Electrophysiological and structural remodeling in heart failure modulate arrhythmogenesis. 2D simulation study

Area of Science:

• Cardiovascular Physiology
• Computational Biology
• Cardiac Electrophysiology

Background:

• Heart failure impairs the heart's ability to pump blood effectively.
• Electrophysiological remodeling, reduced cell-to-cell communication (uncoupling), and fibrosis are key factors causing arrhythmias in heart failure.

Purpose of the Study:

• To investigate the mechanisms of reentry vulnerability in heart failure using computer simulations.
• To assess the combined effects of electrical and structural remodeling on cardiac tissue.

Main Methods:

• Simulated electrical activity in human ventricular tissue using established models (Grandi et al., MacCannell et al.).
• Incorporated varying degrees of fibrosis and intercellular uncoupling under control and heart failure conditions.
• Evaluated the vulnerable window (VW) for reentry using cross-field stimulation.

Main Results:

• No reentry occurred under normal conditions or with only heart failure (HF) electrical remodeling.
• Fibrosis and/or cellular uncoupling were sufficient to induce reentry.
• Intermediate fibrosis and uncoupling significantly widened the VW, increasing reentry risk.
• Very high fibrosis or low conductivity hindered reentry; increased fibrosis correlated with more phase singularities.

Conclusions:

• Structural remodeling (fibrosis, uncoupling) is crucial for developing reentry vulnerability in heart failure.
• Intermediate levels of fibrosis and uncoupling create conditions favorable for reentrant arrhythmias.