Right Ventricular Afterload and the Role of Nitric Oxide Metabolism in Left-Sided Heart Failure

Awareness has grown in recent years that right ventricular (RV) function is equally important as left ventricular (LV) function in the setting of left-sided heart disease. RV dysfunction can be the consequence of an increased afterload imposed by the failing LV. The concept of “afterload” is physically most correctly described by vascular input impedance. However, for clinical purposes, afterload is most often modeled to consist of 3 components; pulmonary vascular resistance (PVR), pulmonary arterial compliance (PAC), and characteristic impedance. Whereas PVR is historically most described, PAC (which represents the distensibility of the vasculature) has rapidly gained recognition for its prognostic ability in both pulmonary arterial hypertension and left-sided heart disease. Owing to the specific anatomy of the pulmonary circulation, PVR and PAC have an inverse hyperbolic relationship, which position can be shifted by varying wedge pressures. Knowledge of the afterload components helps one to understand how elevated left-sided filling pressures increase pulsatile load on the RV. An increase in resistive load (known as “reactive” or “out-of-proportion” pulmonary hypertension) ultimately complements the increase in pulsatile load. Perturbations in nitric oxide metabolism are thought to be crucial in this evolution and have therefore been sought as a major therapeutic target.