Multi- Level and Integrated Analysis of Mechanisms Underlying Atrial Dysfunction

Ischemic Heart Disease Clinical Trial

— STaR-CABG  

Official title:

The National Heart Centre Singapore Prospective CABG Cohort: Multi- Level and Integrated Analysis of Mechanisms Underlying Atrial Dysfunction

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02789943
• Other study ID #: 2013/103/C
• Status: Recruiting
• Phase: N/A
• First received: May 30, 2016
• Last updated: April 5, 2017
• Start date: May 2013
• Est. completion date: April 2021

Study information

• Verified date: May 2016
• Source: National Heart Centre Singapore
• Contact: Muhammad Hafiz Jamal
• Phone: 97547816 /
• Email: muhd.hafiz.jamal[@]nhcs.com.sg
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 750
• Est. completion date: April 2021
• Est. primary completion date: July 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 85 Years

Eligibility

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).

Related Conditions & MeSH terms

• Coronary Artery Disease
• Heart Diseases
• Ischemic Heart Disease
• Myocardial Ischemia

Intervention

Procedure:
• Cardiac Bypass Surgery
elective cardiac bypass surgery during which a sample of right atrial appendage and/ or aortic button can be removed

Locations

Country	Name	City	State
Singapore	National Heart Centre	Singapore

Sponsors (2)

Lead Sponsor	Collaborator
National Heart Centre Singapore	Duke-NUS Graduate Medical School

Country where clinical trial is conducted

Singapore, 

References & Publications (18)

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. — View Citation

Ak K, Akgun S, Tecimer T, Isbir CS, Civelek A, Tekeli A, Arsan S, Cobanoglu A. Determination of histopathologic risk factors for postoperative atrial fibrillation in cardiac surgery. Ann Thorac Surg. 2005 Jun;79(6):1970-5. — View Citation

Alexander KP, Peterson ED. Coronary artery bypass grafting in the elderly. Am Heart J. 1997 Nov;134(5 Pt 1):856-64. Review. — View Citation

Anné W, Willems R, Roskams T, Sergeant P, Herijgers P, Holemans P, Ector H, Heidbüchel H. Matrix metalloproteinases and atrial remodeling in patients with mitral valve disease and atrial fibrillation. Cardiovasc Res. 2005 Sep 1;67(4):655-66. — View Citation

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

Di Salvo G, Caso P, Lo Piccolo R, Fusco A, Martiniello AR, Russo MG, D'Onofrio A, Severino S, Calabró P, Pacileo G, Mininni N, Calabró 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. Epub 2005 Jul 8. — View Citation

Goette A, Juenemann G, Peters B, Klein HU, Roessner A, Huth C, Röcken C. Determinants and consequences of atrial fibrosis in patients undergoing open heart surgery. Cardiovasc Res. 2002 May;54(2):390-6. — View Citation

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, Münzel 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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. Epub 2005 Sep 23. — View Citation

Petretto E, Sarwar R, Grieve I, Lu H, Kumaran MK, Muckett PJ, Mangion J, Schroen B, Benson M, Punjabi PP, Prasad SK, Pennell DJ, Kiesewetter C, Tasheva ES, Corpuz LM, Webb MD, Conrad GW, Kurtz TW, Kren V, Fischer J, Hubner N, Pinto YM, Pravenec M, Aitman TJ, Cook SA. Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass. Nat Genet. 2008 May;40(5):546-52. doi: 10.1038/ng.134. — View Citation

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. Epub 2007 May 21. — View Citation

Serri K, Reant P, Lafitte M, Berhouet M, Le Bouffos V, Roudaut R, Lafitte S. Global and regional myocardial function quantification by two-dimensional strain: application in hypertrophic cardiomyopathy. J Am Coll Cardiol. 2006 Mar 21;47(6):1175-81. Epub 2006 Feb 23. — View Citation

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. — View Citation

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. Review. — View Citation

Weidemann F, Niemann M, Herrmann S, Kung M, Störk S, Waller C, Beer M, Breunig F, Wanner C, Voelker W, Ertl G, Bijnens B, Strotmann JM. A new echocardiographic approach for the detection of non-ischaemic fibrosis in hypertrophic myocardium. Eur Heart J. 2007 Dec;28(24):3020-6. Epub 2007 Nov 1. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	First occurrence of cardiovascular event		One year