Development of simulation system of cardiac arrhythmia and artificial pacemaker

1. Development of simulation system of cardiac arrhythmia and artificial pacemaker Akihiro Takeuchi, Atsushi Hamada, Nozomu Yamanaka, Mototake Taguchi*, Minoru Hirose*, Noriaki Ikeda, Hideo MiyaharaDept. of Medical Informatics, Kitasato University Graduate School, *Dept. of Clinical Engineering, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, 228-8555, Japan

2. Abstract: A simulation system which consisted of the cardiac module and the artificial pacemaker module was developed using a Window-based software technology, ActiveX control. The cardiac module was composed of six kinds of cells, the sinus, atrium, A-V node, ventricle, and ectopic focuses. The electrophysiological properties of the cell were modeled by the phase response curve that defined automaticity, and the excitability recovery curve that defined the conduction delay depending on the previous interval. The ECG waves were drawn in real time on a ladder diagram. The pacemaker module sensed the cardiac impulses, and stimulates the cardiac cell according to the user setting,e.g., ICHD modes, pacing rate, and output level. This system was useful to understand about arrhythmias and the interaction between the cardiac cell and the artificial pacemaker, and to experience the electrophysiological experiment virtually. URL http://info.ahs.kitasato-u.ac.jp/tkweb/tkp/tkpace.html

3. Two mechanisms that produce arrhythmias are automaticity and conductivity. These physiological properties of cardiac cells are represented by a phase response curve and an excitability recovery curve, respectively. Some simulation systems including the curves were developed by the standard programming style [Ikeda et al., 1997, Abramovich-Sivan et al., 1998]. The cells and its mathematical functions can be considered as objects and its properties from a point of view of object-oriented programming. The aim of this study is to develop an integrated simulation system of electrical activity of the heart using a Window-based software technology, ActiveX control, and to reproduce theoretically various arrhythmias. Introduction

4. Electrophysiological properties of the cardiac autorhythmic cells are characterized by the automaticity and conductivity. The autorhythmic cells can periodically generate spontaneous electrical impulses. The oscillatory systems have a phase dependent property; the response of the cell to the external stimuli varies depending on the phase at which the stimuli were applied. The conductivity is represented by an excitability recovery curve (ERC). The ERC of the AV-node, AV-nodal conduction curve, defines the conduction delay and a timing to stimulate the ventricle in this system. The refractory period of the cell was assumed to be proportional to the previous RR interval, so that it was assumed to be equal to the QT interval. Model of cardiac cells

5. Y0 w a T0 c Ymin b Xmin Figure 1. Electrophysiological properties of the cardiac cell. PRC(left) and ERC(right).

6. The electrophysiological functions that were defined by a spontaneous rate, PRC and ERC, were implemented as a set of the ActiveX control (tkpace.ocx 90 kB, Visual C++6.0) (Fig. 1). The PRC that specified the cell activity was defined by four parameters, slopes of three line (a,c,b), and intersection on the time axis (w) by the line c. Cell model by ActiveX control

7. The ERC was approximated by the decaying exponential function  conduction time = (Y0-Ymin)*Exp(-(x-Xmin)/T0) +Ymin, where x is the extrastimulus coupling interval (H1A2), Xmin corresponds to the effective refractory period, Y0 is a maximum connection delay at Xmin, Ymin means an intrinsic conduction time, and T0 means a time constant of the curve. For simplicity, these parameters are not dependent on the autorhythmic rate. The antergrade conduction time was calculated by the ERC, but the retrograde conduction time was assumed to be constant.

8. Sinus Electrophysiological stimulation Atrium Atrial ectopic focus User command antegrade conduction retrograde conduction extra stimuli AV node Ventricle Ventricular ectopic focus Defibrillator Figure 2. Cardiac model using six types of cells

9. The simulation system consisted of the cardiac module and the artificial pacemaker module. The cardiac module (tkp3.exe 130 kB, Visual Basic 6.0) was composed of six types of autorhythmic cardiac cells (Fig. 2).The cardiac cells run independently at every timer event from the cardiac module. The antegrade and retrograde conduction between these cells were controlled by the user's operation on the check boxes in the window. The artificial pacemaker module had two electrodes to sense the cardiac impulses, and recognized the rhythm disturbances automatically. This module stimulated the cardiac cell through a connection lines between the ActiveX controls of two modules. Description of the system

10. The application runs under MS-Windows (98 or higher) with a wide screen on a high performance computer (CPU: Pentium III, 500 MHz or higher). Figure 3 shows the control panel and the ECG panel of the cardiac module. Each electrical activity of the cells is drawn at the predefined position on a ladder diagram. The predicted conduction is drawn with a blue line at the activation of the cell. The slanted yellow lines show the spread of activation transmitted actually. The ECG waveforms are drawn in real time as the integrated activity of all cells. In addition, the dynamic state of contraction and relaxation of the atrium and the ventricle are presented graphically. Result

11. Figure 3. Sample window: normal state of the heart.

12. Figure 4 shows a Wenckebach sequence with 5:4 ratios produced by the special condition of the ERC of the AV-node at a sinus rate of 70/min. User could modify the parameters of PRC and ERC in the dialog box. Figure 5 shows a simulation of cardiac rhythm disturbances induced by the conduction between the atrium and the ectopic focus. Figure 6 shows the ECG sequence of the ventricular flutter, fibrillation, and the defibrillation procedure achieved by the user operation. It shows a pause period caused by the defibrillation that resumed all the activity of the heart.

13. Figure 7 shows the interaction between the heart and an artificial pacemaker. User can experience the artificial pacemaker operation virtually. References Ikeda et al., Arrhythmia curve interpretation using a dynamic system model of the myocardial pacemaker. Meth Inform Med 1997;36:286-9. Abramovich-Sivan et al., A single pacemaker cell model based on the phase response curve. Biol. Cybern. 1998;79:67-76.

14. Figure 4. Wenckebach sequence

15. Figure 5. Reentry in the atrium

16. Figure 6. Defibrillation

17. Figure 7. Interaction between the heart and an artificial pacemaker

18. Figure 8 shows a simulation of the electrophysiological experiment to study the conductivity of the AV node. AV nodal responses to the premature coupling interval S1S2 were recorded and the corresponding V1V2 interval and S2V2 intervals were plotted against S1S2. S1S2 (sinus-stimulation) intervals were decreased with a 20msec decrement. Figure 8. Simulated refractory curve