Skip to main content
OpenTrials
Recruiting

NCT Number: NCT02972008

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

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.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Cognitive Decline Aortic Valve Disease Aortic Valve Stenosis Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Disorders Cognition Disorders Cognitive Dysfunction Heart Diseases Heart Valve Diseases Mental Disorders Nervous System Diseases Neurocognitive Disorders Stroke Vascular Diseases Ventricular Outflow Obstruction

Age range

70 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Hôpital cardiologie, CHRU

Lille, France

Location status: Recruiting

Location contact

Nicolas Debry, MD

PRINCIPAL_INVESTIGATOR

About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Primary outcomes

  1. Pre-operative leukocyte DNA methylation rate

    Time frame: 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 outcomes

  1. Variation of the leukocyte DNA methylation rate during the TAVI procedure

    Time frame: 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)

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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)

    Time frame: 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)

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: Within one week after the procedure

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

Study contacts

Contact information is provided by the study sponsor or research team.

Nicolas Debry, MD

CONTACT

[email protected]

+33 3 20 44 59 62 ext. +33

Sponsors and collaborators

Lead sponsor

University Hospital, Lille

Other

Registry information

Acronym: METHYSTROKE

Important dates

Study start
2017
Primary completion
2027
Study completion
2027
First posted
Nov 23, 2016
Registry last updated
May 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.