DESCRIPTION (provided by applicant): This proposal entails a five-year training program focused on preparing James V Freeman, MD, MPH, MS, for an independent career in patient-oriented academic cardiovascular medicine. This proposal aims to impart the skills and knowledge required for the applicant to achieve his long-term goal of contributing insights into the best clinical treatment strategies for patients with cardiac arrhythmias, and particularly atril fibrillation. The applicant's immediate training objectives are to master fundamental clinical research methods, perform coursework that will expand his understanding of advanced methods, develop administrative skills required to function autonomously, and compose a body of work that will enable him to obtain funding as an independent investigator. Under the guidance of his long-term mentors, Mark Hlatky and Alan Go, as well as a carefully selected advisory committee of senior investigators, he will have the resources and support to achieve these goals and transition to independence. PROJECT DESCRIPTION Atrial fibrillation (AF) affects over 2.3 million adults in the United States and this number is projected to increase to at least 5.6 million by 2050. Catheter ablation for atrial fibrillation (AF), using radiofrequency energy or cryotherapy to electrically isolate the pulmonary veins and eliminate arrhythmia foci, is a new therapy that is currently used to treat 50,000 patients per year in the United States and 60,000 patients per year in Europe. Randomized studies suggest that AF ablation may decrease arrhythmia burden and improve quality of life, but the procedure has also been associated with a 1-10% rate of procedural complications. No randomized studies to date have demonstrated the long term impact of the procedure on death, ischemic stroke, intracranial hemorrhage and hospitalization and the one ongoing randomized study includes a very selected trial population and has had significant patient enrollment challenges. We propose a series of analyses in real- world patients with AF, to close some of the major evidence gaps related to AF ablation. The proposed project will use standard and innovative methods to analyze clinical data from Kaiser Permanente Northern California and Southern California (two health care systems for over 6.5 million people) and a novel cross-sectional survey study to achieve four specific aims: 1) to establish whether atrial fibrillation ablation is associated with long-term mortality, ischemic stroke, intracranial hemorrhage and hospitalization in patients with atrial fibrillation; 2) to determine the risk of procedure-related adverse safety events associated with atrial fibrillatio ablation, the predictors of these adverse events, and the rate of recurrent hospitalization and death after these events; 3) to estimate the cost-effectiveness of atrial fibrillation ablation incorporating long-term estimates of death, ischemic stroke, intracranial hemorrhage and hospitalization; 4) to assess patient-centered characteristics which inform the decision to undergo atrial fibrillation ablation and barriers to treatment with ablation.

PUBLIC HEALTH RELEVANCE: We will evaluate the effects of catheter ablation compared with medical therapy for the treatment of atrial fibrillation on the long-term outcomes of death, ischemic stroke, intracranial hemorrhage and hospitalization, and we will assess the incidence of acute adverse safety events associated with catheter ablation. We will evaluate the cost-effectiveness of AF ablation taking into account these important short and long-term outcomes. Finally, to better understand patient decision-making for atrial fibrillation treatment, we will assess the patient sociodemographic characteristics, medical history, health behaviors and attitudes towards risk that are associated with catheter ablation vs medical therapy.