AF episode lasting ≥ 1 year;
2. AF duration 1-3 years;
3. Age 18 - 75 years;
4. Left atrial diameter (LAD) 43-55 mm on long axis parasternal view;
5. AF recorded within 3 years of enrollment;
6. Patient willing and able to comply with protocol and sign informed consent

Exclusion Criteria:

1. Paroxysmal atrial fibrillation;
2. Persistent AF lasting < 1 year or >3 years;
3. Left atrial thrombosis;
4. Patients with a history of catheter ablation for AF;
5. Patients with severe structural heart disease (severe valvular heart disease, hypertrophic cardiomyopathy, dilated cardiomyopathy, etc.);
6. LAD > 55mm on long axis parasternal view;
7. Left ventricular ejection fraction (LVEF) < 40%;
8. Patients with contraindications to low molecular weight heparin, warfarin or novel oral anticoagulants;
9. One-stop procedure for AF ablation and left atrial appendage occlusion;
10. Alcohol allergy or contrast agent allergy;
11. Patients taking cephalosporin antibiotics within 72 hours prior to ablation;
12. Pulmonary artery systolic pressure > 50mmHg;
13. Patients with unstable angina pectoris;
14. Patients who had undergone percutaneous coronary intervention (PCI) within 3 months;
15. Patients who had undergone surgery within 6 months;
16. Patients ready to receive heart transplantation;
17. Patients with a history of thromboembolism within 6 months;
18. Patients with diagnosed atrial myxoma;
19. Patients with severe respiratory diseases;
20. Patients with infectious diseases in active phase;
21. Patients with poorly controlled systemic immune diseases;
22. Patients with uncured malignant hematological diseases;
23. Patients with uncured malignant solid tumors;
24. Patients with untreated hypothyroidism or hyperthyroidism;
25. Patients with severe liver dysfunction (elevation of transaminases [ALT or AST] >3 times the upper limit of normal range);
26. Patients with end-stage renal failure requiring dialysis;
27. Patients with other serious arrhythmias, such as ventricular tachycardia with hemodynamic instability;
28. Pregnant and lactating women;
29. Patients with psychiatric ailments;
30. BMI < 18.5 or ≥ 30kg/m2;
31. Life expectancy < 2 years;
32. Patients unwilling or unable to give informed consent;
33. Patients unwilling or unable to cooperate to complete follow-up.

The data used and analyzed to support the study are available from the principal investigator on reasonable request.