The COMBINE-AF Trial

The goal of this clinical trial is to test if a more complete ablation procedure works better than the standard procedure for people with long-lasting persistent atrial fibrillation (AF). AF is a heart rhythm problem that can cause a fast or uneven heartbeat. This study will include 430 people with long-lasting AF that has lasted 1 to 3 years. Participants will be put into one of two groups by chance: First group (control): They will receive pulsed-field ablation (PFA), a type of energy that can stop the faulty heart signals. They will have isolation of the pulmonary veins and the posterior wall of the left atrium. Second group (study): They will receive the same PFA procedure plus extra ablation lines (modified linear ablation) using radiofrequency energy. This includes ablation of the mitral isthmus (with ethanol infusion into a small vein called the vein of Marshall) and the cavotricuspid isthmus. Participants will be followed for 12 months after the procedure with clinic visits, electrocardiograms (ECGs), and heart rhythm monitors. The main outcome is whether participants stay in normal heart rhythm (sinus rhythm) without any AF episodes lasting more than 30 seconds at 12 months. Researchers will also look at procedure time, complication rates, quality of life, and other rhythm outcomes. This study will help show if the more complete ablation procedure leads to better long-term results for people with long-lasting AF.

Inclusion Criteria: * Symptomatic patients with long-standing persistent atrial fibrillation. * Duration of atrial fibrillation between 1 and 3 years. * Age 18 to 75 years. * Documentation of atrial fibrillation within 3 years prior to enrollment. * Willing and able to comply with the study protocol and provide written informed consent. Exclusion Criteria: * Paroxysmal atrial fibrillation, or evidence of sinus rhythm on electrocardiogram within the past year. * Persistent atrial fibrillation lasting less than 1 year or more than 3 years. * Left atrial thrombus. * Prior catheter ablation for atrial fibrillation. * Coexisting severe organic heart disease (e.g., severe valvular heart disease, hypertrophic cardiomyopathy, dilated cardiomyopathy, etc.). * Left atrial diameter (LAD) \>55 mm. * Left ventricular ejection fraction (LVEF) \50 mmHg. * Unstable angina pectoris. * Percutaneous coronary intervention (PCI) within the past 3 months. * Cardiac surgery within the past 6 months. * Planned heart transplantation. * History of thromboembolic disease within the past 6 months (including venous thromboembolism: pulmonary embolism, deep vein thrombosis; or arterial thromboembolic disease: acute coronary syndrome, lower extremity arterial embolism, stroke). * Left atrial myxoma. * Severe respiratory disease. * Active infectious disease. * Poorly controlled or active systemic immune disease (equivalent to glucocorticoid use \>2 tablets/day). * Unresolved malignant hematologic disease, or currently receiving chemotherapy, radiotherapy, or immunotherapy. * Unresolved malignant solid tumor, or currently receiving chemotherapy, radiotherapy, or immunotherapy. * Untreated hypothyroidism or hyperthyroidism. * Severe hepatic insufficiency (alanine aminotransferase \[ALT\] or aspartate aminotransferase \[AST\] \>3 times the upper limit of normal). * End-stage renal failure requiring dialysis. * Other serious arrhythmias, such as hemodynamically unstable ventricular tachycardia. * Pregnancy or breast-feeding. * Psychiatric disorder. * Body mass index (BMI) \35.0 kg/m². * Life expectancy \