PET/MRI imaging of mitral valve prolapse

二尖瓣脱垂的 PET/MRI 成像

• 批准号: 10747508
• 负责人: David H Adams
• 金额: $ 204.32万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-25 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10747508
• 关键词: Address; Affect; Affinity; Arrhythmia; Biological Markers; Biopsy Specimen; Blood; Cardiac; Cd68; Characteristics; Chronic; Cicatrix; Clinical; Clinical Management; Clinical Research; Collection; Complex; Cross-Sectional Studies; Data; Detection; Development; Disease; Disease-Free Survival; Echocardiography; Enrollment; Evaluation; Event; Fibroblasts; Fibrosis; Functional disorder; Future; Gadolinium; General Population; Goals; Guidelines; Heart Atrium; Heart failure; Histologic; Histology; Home; Hybrids; Image; Incidence; Inflammation; Inflammatory; Investigation; Left; Left Ventricular Dysfunction; Left Ventricular Ejection Fraction; Location; Macrophage; Magnetic Resonance Imaging; Malignant - descriptor; Measures; Mechanical Stress; Medical; Medical Records; Mitral Valve; Mitral Valve Insufficiency; Mitral Valve Prolapse; Modality; Monitor; Morphology; Myocardial; Myocardium; Myofibroblast; Operative Surgical Procedures; PTPRC gene; Patients; Pattern; Phase; Phenotype; Population Characteristics; Positron-Emission Tomography; Prevalence; Process; Recommendation; Recording of previous events; Risk; Risk Reduction; Role; Series; Serum; Severities; Signal Transduction; Stratification; Stroke; Testing; Therapeutic; Time; Tracer; Traction; Ventricular; Ventricular Arrhythmia; Ventricular Tachycardia; cardiac magnetic resonance imaging; circulating biomarkers; cohort; coronary fibrosis; fluorodeoxyglucose; fluorodeoxyglucose positron emission tomography; follow-up; glucose metabolism; heart function; high risk; image guided; improved; inflammatory marker; longitudinal analysis; mortality risk; myocardial injury; novel; novel strategies; outcome prediction; papillary muscle; primary endpoint; risk stratification; secondary analysis; secondary endpoint; study characteristics; sudden cardiac death; uptake

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.

项目概要 二尖瓣脱垂 (MVP) 是最常见的心脏瓣膜病，一般人群中有 1-3% 患有二尖瓣脱垂 (MVP) 异常，并发症包括心力衰竭、室性心律失常和心源性猝死 （SCD）。据估计，MVP 相关 SCD 的发病率为每年 0.14% 至 1.5%，具体取决于 研究人群的临床特征。虽然有多个功能被确定为 作为风险增加的标志物，左心室替代性纤维化似乎是心律失常的一致发现 MVP。心脏磁共振成像 (MRI) 的晚期钆增强 (LGE) 被认为是 评估替代性纤维化及其分布的最敏感和最具体的方式 与 MVP 患者心律失常事件发生率增加密切相关。初步的 我们小组的研究表明，这些纤维化变化可能先于慢性炎症 阶段，炎症和疤痕可能是心室转化连续体的一部分，并且直接 与心律失常的发展和复杂性相关。我们现在建议对 混合正电子发射的 18F-氟脱氧葡萄糖 (FDG) 摄取强度和模式之间的关系 断层扫描 (PET)/MRI、心律失常负担、MVP 严重程度和二尖瓣反流 (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、轻度、中度和重度 MR 患者的心律失常负荷和特征， 为了建立不同阶段的疾病过程与 PET/MRI 表型之间的相关性。 具体来说，在目标 1 中，我们将在一组患者中确定 18F-FDG 特征的炎症起源 具有 MVP、严重 MR 和二尖瓣手术 I/II 级指征。生物标志物的组织学和血清 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 PET 示踪剂 68Ga-DOTATATE，对炎症更具特异性。在目标 2 中，患有 MVP、轻度或 中度 MR 且有心室异位病史且无手术指征的患者将被纳入 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个月后上涨。最后，在目标 3 中，我们将评估 MV 手术对心肌炎症和 功能，通过在手术后 12 个月重复与目标 2 中相同的评估来探索关联 MV 手术与心肌炎症变化之间的关系。通过这种全面的方法，我们的最终 目标是创建一个用于评估 MVP 的新颖平台，特别是因为它与风险分层相关 室性心律失常和 SCD。我们认为我们的研究结果可能会带来更准确的成像—— 指导患者管理并有可能显着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的时机。