Grant: Project Grant

Heart failure remains one of the most challenging areas in cardiovascular disease. While the preceding decades have seen great strides in developing combination drug treatments for heart failure patients, these interventions are mostly designed to ease stress on the weakened heart muscle and do not reverse or restore function to a normal condition. In addition, a growing segment of the heart failure patient population suffers from a unique form of the disease (referred to as right heart failure or heart failure with preserved ejection fraction-HFpEF) where the traditional drug interventions do not slow the loss of heart function at all. Together these issues have placed heart failure management as one of the costliest areas for the health care system in Canada, with an ever expanding patient population that has non-manageable forms of the disease. Clearly, new drugs/treatments are needed, and treatments that restore heart health to a pre-disease condition would be the most desirable. One area that holds great promise for advancing improvements in heart failure treatment is by harnessing the biology of exercise. Exercise promotes a unique form of heart muscle growth referred to as physiologic cardiac hypertrophy, which itself is well known to protect against the onset of heart failure in its many forms. Therefore we designed a unique robotic based analysis to identify drugs that could remodel heart muscle cells similar to what happens during regular sustained exercise. Using this approach we discovered one drug that is remarkably effective at changing heart muscle cells and intact rodent hearts to resemble an exercised condition. In preliminary studies, this same drug has also shown itself to be protective against agents that induce heart failure. The objective of our project is to understand the biology of how this drug works to remodel the heart and to continue testing the effectiveness of the drug in more severe models of heart failure.