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Benefits of Cardiac Resynchronization Therapy in an Asynchronous Heart Failure Model Induced by Left Bundle Branch Ablation and Rapid Pacing
Published on: December 11, 2017
Cardiac resynchronization therapy corrects dyssynchrony-induced regional gene expression changes on a genomic level
Andreas S Barth1, Takeshi Aiba, Victoria Halperin
1Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD, USA.
Circulation. Cardiovascular Genetics
|December 25, 2009
Summary
Cardiac electromechanical dyssynchrony alters gene expression in the left ventricle, particularly the anterior wall. Cardiac resynchronization therapy (CRT) corrects these transcriptome changes and reduces regional gene expression differences.
Area of Science:
- Cardiology
- Molecular Biology
- Genomics
Background:
- Cardiac electromechanical dyssynchrony creates regional disparities in left ventricular workload, oxygen consumption, and perfusion.
- Dyssynchrony is hypothesized to induce region-specific alterations in the myocardial transcriptome.
Purpose of the Study:
- To investigate region-specific changes in the myocardial transcriptome caused by cardiac electromechanical dyssynchrony.
- To determine if cardiac resynchronization therapy (CRT) can correct these dyssynchrony-induced gene expression alterations.
Main Methods:
- Adult dogs underwent left bundle branch ablation and pacing to induce dyssynchronous heart failure or CRT.
- RNA was isolated from anterior and lateral left ventricular walls for microarray analysis.
- Echocardiography assessed left ventricular function and dyssynchrony.
Main Results:
- Dyssynchronous heart failure showed increased regional heterogeneity of gene expression, primarily in the anterior left ventricle.
- CRT significantly decreased the dyssynchrony index and reversed dyssynchrony-induced gene expression changes in 1050 transcripts.
- CRT remodeled transcripts involved in metabolic and cell signaling functions, reducing regional gene expression heterogeneity.
Conclusions:
- Electromechanical dyssynchrony profoundly impacts the regional cardiac transcriptome, with changes concentrated in the anterior left ventricular wall.
- CRT effectively corrected gene expression alterations in the anterior wall, demonstrating a global effect on the ventricular transcriptome beyond pacing sites.
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