The Substrate and Intervention Mechanisms for Persistent Atrial Fibrillation (SIMPle AF) Trial
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 2
- 主要终点
- Recurrence of Atrial Fibrillation (AF) > 30 Seconds
研究概览
简要总结
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia with increasing morbidity and mortality. A catheter-based AF ablation technique that isolates pulmonary veins (PV) from the left atrium has been established to disrupt AF. Despite significant development, AF ablation with pulmonary vein isolation (PVI) is reported to have a success rate of 40-80% in various AF populations.
Persistent AF appears to be more reliant upon fibroblast proliferation and myocyte-fibroblast coupling than paroxysmal AF with obvious implications on its management. Despite the knowledge that fibrotic substrate is responsible for the perpetuation of persistent AF, several ablation techniques targeting these extra-pulmonary veins sites have failed to prove an additional benefit to PVI alone. Nevertheless, two recently developed technologies, aimed at detecting AF substrate with high precision, seem to constitute a potential breakthrough in the management of persistent AF. On one hand, late gadolinium-enhanced MRI (LGE-MRI) is a well-established method to identify fibrosis in the myocardium. Recent reports from a single center have shown that MRI-based left atrial fibrosis detection is able to predict the outcome of the procedure. Hence, targeting lesions seen on LGE-MRI in the setting of persistent AF is an option yet to be explored and compared to the widely adopted, yet suboptimal, PVI. On another hand, a novel ablation method with promising results is focal impulse and rotor modulation (FIRM). Undergoing wide sampling of the atria with spatiotemporal and computational mapping while in AF has identified areas with stable organized rotational electrical activity (rotors). Several studies are under way to prove the reproducibility of rotor mapping, with more groups reporting improved rates of acute and long-term suppression of AF with ablation of FIRM-identified rotors.
The SIMPle AF study will be a randomized clinical trial designed to test the hypothesis that ablation tailored to the underlying substrate using either LGE-detected dense scar or rotor anchor sites predicted by computational modeling is superior to anatomic non-tailored PVI ablation in patients with persistent AF. For the present study, the investigators plan to enroll a total of 30 patients.
详细描述
Objectives The main objective of the study is to identify the optimal ablation strategy for suppression of persistent AF.
The secondary objectives of the study are:
- To define the local myocardial image characteristics of slow conduction AF substrates.
- To define the local myocardial structural changes post ablation that associate with AF suppression at 1-year follow-up
- To compare cardiac remodeling and atrial function at 1-year follow-up between PVI only and tailored catheter ablation groups
Background
Atrial fibrillation (AF) is associated with increased risk for mortality, heart failure, and thromboembolic events, and has a worldwide prevalence of >33.5 million. Catheter ablation of AF is evolving as an effective therapy for symptomatic AF. Recurrent AF after ablation, however, remains a problem and has been reported to associate with the baseline extent of left atrial (LA) late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR). Mechanistically, persistent AF appears to be more reliant upon fibroblast proliferation and myocyte-fibroblast coupling than paroxysmal AF, which is primarily dependent upon pulmonary vein triggers. Therefore, the investigators hypothesize that the substrate for persistent AF is detectable on atrial LGE-CMR and variable among patients, and that the substrate predicts patient outcomes after anatomic non-tailored ablation, and is more likely to respond to individually tailored ablation approaches. Two individually tailored approaches will be studied including empiric targeting of dense LGE, confirmed on bipolar mapping to have voltage <0.3 mV, and modeling based targeting of rotor anchor sites.
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
- None
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
- •History of persistent atrial fibrillation
- •Indicated for an AF-ablation procedure
- •Agree to participate in the trial
排除标准
- •Are unable or unwilling to provide informed consent for the SIMPle AF study
- •Patients with cardiac devices like pacemakers, internal cardiac defibrillators and Cardiac Resynchronization Therapy Device (CRT). Patients with acute or chronic renal insufficiency (glomerular filtration rate <30 ml/min/1.73 m2), or patients in the perioperative liver transplantation period
- •Pregnant women
- •Patients who are unable to adhere to the follow up protocol
- •Patients with contraindication to MRI, including ferromagnetic aneurysm clips, metal in the eye, and implanted ferromagnetic or other MRI-incompatible devices
- •Patients in whom the LGE Cardiac MRI does not meet quality standards for fibrosis analysis
- •Subjects without daily access to a smart phone or tablet compatible with the mobile-based application and ability to upload ECG tracings for the follow up period
- •Patients with a history of allergic reactions to gadolinium-based contrast agents or ingredients and will not be premedicated**
- •Subjects with a history of reaction to contrast may be premedicated according to institutional protocol prior to receiving intravenous contrast agents
研究组 & 干预措施
Conventional PVI
Conventional PVI by Radio-frequency Ablation: Wide area circumferential pulmonary vein isolation (PVI) only (current standard of care) using radio-frequency ablation catheters.
干预措施: Conventional PVI by Radio-frequency Ablation (Device)
PVI + Scar-based ablation
Scar-Based Radio-frequency Ablation: Pulmonary vein isolation followed by targeting, using radio-frequency ablation, of dense LGE sites on MRI, which are confirmed on bipolar mapping to have voltage <0.3 mV.
干预措施: Scar-Based Radio-frequency Ablation (Device)
PVI + Modeling-predicted rotors ablation
Rotor Anchors Radio-frequency Ablation: Pulmonary vein isolation followed by radio-frequency ablation of rotor anchors predicted by modeling.
干预措施: Rotor Anchors Radio-frequency Ablation (Device)
结局指标
主要结局
Recurrence of Atrial Fibrillation (AF) > 30 Seconds
时间窗: Following the 90 day blanking period up to 12 months post-index pulmonary vein isolation
Primary outcome is defined as symptomatic or asymptomatic AF of at least 30 seconds duration that is documented by an ECG or mobile rhythm monitoring device (AliveCor), occurring after the 3-month blanking period following catheter ablation and up to 12 months.
次要结局
未报告次要终点