National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC)

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Accession Number
HLB01421717a

Study Type
Epidemiology Study

Collection Type
Open BioLINCC Study See bottom of this webpage for request information

Study Period
October 2006 - September 2016

NHLBI Division
DCVS

Dataset(s) Last Updated
January 3, 2018

Consent

Commercial Use Data Restrictions No

Data Restrictions Based On Area Of Research Yes

Commercial Use Specimen Restrictions Yes

Non-Genetic Use Specimen Restrictions Based On Area Of Use Yes

Genetic Use Of Specimens Allowed? Yes

Genetic Use Area Of Research Restrictions Yes

Specific Consent Restrictions
Use of data and/or biospecimens is restricted to research involving heart and blood vessel diseases. Study participants were given the option to consent to commercial use of DNA biospecimens, as well as for the creation of cell lines.

Objectives

The overall objective of GenTAC was to establish a registry of patients with genetically induced thoracic aortic aneurysms and related cardiovascular conditions, and collect associated medical data, as well as blood and tissue samples and make them available to investigators to advance research in diagnosis and management of genetically induced thoracic aortic aneurysms.

Background

Thoracic aortic aneurysms (TAAs) predispose individuals to life threatening aortic complications, including aortic dissection and rupture. The treatment of complications arising from TAAs is complex, with high rates of morbidity, mortality, and surgical procedures. TAAs are associated with loss of vascular smooth muscle cells and degeneration of extracellular matrix in the aortic wall. This degeneration may be caused by hypertension and inflammation, particularly in elderly individuals. Genetic mutations are the main cause of TAAs in many young or middle-aged individuals. Genetic disorders, such as Marfan syndrome, Loeys-Dietz syndrome, and vascular Ehlers-Danlos syndrome, have a high risk for TAA, and up to 20% of individuals with TAAs or dissection have a family history of TAAs without being affected by a known syndrome or known genetic mutation. While diagnostic and treatment advances have dramatically improved care for patients with genetically induced TAAs, many questions remain about how best to identify and treat these disorders. Thus, GenTAC was developed as a longitudinal registry for patients affected by genetically induced thoracic aortic conditions in order to facilitate ongoing and future investigations to improve the diagnosis and clinical management of patients with genetically induced TAAs. Information gained from studying the genetically induced TAAs is expected to benefit the clinical management of non-genetic TAAs, as well.

Subjects

Eligible participants must have one of the following conditions: Marfan syndrome; Turner syndrome; Ehlers-Danlos syndrome; Loeys-Dietz syndrome; Shprintzen-Goldberg syndrome; FBN1, TGFBR1, TGFBR2, ACTA2 or MYH11 genetic mutation; bicuspid aortic valve; Familial Thoracic Aortic Aneurysm and Dissections; other thoracic aortic aneurysms and dissections (not due to trauma) in patients 50 years of age or less; or other congenital heart disease. Over 3,500 participants were enrolled.

Design

GenTAC was a longitudinal observational cohort study of affected individuals with either known or suspected genetic mutation that predisposes them for thoracic aortic aneurysms and dissections (TAAD). There were no interventions planned, and all decisions regarding approaches to treatment were to be made by the patients and their care teams. Enrollment data were abstracted from medical records or obtained through patient interviews. The data collected include clinical evaluations (by several organ systems), historically diagnosed conditions and outcomes and drug treatment; patient reported quality of life, co-morbidities, family history, smoking, alcohol use, and pregnancy history; most recent imaging evaluations, genetic testing, blood chemistry, and surgical interventions. When blood could not be collected from participants, a saliva sample was obtained as a source of DNA. Excess aortic tissue was frozen from participants that underwent surgery. Follow-up data was collected at regular intervals for each participant enrolled, with the interval varying by the diagnosis. Follow-up data include outcomes, clinical and imaging evaluations and treatment and lifestyle changes since the enrollment visit. Images were read by the imaging core according to the study protocol. Diagnosis of each participant was confirmed by the phenotyping core.

Conclusions

GenTAC established a vast biospecimen inventory and clinical database from over 3500 participants that is available to researchers with the ultimate goal of advancing the diagnosis and management of genetically induced thoracic aortic aneurysms and other cardiovascular complications. Some of the publications resulting from analysis of the GenTAC data and biospecimens can be found at https://www.nhlbi.nih.gov/research/resources/gentac/research.

Novel Evaluation of GenTAC Images is Available

The National Registry of Genetically Triggered Thoracic Aortic Aneurysms (GenTAC) was established to advance research in diagnosis and management of genetically induced thoracic aortic aneurysms. GenTAC data and biospecimens now reside at BioLINCC and are available for investigators. Clinical data available through BioLINCC include core laboratory readings of serial 2D echo, CT and MRI images. These images were acquired according to clinical need as determined by the enrolling clinical centers, and therefore the acquisition was not standardized by protocol. Analysis of the images was, however, performed at the Imaging Core Lab according to a pre-specified protocol that was applied to all imaging modalities equally.


MedStar Imaging Core Lab Capacity for Re-Reading Raw GenTAC Images

A special feature of the imaging data is that the raw digitized images reside at MedStar Health Research Institute’s Cardiovascular Core Lab, in Washington, DC (MedStar). MedStar is willing to consider applications from researchers who have obtained GenTAC data through BioLINCC and who wish to have additional or novel evaluation of GenTAC images beyond the image readings obtained under the original GenTAC study protocol.

The GenTAC Imaging Core Lab would be happy to consider scientific proposals and determine feasibility and costs of analysis that investigators propose in order to support their research. Funding for additional image analysis by the Core Lab would be provided by the researcher under a pricing structure to be determined by the Core Lab based upon the scope of effort for the specific proposed project. Agreements for re-reading of images would be between the researcher and the Core Lab.


Application Process

Applications for additional image evaluations will only be accepted by the Imaging Core Lab from investigators who have received GenTAC data from BioLINCC and who have determined that their question cannot be answered by the imaging data available in the GenTAC data. The application form, instructions, and contact information for the Imaging Core Lab will be made available for request upon approval and fulfillment of a GenTAC data request through BioLINCC.

Publications

A list of GenTAC publications can be found on the GenTAC Alliance website.

Additional Details

Subjects:
SYNDROME Frequency
Missing 3
Marfan syndrome 845
Turner syndrome 298
Ehlers-Danlos syndrome, vascular 149
Ehlers-Danlos syndrome, other 26
Loeys-Dietz syndrome 104
FBN1, TGFBR1 or TGFBR2 genetic mutation 65
Bicuspid aortic valve w/out family history 869
Bicuspid aortic valve w/ family history 20
Shprintzen-Goldberg syndrome 4
Familial Thoracic Aortic Aneurysm and Dissection 369
Other due to trama (<40 years old) 592
Other congenital heart disease w/ family history 115
1st or 2nd degree family member of probrand already enrolled in GenTAC 31
BAV with coarctation 79

NOTE: 50 subjects were flagged with multiple syndromes. These subjects are included in each syndrome's count.
 
Age:
age_cat Frequency Percent Cumulative
Frequency
Cumulative
Percent
Missing 1197 34.04 1197 34.04
Discrepant 6 0.17 1203 34.22
<10 107 3.04 1310 37.26
10-19 364 10.35 1674 47.61
20-29 278 7.91 1952 55.52
30-39 372 10.58 2324 66.10
40-49 464 13.20 2788 79.29
50-59 451 12.83 3239 92.12
60-69 205 5.83 3444 97.95
70-79 58 1.65 3502 99.60
>=80 14 0.40 3516 100.00
 
Sex:
GENDER Frequency Percent Cumulative
Frequency
Cumulative
Percent
Missing 1081 30.75 1081 30.75
Male 1370 38.96 2451 69.71
Female 1065 30.29 3516 100.00
 
Race:
race Frequency Percent Cumulative
Frequency
Cumulative
Percent
Missing 1116 31.74 1116 31.74
Discrepant 16 0.46 1132 32.20
White 2129 60.55 3261 92.75
Black/African American 89 2.53 3350 95.28
Asian 80 2.28 3430 97.55
American Indian/Alaska Native 5 0.14 3435 97.70
Native Hawaiian/Pacific Islander 32 0.91 3467 98.61
Mixed 49 1.39 3516 100.00
 
ETHNICITY Frequency Percent Cumulative
Frequency
Cumulative
Percent
Missing 1194 33.96 1194 33.96
Discrepant 5 0.14 1199 34.10
No 2166 61.60 3365 95.71
Yes 151 4.29 3516 100.00
 

Please note that biospecimen availability is subject to review by the NHLBI, BioLINCC, and the NHLBI Biorepository. Certain biospecimens may not be made available for your request. Section 3 of the BioLINCC handbook describes the components of the review process

Material Types:

Aorta Tissue, Plasma, Lymphocytes, EBV Cell Line, DNA, Buffy Coat, PMNC/RBC Pellet

General Freeze/Thaw Status:
01/11/2022
  Number of Freeze/Thaws
0 1 2 3 4 5 6
DRAW VIAL: Material Type 9 . . . . . .
Unknown DNA
Draw 1 Aorta Tissue 523 84 8 6 . . .
Plasma 12046 206 . . . . .
Lymphocytes 1870 . . . . . .
EBV Cell Line 4765 3465 216 . . . .
DNA 237 15103 5703 861 304 16 4
Buffy Coat 857 . . 1 . . .
PMNC/RBC Pellet 1830 . . . . . .
Draw 2 Aorta Tissue 455 14 6 . . . .
Plasma 767 4 . . . . .
Lymphocytes 96 . . . . . .
EBV Cell Line 185 160 22 . . . .
DNA 34 342 166 20 5 . .
Buffy Coat 61 . . . . . .
PMNC/RBC Pellet 109 . . . . . .
Draw 3 Aorta Tissue 5 . . . . . .
Plasma 60 . . . . . .
Lymphocytes 9 . . . . . .
EBV Cell Line 10 15 . . . . .
DNA . 27 10 5 . . .
Buffy Coat 5 . . . . . .
PMNC/RBC Pellet 9 . . . . . .
 
Visits (Vials):
01/11/2022
Table of DRAW by MATTYPE
DRAW MATTYPE(VIAL: Material Type)
Frequency Aorta Tissue Plasma Lymphocytes EBV Cell Line DNA Buffy Coat PMNC/RBC Pellet Total
Unknown 0 0 0 0 9 0 0 9
Draw 1 621 12252 1870 8446 22228 858 1830 48105
Draw 2 475 771 96 367 567 61 109 2446
Draw 3 5 60 9 25 42 5 9 155
Total 1101 13083 1975 8838 22846 924 1948 50715
 
Visits (Subjects):
01/11/2022
  Aorta Tissue
Subject Count Average number of vials per subject
Draw 1 73 8.51
Draw 2 55 8.64
Draw 3 2 2.50
 
 
  Plasma
Subject Count Average volume (mL) per subject
Draw 1 1,820 3.26
Draw 2 99 3.17
Draw 3 7 3.39
 
  Lymphocytes
Subject Count Average number of vials per subject
Draw 1 1,834 1.02
Draw 2 90 1.07
Draw 3 7 1.29
 
 
  EBV Cell Line
Subject Count Average number of vials per subject
Draw 1 1,694 4.99
Draw 2 74 4.96
Draw 3 5 5.00
 
  
  DNA
Subject Count Average mass (ug) per subject
Unknown 1 49.00
Draw 1 3,024 85.52
Draw 2 77 104.71
Draw 3 5 115.21
 
  Buffy Coat
Subject Count Average number of vials per subject
Draw 1 858 1.00
Draw 2 60 1.02
Draw 3 5 1.00

 
  PMNC/RBC Pellet
Subject Count Average number of vials per subject
Draw 1 870 2.10
Draw 2 55 1.98
Draw 3 5 1.80
 

 

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Resources Available

Specimens and Study Datasets

Materials Available

Study Documents

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