Improved transplant-free survival in patients with systemic sclerosis-associated pulmonary hypertension and interstitial lung disease.

Survival in patients with systemic sclerosis (SSc)-associated pulmonary hypertension (PH) and interstitial lung disease (ILD) is poor. Evidence supporting the efficacy of aggressive pulmonary arterial hypertension (PAH)-targeted therapy in this population is limited. The aim of this study was to investigate transplant-free survival in patients with isolated SSc-related PAH or SSc-related PH-ILD who were treated with aggressive PAH-targeted therapy. SSc patients with right-sided heart catheterization (RHC)-diagnosed precapillary PH (mean pulmonary artery pressure ≥25 mm Hg, pulmonary capillary wedge pressure ≤15 mm Hg, and pulmonary vascular resistance ≥240 dynes × second/cm(5) ) were included. Patients were classified as having ILD based on review of high-resolution computed tomography (CT) chest imaging and spirometry. The Kaplan-Meier method was applied and Cox proportional hazards models were constructed to analyze survival and identify predictive variables. Of 99 patients with SSc-related precapillary PH, 28% had SSc-related PAH and 72% had SSc-related PH-ILD. The 1- and 2-year survival estimates were, respectively, 72% and 59% in the SSc-related PH-ILD group versus 82% and 66% in the SSc-related PAH group (P = 0.5). Within 6 months of the diagnostic RHC, 24% of all patients were started on prostanoid therapy; an additional 24% were started on prostanoid therapy after 6 months. In the multivariate model, male sex (hazard ratio [HR] 0.7, P = 0.01) and prostanoid therapy initiation within 6 months of the RHC (HR 1.4, P = 0.01) were the only factors significantly associated with transplant-free survival, after accounting for the presence of ILD and severity of PH. In this study, survival of patients with SSc-related PH-ILD was modestly improved relative to historical series. While these findings may not be generalizable, improved survival may be due partly to aggressive PAH-targeted therapy.

Volkmann ER ，Saggar R ，Khanna D ，Torres B ，Flora A ，Yoder L ，Clements PJ ，Elashoff RM ，Ross DJ ，Agrawal H ，Borazan N ，Furst DE ，Saggar R ... -  《-》

Survival in pulmonary hypertension associated with the scleroderma spectrum of diseases: impact of interstitial lung disease.

Mathai SC ，Hummers LK ，Champion HC ，Wigley FM ，Zaiman A ，Hassoun PM ，Girgis RE ... -  《ARTHRITIS AND RHEUMATISM》

Hemodynamic Response to Treatment and Outcomes in Pulmonary Hypertension Associated With Interstitial Lung Disease Versus Pulmonary Arterial Hypertension in Systemic Sclerosis: Data From a Study Identifying Prognostic Factors in Pulmonary Hypertension Ass

Patients with systemic sclerosis and both pulmonary hypertension and interstitial lung disease (SSc-PH-ILD) generally carry a worse prognosis than patients with SSc and pulmonary arterial hypertension (SSc-PAH) without ILD. There is no evidence of the efficacy of PAH therapies in SSc-PH-ILD. We undertook this study to compare survival of and response to treatment in patients with SSc-PH-ILD and those with SSc-PAH. We analyzed 128 patients (66 with SSc-PH-ILD and 62 with SSc-PAH) from 15 centers, in whom PH was diagnosed by right-sided heart catheterization; they were prospectively included in the PH registry. All patients received PAH-specific therapy. Computed tomography of the chest was used to confirm or exclude ILD. At baseline, patients with SSc-PH-ILD had less severe hemodynamic impairment than those with SSc-PAH (pulmonary vascular resistance 5.7 Wood units versus 8.7 Wood units; P = 0.0005) and lower diffusing capacity for carbon monoxide (median 25% [interquartile range (IQR) 18%, 35%] versus 40% [IQR 31%, 51%]; P = 0.0005). Additionally, patients with SSc-PH-ILD had increased mortality (8.1% at 1 year, 21.2% at 2 years, and 41.5% at 3 years) compared to those with SSc-PAH (4.1%, 8.7%, and 21.4%, respectively; P = 0.04). Upon treatment with PAH-targeted therapy, no improvement in the 6-minute walk distance was observed in either group. Improvement in the World Health Organization functional class was observed less frequently in patients with SSc-ILD-PH compared to those with SSc-PAH (13.6% versus 33.3%; P = 0.02). Hemodynamics improved similarly in both groups. ILD confers a worse prognosis to SSc-PH. Response to PAH-specific therapy is clinically poor in SSc-PH-ILD but was not found to be hemodynamically different from the response observed in SSc-PAH.

Chauvelot L ，Gamondes D ，Berthiller J ，Nieves A ，Renard S ，Catella-Chatron J ，Ahmad K ，Bertoletti L ，Camara B ，Gomez E ，Launay D ，Montani D ，Mornex JF ，Prévot G ，Sanchez O ，Schott AM ，Subtil F ，Traclet J ，Turquier S ，Zeghmar S ，Habib G ，Reynaud-Gaubert M ，Humbert M ，Cottin V ... -  《-》

Systemic sclerosis-related pulmonary hypertension associated with interstitial lung disease: impact of pulmonary arterial hypertension therapies.

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 association with 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. 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. 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. 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.

Le Pavec J ，Girgis RE ，Lechtzin N ，Mathai SC ，Launay D ，Hummers LK ，Zaiman A ，Sitbon O ，Simonneau G ，Humbert M ，Hassoun PM ... -  《-》

Mortality and hospitalization outcomes of interstitial lung disease and pulmonary hypertension in the Singapore systemic sclerosis cohort.

We compared mortality and hospitalization rates in four groups of patients with systemic sclerosis (SSc) [isolated pulmonary arterial hypertension (PAH) or interstitial lung disease (ILD), concomitant ILD-pulmonary hypertension (PH), and no/mild pulmonary involvement]. In the Systemic Sclerosis Cohort Singapore (SCORE), ILD was diagnosed by HRCT and significant ILD was defined by forced vital capacity <70% predicted. Patients were classified as PAH if echocardiographic systolic pulmonary artery pressure (sPAP) ≥50 mmHg or right heart catheterization (RHC) mean PAP ≥25 mmHg. Multivariable regression analyses were performed to determine factors associated with mortality and hospital admissions per year. Cox proportional hazard model was used to analyze survival. Of 490 SSc patients, 50 patients had PAH, 92 patients had ILD and 43 patients had ILD-PH. Of 93 patients with PAH or ILD-PH, 56 were based on echocardiography and 37 on RHC. Patients with ILD-PH (HR 3.77, 95% CI: 2.05-6.93) had the highest risk of death, followed by PAH (HR 3.03, 95% CI: 1.60-5.76) and ILD (HR 1.84, 95% CI: 1.04-3.28). After adjustment for confounders, PAH (HR 2.39, 95% CI: 1.13-5.07) remained independently associated with mortality, but not ILD-PH or ILD. Other factors associated with mortality were male gender, age at SSc diagnosis, malabsorption and digital ulcer/ gangrene. Increased hospitalization rate was associated with renal crisis, right heart failure and PAH medications, but not SSc groups. PAH is an independent risk factor of mortality in SSc. Increased hospitalization rate was not associated with SSc groups. Other factors associated with increased mortality and hospital admissions were identified.

Noviani M ，Saffari SE ，Tan JL ，Yip JWL ，Teng GG ，Law WG ，Chan GYL ，Santosa A ，Lim AYN ，Hong C ，Ng SA ，Tay ELW ，Ruan W ，Yap J ，Low AHL ... -  《-》