Clinical trial NCT02972008: Identification of Epigenetic Risk Factors for Ischemic Complication During the TAVR Procedure in the Elderly
Official title: Identification of Epigenetic Risk Factors for Ischemic Complication During the TAVR Procedure in the Elderly
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Cognitive Decline
Stroke
Keywords: Aortic stenosis
Transaortic valve replacement
stroke
Epigenetic
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
First posted: 2016-11-23
Enrollment: 542
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients over 70 years with severe aortic stenosis requiring percutaneous aortic valve replacement (TAVI)

Brief summary: 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.

Detailed description: 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).

Eligibility criteria: Inclusion Criteria:

* Patients over 70 years with severe aortic stenosis requiring percutaneous aortic valve replacement (TAVI)

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Pre-operative leukocyte DNA methylation rate
timeFrame: Within one week after the procedure
Secondary outcomes:
measure: Variation of the leukocyte DNA methylation rate during the TAVI procedure
timeFrame: At time between the pre (day-1) and postprocedural (day 1) samples
measure: Pre-operative leukocyte DNA methylation rate (stroke/TIA)
timeFrame: One day before the procedure and within one week after the procedure
measure: Mortality
timeFrame: At 1 year after procedure
measure: MMSE score variation
timeFrame: At day-1 before TAVI procedure, at 6 months and at 1 year after procedure
measure: Change of EQ-5D questionnaire
timeFrame: At day-1 before TAVI procedure, at 6 months and at 1 year after procedure
measure: Change of modified Rankin Scale (mRS)
timeFrame: At day-1 before TAVI procedure, at 6 months and at 1 year after procedure
measure: Change of National Institutes of Health Stroke Scale (NIHSS)
timeFrame: At day-1 before TAVI procedure, at 6 months and at 1 year after procedure
measure: Clinical and Biological predictors of new cerebral events
timeFrame: At day-1 before TAVI procedure, at 6 months and at 1 year after procedure
measure: Hemostasis predictors of new cerebral events
timeFrame: At day-1 before TAVI procedure, at 6 months and at 1 year after procedure
measure: Number of complications in peri-procedural according to VARC-2 criteria
timeFrame: Within one week after the procedure
Other outcomes:
Locations:
city: Lille
country: France
facility: Hôpital cardiologie, CHRU
Study officials:
affiliation: University Hospital, Lille
name: Nicolas Debry, MD
role: PRINCIPAL_INVESTIGATOR
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