Investigation of Patients With BAV Requiring Valve and/or Aortic Repair (GISSI Outliers VAR)

NCT02283970 | Completed

• 1 other identifier: K11
• Study Type: observational
• Target: 62
• Locations: 1 country
• Sites: 10

Brief Summary

Prospective longitudinal study on four small groups of surgical patients affected by: BAV with isolated regurgitation, BAV associated with aorta dilatation, or both and BAV with isolated stenosis in over 60 year-old patients. The aim of the study is to select homogeneous small groups of surgical patients with the same subtype of BAV and same aortic behaviour and identify markers/predictors of favorable-unfavorable aortic wall evolution to evaluate if there is a BAV phenotype more likely to be considered at high risk for aortic degeneration.

Conditions

Bicuspid Aortic Valve; Aortic Regurgitation; Aortic Dilatation

Outcome Measures

Primary Outcomes (1)

• Mutation in NOTCH1 gene

  The strongest causative gene associated with BAV is NOTCH1. Its 34 coding exons will be sequenced to search for variants likely to be causative. The presence of sequence variation will be confirmed using a different method, starting from a new amplification (RFLP or High Resolution Melting-HRM). The pathogeneticity of the mutation will be evaluated screening 500 DNA controls (1000 chromosomes) to estimate the alleles' frequencies (HRM; ABI Prism 7900HT). Finally a familial segregation analysis will be performed to verify the association with the disease.

  Enrollment

Study Arms (4)

BAV and aortic regurgitation

BAV Diagnosis, Aortic Regurgitation with surgical indication (according to current clinical guidelines or best clinical practice), normal ascending aorta

BAV and Ascending aorta dilatation

BAV diagnosis, no or trivial Aortic Regurgitation, ascending aorta dilatation with surgical indication (according to current clinical guidelines or best clinical practice)

BAV, aortic regurgitation and dilatation

BAV diagnosis, Aortic Regurgitation and ascending aorta dilatation with surgical indication (according to current clinical guidelines or best clinical practice).

BAV with aortic stenosis in pts>60yrs

BAV diagnosis, Aortic stenosis with surgical indication (according to current clinical guidelines or best clinical practice). Normal ascending aorta

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

BAV patients eligible for cardiac surgery due to each of these conditions: BAV Regurgitation isolated, ascending aorta aneurysm in normal BAV or both AR and ascending aorta aneurysm, BAV stenosis isolated in over 60 year-old patients.

You may qualify if:

• Men and women over 18 years-old and under the age of 60 (age selection will prevent from enrolling patient with age-related valve and aortic wall degeneration). For the BAV stenosis group there will be considered patients over 60 years-old: including the most frequent form of BAV disease and the commonest age, this group could be used as a control group compared to the outlier ones.
• Echo diagnosis of BAV and indication to surgery:
• BAV with isolated regurgitation, BAV with normal valvular function but associated aorta dilatation, BAV with both valve regurgitation and aortic dilatation BAV with isolated stenosis
• \- Signed informed consent

You may not qualify if:

• Patient with a previous cardiac or great vessels surgery
• coexistent coarctation of the aorta
• non-associated cardiac diseases: valve disease (other than aortic), ischemic disease, congenital heart disease.
• Marfan syndrome or other connective tissue disorders involving aortic valve and aortic wall disease (history of disease or clinical signs).
• Other conditions/circumstances likely to lead to poor study adherence (e.g. psychological or organizational reasons).
• Serious disease other than aortic, severely limiting life expectancy.
• Patients who refuse to give informed consent

Sponsors & Collaborators

• Gruppo di Ricerca GISSI: lead

Study Sites (10)

Casa Di Cura Villa Sant'Anna

Catanzaro, CZ, 88100, Italy

Location

Aou Careggi

Florence, FI, 50139, Italy

Location

Ospedale San Raffaele

Milan, MI, 20132, Italy

Location

Centro Cardiologico Monzino

Milan, MI, 20138, Italy

Location

Ospedale Niguarda

Milan, MI, 20162, Italy

Location

Irccs Policlinico San Donato

San Donato Milanese, MI, 20097, Italy

Location

Aou Santa Maria Della Misericordia

Udine, UD, 33100, Italy

Location

Ospedale Dell'Angelo

Mestre, VE, 30171, Italy

Location

Ospedale San Camillo

Roma, 00152, Italy

Location

Azienda Osp. Univ. S. Giovanni Battista

Torino, 10126, Italy

Location

Related Publications (1)

• Merlanti B, De Chiara B, Maggioni AP, Moreo A, Pileggi S, Romeo G, Russo CF, Rizzo S, Martinelli L, Maseri A; VAR Study Group. Rationale and design of GISSI OUTLIERS VAR Study in bicuspid aortic valve patients: prospective longitudinal, multicenter study to investigate correlation between surgical, echo distinctive features, histologic and genetic findings in phenotypically homogeneous outlier cases. Int J Cardiol. 2015 Nov 15;199:180-5. doi: 10.1016/j.ijcard.2015.06.182. Epub 2015 Jul 6.

  PMID: 26197404 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Serum samples and tissue samples

MeSH Terms

Conditions

Bicuspid Aortic Valve Disease; Aortic Valve Insufficiency

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Aortic Valve Disease; Heart Valve Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Attilio Maseri, MD

  Dondazione per il Tuo cuore-HCF Onlus

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: October 17, 2014
• First Posted: November 5, 2014
• Study Start: December 1, 2012
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2017
• Last Updated: August 9, 2018

Record last verified: 2018-08

Locations

IT (10)