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

NCT02972008 | Recruiting DMC

• 3 other identifiers: 2015_922016-A01035-46PHRCI_2015
• Study Type: observational
• Target: 542
• Locations: 1 country
• Sites: 1

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.

Conditions

Cognitive Decline; Stroke

Keywords

Aortic stenosis; Transaortic valve replacement; stroke; Epigenetic

Outcome Measures

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

  Within one week after the procedure

Secondary Outcomes (10)

• 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 EQ-5D questionnaire

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

Study Arms (3)

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

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

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

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Lille: lead

Study Sites (1)

Hôpital cardiologie, CHRU

Lille, France

RECRUITING

Related Publications (7)

• Ghanem A, Kocurek J, Sinning JM, Wagner M, Becker BV, Vogel M, Schroder T, Wolfsgruber S, Vasa-Nicotera M, Hammerstingl C, Schwab JO, Thomas D, Werner N, Grube E, Nickenig G, Muller A. Cognitive trajectory after transcatheter aortic valve implantation. Circ Cardiovasc Interv. 2013 Dec;6(6):615-24. doi: 10.1161/CIRCINTERVENTIONS.112.000429. Epub 2013 Oct 15.

  PMID: 24129642 BACKGROUND

• Kahlert P, Knipp SC, Schlamann M, Thielmann M, Al-Rashid F, Weber M, Johansson U, Wendt D, Jakob HG, Forsting M, Sack S, Erbel R, Eggebrecht H. Silent and apparent cerebral ischemia after percutaneous transfemoral aortic valve implantation: a diffusion-weighted magnetic resonance imaging study. Circulation. 2010 Feb 23;121(7):870-8. doi: 10.1161/CIRCULATIONAHA.109.855866.

  PMID: 20177005 BACKGROUND

• Bjornsson HT, Sigurdsson MI, Fallin MD, Irizarry RA, Aspelund T, Cui H, Yu W, Rongione MA, Ekstrom TJ, Harris TB, Launer LJ, Eiriksdottir G, Leppert MF, Sapienza C, Gudnason V, Feinberg AP. Intra-individual change over time in DNA methylation with familial clustering. JAMA. 2008 Jun 25;299(24):2877-83. doi: 10.1001/jama.299.24.2877.

  PMID: 18577732 BACKGROUND

• Baccarelli A, Wright R, Bollati V, Litonjua A, Zanobetti A, Tarantini L, Sparrow D, Vokonas P, Schwartz J. Ischemic heart disease and stroke in relation to blood DNA methylation. Epidemiology. 2010 Nov;21(6):819-28. doi: 10.1097/EDE.0b013e3181f20457.

  PMID: 20805753 BACKGROUND

• Van Belle E, Juthier F, Susen S, Vincentelli A, Iung B, Dallongeville J, Eltchaninoff H, Laskar M, Leprince P, Lievre M, Banfi C, Auffray JL, Delhaye C, Donzeau-Gouge P, Chevreul K, Fajadet J, Leguerrier A, Prat A, Gilard M, Teiger E; FRANCE 2 Investigators. Postprocedural aortic regurgitation in balloon-expandable and self-expandable transcatheter aortic valve replacement procedures: analysis of predictors and impact on long-term mortality: insights from the FRANCE2 Registry. Circulation. 2014 Apr 1;129(13):1415-27. doi: 10.1161/CIRCULATIONAHA.113.002677. Epub 2014 Feb 24.

  PMID: 24566199 BACKGROUND

• Gilard M, Eltchaninoff H, Iung B, Donzeau-Gouge P, Chevreul K, Fajadet J, Leprince P, Leguerrier A, Lievre M, Prat A, Teiger E, Lefevre T, Himbert D, Tchetche D, Carrie D, Albat B, Cribier A, Rioufol G, Sudre A, Blanchard D, Collet F, Dos Santos P, Meneveau N, Tirouvanziam A, Caussin C, Guyon P, Boschat J, Le Breton H, Collart F, Houel R, Delpine S, Souteyrand G, Favereau X, Ohlmann P, Doisy V, Grollier G, Gommeaux A, Claudel JP, Bourlon F, Bertrand B, Van Belle E, Laskar M; FRANCE 2 Investigators. Registry of transcatheter aortic-valve implantation in high-risk patients. N Engl J Med. 2012 May 3;366(18):1705-15. doi: 10.1056/NEJMoa1114705.

  PMID: 22551129 BACKGROUND

• Van Belle E, Debry N, Vincent F, Kuchcinski G, Cordonnier C, Rauch A, Robin E, Lassalle F, Pontana F, Delhaye C, Schurtz G, JeanPierre E, Rousse N, Casari C, Spillemaeker H, Porouchani S, Pamart T, Denimal T, Neiger X, Verdier B, Puy L, Cosenza A, Juthier F, Richardson M, Bretzner M, Dallongeville J, Labreuche J, Mazighi M, Dupont-Prado A, Staels B, Lenting PJ, Susen S. Cerebral Microbleeds During Transcatheter Aortic Valve Replacement: A Prospective Magnetic Resonance Imaging Cohort. Circulation. 2022 Aug 2;146(5):383-397. doi: 10.1161/CIRCULATIONAHA.121.057145. Epub 2022 Jun 20.

  PMID: 35722876 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

We compare the pre-operative leukocyte DNA methylation rate measured by the Luminometric Methylation Assay (LUMA) method in patients treated with TAVI and patients with constitutional von Willebrand factor (vWF) deficiency according to the presence or absence of at least one new cerebral ischemic lesion detected on postoperative cerebral MRI.

MeSH Terms

Conditions

Cognitive Dysfunction; Stroke; Aortic Valve Stenosis

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Ventricular Outflow Obstruction

Study Officials

• Nicolas Debry, MD

  University Hospital, Lille

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nicolas Debry, MD

CONTACT

+33 3 20 44 59 62; nicolas.debry@chru-lille.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2016
• First Posted: November 23, 2016
• Study Start: March 9, 2017
• Primary Completion: February 1, 2026
• Study Completion: February 1, 2026
• Last Updated: December 23, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)