A Novel Combinatorial Therapy for Treating Adverse Cardiac Remodelling Following Myocardial Infraction

Abstract

Last year, heart failure accounted for 400,000–700,000 deaths per year, $20–$40 billion in yearly healthcare costs, and was the leading diagnosis of hospital discharge in the United States. Increasingly, heart failure is attributed to changes in myocardial structure and function following the survival of an acute injury, such as myocardial infarction. Collectively referred to as adverse myocardial remodeling, these structural alterations include myocardial fibrosis and ventricle dilation. Fibrosis is the pathological manifestation of uncontrolled scar tissue formation following injury, and has important long-term functional consequences for the heart. Ventricle dilation is an increase in chamber size due to restructuring associated with adverse matrix remodeling. Over the long term, both ventricle dilation and myocardial fibrosis can permanently compromise cardiac function and lead to chronic heart failure. Despite the increasing frequency of adverse cardiac remodeling following myocardial infarction in Western populations, no direct therapeutic solutions presently exist. We explore four different approaches; each targets the extracellular matrix in different ways and at different stages of infarct repair. We show how each strategy may help attenuate pathological remodeling and how these therapies can be used together. Currently, the strategies we propose exist as research concepts that have yet to enter drug development. We believe that used in combination these strategies may be more successful at attenuating pathological remodeling, and will provide more flexibility in treating different types of cardiac remodeling than if used independently.