Clinical trial NCT02789943: Multi- Level and Integrated Analysis of Mechanisms Underlying Atrial Dysfunction
Official title: The National Heart Centre Singapore Prospective CABG Cohort: Multi- Level and Integrated Analysis of Mechanisms Underlying Atrial Dysfunction
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Ischemic Heart Disease
Keywords: IHD Normal EF
Lead sponsor: National Heart Centre Singapore
Sponsor class: OTHER
Collaborators: name: Duke-NUS Graduate Medical School
First posted: 2016-06-03
Enrollment: 750
Sex: ALL
Minimum age (years): 21
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients will be recruited from wards or referral from clinics at the National Heart Centre Singapore if criteria is fulfil

Brief summary: Integrated and cross-disciplinary analysis of human physiology and disease provides unbiased and deeply informative insights into human health and disease. In this study the investigators will recruit patients undergoing coronary artery bypass surgery to study the atrium of the heart or the aortic wall that when diseased can cause strokes.

Hypothesis: Systems-level analysis of the left atrium and aorta cells that integrates imaging, histological, cellular and molecular data will identify new mechanism for cardiovascular form and function.

Detailed description: While there are many sub-aims to this study, the overarching goal is to define molecular mechanisms underlying atrial dysfunction. Here the investigator provide a power calculation based on detecting the genetic control points of gene expression (eQTLs) in the human atrial fibroblast. The investigator and many others have shown that tissue-specific eQTLs can be robustly identified at genome-wide significance in segregating populations of \~200. In this study the investigator propose eQTL association analysis in humans, which have previously been successfully performed in cohorts of less than 1000 subjects. The general applicability of this approach has been validated in multiple studies across multiple tissues in cohorts of between 200-1000 subjects.Based on published imaging genetic studies that have been successfully applied in small cohorts (\<500) and the success of echo-based, semi-quantitative studies of ventricular dimensions, the investigator are confident that our quantitative studies of 750 individuals are powered to detect genome wide significant loci for the traits under study.

Despite intensive research there is a critical gap in our knowledge in the mechanisms underlying atrial fibrillation, which is a major cause of stroke and heart failure and increasingly common as it is a disease of the elderly. This project will address this important gap in our knowledge and provide new insights into disease pathogenesis with the goal of stratifying participants to prevent strokes and for treating the underlying substrate.

Eligibility criteria: Inclusion Criteria:

* Patients undergoing elective cardiac bypass surgery during which a sample of right atrial appendage and/or aortic button can be removed.

Exclusion Criteria:

* Infection within 2 weeks preceding the operation or immunosuppressive therapy.
* Patients not able or willing to consent for study.
* Previous atrial intervention.
* Patients who cannot be followed up.
* Exclude patients with significant valvular disease (any planned valvular surgery, MR \> severe, AS \> severe, TR \> severe).

Primary outcomes:
measure: First occurrence of cardiovascular event
timeFrame: One year
Secondary outcomes:
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: National Heart Centre
Study officials:
affiliation: National Heart Centre Singapore / Duke NUS Graduate Medical School
name: Stuart Alexander Cook
role: PRINCIPAL_INVESTIGATOR
References:
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