Systemic sclerosis–related pulmonary hypertension associated with interstitial lung disease: Impact of pulmonary arterial hypertension therapies

Abstract

Objective. Precapillary pulmonary hypertension (PH) is an important cause of death in patients with systemic sclerosis (SSc). It can occur in isolation (pulmonary arterial hypertension [PAH]) or in associationwith interstitial lung disease (ILD). Importantly, the outcomes and efficacy of PAH therapies in patients with SSc-related PH complicating ILD (PH-ILD) remain unknown. This study was undertaken to evaluate our experience with PH-ILD with regard to the efficacy and safety of PAH therapies in this patient cohort.Methods. We conducted a retrospective analysis of consecutive SSc patients from 2 large referral centers who had PH-ILD confirmed by right-sided heart catheterization and who received targeted PAH therapies. World Health Organization (WHO) functional class, 6-minute walk distance, and hemodynamic parameters were assessed at baseline and after a mean ؎ SD of 7.7 ؎ 6.2 months of treatment for PAH. Kaplan-Meier and Cox proportional hazards models were used to analyze survival and to identify prognostic factors.Results. Seventy patients were included in the study. No significant changes were observed in WHO functional class, 6-minute walk distance, or hemodynamic parameters after therapy. The 1-, 2-, and 3-year survival estimates were 71%, 39%, and 21%, respectively. In the multivariate model, worsening oxygenation during followup and reduced renal function were the only significant risk factors for death.Conclusion. This study represents the largest series to date in which the impact of PAH therapies in SSc-related PH-ILD was examined. In this cohort, PAH therapies were associated with no clear benefits. Deterioration in oxygenation was an important determinant of long-term survival. Prospective clinical trials focusing on this group of patients are warranted.Systemic sclerosis (SSc) is a heterogeneous disorder characterized by dysfunction of the endothelium,

Editorial: Tackling the Challenges of Systemic Sclerosis–Associated Pulmonary Hypertension: One Step Forward

“…This study largely extends previous single-center observations (3,4) as well as findings from large registries (5,6), which suggest that survival in this population is generally poor, with worse 3-year survival in patients with ILD-associated PH compared with that in patients with PAH (7,8). The results also confirm the value of previously known prognostic factors in this disease, such as age at the time of PAH diagnosis, pulmonary vascular resistance (PVR), and pericardial effusion (9).…”

Improved Transplant‐Free Survival in Patients With Systemic Sclerosis–Associated Pulmonary Hypertension and Interstitial Lung Disease

“…This concern is reflected in reduced prostanoid use (between 9% and 17%) in prior SSc-related PH-ILD cohorts (5,6,18). In contrast, approximately half of the present SSc-related PH-ILD cohort received prostanoid therapy during the study period.…”

“…Compared with patients with SSc-related PAH, patients with SSc-related PH-ILD historically have inferior survival rates, with an estimated 3-year survival rate of 21-35% in prior series (4,6,13). Despite the fact that heterogeneous methodology was used to define ILD in some of these prior studies, the present cohort of patients with SSc-related PH-ILD had a 3-year survival * RHC ϭ right heart catheterization; PVR ϭ pulmonary vascular resistance (see Table 1 for other definitions).…”

“…In contrast, approximately half of the present SSc-related PH-ILD cohort received prostanoid therapy during the study period. Despite the gas exchange concerns, SSc-related PH-ILD may in fact be the ideal phenotype for prostanoid therapy given the often severely advanced and progressive pulmonary vascular disease evident at diagnosis (including World Health Organization [WHO] functional class III or IV symptomatology [6], baseline oxygen requirements greater than those required in SSc-related PAH [5], and increasing oxygen requirements over time [6]). …”

“…Despite use of PAH-targeted therapy, SSc-related PH-ILD has a 3-year survival rate of 21% (6). However, aggressive PAH-targeted therapy, defined as either combination therapy or the use of parenteral prostanoid, is underutilized in patients with SSc-related PAH and SSc-related PH-ILD as compared with patients with idiopathic PAH (7).…”