Biomechanics of diastolic dysfunction: a one-dimensional computational modeling approach

Area of Science:

• Cardiovascular Physiology
• Computational Biology
• Biomedical Engineering

Background:

• Diastolic dysfunction (DD) is a key factor in heart failure with preserved ejection fraction (HFpEF).
• Understanding the biomechanical basis of DD is crucial for elucidating HFpEF mechanisms.
• Existing models require further development to capture the nuances of DD pathologies.

Purpose of the Study:

• To develop a computational model simulating diastolic dysfunction (DD).
• To investigate the biomechanical roles of active myocardial relaxation and passive ventricular stiffness in DD.
• To replicate and differentiate the primary phenotypes of DD using computational parameters.

Main Methods:

• Developed a computational model coupling a 1D arterial network with a 0D four-chambered cardiac model.
• Quantified pathologies using parameters for active relaxation delay (early/late phases) and passive ventricular stiffness.
• Performed parameter sensitivity analysis and concurrently adjusted parameters to simulate DD phenotypes.

Main Results:

• The impaired relaxation phenotype was primarily replicated by altering active relaxation parameters.
• The pseudo-normal phenotype resulted from combined adjustments in active relaxation and passive stiffness.
• The restricted phenotype was predominantly reproduced by modifying passive stiffness parameters.

Conclusions:

• A validated computational model successfully replicated the main phenotypes of diastolic dysfunction (DD).
• Novel biomechanical insights were gained into how myocardial relaxation and stiffness influence DD development.
• The study elucidates the interplay of relaxation and stiffness pathologies in creating diverse DD manifestations.