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

这个项目将结合动力系统理论和时间序列分析的数学领域的方法来理解和预测被称为“交替”的心脏行为。交替性心律是一种不规则的心律，其特点是强搏动和弱搏动交替。交替很重要，因为已知它是另一种称为心室颤动的异常心脏行为的前兆，这种异常心脏行为可导致心脏骤停（SCA）死亡。该项目将首先创建单个心肌纤维的数学模型，然后将其扩展到代表心肌的大区域。数学模型将被用于产生新的无模型、数据驱动的方案，首先预测交替的发生，然后控制或预防它。数学结果将在兔心脏的实验研究中得到验证。这一项目的结果将对预测和预防SCA有价值，SCA是工业化世界的主要死亡原因。目前，心室颤动是用破坏性电流治疗的，希望心脏此后能恢复正常的心律。目前，已知有心室颤动风险的患者可以在他们的胸部植入一个电子装置，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在危及生命的事件发生之前，轻轻地引导心脏远离危险的心律失常的设备。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的重要性的认识。心电交替是公认的心脏骤停的先兆，在细胞水平上表现为动作电位持续时间的搏动交替，或在全心水平上表现为心电图形态的搏动交替。目前基于心脏恢复特性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，直接通过动作电位测量来估计心律稳定性，而不需要恢复假设和复杂的起搏方案。具体而言，该方法基于动力系统理论，利用鲁棒统计方法估计心脏振荡的主要特征值。为了模拟心率变异性，该方法将在不同的起搏方案下进行评估。基于线性稳定性分析的反馈控制技术已被用于抑制分离心肌细胞和纤维中的交替。该项目将进行广泛的分岔和稳定性分析，以了解扩展组织中交替的可控性问题，并创建新的控制方案来防止心脏组织扩展区域的交替。这些新见解的分支和控制机制的交替可能有更广泛的社会影响，通过其对纤颤的医学意义。本项目将在多学科环境下培养研究生和本科生，并使高中师生接触到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.