Severe pulmonary arterial hypertension: treatment options and the bridge to transplantation

Abstract

Pulmonary arterial hypertension (PAH) is a rare disease leading to right heart failure and death. Prognosis remains poor, particularly for patients with severe disease, i.e. World Health Organization functional class IV. There have been significant improvements in treatment options. Several agents are available that target the three main established PAH disease pathways, and can be combined sequentially or upfront. Strong scientific evidence supports the use of intravenous epoprostenol in severe PAH; however, despite recommendations, many patients do not receive parenteral prostanoids and there is a lack of evidence from randomised clinical trials supporting the value of other PAH medications alone in severe PAH. Lung transplantation is an important option in patients with severe PAH who have not responded sufficiently to therapy, or who have worsened despite maximal treatment. Bridging techniques are available for patients who worsen while awaiting transplantation. The type of bridging technique used depends on various factors including patient illness severity, physician experience and the anticipated waiting time for transplantation. With the aim to facilitate the treatment decision-making process, herein we review the medical treatment options available for patients with severe PAH, and the bridging techniques that may be used to sustain patients awaiting transplantation.

Figure 1.

Updated treatment algorithm for patients with pulmonary arterial hypertension (PAH) in World Health Organization (WHO) functional class IV. ERA: endothelin receptor antagonist; PDE-5i: phosphodiesterase type-5 inhibitor; sGCS: soluble guanylate cyclase stimulators; BAS: balloon atrial septostomy. ^#: based on the WHO functional class of the majority of patients in the studies; ^¶: morbidity and mortality were the primary end-point in a randomised controlled study or reduction in all-cause mortality (prospectively defined). Reproduced from [7] with permission from the publisher.

Figure 2.

Use of parenteral prostanoids in 192 patients with pulmonary arterial hypertension (PAH) in functional class IV at the time of all-cause mortality. Results from the US REVEAL (Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management) registry. Data from [30].