Detection and Longitudinal Follow-up of Non-calcified and Calcified Coronary Lesions in Heterozygous Familial Hypercholesterolemia (DESTINY-FH)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 300
- 试验地点
- 3
- 主要终点
- Progression of coronary artery disease over 5 years in patients with heterozygous familial hypercholesterolemia
研究概览
简要总结
This multicenter, non-randomized interventional study aims to assess coronary artery disease progression over 5 years in patients with genetically confirmed heterozygous familial hypercholesterolemia (HeFH), using coronary computed tomography angiography (CCTA).
The primary endpoint is the visual evaluation of coronary stenosis using CAD-RADS v2.0, identifying changes between baseline (2018-2022) and study inclusion. The study will enroll 300 patients (100 protected, 200 non-protected) from La Pitié-Salpêtrière hospital and Saint Antoine Hospital (Paris). Participation lasts up to one week. Total study duration is 2 years, with extended follow-up through routine care data over 10 years.
详细描述
HeFH is an autosomal dominant genetic disorder characterized by lifelong elevated LDL-C levels, which significantly increase the risk of premature coronary atherosclerosis. Cardiovascular risk stratification in HeFH remains challenging due to limitations of traditional risk scores and stress testing. The coronary artery calcium (CAC) score is a useful tool for reclassifying cardiovascular risk but fails to detect non-calcified plaques, which may be prevalent in HeFH despite a CAC score of zero. Previous studies suggest a prevalence of non-calcified plaques as high as 30% in molecularly diagnosed HeFH patients.
This multicenter interventional, non-randomized comparative study aims to evaluate the progression of coronary artery disease over a 5-year period in patients with genetically confirmed heterozygous familial hypercholesterolemia (HeFH). Using coronary computed tomography angiography (CCTA), the study will assess both calcified and non-calcified plaque burden in this high-risk population.
The primary outcome is the visual, semi-quantitative evaluation of coronary stenosis severity using CAD-RADS v2.0 classification to identify high-risk plaques and categorize patients as having regression, stability, or progression of coronary disease based on changes in CAD-RADS categories between baseline (2018-2022) and the DESTINY-FH study visit.
The study will enroll 300 patients (100 "protected" and 200 "non-protected") from La Pitié-Salpêtrière hospital and Saint Antoine Hospital (Paris). Individual participation will last from one day to one week. Total study duration is 2 years, with additional 10-year follow-up using routinely collected medical records.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 30 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with heterozygous familial hypercholesterolemia
- •Aged 30 to 60 years.
- •Patients who underwent a CAC score and a coronary CT angiogram at least 5 years ago, exclusively at the same imaging center (ICT de la Pitié Salpetrière).
- •Patient asymptomatic for exertional chest pain at the time of CCTA
- •Clinical examination performed
- •Beneficiary of a social protection scheme or entitled person (excluding AME)
- •Patient informed and consent form signed
排除标准
- •Patient under guardianship, or unable to give consent
- •Pregnancy, breast-feeding
- •Technical contraindication: weight > 250 kg
- •Simultaneous participation in other interventional research involving the human body, or period of exclusion following previous research involving the human body still in progress.
- •Adults subject to a legal protection order
- •Contraindication to esmolol and/or atenolol
- •Only for patients who need to undergo a CT angiogram and a thoraco-abdominal-pelvic CT scan:
- •Renal insufficiency (LC<60)
- •Unbalanced diabetes when acquiring a previous coronary angioscanner
- •Personal history of cardiovascular disease and myocardial infarction at the time of CCTA
- •Contraindication to iodinated contrast media
- •Patient having already had an adverse event (AE) during the acquisition of a prior coronary angioscanner
研究组 & 干预措施
Patients with protected and unprotected familial hypercholesterolemia
Coronary computed tomography angiography with injection of iodinated contrast material
干预措施: Coronary computed tomography angiography (Other)
结局指标
主要结局
Progression of coronary artery disease over 5 years in patients with heterozygous familial hypercholesterolemia
时间窗: 1 day
The evolution of coronary artery disease will be assessed over 5 years in patients with heterozygous familial hypercholesterolemia using coronary CT angiography (CTA). The number of patients with regression, stability, or progression of coronary stenosis will be determined using semi-quantitative visual assessment of coronary stenoses according to the CAD-RADS v2.0 classification, including visual characterization of high-risk plaque features.Time Frame: 5 years Unit of Measure: Number and percentage of participants with regression, stability, or progression of coronary stenosis
次要结局
- Gut microbiota composition at baseline using metabolomics and metagenomics.(1 day)
- Association between baseline omics data and coronary plaque progression.(1 day)
- Change in total coronary plaque volume, lesion type, and proximal aortic calcifications.(1 day)
- Survival curve of major cardiovascular events incidence.(1 day)
- Cox regression analysis of cardiovascular event occurrence and associated clinical, biological, and omics data.(1 day)
- Linear regression of clinical and biological variables by CAD-RADS category change.(1 day)
- Comparison of omics data by plaque volume change and CAD-RADS category shift.(1 day)
- Baseline prevalence of carotid plaque by group(1 day)
- Baseline prevalence of femoral plaque by group(1 day)
- Baseline aortic valve calcium score by group(1 day)
- Baseline thoracic aorta calcium score by group(1 day)
- Baseline diameters of the ascending and descending aorta by group(1 day)
- Correlation between baseline carotid plaque presence and change in coronary plaque volume(Baseline to 5 years)
- Correlation between baseline femoral plaque presence and change in coronary plaque volume(Baseline to 5 years)
- Correlation between baseline CAC score (aortic valve and thoracic aorta) and coronary plaque progression(1 day)
- Correlation between baseline aortic diameters and coronary plaque progression(1 day)
- Baseline epicardial fat volume by group(1 day)
- Baseline epicardial fat density by group(1 day)
- Baseline subdiaphragmatic abdominal adipose tissue volume at L1 by group(1 day)
- Baseline subdiaphragmatic abdominal adipose tissue density at L1 by group(1 day)
- Baseline arterial wall thickness by group(1 day)
- Baseline arterial lumen diameter by group(1 day)
- Baseline arterial wall-to-lumen ratio by group(1 day)
- Baseline arterial wall cross-sectional area by group(1 day)
- Correlation between retinal arterial wall thickness and coronary plaque progression(1 day)
- Correlation between retinal lumen diameter and coronary plaque progression(1 day)
- Correlation between retinal wall-to-lumen ratio and coronary plaque progression(1 day)
- Change in gut microbiota composition between baseline and inclusion(1 day)
- Correlation between retinal arterial wall cross-sectional area and coronary plaque progression(1 day)
- Comparison of liver and spleen density at baseline between groups(1 day)
- Comparison of arterial stiffness at baseline between groups.(1 day)
- SF-36 Health Survey score at inclusion(1 day)
- Seattle Angina Questionnaire-7 (SAQ-7) score at inclusion(1 day)
- Rose Dyspnea Scale score at inclusion(1 day)
- Patient Health Questionnaire-2 (PHQ-2) score at inclusion(1 day)
- Hospital Anxiety and Depression Scale (HADS) score at inclusion(1 day)
- CONSTANCES study questionnaire scores at inclusion(1 day)
- Incidence of major cardiovascular events at 5 and 10 years(5 and 10 years)