A perspective on the future of heart failure research.

Heart failure is chronic condition that is diagnosed when the heart is no longer able to pump enough blood to meet the physiological needs of the body. It is a progressive condition and typically manifests early on as exercise intolerance due to insufficient cardiac output before developing into the end stage disease. Nearly 7 million U.S. adults currently live with some form of heart failure, roughly accounting for 14% of all deaths. Various etiologies of heart failure have been identified which stem from a constellation of perfusion, pressure, morphological, electrical, and/or metabolic origins. An underlying issue for nearly all forms of heart failure is what is known as bioenergetic abnormalities. Although mitochondrial dysfunction is widely implicated, the precise molecular mechanisms underlying bioenergetic abnormalities remain incompletely understood. In this commentary, we describe the most prevalent heart failure types and offer a possible mechanism capable of explaining these bioenergetic abnormalities. We explore a novel hypothesis that links oxidative stress caused by intrinsic and extrinsic factors, which leads to depressed oxidative capacities induced by the presence of mitochondrial calcium phosphate granules. This hypothesis is supported by evidence previously reported in literature and may offer a new etiology of heart failure. We conclude by outlining a bold strategy to advance heart failure research through innovative approaches and unexplored domains.