Chest
Volume 144, Issue 4, October 2013, Pages 1282-1290
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Original Research
Pulmonary Vascular Disease
Survival in Systemic Sclerosis With Pulmonary Arterial Hypertension Has Not Improved in the Modern Era

https://doi.org/10.1378/chest.12-0653Get rights and content

Background

The impact of modern therapy on survival in pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc) is not clear. We sought to determine associations among commonly used clinical and hemodynamic variables, treatment, and long-term survival in PAH associated with SSc compared with PAH defined as idiopathic, familial, or associated with anorexigens.

Methods

The observation period (1996-2010) included the option for epoprostenol and the availability of oral agents in 2002 (modern era of endothelin antagonists and phosphodiesterase-5 inhibitors). Primary outcome was all-cause mortality.

Results

Eighty-three patients had SSc (mean age, 59 years), and 120 had PAH (mean age, 51 years) (P < .0001, > 80% were functional class III or IV in both groups). Compared with PAH, SSc had a lower mean pulmonary artery pressure (48 mm Hg vs 58 mm Hg, P < .0001) and pulmonary vascular resistance (10 resistance units vs 15 resistance units, P < .0001), and a higher cardiac index (2.3 L/min/m2 vs 1.8 L/min/m2, P < .0001). PAH was more often treated with prostacyclin (71% vs 44%, P < .0001), but there were no differences in the use of monotherapy or combination oral therapy. SSc had a twofold-higher mortality over the 14 years. The 5-year survival in the modern era for PAH was 87%, compared with 51% for SSc (P < .001).

Conclusions

Despite an improvement in clinical status, unlike in PAH, mortality in SSc has not improved since the introduction of epoprostenol.

Section snippets

Study Patients

Patients registered in the University of Michigan pulmonary hypertension database from April 1996 to October 2010 were included (Institutional Review Board [HUM 41444]). The total study period was chosen to be inclusive of the epoprostenol option. The “modern era” was used to be consistent with Condliffe et al11 and Humbert et al13 as corresponding to the availability of oral PAH-specific therapies beginning in 2002 (endothelin receptor antagonists [ETas] and phosphodiesterase-5 inhibitors

Results

The characteristics of patients with SSc-PAH (n = 83) and PAHifa (n = 120) (IPAH, 107 [89%]; FPAH, seven [6%]; anorexigen, six [5%]) at the time of first visit are summarized in Table 1. About 80% were women in both groups. SSc was characterized as limited scleroderma in 79%, diffuse scleroderma in 18%, and sine scleroderma in 2%. The mean time from onset of non-Raynaud SSc symptoms to the RHC was 10.4 ± 7.1 years. Antinuclear antibody characteristics were available in 73 of the 83 patients

Discussion

In this single-center study with a median follow-up of 35 months (IQR, 18-75 months), patients presenting in the “modern era” with SSc-PAH had an 84% 1-, 60% 3-, and 51% 5-year survival, which did not differ from pre-2002, when the sole PH-specific treatment was epoprostenol. SSc-PAH had a greater than twofold increase in mortality when compared with PAHifa, as demonstrated by the survival curves in Figure 1. After adjusting for age, sex, and hemodynamic risk factors, SSc-PAH was associated

Conclusions

Despite the relatively somber results of our study and in the literature, there is evidence that an early detection strategy may improve outcome in SSc-PAH. When compared with a small cohort with incident SSc found in routine clinical practice and patients participating in the French PAH Registry, those in a systematic SSc PAH detection program had an impressive improvement in survival.37 Our data argue persuasively that passive approaches to recognition do not serve this population well.

Acknowledgments

Author contributions: Dr Rubenfire is the guarantor of the paper and takes responsibility for the integrity of the work as a whole, from inception to published article.

Dr Rubenfire: contributed to the study design, database, interpretation of data, drafting of the manuscript, and manuscript revision and review.

Dr Huffman: contributed to the abstraction of data from charts, database entry, interpretation of data, and drafting of the manuscript.

Ms Krishnan: contributed to the management of the

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    Funding/Support: The authors have reported to CHEST that no funding was received for this study.

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