Influence of EPICardial Adipose Tissue in HEART Diseases: EPICHEART Study

Coronary Artery Disease Clinical Trial

— EPICHEART  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03280433
• Other study ID #: SFRH/BD/104369/2014
• Status: Recruiting
• Phase: N/A
• First received: September 8, 2017
• Last updated: September 13, 2017
• Start date: September 1, 2014
• Est. completion date: November 25, 2018

Study information

• Verified date: September 2017
• Source: Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.
• Contact: Jennifer Mancio, MD, PhD candidate
• Phone: 00351961529516
• Email: jennifer.mancio[@]cardiov.ox.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: November 25, 2018
• Est. primary completion date: November 25, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Aortic Valve Stenosis
• Arteriosclerosis
• Atrial Fibrillation
• Constriction, Pathologic
• Coronary Arteriosclerosis
• Coronary Artery Disease
• Coronary Disease
• Left Atrial Abnormality
• Myocardial Ischemia
• Severe Aortic Stenosis

Intervention

Other:
• Aortic valve replacement

Locations

Country	Name	City	State
Portugal	Faculty of Medicine of Porto	Porto
Portugal	Centro Hospitalar de Vila Nova de Gaia/Espinho	Vila Nova de Gaia	Porto

Sponsors (2)

Lead Sponsor	Collaborator
Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.	Universidade do Porto

Country where clinical trial is conducted

Portugal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mortality	Incidence of all-cause death after aortic valve replacement	3- to 5-year after aortic valve replacement
Primary	New onset atrial fibrillation	Incidence of atrial fibrillation after aortic valve replacement	Intra-hospital (i.e. from surgery until hospital discharge which means 7 days on average)
Primary	Left atrial remodelling by transthoracic echocardiography and magnetic resonance imaging	Change in left atrial strain and volumes	6-month following aortic valve replacement
Primary	Frailty syndrome according to Fried et al. scale	Change in frailty syndrome classification	6-month following aortic valve replacement
Primary	Coronary artery disease according to the presence of coronary stenosis and/or calcification	Prevalent coronary artery stenosis and coronary calcification	Baseline
Secondary	Left ventricular hypertrophy by transthoracic echocardiography and magnetic resonance imaging	Regression of left ventricular mass after aortic valve replacement	6-month following aortic valve replacement
Secondary	Right ventricular structure and function by transthoracic echocardiography and magnetic resonance imaging	Changes in right ventricular structure and function after aortic valve replacement	6-month following aortic valve replacement