METHYSTROKE: Identification of Epigenetic Risk Factors for Ischemic Complication During the TAVR Procedure in the Elderly

Sponsor
University Hospital, Lille (Other)
Overall Status
Recruiting
CT.gov ID
NCT02972008
Collaborator
(none)
542
1
82.8
6.5

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase

    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).

    Study Design

    Study Type:
    Observational
    Anticipated Enrollment :
    542 participants
    Observational Model:
    Cohort
    Time Perspective:
    Prospective
    Official Title:
    Identification of Epigenetic Risk Factors for Ischemic Complication During the TAVR Procedure in the Elderly
    Actual Study Start Date :
    Mar 9, 2017
    Anticipated Primary Completion Date :
    Feb 1, 2024
    Anticipated Study Completion Date :
    Feb 1, 2024

    Arms and Interventions

    Arm Intervention/Treatment
    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

    Outcome Measures

    Primary Outcome Measures

    1. Pre-operative leukocyte DNA methylation rate [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

    Secondary Outcome Measures

    1. Variation of the leukocyte DNA methylation rate during the TAVI procedure [At time between the pre (day-1) and postprocedural (day 1) samples]

      This rate will be measured by the LINE-1 method in all patients

    2. Pre-operative leukocyte DNA methylation rate (stroke/TIA) [One day before the procedure and 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 a neurological deficit (stroke, transient ischemic attack)

    3. Mortality [At 1 year after procedure]

      The mortality in patients treated with TAVI according to the presence of at least one new micro-ischemic cerebral lesion and/or one new microbleeds cerebral lesion detected on postoperative cerebral MRI and / or postprocedural ischemic stroke / TIA

    4. MMSE score variation [At day-1 before TAVI procedure, at 6 months and at 1 year after procedure]

      The MMSE score variation is compared according to the presence or not of at least one new micro-ischemic cerebral lesion and/or one new microbleeds cerebral lesion

    5. Change of EQ-5D questionnaire [At day-1 before TAVI procedure, at 6 months and at 1 year after procedure]

      The evolution of quality of life is compared to the occurrence of new cerebral events one new micro-ischemic cerebral lesion and/or one new microbleeds cerebral lesion

    6. Change of modified Rankin Scale (mRS) [At day-1 before TAVI procedure, at 6 months and at 1 year after procedure]

      The MRS (measure degree of disability- troke) is compared to the occurrence of new cerebral events one new micro-ischemic cerebral lesion and/or one new microbleeds cerebral lesion

    7. Change of National Institutes of Health Stroke Scale (NIHSS) [At day-1 before TAVI procedure, at 6 months and at 1 year after procedure]

      TheNIHSS (quantify the impairment caused by a stroke) is compared to the occurrence of new cerebral events one new micro-ischemic cerebral lesion and/or one new microbleeds cerebral lesion

    8. Clinical and Biological predictors of new cerebral events [At day-1 before TAVI procedure, at 6 months and at 1 year after procedure]

      The clinical (measured before the procedure) and biological characteristics of the patients (measured before the procedure and after the procedure) and of the peri-procedural parameters associated with the occurrence of new events detected on post-procedural MRI (new ischemic and/or new microbleeds cerebral lesion appearing on post-procedural MRI)

    9. Hemostasis predictors of new cerebral events [At day-1 before TAVI procedure, at 6 months and at 1 year after procedure]

      Hemostasis parameters (measured before the procedure and after the procedure) including Willebrand factor parameters associated with the occurrence of new events detected on postoperative MRI (new ischemic and/or new microbleeds cerebral lesion)

    10. Number of complications in peri-procedural according to VARC-2 criteria [Within one week after the procedure]

      Evaluation of multi criteria according to the Valve academic Research Consortium (VARC-2)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    70 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Hôpital cardiologie, CHRU Lille France

    Sponsors and Collaborators

    • University Hospital, Lille

    Investigators

    • Principal Investigator: Nicolas Debry, MD, University Hospital, Lille

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    University Hospital, Lille
    ClinicalTrials.gov Identifier:
    NCT02972008
    Other Study ID Numbers:
    • 2015_92
    • 2016-A01035-46
    • PHRCI_2015
    First Posted:
    Nov 23, 2016
    Last Update Posted:
    Feb 15, 2022
    Last Verified:
    Jan 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by University Hospital, Lille
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Feb 15, 2022