Controllability of voltage- and calcium-driven cardiac alternans in a map model

Area of Science:

• Cardiology
• Computational Biology
• Systems Biology

Background:

• Cardiac alternans, characterized by beat-to-beat variation in action potential duration, can precede arrhythmias.
• Alternans can be driven by voltage or intracellular calcium cycling instabilities.
• Existing control methods often lack validation for calcium-driven alternans.

Purpose of the Study:

• To assess control strategies for cardiac alternans, particularly when driven by calcium cycling.
• To compare the efficacy of different controllability measures in predicting control effort.
• To identify optimal variables for suppressing cardiac alternans.

Main Methods:

• Applied controllability analysis to a discrete map model of cardiac cell alternans dynamics.
• Compared modal controllability and minimum singular value of the controllability matrix.
• Tested control predictions using three distinct feedback controllers.

Main Results:

• Modal controllability consistently identified control strategies with minimal effort and smallest closed-loop eigenvalues.
• Action potential duration emerged as the most effective control variable across all alternans mechanisms.
• Sarcoplasmic reticulum calcium load was also effective for calcium-driven alternans.

Conclusions:

• Controllability analysis provides valuable insights into suppressing cardiac alternans.
• Modal controllability is a robust measure for selecting effective control strategies.
• Targeting action potential duration offers a promising approach for managing cardiac alternans.