MAESTRO-PAF for Major Adverse Events and Stroke in Paroxysmal Atrial Fibrillation

 描述（由申请人提供）：房颤（AF）是一个主要的临床和公共卫生问题。AF与卒中、栓塞事件、心力衰竭恶化和全因死亡的风险增加相关。大多数关于房颤后果的证据都集中在持续性房颤患者身上。然而，美国最常见的房颤类型是阵发性房颤（PAF），通常无症状，除非受试者接受连续心脏监测，否则不太可能被识别。因此，PAF的自然史和健康后果及其向持续性AF的进展仍不完全清楚。最近致力于了解PAF在触发卒中和其他主要不良事件中的作用的努力尚未得出结论，由于随访和样本量有限，目前的证据不足以量化卒中和其他与PAF发作相关的主要不良事件的风险。 为了更好地了解PAF对死亡和其他心血管事件风险的短期和长期影响，我们将收集一个独特的数据集，该数据集包含约238，000名在2006-2017年期间使用远程监测植入双腔植入式心律转复除颤器（ICD）的患者，这些患者在植入时没有持续性/永久性AF，但PAF风险特别高。该数据集代表了持续监测心房颤动事件的最大人群，是来自三大ICD制造商（Medtronic、Boston Scientific和St. Jude Medical）的前所未有的数据组合的结果，这三家制造商共占美国ICD市场的95%。所有双腔ICD均提供可靠的自动算法，用于检测持续时间>30分钟的PAF发作，记录发作时间、持续时间和心率。我们将通过使用间接数据元素的成熟链接方法，将PAF发作数据与来自国家心血管数据登记系统的植入时患者特征以及来自医疗保险利用文件和国家死亡指数的住院结局数据（随访时间长达12年（约990，000人-年））相关联。主要终点为缺血性卒中（预期事件数量约为4，700起），次要终点为心肌梗死（约8，600起事件）、其他栓塞事件（约4，500起事件）、因心力衰竭加重住院（约20，500起事件）和全因死亡（约96，700起事件）。我们假设阵发性房颤发作增加了主要和次要终点的短期和长期风险，并且持续性房颤进展速度加快也与结局风险增加相关。这项研究的范围和规模将使我们能够描述PAF的后果和进展，并首次定量估计与PAF发作相关的短期和长期风险增加。这些结果将对临床风险评估和卫生政策具有重要意义。

 DESCRIPTION (provided by applicant): Atrial fibrillation (AF) is a major clinical and public health problem. AF is associated with an increased risk of stroke, embolic events, heart failure exacerbation, and all-cause mortality. Most of the evidence on the consequences of AF has focused on patients with persistent AF. However, the most common type of AF in the US is paroxysmal AF (PAF) which is often asymptomatic and unlikely to be identified except in subjects undergoing continuous cardiac monitoring. Hence, the natural history and health consequences of PAF and its progression towards persistent AF remain incompletely understood. Recent efforts focusing on understanding the role of PAF in triggering strokes and other major adverse events have been inconclusive and current evidence is insufficient to quantify the risk of stroke and other major adverse events associated with PAF episodes due to limited follow-up and sample size. To better understand the short- and long-term effects of PAF on the risk of death and other cardiovascular events, we will assemble a unique dataset of ~238,000 patients with dual-chamber implantable cardioverter defibrillators (ICDs) using remote monitoring implanted from 2006-2017 and with no persistent/permanent AF at the time of implant but who are at particularly high risk for PAF. This dataset represents the largest cohort of individuals with continuous monitoring of atrial arrhythmic events and is the result of an unprecedented combination of data from the three major ICD manufacturers (Medtronic, Boston Scientific, and St. Jude Medical), which collectively have 95% of the US ICD market. Reliable automated algorithms for detecting PAF episodes of duration >30 minutes are available in all dual-chamber ICDs which record time of onset, duration and heart rates. We will link PAF episode data with patient characteristics at the time of implant from the National Cardiovascular Data Registry and with hospitalization outcomes data from the Medicare utilization files and the National Death Index with up to 12 years of follow-up (~990,000 person-years of follow-up) through well-established linking methodologies using indirect data elements. The primary endpoint will be ischemic stroke (expected number of events ~4,700) and the secondary endpoints will be myocardial infarction (~8,600 events), other embolic events (~4,500 events), hospitalization for heart failure exacerbation (~20,500 events) and all-cause mortality (~96,700 events). We hypothesize that PAF episodes increase the short-term and the long-term risk of the primary and secondary endpoints and that faster rates of progression toward persistent AF are also associated with an increased risk of outcomes. The scope and size of this study will allow us to describe the consequences and progression of PAF and to quantitatively estimate, for the first time, the short- and long-term increase in risk associated with PAF episodes. These results will have important implications for clinical risk assessment and health policy.