Contributor: Seyedeh Maryam Hosseini, MD

Heart failure with preserved ejection fraction is characterized by impaired cardiovascular reserve and coronary microvascular dysfunction. Tissue hypoxia activates endogenous adenosine secretion leading to vasodilation of the myocardial microvasculature. By increasing tissue perfusion in working myocardium, adenosine responds to increased metabolic demand. Davila et al. demonstrate that this adenosine vasodilation mechanism is impaired in HFpEF due to up-regulation of the adenosine kinase (ADK) enzyme gene. ADK changes adenosine to its inactive form. Increasing endogenous adenosine by inhibiting the ADK enzyme pharmacologically may have therapeutic potential to improve coronary vasodilation, myocardial perfusion and LV diastolic dysfunction in HFpEF.