Transcriptome, proteome, and metabolome in dyssynchronous heart failure and CRT

Area of Science:

• Cardiology
• Molecular Biology
• Genomics

Background:

• Symptomatic systolic heart failure with ventricular conduction delay negatively impacts morbidity and mortality.
• Cardiac resynchronization therapy (CRT) is a proven treatment for select heart failure patients.
• Understanding the molecular basis of CRT's efficacy is crucial for optimizing patient selection and outcomes.

Purpose of the Study:

• To review how high-throughput technologies advance the understanding of electromechanical dyssynchrony pathophysiology.
• To elucidate the molecular mechanisms underlying CRT's beneficial effects.
• To explore the potential of 'omic' techniques in identifying CRT response biomarkers.

Main Methods:

• Gene expression profiling and proteomics were employed to analyze cardiac tissue.
• Comparison of gene expression in early-activated anterior vs. late-activated lateral left ventricular myocardium in an animal model of heart failure.
• Assessment of transcriptomic and proteomic changes before and after CRT intervention.

Main Results:

• Electromechanical dyssynchrony significantly alters the regional cardiac transcriptome, primarily in early-activated myocardium.
• CRT effectively reverses the regional heterogeneity of gene expression within the left ventricle.
• CRT-induced remodeling impacts transcripts involved in metabolic and cell signaling pathways, confirmed by proteomic data.

Conclusions:

• High-throughput 'omic' technologies provide critical insights into the molecular mechanisms of heart failure and CRT.
• CRT normalizes regional gene expression patterns, suggesting a direct molecular impact on cardiac function.
• Future research using 'omic' approaches may identify predictive biomarkers for CRT responders versus nonresponders.