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％的一般人群中确定，是最常见的心脏瓣膜 异常，并发症包括心力衰竭，心室心律不齐和心脏猝死 （SCD）。据估计，与MVP相关的SCD的事件为每年0.14％至1.5％，具体取决于 人口研究的临床特征。尽管有多个功能被确定为 风险增加的标记，左心室替代纤维化似乎是心律不齐的一致发现 MVP。通过心脏磁共振成像（MRI）的晚期增强（LGE）被认为是 评估替代纤维化的存在和分布的最灵敏和特定的方式， 与MVP患者的心律不齐事件的增加密切相关。初步的 我们小组的调查表明，这些纤维化变化可能是慢性炎症的 相位和感染和疤痕可能是连续心室转化的一部分，直接 与心律不齐和复杂性有关。现在，我们提出了深入的表征 在混合正电子发射时的强度与模式之间的强度与模式之间的关系 断层扫描（PET）/MRI，心律不齐，MVP的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， 在MVP，轻度，中度和重度MR的患者中，将获得心律不齐的燃烧和表征 为了在其各个阶段与PET/MRI表型之间建立疾病过程之间的相关性。 具体而言，在AIM 1中，我们将在一群患者中建立18F-FDG签名的炎症起源 使用MVP，二尖瓣手术的严重MR和I/II级适应症。生物标志物的组织学和血清 分析将在手术时收集。患者还将与 一种新型的宠物示踪剂，68GA-凝集酸盐，对炎症更具体。在AIM 2中，MVP，轻度或 中度MR和没有手术指示的心室术史将被录入 一项纵向观察临床研究。我们将执行18F-FDG PET/MRI成像，超声心动图，7天 事件监测（PVC燃烧和复杂性），并在基线和后续收集循环生物标志物 24个月后上升。最后，在AIM 3中，我们将评估MV手术对心肌注射和 功能，通过重复与AIM 2中相同的评估，手术后12个月来探索关联 MV手术与心肌炎症的变化之间。采用这种全面的方法，我们的最终 目标是创建一个新颖的平台来评估MVP，尤其是与风险分层有关 心室心律不齐和SCD。我们指出，我们的研究结果可能会导致更准确的成像 - 指导患者管理，并有可能极大地影响当前的准则建议 用于风险分层评估，医疗疗法和手术干预时机。