Collaborative Research: Heart Dynamics: Bifurcation Estimation and Alternans conTrol (HeartBEAT)

本计画将结合动力系统理论与时间序列分析等数学领域的联合收割机方法，以了解并预测心脏的交替行为。“交替是一种不规则的心律，其特征是交替的强和弱心跳。交替糖很重要，因为它是另一种称为心室颤动的异常心脏行为的前兆，可导致心脏骤停（SCA）死亡。该项目将开始建立一个单一的心肌纤维的数学模型，然后将扩展到代表心肌的大区域。这些数学模型将被用于产生新的无模型、数据驱动的方案，以首先预测交替发作，然后控制或预防交替发作。数学结果将在兔子心脏的实验研究中得到验证。该项目的结果将在预测和预防SCA方面具有价值，SCA是工业化国家的主要死亡原因。目前，心室纤维性颤动是用破坏性电流治疗的，希望心脏此后能恢复正常节律。目前，已知有室颤风险的患者可能在胸部植入了一个电子设备，将这种破坏性电流直接施加到心脏。从这个项目中获得的知识可能会导致设备，而不是轻轻地引导心脏远离危险的心律失常，在危及生命的事件发生之前。该项目还包括外展活动，向明尼苏达州和田纳西州的高中生介绍心脏电生理学。除了鼓励学生对生物医学工程感兴趣外，这些课程还将提高人们对心脏动力学在日常健康中重要性的认识。心脏交替是公认的心脏骤停的先兆，表现为细胞水平上动作电位时程的搏动交替，或整个心脏水平上的心电图形态。目前基于心脏的恢复特性来预测心脏交替的方法要么太简单而无效，要么太复杂而无用。该项目将开发一种新颖实用的方法，直接从动作电位测量中估计心律稳定性，而无需恢复假设和复杂的起搏协议。具体地，基于动力系统理论，该方法使用鲁棒的统计方法估计心脏振荡的主导特征值。为了模拟心率变异性，将在各种起搏方案下评价该方法。基于线性稳定性分析的反馈控制技术已被用于抑制离体心肌细胞和心肌纤维中的交替糖。该项目将进行广泛的分叉和稳定性分析，以了解在扩展组织中交替的可控性问题，并创建新的控制方案，以防止心脏组织扩展区域中的交替。这些新的见解交替的分叉和控制机制可能有更广泛的社会影响，通过其医疗意义上的纤维性颤动。该项目将在多学科环境中培养研究生和本科生，并将使高中教师和学生接触心脏动力学的非线性思维和定量推理。超过65%的美国人不了解心脏骤停，低估了它的严重性。本项目中的外展、教育和研究传播活动将提高对心脏骤停的认识。

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.