Systemic sclerosis-associated pulmonary arterial hypertension

Abstract

Pulmonary arterial hypertension (PAH) is the leading cause of death in systemic sclerosis (SSc) and affects up to 12% of all patients with SSc, with a 50% mortality rate within 3 years of PAH diagnosis. Compared with the idiopathic form of PAH (IPAH), patients with SSc-associated PAH (SSc-PAH) have a threefold increased risk of death and may receive a diagnosis late in the course of disease because of insidious onset and the high prevalence of cardiac, musculoskeletal, and pulmonary parenchymal comorbidities. Treatment with conventional forms of PAH therapy often yield poor results compared with IPAH cohorts; unfortunately, the exact reasons behind this remain poorly understood but likely include variations in the pathologic mechanisms, differences in cardiovascular response to increasing afterload, and inadequate strategies to detect and treat SSc-PAH early in its course. Current methods for screening and longitudinal evaluation of SSc-PAH, such as the 6-min walk test, transthoracic echocardiography, and MRI, each have notable advantages and disadvantages. We provide an up-to-date, focused review of SSc-PAH and how it differs from IPAH, including pathogenesis, appropriate screening for disease onset, and new approaches to treatment and longitudinal assessment of this disease.

Figure 1.

Treatment algorithm for SSc-PAH used in the Johns Hopkins pulmonary hypertension program. 6MWT = 6-min walk test; ERA = endothelin receptor antagonist; FC = functional class; NT-proBNP = N-terminal pro-brain natriuretic peptide; PDE-5I = phosphodiesterase-5 inhibitor; RHC = right-sided heart catheterization; SQ = subcutaneous; SSc-PAH = systemic sclerosis-associated pulmonary arterial hypertension; WHO = World Health Organization.