Right Ventricular Contractile Reserve: A Key Metric to Identifying when Cardiorespiratory Fitness will Improve with Pulmonary Vasodilators.

Cardiorespiratory fitness (CRF) has been proposed as a vital sign for the past several years, supported by a wealth of evidence demonstrating its significance as a predictor of health trajectory, exercise/functional capacity, and quality of life. According to the Fick equation, oxygen consumption (VO2 ) is the product of cardiac output (CO) and arterial-venous oxygen difference, with the former being a primary driver of one's aerobic capacity. In terms of the dependence of aerobic capacity on a robust augmentation of CO from rest to maximal exercise, left ventricular (LV) CO has been the historic focal point. Patients with pulmonary arterial hypertension (PAH) or secondary pulmonary hypertension (PH) present with a significantly compromised CRF; as pathophysiology worsens, so too does CRF. Interventions to improve pulmonary hemodynamics continue to emerge and are now a standard of clinical care in several patient populations with increased pulmonary pressures; new pharmacologic options continue to be explored. Improvement in CRF/aerobic capacity has been and continues to be a primary or leading secondary endpoint in clinical trials examining the effectiveness of pulmonary vasodilators. A central premise for including CRF/aerobic capacity as an endpoint is that pulmonary vasodilation will lead to a significant downstream increase in LV CO and therefore peak VO2 . However, the importance of right ventricular (RV) CO to the peak VO2 response continues to be overlooked. The current review provides an overview of relevant principles of exercise physiology, approaches to assessing RV contractile reserve and proposals for clinical trial design and subject phenotyping.