Introduction: The presence of beat-to-beat alternation of the action potential duration (so-called APD alternans) has been linked to the development of various rapid rhythm disorders, including ventricular fibrillation. The diastolic interval (DI) associated with each beat is well-known to play a critical role in the development of voltage-driven alternans. Here, we study the effectiveness of pacing methods that target the DI in suppressing alternans in computer models that (1) contain cardiac memory, (2) contain calcium-handling dynamics, (3) both, and (4) include effects associated with the finite propagation speed of the action potential waves.
Methods: Several dynamical computer simulation models relating quantities such as the APD, DI and intracellular calcium concentration from one beat to the next are subjected to linear and nonlinear stability analysis. Simulations using the amplitude equations, modified to include memory and calcium dynamics, are employed to study the effects of wave propagation.
Results: We find that (1) pacing methods that enforce a constant DI from one beat to the next completely eliminate alternans in a memory-based system, but do not produce results that agree with experiments [1], (2) inclusion of both memory and calcium handling provide better agreement with experiments, but (3) inclusion of finite propagation speed of waves only allows control of alternans over a small region of size ~1 cm. We find, however, that inclusion of a key nonlinear effect currently not included in the standard amplitude equations has the right properties to allow control of larger regions.
Conclusions: Control of alternans using methods that target the diastolic interval is possible in small regions in models that reproduce experiments. Control of large enough regions remains problematic; however, a key nonlinear effect provides a new target that may allow the controlled region to be expanded.