Influence of EPICardial Adipose Tissue in HEART Diseases: EPICHEART Study

Sponsor

Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E. (Other)

Overall Status

Unknown status

CT.gov ID

NCT03280433

Collaborator

Universidade do Porto (Other)

500

Enrollment

Locations

50.8

Anticipated Duration (Months)

250

Patients Per Site

4.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease Coronary Arteriosclerosis Atrial Fibrillation Left Atrial Abnormality Severe Aortic Stenosis	Other: Aortic valve replacement

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

500 participants

Observational Model:

Cohort

Time Perspective:

Prospective

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

Actual Study Start Date :

Sep 1, 2014

Actual Primary Completion Date :

Nov 25, 2015

Anticipated Study Completion Date :

Nov 25, 2018

Outcome Measures

Primary Outcome Measures

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
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
Coronary artery disease according to the presence of coronary stenosis and/or calcification [Baseline]
Prevalent coronary artery stenosis and coronary calcification

Secondary Outcome Measures

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 Outcome Measures

Mortality [3- to 5-year after aortic valve replacement]
Incidence of all-cause death after aortic valve replacement

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).