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

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

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.

Study Overview

• Status: Unknown
• Conditions: Coronary Artery Disease; Atrial Fibrillation; Coronary Arteriosclerosis; Severe Aortic Stenosis; Left Atrial Abnormality
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Anticipated): 500

Contacts and Locations

• Study Contact: Name: Jennifer Mancio, MD, PhD candidate; Phone Number: 00351961529516; Email: jennifer.mancio@cardiov.ox.ac.uk
• Study Contact Backup: Name: Nuno Bettencourt, MD, PhD; Phone Number: 00351934258281; Email: bettencourt.n@gmail.com

Study Locations

• Portugal
  • Porto, Portugal, 4200-319
    • Enrolling by invitation
    • Faculty of Medicine of Porto
  • Porto
    • Vila Nova de Gaia, Porto, Portugal, 4430-502
      • Recruiting
      • Centro Hospitalar de Vila Nova de Gaia/Espinho
      • Contact: Jennifer Mancio, MD, PhD candidate; Phone Number: 00351 961529516; Email: jennifer.mancio@cardiov.ox.ac.uk
      • Contact: Nuno Bettencourt, MD, PhD; Phone Number: 00351 934258281; Email: bettencourt.n@gmail.com
      • Sub-Investigator: Vasco Gama Ribeiro, MD
      • Sub-Investigator: Luis Vouga, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Symptomatic severe aortic stenosis referred to aortic valve replacement.

Description

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).

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
Left atrial remodelling by transthoracic echocardiography and magnetic resonance imaging	Change in left atrial strain and volumes	6-month following aortic valve replacement
Frailty syndrome according to Fried et al. scale	Change in frailty syndrome classification	6-month following aortic valve replacement
Coronary artery disease according to the presence of coronary stenosis and/or calcification	Prevalent coronary artery stenosis and coronary calcification	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Incidence of all-cause death after aortic valve replacement	3- to 5-year after aortic valve replacement

Collaborators and Investigators

• Sponsor: Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.
• Collaborators: Universidade do Porto

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2014
• Primary Completion (ACTUAL): November 25, 2015
• Study Completion (ANTICIPATED): November 25, 2018

Study Registration Dates

• First Submitted: September 8, 2017
• First Submitted That Met QC Criteria: September 9, 2017
• First Posted (ACTUAL): September 12, 2017

Study Record Updates

• Last Update Posted (ACTUAL): September 14, 2017
• Last Update Submitted That Met QC Criteria: September 13, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Coronary artery disease; Atrial fibrillation; Computed tomography; Mass spectrometry; Epicardial adipose tissue; Proteome; Severe aortic stenosis
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arterial Occlusive Diseases; Pathological Conditions, Anatomical; Arrhythmias, Cardiac; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Atrial Fibrillation; Aortic Valve Stenosis; Arteriosclerosis; Constriction, Pathologic
• Other Study ID Numbers: SFRH/BD/104369/2014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No