Clinical trial NCT04751058: Genetic Profile in Patients With Aortic Syndrome
Official title: Genetic Profile in Patients With Aortic Syndrome
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Gene Abnormality
Acute Aortic Syndrome
Lead sponsor: Hospitales Universitarios Virgen del Rocío
Sponsor class: OTHER
First posted: 2021-02-11
Enrollment: 73
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study includes all patients who are admitted with the diagnosis of Acute Aortic Syndrome verified by imaging techniques (CT Angiography) in the Intensive Care Unit of a tertiary Hospital with a 24-hour Cardiac and Vascular Surgery Service

Brief summary: The overall prevalence has increased significantly in the general population, which may be due in part to advances in diagnostic techniques, such as improved imaging techniques. Aortic dissection (AD) can cause sudden cardiac death (SCD). Approximately 95% of thoracic AAS are clinically "silent" until a life-threatening complication arises in an unpredictable manner and presents as sudden cardiac death. The peak incidence of death caused by aortic dissection occurs within 48 hours, therefore, timely diagnosis is essential and saves lives.

We have traditionally associated as risk factors in patients with ASA long-term arterial hypertension, present in 66-75% of cases, smoking, dyslipidemia or atherosclerotic disease. Likewise, any condition that alters the structure of the aorta such as: collagen diseases, aneurysms, bicuspid aorta, and manipulation of the thoracic aorta (cardiac surgery, 18%, or percutaneous intervention that can injure the intima) is involved in ASA. In addition to the well-known hereditary syndromes that affect collagen (Marfan, Elher-Danlos ...) there is a clear familial aggregation: 13-19% of patients without identifiable syndrome have first-degree relatives with thoracic aortic aneurysms or ICD, something that has been called "thoracic aortic dissection and familial aneurysm syndrome."

Notable achievements have been made in the discovery of genetic mutations associated with SAA and key regulatory molecules involved, including the extracellular matrix (ECM), cytoskeletal proteins, and the TGF-β signaling pathway. Identification of the causative gene is advantageous for both patients and their families, especially those who do not show symptoms. The specific underlying genotype could benefit the process of diagnosis, surveillance and surgery, with the aim of reducing morbidity and mortality

Detailed description: HYPOTHESIS.:

A proportion of patients admitted to the Hospital with a diagnosis of Aortic Syndrome without phenotypic characteristics are carriers of mutations. The presence of these mutations can condition both the indication for treatment, post-surgical aortic remodeling, and family traceability.

OBJECTIVE.:

The objective of this study is to analyze the prevalence of mutations in non-phenotypic patients admitted urgently due to Aortic Syndrome.

Material and method:

Patients admitted to the Intensive Care Unit of the Virgen del Rocio University Hospital in Seville (third level Hospital) with the diagnosis of Aortic Syndrome will be included. The clinical and angiographic variables were analyzed. All patients will undergo, with prior informed consent, a peripheral blood extraction, from which a DNA sample will be obtained using the ChemagicTM 360 equipment. This DNA will be processed for massive sequencing on Illumina's NextSeq500 platform using the technology Capture SeqCap EZ Choice Library NimbleGen. The data generated will be analyzed bioinformatically and the identified variants prioritized based on their population frequency (\<0.01), location (exonic and close to splicing sites), their presence in databases of clinical significance ClinVar, HGMD and LOVD and the phenotypic association of the mutated gene OMIM and Orphanet.

Eligibility criteria: Inclusion Criteria:

* Patient older than 16 years
* Patients admitted alive with a diagnosis of acute aortic syndrome
* Written consent to be DNA analysis and conservation in the DNA bank

Exclusion Criteria:

* Refusal to participate in the study and , or analysis of their DNA.
* Without life expectancy and , or Income without life.

Primary outcomes:
measure: % of patients with presence of Missense mutations
timeFrame: post-treatment
measure: % of patients with presence of splicing mutations
timeFrame: post-treatment
measure: % of patients with presence of frameshift mutations
timeFrame: post-treatment
measure: % of patients with presence of nonframeshift mutations
timeFrame: post-treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
state: Andalucia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
Study officials:
affiliation: Andaluz Health Service
name: Antonio M Puppo Moreno, MD;PhD
role: PRINCIPAL_INVESTIGATOR
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