Influence of EPICardial Adipose Tissue in HEART Diseases: EPICHEART Study
Influence of EPICardial Adipose Tissue in HEART Diseases: EPICHEART Study
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.
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.
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).