Ignite Creation Date:
2024-05-06 @ 8:22 PM
Last Modification Date:
2024-10-26 @ 3:26 PM
Study NCT ID:
NCT06353607
Status:
RECRUITING
Last Update Posted:
2024-04-22
First Post:
2024-04-02
Brief Title:
Genetic Architecture of Acute Aortic Syndromes and Aortic Aneurysm
Sponsor:
University Hospital Basel Switzerland
Organization:
University Hospital Basel Switzerland
Study Overview
Official Title:
Genetic Architecture of Acute Aortic Syndromes and Aortic Aneurysm
Status:
RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The aim of this study is to explore the genetic information associated with the development of TAA and aAD in individuals without history or syndromic features Marfan syndrome Ehlers-Danlos syndrome Turner syndrome etc for aortic disease For this purpose whole genome sequencing will be performed in patients with documented aortic aneurysm orand aortic dissection
Detailed Description:
Acute aortic dissection aAD is a life-threatening condition associated with increased morbidity and mortality The incidence of aAD has been estimated to occur at a rate of 6-7 cases per 100000 persons per year and is associated with high mortality With the increasing availability of computed tomography scan CT in emergency settings the diagnosis of aAD was increasing in past decades increasing up to 17 cases per 100000 persons per year Acute aortic event is associated with a high mortality rate ranging from 26 in surgically treated patients to 58 in medically treated patients
Thoracic aortic aneurysm TAA is a well-established risk factor for aAD but it is not a prerequisite Recent evidence suggests that almost 90 of aADs occur mostly in younger patients with aortic dimensions of 55 cm and only 5 of patients with diagnosed TAA are symptomatic prior to dissection or rupture
The majority of aAD patients are misdiagnosed which puts them at a higher risk of death Timely diagnosis and surgical management of patients with TAA prior to aAD reduces the risk of complications and death Therefore there is an unmet need for better and more refined risk prediction tools to identify high-risk patients with TAA who may benefit from early screening and tuned surgical intervention
Previous studies found that more than 20 of patients with TAA report a positive family history and the genetics of thoracic aortic aneurysm and dissection has been extensively investigated as a potential tool for both diagnosis and risk stratification
Traditionally TAA is divided into syndromic-with other organ system abnormalities other than the aorta-and non-syndromic-with no systemic abnormalities present Several monogenic causes for syndromic TAA are well described such as Marfan syndrome MFS Loeys-Dietz syndrome LDS and Ehlers-Danlos syndrome EDS However the non-syndromic TAA and aAD are more prevalent and identifying these patients can be challenging Some evidence exist that mutations of genes observed in syndromic patients may be involved in TAA and aAD in non-syndromic patients The fact that approximately 20 of non-syndromic TAA patients have at least one affected family member indicates that TAA could be a heritable disease and there might be a genetic link in non-syndromic patients
Given the inherent challenges in the diagnosis of the TAA as a precursor of aAD in non-syndromic patients there is a clinical need for the development of an accurate risk prediction tools To address the mentioned clinically relevant question in an observational cohort study of patients with aortic disease a molecular genetic investigation will be conducted to investigate the genetic architecture of TAA and individuals at high risk for aAD and to use this information to propose patient specific risk assessment and individually tailored management and therapy This data will be coupled to the routinely collected standard clinical and imaging data including computed tomography angiography CTA perioperative transesophageal echocardiogram TEE and transthoracic echocardiogram TTE with the aim to further refine risk stratification in aADTAA patients
Thoracic aortic aneurysm TAA is a well-established risk factor for aAD but it is not a prerequisite Recent evidence suggests that almost 90 of aADs occur mostly in younger patients with aortic dimensions of 55 cm and only 5 of patients with diagnosed TAA are symptomatic prior to dissection or rupture
The majority of aAD patients are misdiagnosed which puts them at a higher risk of death Timely diagnosis and surgical management of patients with TAA prior to aAD reduces the risk of complications and death Therefore there is an unmet need for better and more refined risk prediction tools to identify high-risk patients with TAA who may benefit from early screening and tuned surgical intervention
Previous studies found that more than 20 of patients with TAA report a positive family history and the genetics of thoracic aortic aneurysm and dissection has been extensively investigated as a potential tool for both diagnosis and risk stratification
Traditionally TAA is divided into syndromic-with other organ system abnormalities other than the aorta-and non-syndromic-with no systemic abnormalities present Several monogenic causes for syndromic TAA are well described such as Marfan syndrome MFS Loeys-Dietz syndrome LDS and Ehlers-Danlos syndrome EDS However the non-syndromic TAA and aAD are more prevalent and identifying these patients can be challenging Some evidence exist that mutations of genes observed in syndromic patients may be involved in TAA and aAD in non-syndromic patients The fact that approximately 20 of non-syndromic TAA patients have at least one affected family member indicates that TAA could be a heritable disease and there might be a genetic link in non-syndromic patients
Given the inherent challenges in the diagnosis of the TAA as a precursor of aAD in non-syndromic patients there is a clinical need for the development of an accurate risk prediction tools To address the mentioned clinically relevant question in an observational cohort study of patients with aortic disease a molecular genetic investigation will be conducted to investigate the genetic architecture of TAA and individuals at high risk for aAD and to use this information to propose patient specific risk assessment and individually tailored management and therapy This data will be coupled to the routinely collected standard clinical and imaging data including computed tomography angiography CTA perioperative transesophageal echocardiogram TEE and transthoracic echocardiogram TTE with the aim to further refine risk stratification in aADTAA patients
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None