PET/MRI imaging of mitral valve prolapse

项目总结 二尖瓣脱垂(MVP)是最常见的心脏瓣膜，占总人口的1-3%。 异常，并发症包括心力衰竭、室性心律失常和心脏性猝死 (SCD)。据估计，与MVP相关的SCD的发病率每年为0.14%至1.5%，具体取决于 研究人群的临床特征。虽然已经有多个功能被标识为 作为风险增加的标志，左心室替代性纤维化似乎是心律失常患者一致的发现 最有价值球员。心脏磁共振成像(MRI)的晚期Gd增强(LGE)被认为是 评估替代性纤维化的存在和分布的最敏感和特异的方法 与MVP患者心律失常事件的发生率增加密切相关。初步 我们小组的研究表明，这些纤维化改变可能先于慢性炎症性疾病 炎症和疤痕形成可能是脑室转化连续体的一部分，并直接 与心律失常的发展和复杂性有关。我们现在建议深入描述 混合正电子发射中18F-脱氧葡萄糖(FDG)摄取强度与模式的关系 CT(PET)/MRI、心律失常负荷、MVP严重程度和二尖瓣关闭不全(MR)。详细数据 包括患者的基线特征、超声心动图特征、组织学和生物标志物数据， 将获得MVP患者的心律失常负荷和特征，轻度、中度和重度MR，在 目的：建立不同病程与PET/MRI表现型之间的相关性。 具体地说，在目标1中，我们将在一组患者中建立18F-FDG特征的炎症来源 MVP、重度MR和二尖瓣手术的I/II级适应证。生物标志物的组织学和血清学检测 分析将在手术时收集。患者还将接受第二次成像治疗， 一种新型的PET示踪剂，68Ga-DOTATE，更具炎症特异性。在AIM 2中，MVP患者，轻度或 没有手术指征的中度MR和脑室异位病史将被纳入 一项纵向观察性临床研究。我们将进行18F-FDG PET/MRI成像，超声心动图，7天 事件监测(PVC负担和复杂性)以及在基线和后续收集循环生物标志物- 24个月后回升。最后，在目标3中，我们将评估MV手术对心肌炎症和 功能，重复与目标2相同的评估，但在术后12个月探索联系 MV手术与心肌炎性改变之间的关系。通过这种全面的方法，我们的终极 目标是创建一个评估MVP的新平台，特别是在与风险分层有关的情况下 室性心律失常和心源性心脏病。我们假设，我们的研究结果可能会导致更准确的成像- 指导患者管理，并有可能显著影响当前的指南建议 用于风险分层评估、药物治疗和手术干预时机。

PROJECT SUMMARY Mitral valve prolapse (MVP), identified in 1-3% of the general population, is the most common cardiac valvular abnormality, with complications that include heart failure, ventricular arrhythmias and sudden cardiac death (SCD). It has been estimated that the incidence of MVP-related SCD is 0.14% to 1.5% per year, depending on the clinical characteristics of the population studied. While there have been multiple features identified as markers of increased risk, left ventricular replacement fibrosis appears to be a consistent finding in Arrhythmic MVP. Late gadolinium enhancement (LGE) by cardiac magnetic resonance imaging (MRI) is considered the most sensitive and specific modality for assessing the presence and distribution of replacement fibrosis and it has been strongly associated with increased incidence of arrhythmic events in patients with MVP. Preliminary investigations from our group suggest that these fibrotic changes may be preceded by a chronic inflammatory phase and that inflammation and scarring may be part of a continuum of ventricular transformation and directly associated with arrhythmia development and complexity. We now propose an in-depth characterization of the relationship between intensity and pattern of 18F-fluorodeoxyglucose (FDG) uptake on hybrid Positron Emission Tomography (PET)/MRI, arrhythmia burden, severity of MVP and mitral regurgitation (MR). Detailed data including patients’ baseline characteristics, echocardiographic features, histological and biomarker data, arrhythmic burden and characterization will be obtained in patients with MVP, mild, moderate and severe MR, in order to establish the correlation between the disease process in its various stages and the PET/MRI phenotype. Specifically, in Aim 1 we will establish the inflammatory origin of the 18F-FDG signature in a cohort of patients with MVP, severe MR and class I/II indications for mitral valve surgery. Histology and serum for biomarker analysis will be collected at the time of surgery. Patients will additionally undergo a second imaging session with a novel PET tracer, 68Ga-DOTATATE, more specific for inflammation. In Aim 2, patients with MVP, mild or moderate MR, and a history of ventricular ectopy, who do not have an indication for surgery, will be enrolled into a longitudinal observational clinical study. We will perform 18F-FDG PET/MRI imaging, echocardiography, 7-day event monitoring (PVC burden and complexity) as well as collect circulating biomarkers at baseline and at follow- up after 24 months. Lastly, in Aim 3, we will assess the impact of MV surgery on myocardial inflammation and function, by repeating the same assessment as in Aim 2 but 12 months post-surgery to explore associations between MV surgery and changes in myocardial inflammation. With this comprehensive approach, our ultimate goal is the creation of a novel platform for the assessment of MVP, particularly as it relates to risk stratification of ventricular arrhythmias and SCD. We posit that the results of our studies may lead to more accurate imaging- guided patient management and have the potential to significantly influence current guideline recommendations for risk stratification assessment, medical therapy, and timing for surgical intervention.