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.

项目总结