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Research: Cardiac Electrophysiology, Cardiac Imaging, Numerical Modeling

The mechanical contractions of the heart are triggered by electrical waves of excitation propagating through cardiac tissue. Abnormalities in the wave propagation, including fast and chaotic propagation in the heart, may lead to fatal cardiac arrhythmias, such as ventricular fibrillation (VF). VF is believed to be the primary reason underlying sudden cardiac death, a major public health problem, and one of the leading causes of mortality in the Western world. While it is generally agreed that the likeliest mechanism of VF is reentry, a major challenge in the field of cardiac electrophysiology is to understand how events at the cellular and molecular levels translate into arrhythmic behavior in the whole heart. The general goal of my group is to investigate the electrical activity of cardiac cells and whole heart from a nonlinear dynamics perspective, aiming to reveal mechanisms of complex cardiac rhythms leading to VF and sudden cardiac death.

Novel approaches to identify pivot points of the rotors in AF.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in humans, which is believed to be maintained by rapid reentry sources (rotors). One treatment option is catheter ablation, which targets the tissue responsible for the AF initiation and maintenance, i.e. pivot points of rotors. Existing commercial mapping systems have not been able to consistently and accurately predict the location of the pivot points of the rotor outside of the pulmonary veins. The aim of this study is to evaluate four recently developed signal processing approaches (multiscale frequency (MSF), Shannon entropy (SE), Kurtosis (Kt), and multiscale entropy (MSE)) in their ability to identify the pivot point of rotors. These proposed techniques utilize different cardiac signal characteristics to uncover the intrinsic complexity of the electrical activity in the rotors, which are not taken into account in current mapping methods. We validated these techniques using high-resolution optical mapping experiments in which direct visualization and identification of rotors in ex-vivo Langendorff-perfused rabbit hearts were possible. Two episodes of ventricular tachycardia were used to evaluate the performance and robustness of MSF, Kt, SE, and MSE approaches with respect to the following simulated clinical limitations: shortened electrogram duration and decreased spatial resolution. To quantitatively assess the performance of the four techniques, results were compared to the true rotor(s) identified using optical mapping-based phase maps. The results demonstrate that MSF, Kt, and MSE accurately identified both stationary and meandering rotors. In addition, these techniques remained accurate under simulated clinical limitations: shortened electrogram duration and decreased spatial resolution. These results motivate further validation using intracardiac electrograms to see if these approaches can map rotors in a clinical setting and whether they apply to more complex arrhythmias.

This study was recently published in TBME, 2017.

Anti-arrhythmic Constant-DI pacing protocol: Real-Time Closed Loop Implementation in Whole Rabbit Hearts.

Periodic pacing of the heart is incorporated in various medical devices and is clinically used to treat cardiovascular diseases. The widely accepted periodic pacing algorithm, however, suffers drawbacks and inherently has pro-arrhythmic properties. Cardiac alternans, a beat-to-beat alternation in action potential duration (APD), is a precursor to fatal arrhythmias. During periodic pacing, changes in diastolic interval (DI) depend on subsequent changes in APD, thus enhancing cardiac instabilities through feedback mechanism. Recently, an anti-arrhythmic Constant DI pacing protocol was proposed and shown to be effective in suppressing alternans in 0D, and 1D in-silico studies, . Here, we developed a novel closed loop system to detect T-waves from real-time ECG data, enabling successful implementation of Constant DI, and performed high-resolution optical mapping experiments on isolated whole rabbit hearts to validate its anti-arrhythmic effects. The results were compared with: (1) Periodic pacing and (2) pacing with heart rate variability (HRV) introduced by using either Gaussian or Physiological patterns.

This study was recently published in Annals of BME, 2017.

Autonomic neuromodulation of the heart.

The autonomic nervous system has been shown to play an important role in the regulation of cardiac function. It is recognized that an imbalance of the nervous system, i.e. increased sympathetic activity and reduced parasympathetic (vagal) activity, contributes to increased mortality both in myocardial infarction and heart failure. We use a new therapeutic technique, vagus nerve stimulation (VNS), to restore the autonomic nervous system balance that is compromised in several disease conditions, such as myocardial infarction, heart failure, hypertension, and therefore contributes to increased mortality. One of the main focus of our laboratory is the application of VNS therapy in experimental in vivo animal studies to investigate the effects on the functional and electrical properties of the heart. Furthermore, we research mechanisms by which VNS offers treatment to the diseased heart. Optical recordings with voltage and calcium sensitive dyes in the whole heart allow us to analyze normal electrical function, study complicated spatio-temporal changes in electrical activity encountered in cardiac arrhythmias and fibrillation, and investigate the electrophysiological properties induced by VNS in both healthy and diseased hearts.

Here are our recent studies investigating the effect of VNS on hypertensive heart disease, and electrophysiological changes of the whole heart induced by VNS

Visualization of clinical intracardiac electrograms on a patient-specific 3D heart model.

Visualization of clinical intracardiac electrograms on a patient-specific 3D heart model

Currently, novel techniques for analyzing intracardiac electrograms (iEGMs) are being developed to identify the atrial fibrillation (AF) maintaining sites. Proprietary electroanatomical mapping systems used in clinics like CARTO (Biosense Webster), EnSite Precision (Abbott), etc., are used for mapping the results of the analysis on a patientís 3D heart model. The constrained access to these mapping systems has had been a hurdle in the development of novel techniques. The open-source platform is developed for mapping the results of the analysis on a patientís 3D heart model. It eliminates the dependency on the proprietary mapping systems thereby making the process of retrospective mapping extremely convenient and time-efficient for academic researchers. The developed software can be used for visual inspection of electrograms and implementing different techniques on extracted iEGM dataset. It allows performing region-wise analysis of atria. Also, CT/MRI based 3D heart model can be integrated with the generated 3D model to incorporate fibrosis and scar data. The ability to visualize novel approaches as 3D maps and their availability help in the development of spatial analysis techniques and region-specific monitoring of Human atria for academicians, thus providing a testing and validation capability prior to clinical implementation.