Dr. Leon Glass
Centre for Nonlinear Dynamics in Physiology and Medicine
Department of Physiology
mcGill University
glass@cnd.mcgill.ca
http://www.cnd.mcgill.ca/bios/glass/glass.html

Dr. Edward J. Vigmond
Department of Electrical & Computer Engineering
University of Calgary
vigmond@ucalgary.ca
http://www.enel.ucalgary.ca/~vigmond/index.html

Cardiac arrhythmias are abnormal heart rhythms. In some cases cardiac arrhythmias are benign and it is best not to try to treat them. In other situations, cardiac arrhythmias may lead to significant impairment of physical activity and may have a high risk for other serious medical problems such as stroke or sudden death. Finally, some cardiac arrhythmias are fatal, and will lead to death within a few minutes unless dramatic steps are undertaken to terminate the abnormal rhythm. A major problem facing providers of health care is to be able to properly diagnose patients at high risk for serious arrhythmia so that steps might be taken to prevent the negative effects of such arrhythmias, or for patients who already have serious arrhythmia, to initiate appropriate steps to control the arrhythmia. This project uses mathematics to help develop an understanding of cardiac arrhythmias from a perspective of basic science. We intend to use these insights to develop new methods to predict patients at risk for serious arrhythmia, and to develop new methods to control arrhythmia in patients. We focus on two types of arrhythmia: atrial fibrillation and ventricular arrhythmias that are associated with sudden cardiac death.

Atrial fibrillation is the most commonly treated cardiac arrhythmia. It is a serious arrhythmia that can lead to reduced ability to undertake physical activity in mild cases to severe impairment or death in severe cases. One of the serious complications associated with atrial fibrillation is stroke. Since atrial fibrillation has increased incidence with age, it is an increasingly common medical problem in Canada. In addition, atrial fibrillation often occurs in the days following open-heart surgery, delaying the recovery of the patients and prolonging the time and cost of stay in the intensive care unit.

Sudden cardiac death is estimated to occur in more than 30,000 Canadians each year. It is usually associated with arrhythmias originating in the ventricles that are characterized by rapid, circulating waves. The heart is then unable to contract adequately to supply the requisite amount of blood to the body, and itself. Such arrhythmias are rapidly fatal if not terminated, and are a common consequence of heart diseases which impair the pumping function of the heart. One therapy for these arrhythmias is the implantable cardiac defibrillator, which automatically detects the abnormal rhythm and delivers an electrical shock directly to the heart, resetting the rhythm to normal. However, this therapy is very expensive and there is a need to optimize the selection of patients for the procedure, as well as to optimize defibrillator technology.

In order to improve risk assessment and treatment for these rhythm problems, we need a better understanding of the underlying mechanisms. Recent developments in mathematical theory and high-speed computing can be applied to greatly refine our understanding of underlying mechanisms and to improve risk assessment and therapeutic technologies.

To develop new mathematically-based methods to control cardiac arrhythmias, we have assembled an interdisciplinary team consisting of physicians, engineers, physical scientists, physiologists, and industrial partners involved in drug and device manufacture. Strategies that are being pursued by our MPRIME group include better analysis of electrocardiographic records to predict the onset of atrial fibrillation (Vinet) or sudden cardiac death (Glass) prior to its occurrence, analysis of electrocardiographic data to determine the presence of atrial fibrillation (Glass), development of accurate models of the heart to study the effects of drugs on the initiation and termination of arrhythmias (Nattel, Vinet, Vigmond), development of anatomically and physiologically accurate models of the heart to simulate the performance of defibrillators and pacemakers with a view of optimizing their design and performance (Vinet, Vigmond, Comtois, Leon, Nattel), development of special purpose computing hardware/software to accelerate computation (Leon, Vigmond), and analysis of gene expression to better understand the physiological substrate of serious arrhythmias in order to develop novel therapeutic approaches (Nattel, Shrier, Glass). In addition to the theoretical analyses, we are pursuing experimental studies in fundamental aspects of cardiac electrophysiology (Nattel, Shrier, Vinet).