Multi- Level and Integrated Analysis of Mechanisms Underlying Atrial Dysfunction

NCT ID: NCT02789943

Last Updated: 2017-04-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

750 participants

Study Classification

OBSERVATIONAL

Study Start Date

2013-05-31

Study Completion Date

2021-04-30

Brief Summary

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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

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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.

Conditions

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Ischemic Heart Disease

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Interventions

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Cardiac Bypass Surgery

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

Intervention Type PROCEDURE

Eligibility Criteria

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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).
Minimum Eligible Age

21 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Duke-NUS Graduate Medical School

OTHER

Sponsor Role collaborator

National Heart Centre Singapore

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stuart Alexander Cook

Role: PRINCIPAL_INVESTIGATOR

National Heart Centre Singapore / Duke NUS Graduate Medical School

Locations

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National Heart Centre

Singapore, Singapore, Singapore

Site Status RECRUITING

Countries

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Singapore

Central Contacts

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Muhammad Hafiz Jamal

Role: CONTACT

97547816 / ext. +65

Facility Contacts

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Muhammad Hafiz Jamal

Role: primary

97547816 ext. +65

References

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Hogue CW Jr, Creswell LL, Gutterman DD, Fleisher LA; American College of Chest Physicians. Epidemiology, mechanisms, and risks: American College of Chest Physicians guidelines for the prevention and management of postoperative atrial fibrillation after cardiac surgery. Chest. 2005 Aug;128(2 Suppl):9S-16S. doi: 10.1378/chest.128.2_suppl.9s.

Reference Type BACKGROUND
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Chew JT, Ong KK. Atrial arrhythmias post coronary bypass grafting. Singapore Med J. 1993 Oct;34(5):430-4.

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Alexander KP, Peterson ED. Coronary artery bypass grafting in the elderly. Am Heart J. 1997 Nov;134(5 Pt 1):856-64. doi: 10.1016/s0002-8703(97)80008-7. No abstract available.

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PMID: 9398097 (View on PubMed)

Ad N, Snir E, Vidne BA, Golomb E. Histologic atrial myolysis is associated with atrial fibrillation after cardiac operation. Ann Thorac Surg. 2001 Sep;72(3):688-93. doi: 10.1016/s0003-4975(01)02882-x.

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Richand V, Lafitte S, Reant P, Serri K, Lafitte M, Brette S, Kerouani A, Chalabi H, Dos Santos P, Douard H, Roudaut R. An ultrasound speckle tracking (two-dimensional strain) analysis of myocardial deformation in professional soccer players compared with healthy subjects and hypertrophic cardiomyopathy. Am J Cardiol. 2007 Jul 1;100(1):128-32. doi: 10.1016/j.amjcard.2007.02.063. Epub 2007 May 21.

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Park TH, Nagueh SF, Khoury DS, Kopelen HA, Akrivakis S, Nasser K, Ren G, Frangogiannis NG. Impact of myocardial structure and function postinfarction on diastolic strain measurements: implications for assessment of myocardial viability. Am J Physiol Heart Circ Physiol. 2006 Feb;290(2):H724-31. doi: 10.1152/ajpheart.00714.2005. Epub 2005 Sep 23.

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PMID: 16183729 (View on PubMed)

Verma A, Wazni OM, Marrouche NF, Martin DO, Kilicaslan F, Minor S, Schweikert RA, Saliba W, Cummings J, Burkhardt JD, Bhargava M, Belden WA, Abdul-Karim A, Natale A. Pre-existent left atrial scarring in patients undergoing pulmonary vein antrum isolation: an independent predictor of procedural failure. J Am Coll Cardiol. 2005 Jan 18;45(2):285-92. doi: 10.1016/j.jacc.2004.10.035.

Reference Type BACKGROUND
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Hwang HJ, Choi EY, Rhee SJ, Joung B, Lee BH, Lee SH, Kim J, Lee MH, Jang Y, Chung N, Kim SS. Left atrial strain as predictor of successful outcomes in catheter ablation for atrial fibrillation: a two-dimensional myocardial imaging study. J Interv Card Electrophysiol. 2009 Nov;26(2):127-32. doi: 10.1007/s10840-009-9410-y. Epub 2009 Jun 16.

Reference Type BACKGROUND
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Di Salvo G, Caso P, Lo Piccolo R, Fusco A, Martiniello AR, Russo MG, D'Onofrio A, Severino S, Calabro P, Pacileo G, Mininni N, Calabro R. Atrial myocardial deformation properties predict maintenance of sinus rhythm after external cardioversion of recent-onset lone atrial fibrillation: a color Doppler myocardial imaging and transthoracic and transesophageal echocardiographic study. Circulation. 2005 Jul 19;112(3):387-95. doi: 10.1161/CIRCULATIONAHA.104.463125. Epub 2005 Jul 8.

Reference Type BACKGROUND
PMID: 16006491 (View on PubMed)

Kuppahally SS, Akoum N, Burgon NS, Badger TJ, Kholmovski EG, Vijayakumar S, Rao SN, Blauer J, Fish EN, Dibella EV, Macleod RS, McGann C, Litwin SE, Marrouche NF. Left atrial strain and strain rate in patients with paroxysmal and persistent atrial fibrillation: relationship to left atrial structural remodeling detected by delayed-enhancement MRI. Circ Cardiovasc Imaging. 2010 May;3(3):231-9. doi: 10.1161/CIRCIMAGING.109.865683. Epub 2010 Feb 4.

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Anne W, Willems R, Roskams T, Sergeant P, Herijgers P, Holemans P, Ector H, Heidbuchel H. Matrix metalloproteinases and atrial remodeling in patients with mitral valve disease and atrial fibrillation. Cardiovasc Res. 2005 Sep 1;67(4):655-66. doi: 10.1016/j.cardiores.2005.04.016.

Reference Type BACKGROUND
PMID: 15913581 (View on PubMed)

Ware JS, Petretto E, Cook SA. Integrative genomics in cardiovascular medicine. Cardiovasc Res. 2013 Mar 15;97(4):623-30. doi: 10.1093/cvr/cvs303. Epub 2012 Sep 27.

Reference Type BACKGROUND
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Heinig M, Petretto E, Wallace C, Bottolo L, Rotival M, Lu H, Li Y, Sarwar R, Langley SR, Bauerfeind A, Hummel O, Lee YA, Paskas S, Rintisch C, Saar K, Cooper J, Buchan R, Gray EE, Cyster JG; Cardiogenics Consortium; Erdmann J, Hengstenberg C, Maouche S, Ouwehand WH, Rice CM, Samani NJ, Schunkert H, Goodall AH, Schulz H, Roider HG, Vingron M, Blankenberg S, Munzel T, Zeller T, Szymczak S, Ziegler A, Tiret L, Smyth DJ, Pravenec M, Aitman TJ, Cambien F, Clayton D, Todd JA, Hubner N, Cook SA. A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk. Nature. 2010 Sep 23;467(7314):460-4. doi: 10.1038/nature09386. Epub 2010 Sep 8.

Reference Type BACKGROUND
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Reference Type BACKGROUND
PMID: 18443592 (View on PubMed)

Other Identifiers

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2013/103/C

Identifier Type: -

Identifier Source: org_study_id

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