Clinical trial NCT05389865: Proximal Aortopathy in Scotland - Epidemiology and Surgical Outcomes
Official title: An Investigation Into the Epidemiology and Surgical Intervention for Proximal Aortic Disease in Scotland
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Aortic Diseases
Aortic Dissection
Aortic Aneurysm, Thoracic
Aortic Ectasia
Aortic Valve Insufficiency
Bicuspid Aortic Valve
Marfan Syndrome
Ehlers-Danlos Syndrome
Loeys-Dietz Syndrome
Keywords: aortic surgery
aortic root
ascending aorta
surgical outcomes
thoracic aortopathy epidemiology
Lead sponsor: Golden Jubilee National Hospital
Sponsor class: OTHER_GOV
Collaborators: name: Aberdeen Royal Infirmary
name: Royal Infirmary of Edinburgh
name: Network for Inherited Cardiac Conditions Scotland
name: University of Glasgow
First posted: 2022-05-25
Enrollment: 1662
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 1. Surgical cohort (Observational cohort design)- Adult patients (18 years of age and above) who have had a surgical intervention on the proximal aorta in the three Scottish Cardiothoracic Surgery units based in Glasgow, Edinburgh, Aberdeen.
2. Non-surgical cohort (Cross-sectional design) - Adult patients (18 years of age and above) who have a diagnosis of proximal aortopathy, but have not had surgical intervention (non-surgical/un-intervened proximal aortopathy). This cohort will be obtained from three sources:

   1. Scottish national radiological database based on specific imaging codes
   2. Regional genetic/inherited cardiac conditions services
   3. Public Health Scotland via specific diagnostic ICD-10 codes.

Brief summary: The aorta is the principal arterial vessel arising from the left heart that transfers blood to the body. Certain genetic and familial disease processes are known to weaken the aortic wall resulting in dilation and potential rupture. These aortic complications carry high mortality (\>25%) and current management is orientated towards early detection and preventive treatment. Aortic dilation can also result in aortic valve dysfunction leading to heart failure. The estimated UK incidence of aortic disease per year is around 10 per 100,000 individuals, with 2000 people per year dying from aortic complications.

The 2017-2020 National Adult Cardiac Surgery Audit report identified the number of people receiving surgery for aortic dissection in Scotland is per population proportionately lower compared to England (4.6 per million per year in Scotland vs. 6.6 per million per year in England). The reasons for this are unclear but may relate to the prevalence of aortic disease or a large geographic distribution with compromised access to specialized centres.

Currently surgery is recommended when the aortic diameter exceeds a certain threshold. There are several types of effective surgical procedures, but there is still limited information on their long-term outcomes and the advantage of one procedure over another.

The aims of the project are firstly to determine the clinical outcomes of the surgical procedures that are currently employed in Scotland to treat proximal aortic disease and secondly to describe the prevalence and distribution of proximal aortic disease within the Scottish population. The project will be hosted by the Golden Jubilee Research Institute. Contemporary and retrospective data will be collected from all the Scottish Cardiothoracic Surgery units which are based in Glasgow, Edinburgh and Aberdeen.

This will be the first study to analyse surgical outcomes for ascending aortic disease in Scotland, and the first to describe the epidemiology of aortic disease within the population. It is anticipated that the results will guide current surgical practise, and provide data to inform national service provision for the management of proximal aortic disease.

Detailed description: The study has two principal aims:

1. Determine the patient demographics, procedural types and related clinical outcomes in patients who underwent surgery of the proximal thoracic aorta in Scotland
2. Describe the epidemiology of proximal aortopathy within the Scottish population, by determining the prevalence of disease, geographic distribution and patient demographics

This study will be the first to look at outcomes from a nation-wide cohort of patients following surgery of the thoracic aorta in the UK. The investigators anticipate that results from this study will inform future aortic practice and guide decisions on intervention timing and type.

Information on the prevalence and geographic distribution of aortic disease within Scotland will guide resource allocation and service configuration to allow equity in access to treatment. By raising awareness among the medical professionals and the wider community, the study should lead to improved recognition and better outcomes for patients with aortic disease.

Data will be recorded in a contemporary and retrospective manner for two patient cohorts:

1. Surgical cohort - Adult patients who have had a surgical intervention on the proximal aorta in the three Scottish Cardiothoracic Surgery units based in Glasgow, Edinburgh, Aberdeen in the last 13 years (2008 - 2021).
2. Non-surgical cohort - Adult patients who have a diagnosis of proximal aortopathy, but have not had surgery. This cohort will be obtained from three sources:

   1. Patients with a diagnosis of thoracic aortopathy identified via National Interim Clinical Imaging Procedure (NICIP) codes sourced from the Scottish Radiology Information System (RIS) and Picture Archive and Communication System (PACS) databases.
   2. Patients with a diagnosis of thoracic aortopathy identified from regional genetic services via the Network for Inherited Cardiac Conditions Scotland.
   3. Deceased patients diagnosed with proximal thoracic aortopathy or a complication thereof (aortic dissection, aortic rupture) registered at death certification and/or post mortem accessed from Public Health Scotland using ICD-10 codes.

The three data collection sites will be the Golden Jubilee National Hospital in Glasgow, the Edinburgh Royal Infirmary and Aberdeen Royal Infirmary.

The surgical cohort sample size is expected to be around 1300 patients. The non-surgical cohort is difficult to estimate, but around 500 cases yearly are expected to be identified. The research project will be hosted by the NHS Golden Jubilee Research Department.

The principal investigator (George Gradinariu) will undertake this research project as part of an postgraduate research programme (MD degree) at the University of Glasgow under the supervision of Professor Mark Danton (Congenital Cardiac Surgeon with interest in proximal aortic surgery), Professor Alex McConnachie Professor of Biostatistics, University of Glasgow) and Professor Faisal Ahmed (Samson Gemmell Chair of Child Health, University of Glasgow)

Statistical analysis will be overseen and supervised by Professor McConnachie. Descriptive statistics will be applied. Survival data will be analysed using Kaplan-Meier. Multivariable survival and logistic regression models will be used to identify variables predicting the risk of adverse outcomes. Predictive modelling to estimate the risk of adverse outcomes based on aortic root dimension will be assessed using ROC analysis. In comparing survival by procedures propensity matching will be used to minimize confounding. Analysis will be performed using R statistical analysis software (R Foundation for Statistical Computing, Vienna, Austria).

Eligibility criteria: Surgical cohort

Inclusion Criteria:

* all adults (\>18 years of age) that underwent surgical intervention on the proximal aorta in Scotland between 2008 and 2021.

Exclusion Criteria:

* Isolated surgery on the descending thoracic aorta

Non-surgical cohort

Inclusion Criteria:

- all adult patients (\>18 years of age) with a radiological, genetic or post-mortem diagnosis of thoracic aortic disease

Primary outcomes:
measure: Early survival following surgery of the proximal aorta
timeFrame: In-hospital or 30 days (whichever is longer)
measure: Late survival following surgery of the proximal aorta
timeFrame: 5 years or latest available follow-up (whichever is longer)
measure: Patient demographics and geographic distribution of thoracic aortopathy within the Scottish population
timeFrame: Cross-sectional analysis (2011-2021)
Secondary outcomes:
measure: Cardiovascular reintervention
timeFrame: 1 year or latest available follow-up (whichever is longer)
measure: Specified adverse events following surgery
timeFrame: 1 year or latest available follow-up (whichever is longer)
measure: Left ventricular ejection fraction (LVEF) following surgery
timeFrame: 1 year or latest available follow-up (whichever is longer)
measure: Aortic valve mean gradient and degree of regurgitation following surgery
timeFrame: 1 year or latest available follow-up (whichever is longer)
measure: Genotypes and phenotypes prevalent in the Scottish population
timeFrame: Previous 5 years
Other outcomes:
Locations:
city: Glasgow
country: United Kingdom
facility: Golden Jubilee National Hospital
Study officials:
affiliation: Golden Jubilee National Hospital
name: George Gradinariu, MD
role: PRINCIPAL_INVESTIGATOR
References: