Novel Methods to Evaluate the Cardiac Activity of Pharmaceuticals: Identifying New Therapies and Predicting Cardiac Toxicity

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Heart failure is the leading cause of death and disability within Canada, creating significant medical and socioeconomiccosts. Developing new therapies for heart failure is challenging, primarily because we do not have good ways to model theaction of heart cells. Similarly, certain medications are known to have adverse effects on the heart (particularly cancerchemotherapeutics), although the degree of adverse effect is tremendous. Determining which medications a patient can (orcannot) receive safely also suffers from the lack of ability to properly model the action of the heart. Our collaborative grouphas worked together to develop new ways to measure heart cell function in ways that accurately represent what happens inthe patient. As part of this work, we are developing a new platform device that uses carbon nanotubes to quantify thecomplex function of the heart cell. This device will allow for simultaneous measurement of the key components of heart cellfunction beating rate, beating rhythm and contractility (how much the heart cell, and therefore the heart, can squeeze bloodout). There is currently no single device that can quantify all of these metrics, limiting the development of new medicationsfor heart failure and limiting the testing of medications for their potential damage to the heart. Using heart cells derived frompatients who have had severe reactions to heart toxic medications, we will show how we could have predicted the heartfailure that occurred in these patients, and how our device would have been able to guide therapy choices. Capitalizing onthe creation of patient-derived heart cells, our platform technology will allow for accurate modeling of heart cell action,leading to the development of new medications for heart failure or determining if a particular patient can receive a certaindrug without experiencing adverse effects on the heart.