Clinical trial NCT03280433: Influence of EPICardial Adipose Tissue in HEART Diseases: EPICHEART Study
Official title: Association of the Volume and Proteome of Epicardial Adipose Tissue With Coronary Artery Disease, Left Atrial Remodelling and Atrial Fibrillation in Severe Aortic Stenosis Patients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Coronary Artery Disease
Coronary Arteriosclerosis
Atrial Fibrillation
Left Atrial Abnormality
Severe Aortic Stenosis
Keywords: Epicardial adipose tissue
Coronary artery disease
Atrial fibrillation
Severe aortic stenosis
Proteome
Mass spectrometry
Computed tomography
Lead sponsor: Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.
Sponsor class: OTHER_GOV
Collaborators: name: Universidade do Porto
First posted: 2017-09-12
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Symptomatic severe aortic stenosis referred to aortic valve replacement.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: New onset atrial fibrillation
timeFrame: Intra-hospital (i.e. from surgery until hospital discharge which means 7 days on average)
measure: Left atrial remodelling by transthoracic echocardiography and magnetic resonance imaging
timeFrame: 6-month following aortic valve replacement
measure: Frailty syndrome according to Fried et al. scale
timeFrame: 6-month following aortic valve replacement
measure: Coronary artery disease according to the presence of coronary stenosis and/or calcification
timeFrame: Baseline
Secondary outcomes:
measure: Left ventricular hypertrophy by transthoracic echocardiography and magnetic resonance imaging
timeFrame: 6-month following aortic valve replacement
measure: Right ventricular structure and function by transthoracic echocardiography and magnetic resonance imaging
timeFrame: 6-month following aortic valve replacement
Other outcomes:
measure: Mortality
timeFrame: 3- to 5-year after aortic valve replacement
Locations:
city: Vila Nova de Gaia
country: Portugal
facility: Centro Hospitalar de Vila Nova de Gaia/Espinho
state: Porto
city: Porto
country: Portugal
facility: Faculty of Medicine of Porto
Study officials:
References: