Maintaining Cardiac Output
Systolic RV failure may require a strategy to directly augment contractility to stabilize blood pressure and cardiac output. Broadly the agents used are β-agonists, phosphodiesterase (PDE) inhibitors, and calcium channel sensitizers. The relative merits of different agents were nicely presented in a systematic review by Price et al. However, no study of any agent has evaluated more relevant outcomes or conclusively demonstrated superiority of one agent over another. The β1-agonist dobutamine augments myocardial contractility and reduces PVR making it an attractive agent in RV failure. However, it may also lead to a reduction in systemic vascular resistance and require the concomitant use of a systemic vasoconstrictor. The dose of dobutamine used is often limited by tachycardia. Consequently agents that are devoid of effects on heart rate such as PDE-3 inhibitors may be preferable in some patients. PDE-3 inhibitors may have direct inotropic effects by increasing levels of endogenous cyclic adenosine monophosphate and indirectly augment cardiac function by reducing the afterload. Although, these agents received a high recommendation in the systematic review by Price et al, most of the referenced studies were completed in patients with PH secondary to LV failure, postventricular assist or cardiac transplant. More recently PDE-5 inhibitors have been evaluated in the treatment of RV failure. In addition to their role as pulmonary vasodilators these agents may have a direct inotropic effect on the failing RV. Despite potential advantages of these agents, systemic vasodilation is often dose limiting. Phosphodiestrase inhibitors may also require concomitant administration of a systemic vasoconstrictor.
Levosimendan, a calcium-sensitizing agent with positive inotropic and vasodilatory effects, holds promise for patients with PH and RV failure but it has not yet been thoroughly investigated in these patients. A recent study found that levosimendan was superior to dobutamine in the treatment of PH following cardiac surgery in children. However, there was no control group and the relative improvement in cardiac index was minimal and of uncertain clinical relevance.