Identification of Epigenetic Risk Factors for Ischemic Complication During the TAVR Procedure in the Elderly
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 542
- 试验地点
- 2
- 主要终点
- Pre-operative leukocyte DNA methylation rate
研究概览
简要总结
Over the past ten years, the number of endovascular procedures has increased by 5% per year in Europe with the development of interventional cardiology, such as percutaneous coronary angioplasty, aortic valve replacements (TAVR), and vascular endoprosthesis.
The neurological lesions detected on cerebral MRI caused by these endovascular procedures are frequent with an incidence of about 30-70%. These events, although subclinical, have an impact on morbidity and mortality and especially on long-term cognitive decline.
TAVR is the reference treatment for symptomatic elderly patients with stenosis of the aortic valve, considered by a multidisciplinary "Heart Team" as at high surgical risk due to comorbidities, age and high perioperative risk scores ( Euroscore 2 and STS scores). Despite the net clinical benefit, an increase of silent neurological events was detected on post-procedural cerebral MRI with an incidence of approximately 70%.
The epigenetic involvement in the occurrence of ischemic cerebral lesions is still largely unknown. Epigenetic mechanisms, such as DNA methylation, can be associated with aging processes and modulate the risk of developing cerebrovascular pathologies. They are likely to provide new biomarkers that predict the risk of brain damage.
Hypomethylation of leukocyte DNA is directly related to atherosclerosis in humans. This hypomethylation of DNA would represent an easily measurable marker reflecting the presence and progression of atherosclerosis. Because atherosclerotic lesions often precede the clinical manifestation of ischemic cardiovascular disease, such as ischemic heart disease and stroke, DNA hypomethylation could be used to identify individuals at risk for cerebrovascular events.
The investigator hypothesize that hypomethylation of leukocyte DNA can predict the risk of developing new ischemic brain lesions especially after a TAVI procedure.
详细描述
This is a french multicenter prospective cohort study. Patients with severe symptomatic aortic stenosis referred for a TAVI procedure to the cardiology departments of the university hospitals of Lille, Caen, Amiens and the Pitié-Salpêtrière hospital (APHP) are analyzed for inclusion in this prospective study. The cases are selected after a discussion between the members of the local TAVI "Heart Team" (cardiologists, cardiac surgeons, anesthetists), as recommended by the guidelines of the European Society of Cardiology. Written consent is obtained in accordance with international recommendations for clinical research (Helsinki Declaration). Participation in the study is proposed to patients during preoperative consultation.
The collection of clinical data, including postoperative cerebral MRI, is collected prospectively during hospitalization and during the clinical visit to each institution at one year. An evaluation of cognitive function is performed by a mini-mental state (MMS) the day before the TAVI intervention and then at 1 year. The study ends after the last evaluation. A cerebral MRI is performed within 1-3 days after the TAVI procedure to detect new cerebral ischemic lesions (emboli).
Blood samples will be taken during the patient's stay: the day before TAVI, during the procedure and after the TAVI procedure at day 1 and day 4.
The follow-up visit to 1 year will be conducted by cardiologists or cardiac surgeons with an evaluation of the cognitive function by the mini-mental state (MMS).
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
- 70 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients over 70 years with severe aortic stenosis requiring percutaneous aortic valve replacement (TAVI)
排除标准
- •Patient contraindicated for the TAVI procedure
- •Patient with a pace-maker
- •Patient with contra-indication for cerebral MRI
- •Ongoing cancer
- •Patient already involved in therapeutic research
- •Major persons under protection of justice.
研究组 & 干预措施
Cerebral Lesion
Patient over 70 years with severe aortic stenosis requiring percutaneous aortic valvular replacement (TAVI) having at least one new cerebral ischemic lesion on postoperative cerebral MRI
No Cerebral Lesion
Patient over 70 years with severe aortic stenosis requiring percutaneous aortic valvular replacement (TAVI) with no cerebral ischemic lesion on postoperative cerebral MRI
patients with constitutional von Willebrand factor (vWF) deficiency
结局指标
主要结局
Pre-operative leukocyte DNA methylation rate
时间窗: Within one week after the procedure
This rate will be measured by the LUMA method in patients treated with TAVI according to the presence of at least one new cerebral ischemic lesion and/or microbleeds cerebral lesion appearing on post-procedural MRI
次要结局
- Change of EQ-5D questionnaire(At day-1 before TAVI procedure, at 6 months and at 1 year after procedure)
- Change of National Institutes of Health Stroke Scale (NIHSS)(At day-1 before TAVI procedure, at 6 months and at 1 year after procedure)
- Number of complications in peri-procedural according to VARC-2 criteria(Within one week after the procedure)
- Variation of the leukocyte DNA methylation rate during the TAVI procedure(At time between the pre (day-1) and postprocedural (day 1) samples)
- Pre-operative leukocyte DNA methylation rate (stroke/TIA)(One day before the procedure and within one week after the procedure)
- Mortality(At 1 year after procedure)
- MMSE score variation(At day-1 before TAVI procedure, at 6 months and at 1 year after procedure)
- Change of modified Rankin Scale (mRS)(At day-1 before TAVI procedure, at 6 months and at 1 year after procedure)
- Clinical and Biological predictors of new cerebral events(At day-1 before TAVI procedure, at 6 months and at 1 year after procedure)
- Hemostasis predictors of new cerebral events(At day-1 before TAVI procedure, at 6 months and at 1 year after procedure)