Chest
Recent Advances in Chest MedicineSystemic Sclerosis-Associated Pulmonary Arterial Hypertension
Section snippets
Epidemiology
PAH is defined by an elevated mean pulmonary artery pressure (mPAP) of > 25 mm Hg, with a pulmonary capillary wedge pressure of < 15 mm Hg.7 Prevalence of SSc-PAH among patients with SSc varies but is between 10% and 12%.4, 8, 9, 10 Thus, the prevalence of SSc-PAH may be as high as four to five times that of IPAH.11 In contrast, the prevalence data from REVEAL (Registry to Evaluate Early and Long-term PAH Disease Management) suggest that IPAH is more than twice as common as SSC-PAH.12 This
Pathogenesis
SSc-PAH occurs as a consequence of progressive remodeling of the small- to medium-sized pulmonary vasculature. The exact mechanisms of disease progression remain unclear, but it is believed that inflammation and endothelial injury are common precursors. Functionally, the inflammatory process creates a disequilibrium between vasoactive, proliferative mediators (eg, thromboxane A2 and endothelin-1) and antiproliferative vasodilators (eg, nitric oxide and prostacyclin) within the endothelium.
Screening for SSc-PAH
Unfortunately, there are no telltale pathognomonic features to easily identify the presence of SSc-PAH. In fact, the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS) study showed that 22% of patients with SSc-PAH had minimal or no dyspnea.16 The American College of Cardiology Foundation and American Heart Association recommend annual transthoracic echocardiography (TTE) screening in all patients with SSc regardless of symptoms.40 Adherence to these
Current Therapy
Despite an improved understanding of SSc-PAH, little progress has been made in modifying outcomes with the available three main therapeutic modalities: prostacyclin analogs, endothelin receptor antagonists (ERAs), and phosphodiesterase inhibitors. Despite the frequent use of CCBs for relief of Raynaud phenomenon in SSc, they are not recommended for treatment of SSc-PAH.
Epoprostenol, a prostacyclin analog, remains the most effective PAH therapy known, and in IPAH, it is the only therapy that
Conclusion
SSc-PAH remains a disease with high morbidity and mortality and is unique from IPAH in several ways. Despite recent advances in understanding the epidemiology, pathology, treatment, and outcomes, there remains a deep chasm between where we are and where we need to be. Incremental steps are being made. A comprehensive approach to this disease will afford a better understanding of relevant areas for further study.
Acknowledgments
Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Hassoun has been on scientific advisory boards for Gilead; Pfizer, Inc; Novartis Corporation; and Merck Sharp & Dohme Corp and has received research funding (REVEAL registry of patients with PAH) from Actelion Pharmaceuticals US, Inc. Dr Chaisson has reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in
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Funding/Support: Dr Chaisson is supported by the National Institutes of Health [Grant 5T32HL007534-30]. Dr Hassoun is supported by the National Institutes of Health/National Heart, Lung, and Blood Institute [Grants P50 HL084946 and R01 HL114910].
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