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

Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age70+
SponsorUniversity Hospital, Lille

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

Patient contraindicated for the TAVI procedure

Patient with a pace-maker

Patient with contra-indication for cerebral MRI

Ongoing cancer

Trial population

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

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

Not listed

Trial groups

542 Participants
are grouped into 3 trial groups
Group A: Cerebral Lesion
Group B: No Cerebral Lesion
Group C: patients with constitutional von Willebrand factor (vWF) deficiency

Trial outcomes

Primary outcomes

1

Pre-operative leukocyte DNA methylation rate

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

Time frame
Within one week after the procedure

Secondary outcomes

1

Variation of the leukocyte DNA methylation rate during the TAVI procedure

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

Time frame
At time between the pre (day-1) and postprocedural (day 1) samples
2

Pre-operative leukocyte DNA methylation rate (stroke/TIA)

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)

Time frame
One day before the procedure and within one week after the procedure
3

Mortality

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

Time frame
At 1 year after procedure
4

MMSE score variation

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

Time frame
At day-1 before TAVI procedure, at 6 months and at 1 year after procedure

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.