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Gene Expression Profiles in Patients With Permanent Atrial Fibrillation (AF) Versus Sinus Rhythm (SR)

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified September 2009 by Ankara University.
Recruitment status was:  Recruiting
Information provided by:
Ankara University Identifier:
First received: September 1, 2009
Last updated: September 2, 2009
Last verified: September 2009
The aim of this project is to determine the morphological criteria of apoptosis in atrial tissues of patients with AF versus SR at transcriptome and genomic size.

Mitral Regurgitation
Atrial Fibrillation
Sinus Rhythm

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Comparative Gene Expression Profiles in Patients With Permanent Atrial Fibrillation and Normal Sinus Rhythm

Resource links provided by NLM:

Further study details as provided by Ankara University:

Primary Outcome Measures:
  • Expression profiles of genes related to apoptosis [ Time Frame: 6 months ]

Secondary Outcome Measures:
  • Expression profiles of pro-apoptotic and anti-apoptotic proteins [ Time Frame: 6 months ]

Biospecimen Retention:   Samples With DNA
Human atrial tissue

Estimated Enrollment: 60
Study Start Date: December 2008
Estimated Study Completion Date: December 2011
Patients with degenerative mitral valve regurgitation and permanent atrial fibrillation who require mitral valve repair or replacement.
Patients with degenerative mitral valve regurgitation and maintaining sinus rhythm who require mitral valve repair or replacement.

Detailed Description:

Mitral valve regurgitation (MR) is the second most common valvular heart disease encountered in adults. Furthermore, atrial fibrillation (AF) is the most common cardiac arrhythmia seen in clinical practice. Overall, 70% of the patients with severe MR are associated with AF independent from etiopathogenesis of MR. AF is clinically divided into three subgroups; 1) paroxysmal AF, occurs as episodes and ends spontaneously, 2) persistent AF, episodes terminate only with medical or electrical cardioversion, and 3) permanent AF, current medical treatments and electrical cardioversion does not restore a normal sinus rhythm. Despite intensive electrophysiological studies, the molecular mechanisms and pathways of AF are still not fully elucidated.

Apoptosis which has distinctive morphological and biochemical characteristics is genetically regulated, active programmed cell death process. It is known that cardiac morphogenesis restore from apoptosis. In addition, apoptosis has an important role in several cardiovascular system pathologies. It has been shown that atrial apoptosis causes numerous arrhythmias including AF. Likewise, in the pilot study which has been performed by our study group, AF is associated with apoptosis by immunohistochemical and DNA fragmentation analysis methods.

The aim of this project is to determine the morphological criteria of apoptosis in atrial tissues of patients with AF by using electron microscopy and immunohistochemistry. Moreover, we will investigate the transcriptional profile of AF associated genes by oligonucleotide microarray method. The gene expression profiles of patients with AF and degenerative MR will be compared with the atrial tissue samples from the patients with degenerative MR who preserve normal sinus rhythm which will serve as controls. In summary the apoptotic pathways would be analyzed at transcriptomic and genomic level. Besides, the pathways that may interfere AF pathophysiology would also be evaluated. The expression profiles of the genes primarily verified by quantitative real time RT-PCR will be further confirmed by translation of end-result proteins determined with Western blot technique. Thus, brand-new clues about physiology of fibrillating atrial cells would be achieved.

Keywords: Atrial fibrillation, apoptosis, oligonucleotide microarray


Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Degenerative mitral valve regurgitation who require cardiac valve surgery

Inclusion Criteria:

  • Patients with permanent atrial fibrillation or sinus rhythm and degenerative mitral valve regurgitation who require cardiac surgery
  • Pulmonary hypertension (systolic PA > 45 mmHg)
  • Left ventricular ejection fraction > 30%

Exclusion Criteria:

  • Paroxysmal AF or atrial flutter
  • Second or third degree heart block
  • Permanent pacemaker
  • Wolff-Parkinson-White syndrome
  • Brugada syndrome
  • Ischemic or rheumatic mitral valve disease
  • Dilated cardiomyopathy
  • LVEF < 30%
  • Infective endocarditis, myocarditis
  • Trauma
  • Active HBV, HCV, HIV infection
  • Chronic renal failure
  • Autoimmune diseases
  • Vasculitis
  • Known genetic disorders
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00970034

Contact: RUCHAN AKAR, Assoc. Prof. +905336460684
Contact: HILAL OZDAG, Assoc. Prof. +905333717401

Ankara University Medical Faculty, Department of Cardiovascular Surgery, Recruiting
Ankara, Turkey, 06340
Contact: GUNSELI CUBUKCUOGLU    +905336424994   
Contact: SERKAN DURDU    +905336373535   
Principal Investigator: RUCHAN A AKAR, Assoc. Prof.         
Sub-Investigator: HILAL OZDAG, Assoc. Prof.         
Sub-Investigator: ARZU ATALAY, PhD         
Sub-Investigator: NALAN AKYUREK, PhD         
Sub-Investigator: HAKAN GURDAL, Prof.         
Sub-Investigator: OMER AKYUREK, Prof.         
Sub-Investigator: UMIT OZYURDA, Prof.         
Sub-Investigator: GUNSELI CUBUKCUOGLU, MSc         
Sub-Investigator: SERKAN DURDU, MD         
Sub-Investigator: CAGIN ZAIM, MD         
Sponsors and Collaborators
Ankara University
Principal Investigator: RUCHAN A AKAR, Assoc. Prof. Ankara University
  More Information

Responsible Party: A. Ruchan Akar, Assoc. Prof., Ankara University Identifier: NCT00970034     History of Changes
Other Study ID Numbers: 108S375
Study First Received: September 1, 2009
Last Updated: September 2, 2009

Keywords provided by Ankara University:
Atrial fibrillation, apoptosis, oligonucleotide microarray

Additional relevant MeSH terms:
Atrial Fibrillation
Mitral Valve Insufficiency
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Heart Valve Diseases processed this record on May 25, 2017