C atheter ablation has become a routine treatment option for patients experiencing symptomatic paroxysmal atrial fibrillation (AF). Long-term clinical success rates of ≤80% after 5 years have been reported for the treatment of paroxysmal AF by initial stand-alone pulmonary vein isolation (PVI) as the accepted cornerstone of all AF ablation strategies; however, to achieve permanent PVI, multiple procedures are often required. 1,2 In contrast, the results for ablation of persistent AF are less convincing. 3 The optimal strategy for persistent AF is not known, and previous studies investigating more extensive ablation strategies in addition to PVI demonstrated heterogeneous results.  The recently published STAR AF 2 trial (Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial) compared initial stand-alone PVI to PVI with additional ablation of complex fractionated atrial electrograms (CFAEs) or additional linear ablation and could not demonstrate a superior outcome for the additional ablation strategies. 13 The prospective and randomized Alster-Lost-AF © 2017 American Heart Association, Inc. Original ArticleBackground-Pulmonary vein isolation (PVI) for persistent atrial fibrillation is associated with limited success rates and often requires multiple procedures to maintain stable sinus rhythm. In the prospective and randomized Alster-Lost-AF trial (Ablation at St. Georg Hospital for Long-Standing Persistent Atrial Fibrillation), we sought to assess, in patients with symptomatic persistent or long-standing persistent atrial fibrillation, the outcomes of initial ablative strategies comprising either stand-alone PVI (PVI-only approach) or a stepwise approach of PVI followed by complex fractionated atrial electrogram ablation and linear ablation (Substrate-modification approach). Methods and Results-Patients were randomized 1:1 to stand-alone PVI or PVI plus substrate modification. The primary study end point was freedom from recurrence of any atrial tachyarrhythmia, outside a 90-day blanking period, at 12 months. A total of 124 patients were enrolled, with 118 patients included in the analysis (61 in the PVI-only group, 57 in the Substrate-modification group). Atrial tachyarrhythmias recurred in 28 PVI-only group patients and 24 Substratemodification group patients, for 1-year freedom from tachyarrhythmia recurrence after a single ablation procedure of 54% (95% confidence interval, 43%-68%) in the PVI-only and 57% (95% confidence interval, 46%-72%) in the Substratemodification group (P=0.86). Twenty-four patients in the PVI-only group (39%) and 18 in the Substrate-modification group (32%) were without arrhythmia recurrence and off antiarrhythmic drug therapy at the end of the 12-month follow-up.