Atrial Fibrillation, Coronary Arteriosclerosis, Coronary Artery Disease, Left Atrial Abnormality, Severe Aortic Stenosis
Conditions
Keywords
Epicardial adipose tissue, Coronary artery disease, Atrial fibrillation, Severe aortic stenosis, Proteome, Mass spectrometry, Computed tomography
Brief summary
This translational study was designed to explore the association of the quantity and quality of epicardial adipose tissue (EAT) with coronary artery disease (CAD), left atrial remodeling and postoperative atrial fibrillation in a high cardiovascular disease-risk population. The investigators expect to identify new biochemical factors and biomarkers in the crosstalk between the epicardial adipocytes, coronary plaques and atrial cardiomyocytes that are involved in the pathogenesis of atherosclerosis and atrial fibrillation, respectively.
Detailed description
Background: EAT has emerged as a new independent, and, potentially, modifiable cardiovascular risk factor for CAD. EAT volume assessed by computed tomography (CT) was independently associated with the presence of coronary stenosis, coronary calcification and myocardial ischemia in cross-sectional studies, and, prospectively, with major adverse cardiovascular events. Most of these clinical studies were, however, derived from community-based patients with low-to intermediate-risk profile and the role of EAT in high-risk patients is currently unclear. Accumulation of EAT has been also associated with left atrial (LA) dilation, presence, chronicity, and recurrence of atrial fibrillation (AF). Although there is evidence suggesting that EAT may be a major determinant of the LA vulnerable substrate of AF, the mechanisms in the causal pathway between the EAT and LA remodeling are not completely elucidated. Aims: The main aims are to investigate if the volume of the EAT on CT and EAT proteome assessed by SWATH-mass spectrometry are associated with extent, distribution and complexity of coronary stenosis and coronary artery calcification, left atrial strain and incidence of postoperative atrial fibrillation in patients with symptomatic severe aortic stenosis. Methods: This a prospective study enrolling symptomatic severe aortic stenosis patients referred to aortic valve replacement. The protocol includes preoperative detailed clinical and nutritional evaluations, echocardiography, CT, cardiac magnetic resonance imaging and invasive coronary angiography. During cardiac surgery, biopsies from the EAT, mediastinal and subcutaneous thoracic adipose tissues will be performed to undergo analysis of proteome using SWAT-mass spectrometry. Samples from the pericardial fluid, circulating and coronary sinus blood samples will be collected as well in order to find local and peripheral adipose tissue-derived biomarkers of the disease.
Interventions
OTHERAortic valve replacement
Sponsors
Universidade do Porto
Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* symptomatic severe aortic stenosis patients (defined as aortic valve area of \< 1 cm2 or 0.6 cm2/m2 by transthoracic echocardiography) referred to aortic valve replacement.
Exclusion criteria
* diagnosis of acute coronary syndrome in the last 3 months. * prior history of persistent or permanent atrial or flutter fibrillation. * coexisting moderate to severe aortic valve regurgitation or moderate to severe mitral valve disease, bicuspid aortic valve. * left ventricular dilatation \[end-diastolic volume index \>75 mL/m²\]. * left ventricular ejection fraction \<55%. * chronic renal failure stage 3 to 5 defined as glomerular filtration rate GFR estimated by Cockcroft-Gault formula adjusted for body surface area \< 30 mL/min/1.73m². * moderate to severe chronic obstructive pulmonary disease defined as forced expiratory volume in one second \<50% according to the 2011 Global Initiative for Chronic Obstructive Pulmonary Disease guidelines. * active malignancy (i.e. With no evidence of recurrence and no longer receiving active treatment).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Coronary artery disease according to the presence of coronary stenosis and/or calcification | Baseline | Prevalent coronary artery stenosis and coronary calcification |
| Left atrial remodelling by transthoracic echocardiography and magnetic resonance imaging | 6-month following aortic valve replacement | Change in left atrial strain and volumes |
| Frailty syndrome according to Fried et al. scale | 6-month following aortic valve replacement | Change in frailty syndrome classification |
| New onset atrial fibrillation | Intra-hospital (i.e. from surgery until hospital discharge which means 7 days on average) | Incidence of atrial fibrillation after aortic valve replacement |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Left ventricular hypertrophy by transthoracic echocardiography and magnetic resonance imaging | 6-month following aortic valve replacement | Regression of left ventricular mass after aortic valve replacement |
| Right ventricular structure and function by transthoracic echocardiography and magnetic resonance imaging | 6-month following aortic valve replacement | Changes in right ventricular structure and function after aortic valve replacement |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mortality | 3- to 5-year after aortic valve replacement | Incidence of all-cause death after aortic valve replacement |
Countries
Portugal
Contacts
Primary ContactJennifer Mancio, MD, PhD candidate
Backup ContactNuno Bettencourt, MD, PhD
Outcome results
None listed