AbstractBackgroundAtrial fibrillation (AF) is the most common arrhythmia and can be treated with catheter ablation (CA) combined with left atrial appendage occlusion (LAAO). The study is designed to compare the safety and efficacy of guiding the combined procedure by digital subtraction angiography (DSA) with or without transesophageal echocardiography (TEE).MethodsFrom February 2019 to December 2020, 138 patients with nonvalvular AF who underwent CA combined with LAAO procedure were consecutively included, and two cohorts were built according to intraprocedural guidance (DSA or DSA with TEE). Periprocedural and follow‐up outcomes were compared with investigate the feasibility and safety between the two cohorts.Results71 patients and 67 patients were included in the DSA cohort and TEE cohort, respectively. Age and gender were comparable, despite the TEE cohort having a higher proportion of persistent AF (37 [55.2%] vs. 26 [36.6%]) and hemorrhage history (9 [13.4%] vs. 0). The procedure time of the DSA cohort was significantly reduced (95.7 ± 27.6 vs. 108.9 ± 30.3 min,p= .018), with a nonsignificant longer fluoroscopic time (15.2 ± 5.4 vs. 14.4 ± 7.1 min,p= .074). And the overall incidence of peri‐procedural complications was similar between cohorts. After an average of 24 months of clinical follow‐up, only three patients in the TEE cohort had ≤3 mm residual flow (p= .62). Kaplan–Meier estimates showed nonsignificant differences between the cohorts for freedom from atrial arrhythmia (log‐rankp= .964) and major adverse cardiovascular events (log‐rankp= .502).ConclusionsCompared with DSA and TEE guidance, DSA‐guided combined procedure could shorten the procedural time, while achieving similar periprocedural and long‐term feasibility and safety.