This project will combine methods from the mathematical fields of dynamical systems theory and time-series analysis to understand and predict the cardiac behavior called "alternans." Alternans is a type of irregular heart rhythm, characterized by alternating strong and weak beats. Alternans is important because it is known to be a precursor to another type of abnormal cardiac behavior called ventricular fibrillation, which can lead to death from sudden cardiac arrest (SCA). The project will begin by creating mathematical models of a single heart muscle fiber, which will then be extended to represent large regions of heart muscle. The mathematical models will be used to produce novel model-free, data-driven schemes to first predict the onset of alternans, and then to control or prevent it. The mathematical results will be validated in experimental studies on rabbit hearts. Results of this project will be valuable in predicting and preventing SCA, which is the leading cause of death in the industrialized world. At present, ventricular fibrillation is treated with a disruptive electrical current, in the hopes that the heart will thereafter resume a normal rhythm. Currently, patients known to be at risk for ventricular fibrillation may have an electrical device implanted in their chest to apply this disruptive current directly to the heart. Knowledge gained from this project could lead to devices that instead gently steer the heart away from dangerous arrhythmias, before life-threatening events can occur. This project also includes outreach activities, to introduce high school students in Minnesota and Tennessee to cardiac electrophysiology. In addition to encouraging students to pursue interests in biomedical engineering, these programs will increase awareness of the importance of cardiac dynamics in everyday health.
Cardiac alternans, a recognized harbinger of sudden cardiac arrest, manifests as beat-to-beat alternation in action potential duration at the cellular level, or in electrocardiogram morphology at the whole-heart level. Current approaches to predict cardiac alternans based on restitution properties of the heart are either too simple to be valid or too complex to be useful. This project will develop a novel, practical method to estimate rhythm stability directly from action-potential measurements without the need for a restitution hypothesis and complex pacing protocols. Specifically, based on dynamical systems theory, the method estimates the dominant eigenvalues of cardiac oscillations using robust statistical approaches. To simulate heart rate variability, the method will be evaluated under various pacing protocols. Feedback control techniques based on linear stability analysis have been exploited to suppress alternans in isolated cardiac myocytes and fibers. This project will carry out extensive bifurcation and stability analyses to understand the controllability issues of alternans in extended tissue, and to create novel control schemes to prevent alternans in extended regions of cardiac tissue. These new insights into the bifurcation and control mechanisms of alternans may have a broader social impact through its medical implications on fibrillation. This project will train graduate and undergraduate students in a multidisciplinary environment, and will expose high school teachers and students to nonlinear thinking and quantitative reasoning of cardiac dynamics. More than 65 percent of Americans do not understand sudden cardiac arrest and underestimate its seriousness. The activities in outreach, education, and research dissemination in this project will advance the awareness of sudden cardiac arrest.
