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

Study Website
https://www.nhlbi.nih.gov/science/national-registry-genetically-triggered-thoracic-aortic-aneurysms-and-cardiovascular

Clinical Trial URLs
https://clinicaltrials.gov/ct2/show/NCT01322165

Primary Publication URLs
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3190125/

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.

Participants

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

Study Population

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 aneurysms/dissections of the thoracic aorta not due to trauma (<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

Available Biospecimens

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	9	.	.	.	.	.	.
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

Study Catalog

Study Publications (2)

Materials Available

Aorta Tissue
Buffy Coat
DNA
EBV Cell Line
Lymphocytes
Plasma
Polymorphonuclear Cells/RBC Pellets
Novel Image Evaluations
More Details

Study Documents

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