Mechano-energetic uncoupling in the right ventricle in pulmonary hypertension

Pulmonary Hypertension (PH) affects up to 1% of the world population and is commonly associated with cardiopulmonary diseases. Right ventricular (RV) dysfunction and failure in response to the persistently increased RV afterload are the main cause of the morbidity and mortality in PH. As PH progresses, there is uncoupling of the RV-pulmonary artery (PA), resulting in RV failure. Strategies to optimize RV-PA coupling so far have mainly focused on lowering RV afterload with fewer options available to increase RV contractility. Here, we provide a perspective that there exists another type of “uncoupling”, between energy production and mechanical work within the RV, that reflects the competition between contractility (demand) and metabolism (supply). This uncoupling is a result of increased myocardial stiffness in the RV in PH, along with decreased energy production. We propose that optimizing mechano-energetic uncoupling by decreasing stiffness and increasing energetic capacity would be important as we seek to target the failing RV to improve RV-PA coupling and ultimately outcomes in patients with PH.