Investigation of Patients With BAV Requiring Valve and/or Aortic Repair. Correlation of Surgical and ECO Distinctive Features With Histologic and Genetic Findings in Phenotypically Homogeneous Outlier Cases (GISSI VAR)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 62
- 试验地点
- 10
- 主要终点
- Mutation in NOTCH1 gene
研究概览
简要总结
Prospective longitudinal study on four small groups of surgical patients affected by: BAV with isolated regurgitation, BAV associated with aorta dilatation, or both and BAV with isolated stenosis in over 60 year-old patients.
The aim of the study is to select homogeneous small groups of surgical patients with the same subtype of BAV and same aortic behaviour and identify markers/predictors of favorable-unfavorable aortic wall evolution to evaluate if there is a BAV phenotype more likely to be considered at high risk for aortic degeneration.
详细描述
The aim of the study is to select homogeneous small groups of surgical patients with the same subtype of BAV and same aortic behaviour and identify markers/predictors of favorable-unfavorable aortic wall evolution to evaluate if there is a BAV phenotype more likely to be considered at high risk for aortic degeneration. The study will focus on multiple aspects of BAV disease. What follows will be considered and combined:
Aortic valve, aorta root and ascending aorta morphology The use of two- (2DE) and three-dimensional (3DE) trans-thoracic (TTE) and/or transoesophageal (TOE) echocardiography can identify all kind of BAV morphology (leaflet position and coronary ostia displacement). It also gives quali- quantitative information about root and ascending aorta morphology and size.
BAV genetics Recently, missense mutations in the NOTCH1 gene have been shown to be associated with calcific aortic valve disease plus BAV. However mutations in the NOTCH1 gene only partially explain the presence of BAV in the absence of other syndromic diseases (i.e. Marfan Syndrome, Loeys Dietz Syndrome type I and II and Ehlers Danlos type IV Syndrome).
BAV Histology In all enrolled patients, during operation, tissue samples will be collected from valve cusps (in case of valve involvement), aortic wall (aortic root, concavity or convexity of ascending aorta) or from both of them. Samples will be analyzed in order to classify medial and intimal disruption and changes.
Study Design and Setting of the Study The first step will consist in enrolling patients with echocardiographic diagnosis of BAV and indication for surgery. From the echo data, aortic valve, as well as aortic root and ascending aorta morphology will be assessed in order to classify patients in each phenotypic pattern. The echo images from participating centres will be sent to an echo core lab for quali- quantitative analysis (see below) and all data will be recorded in a specific database.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women over 18 years-old and under the age of 60 (age selection will prevent from enrolling patient with age-related valve and aortic wall degeneration). For the BAV stenosis group there will be considered patients over 60 years-old: including the most frequent form of BAV disease and the commonest age, this group could be used as a control group compared to the outlier ones.
- •Echo diagnosis of BAV and indication to surgery:
- •BAV with isolated regurgitation, BAV with normal valvular function but associated aorta dilatation, BAV with both valve regurgitation and aortic dilatation BAV with isolated stenosis
- •Signed informed consent
排除标准
- •Patient with a previous cardiac or great vessels surgery
- •coexistent coarctation of the aorta
- •non-associated cardiac diseases: valve disease (other than aortic), ischemic disease, congenital heart disease.
- •Marfan syndrome or other connective tissue disorders involving aortic valve and aortic wall disease (history of disease or clinical signs).
- •Other conditions/circumstances likely to lead to poor study adherence (e.g. psychological or organizational reasons).
- •Serious disease other than aortic, severely limiting life expectancy.
- •Patients who refuse to give informed consent
结局指标
主要结局
Mutation in NOTCH1 gene
时间窗: Enrollment
The strongest causative gene associated with BAV is NOTCH1. Its 34 coding exons will be sequenced to search for variants likely to be causative. The presence of sequence variation will be confirmed using a different method, starting from a new amplification (RFLP or High Resolution Melting-HRM). The pathogeneticity of the mutation will be evaluated screening 500 DNA controls (1000 chromosomes) to estimate the alleles' frequencies (HRM; ABI Prism 7900HT). Finally a familial segregation analysis will be performed to verify the association with the disease.
次要结局
未报告次要终点