Patient-Specific Heart Rate Modulates Developmental Electrophysiology in Transcriptomic-Guided In Silico Models of...

Area of Science:

• Computational biology
• Pediatric cardiology
• Cardiac electrophysiology

Background:

• Pediatric cardiac electrophysiology undergoes significant developmental changes.
• Previous models did not fully account for age- and patient-specific heart rates.
• Understanding these dynamics is crucial for pediatric cardiac health.

Purpose of the Study:

• To investigate the interplay between developmental maturation and heart rate in pediatric atrial electrophysiology.
• To develop gene expression-guided computational models incorporating intrinsic heart rate.
• To predict age- and rate-dependent electrophysiological biomarker changes.

Main Methods:

• Generated virtual patient-specific atrial cardiomyocyte populations (n=117) using gene expression data.
• Simulated populations at intrinsic and fixed pacing rates.
• Quantified action potential and calcium transient biomarkers; used partial least squares regression.

Main Results:

• Intrinsic-rate pacing showed increased action potential duration and upstroke velocity with age.
• Early repolarization shortened, resting membrane potential became more negative, and alternans decreased with age.
• Developmental differences persisted at fixed rates; intrinsic-rate simulations showed stronger age associations.

Conclusions:

• Pediatric atrial electrophysiology is shaped by both intrinsic developmental remodeling and heart rate modulation.
• Interactions among ionic conductances, calcium handling, age, and heart rate determine electrophysiological phenotypes.
• Age- and rate-dependent factors are critical for understanding pediatric cardiac electrical activity.