Grant: Project Grant

Heart failure is not simply a condition that results from the classical "heart attack" due to blocked arteries. Many other conditions, such as diabetes and hypertension, damage heart muscle in ways that are poorly understood and not as well recognized. In fact, 50% of heart failure patients have hearts that pump out normal volumes of blood but are nonetheless functionally diseased. These patients have what cardiologists refer to as heart failure with preserved ejection fraction (HFpEF). The condition develops silently and slowly and is not diagnosed until the late stages when irreversible heart damage has set in, at which time the 5-year death rate is on par with that of heart attack survivors at over 50%. The grim reality for this growing HFpEF population is that, unlike heart attack survivors, there is no defined diagnostic or proven therapy from which they can benefit. In this project, we propose a paradigm-shifting concept for early detection of HFpEF: detect microvascular dysfunction (mvD) throughout the body. The known comorbid conditions in HFpEF all involve damage to the small blood vessels early in HFpEF development. Our pilot data revealed mvD in skeletal muscle of diabetic rats when the heart was still structurally and functionally normal on ultrasound imaging. In other words, microvessel damage is an early biomarker of HFpEF. The objective of this project is to develop a magnetic resonance imaging (MRI) biomarker of mvD in key organs, including the heart and skeletal muscle, with the long-term goal of using this biomarker for early detection and intervention before the HFpEF heart becomes stiff and dysfunctional. Through a transformative approach to the currently intractable task of early HFpEF diagnosis, we are taking the first critical step in detection technology development towards solving the dilemma of managing the HFpEF epidemic.