Electrophysiological and structural remodeling in heart failure modulate arrhythmogenesis. 1D simulation study.

Area of Science:

• Cardiovascular Physiology
• Computational Biology
• Cardiac Electrophysiology

Background:

• Heart failure is a common pathway for cardiac diseases, often leading to sudden cardiac death due to ventricular arrhythmias.
• Key arrhythmogenic factors include electrophysiological remodeling, intercellular uncoupling, fibrosis, and autonomic imbalance.

Purpose of the Study:

• To investigate the in silico effects of electrophysiological and structural remodeling in heart failure on arrhythmogenic substrates.
• To analyze the modulation of electrophysiological gradients and abnormal impulse propagation in failing ventricles.

Main Methods:

• Utilized two mathematical models of human ventricular action potentials to create failing myocyte models.
• Simulated electrical activity in a transmural ventricular strand to study remodeling effects.

Main Results:

• Heterogeneous remodeling, particularly of the Na+/Ca2+ exchanger and SERCA pump, reduced repolarization heterogeneities.
• Fibroblast proliferation and cellular uncoupling significantly increased repolarization heterogeneities.
• Progressive structural remodeling reduced conduction velocity and the safety factor for conduction.

Conclusions:

• Electrophysiological remodeling significantly alters ventricular repolarization gradients as heart failure progresses.
• Enhanced fibrosis and reduced intercellular coupling in failing hearts increase electrophysiological gradients and impair electrical propagation, promoting arrhythmias.