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.

项目摘要 二尖瓣脱垂（MVP），在1-3%的普通人群中发现，是最常见的心脏瓣膜病 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。虽然有多个特征被确定为 作为风险增加的标志物，左心室替代纤维化似乎是心律失常患者的一致发现。 最有价值球员。心脏磁共振成像（MRI）显示的晚期钆增强（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式， 与MVP患者的血液透析事件发生率增加密切相关。初步 我们小组的研究表明，这些纤维化变化可能是由慢性炎症引起的， 炎症和瘢痕形成可能是心室转化连续体的一部分， 与心律失常的发展和复杂性相关。我们现在提出一个深入的特点， 18F-氟脱氧葡萄糖（FDG）摄取强度与杂合正电子发射模式的关系 断层扫描（PET）/MRI、心律失常负荷、MVP和二尖瓣返流（MR）的严重程度。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患者的药物负荷和特征， 为了建立疾病过程在其不同阶段与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建立18F-FDG标记的炎症起源 MVP、重度二尖瓣返流和二尖瓣手术的I/II类适应症。生物标志物的组织学和血清 将在手术时收集分析结果。患者还将接受第二次成像， 一种新的PET示踪剂，68 Ga-DOTATATE，对炎症更特异。在目标2中，MVP患者，轻度或 中度二尖瓣返流和心室异位病史，没有手术指征，将入组 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负荷和复杂性）以及收集基线和随访时的循环生物标志物- 24个月后。最后，在目标3中，我们将评估二尖瓣手术对心肌炎症的影响， 功能，通过重复与目标2相同的评估，但术后12个月，以探索相关性 二尖瓣手术和心肌炎症变化之间的关系。通过这种全面的方法， 目标是创建一个新的评估MVP的平台，特别是因为它涉及到风险分层 室性心律失常和SCD我们认为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的时机。