A Randomized Trial Comparing Pulmonary Vein Isolation to Pulmonary Vein Isolation + OPTIMA Ablation in Patients Undergoing Ablation for Atrial Fibrillation
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 67
- 试验地点
- 2
- 主要终点
- Freedom from atrial arrhythmias (>30s)
研究概览
简要总结
Catheter ablation is an established cornerstone of therapy for patients with symptomatic atrial fibrillation (AF) who wish to avoid anti-arrhythmic drug therapy or for whom anti-arrhythmics have proven ineffective. Pulmonary vein isolation (PVI), in which circumferential ablation is performed around the ostia of the pulmonary vein - left atrial junctions, is the standard ablation approach internationally. Single-procedure success rates (1y, freedom from AF, off anti-arrhythmics) for patients with paroxysmal AF is roughly 70%, and even worse (roughly 50%) for patients with persistent AF.
A number of strategies have been developed to improve outcomes in patients undergoing AF ablation, particularly in patients with persistent AF. Unfortunately, large prospective randomized trials (including STAR-AF II, published in NEJM in 2015) have demonstrated a failure of ancillary ablation techniques to improve AF ablation outcomes relative to PVI alone.
In a collaborative effort between the Cardiology electrophysiology group and the Trayanova laboratory (Biomechanical Engineering), investigators have developed a strategy of patient-specific modeling to identify pro-arrhythmic sites in AF patients that may be amenable to ablation. In this approach, patients undergo a pre-ablation cardiac MRI with late gadolinium enhancement, to delineate regions of healthy atrial tissue and regions of scar (this scan is clinically indicated, and performed currently in patients undergoing PVI for AF). A novel in silico modeling to determine regions supporting electrical reentry in the atrium, driving ongoing AF, has been developed by the Trayanova lab. In preliminary studies, investigators have demonstrated the ability to identify and target these regions with catheter ablation in patients undergoing PVI.
Investigators would like to conduct a prospective, randomized clinical trial in patients undergoing ablation for symptomatic persistent AF. All patients enrolled would undergo standard pre-procedure imaging (LGE-MRI) prior to the day of procedure. Investigators have developed methodology termed OPTIMA (OPtimal Target Identification via Modeling of Arrhythmogenesis) to determine, based on non-invasive patient-specific anatomic and tissue data from late gadolinium enhancement cardiac MRI (LGE-CMR) and simulation of cardiac electrical function, personalized ablation targets for persistent AF in patients with fibrotic remodeling.. Patients would be randomized to receiving PVI only versus PVI + OPTIMA ablation at the time of ablation. Patients would then be followed in standard clinical fashion at 3m, 6m, and 12m to assess for ablation efficacy and for procedural complications.
Investigators postulate a 20% improvement in freedom from AF with PVI + OPTIMA ablation form 50% to 70% (compared to PVI alone), investigators anticipate that in 1:1 randomization, a sample size of 80 patients in each arm will yield a power calculation of 80% with an alpha of 0.05. Investigators anticipate that enrollment and 1y clinical follow-up for 160 patients (total) undergoing AF ablation will require a 4y timeline.
详细描述
Background: Atrial fibrillation (AF) is the most commonly encountered clinical arrhythmia. Symptoms arising from AF are common, and may include palpitations, fatigue, exertional intolerance, and angina. Relief of symptoms is achieved by rhythm control strategies including drug therapy and catheter ablation for AF. Catheter ablation is more effective than drug therapy, is the preferred method of rhythm control for patients in whom drug therapy has been ineffective or intolerable, and is increasingly used as first-line therapy. However, success rates for AF control after catheter ablation are imperfect, with AF recurrence rates between 30 - 50% at 1 year. Currently, catheter ablation focuses almost exclusively on electrical isolation of the pulmonary vein (PV) ostia (PV isolation; PVI), to eliminate triggering activity from ectopic foci in the PVs that, in the vast majority of patients, initiate AF. A number of strategies have been developed to improve outcomes in patients undergoing AF ablation, particularly in patients with persistent AF. Unfortunately, large prospective randomized trials (including STAR-AF II, NEJM 2015) have demonstrated a failure of ancillary ablation techniques to improve AF ablation outcomes relative to PVI alone. The failure of PVI and ancillary ablation techniques to deliver reasonable outcomes is exacerbated in patients with persistent AF (PsAF), who develop fibrosis in the atria. These patients have AF ablation outcomes that are demonstrably worse than those seen in patients with persistent AF. Investigators have recently developed methodology (termed OPTIMA, OPtimal Target Identification via Modeling of Arrhythmogenesis) to determine, based on non-invasive patient-specific anatomic and tissue data from late gadolinium enhancement cardiac MRI (LGE-CMR) and simulation of cardiac electrical function, personalized ablation targets for persistent AF in patients with fibrotic remodeling. These targets, which are determined off line pre-procedure, are then used to steer patient treatment. This technology is intended to make the procedure accurate and efficacious in persistent AF patients with fibrosis, and to eliminate the need for repeat ablations, offering long-term freedom from AF.
Hypothesis: In patients undergoing ablation for the treatment of persistent AF, using the OPTIMA approach and performing PV isolation during ablation for AF will improve outcomes compared to performing PV isolation alone.
Importance: In United States, Center for disease control estimates that 2.7-6.1 million people suffer with AF and expects this number to increase with the aging population. Ablation for AF is performed at increasing rates, and in certain population (eg patients with paroxysmal AF) is moderately effective. Even in optimal patients, however, the rate of AF recurrence following apparently successful PV isolation is high (2017 Heart Rhythm Society (HRS) Consensus statement on AF ablation). Strategies to improve AF ablation outcomes should result in improved patient health (symptom elimination), lower patient risk (reduction of the number of patients undergoing redo ablation procedures), and reduced economic burden from healthcare costs (reducing post-ablation treatment for AF, including redo ablation procedures). Furthermore, demonstration of the arrhythmogenic propensity of fibrotic remodeling in patients with persistent AF will add to investigators' collective understanding of the fundamental mechanisms underlying AF initiation and perpetuation.
Objectives: The goal of this study is to test the efficacy of the OPTIMA approach for determining the optimal ablation targets in patients with persistent AF and fibrosis, and to demonstrate that elimination of AF-perpetuating sources in the fibrotic substrate, in conjunction with PVI, during AF ablation improves rate of AF-free survival at 1 year compared to patients undergoing standard PVI alone.
Study Procedures
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
盲法说明
Blinding of patient and outcomes assessor to ablation protocol.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Eligible patients must be at least 18 years old at the time of enrollment.
- •Patient was referred to Johns Hopkins cardiac electrophysiology division for clinically indicated catheter ablation for persistent or long standing persistent AF either for index ablation or redo ablation.
- •Patient is currently on systemic anticoagulation or has no contraindication to initiate systemic anticoagulation.
- •Capable of undergoing informed consent.
- •A Pre-Op cardiac MRI including LGE in sinus rhythm must be performed prior to ablation and patient should be capable of undergoing cardioversion and cardiac MRI.
- •MRI scan should show evidence of left atrial scarring.
排除标准
- •Patient is not a suitable candidate for AF ablation.
- •Patient is currently not on anticoagulation and has significant contraindications to initiate systemic anticoagulation.
- •Pregnant women may not participate in the study because gadolinium MRI contrast is contraindicated in pregnancy.
- •Patient with Body weight more than 300 lbs as they cannot undergo MRI scans.
- •Patients with Glomerular Filtration Rate (GFR) < 30 mL/min should not be enrolled in the study due to the use of intravenous gadolinium as an MRI contrast agent.
- •No evidence of Left Arial fibrosis in MRI scan as these images are not suitable for simulation.
- •Inability to get MRI in sinus rhythm.
- •Long standing persistent AF more than 3 years of duration.
- •Prior surgical maze procedure.
结局指标
主要结局
Freedom from atrial arrhythmias (>30s)
时间窗: 1 year
Freedom from recurrent Atrial fibrillation (AF)/Atrial Tachycardia (AT)/Atrial Flutter (\> 30s) after 90 day blanking period. This will be measured as the percentage of the study population that is free from atrial arrhythmias during the 1y follow-up period.
次要结局
- Freedom from major complications(1 year)
- Change in AF burden(1 year)
- Percent participants with 70% or more reduction in AF burden(1 year)