Non-Group 1 Pulmonary Hypertension Associated With Systemic Sclerosis: An Under-studied Patient Population

Abstract

Background: Systemic sclerosis (SSc) is a heterogeneous disorder that results in multiorgan dysfunction. The most common pulmonary manifestations are pulmonary hypertension (PH) and interstitial lung disease (ILD). Systemic sclerosis may be complicated by World Health Organization (WHO) Group 1 PH (SSc-PAH), which is the most well-studied subtype. The PH associated with SSc may also be secondary to underlying left heart disease (SSc-PH-LHD) or ILD (SSc-PH-ILD), and these subgroups are classified as WHO Group 2 and Group 3 PH, respectively. These non-WHO Group 1 PH subsets are notoriously under-studied. Available data suggest that the impact of PH-specific therapy in SSc-PH-LHD and SSc-PH-ILD is limited and survival is poor despite attempted treatment. Implication for clinicians: Most research and clinical trials surrounding PH in SSc have thus far focused on WHO Group 1 SSc-PAH. There are limited data surrounding therapeutic options for WHO Group 2 (SSc-PH-LHD) and Group 3 PH (SSc-PH-ILD) phenotypes. This review aims to summarize and consolidate the data surrounding these 2 distinct clinical phenotypes and to emphasize the available prognostic and treatment considerations. Conclusions: Given the unique pathophysiology, prognostic implications, and poor response to treatment of WHO Group 2 and 3 SSc-PH phenotypes, there is an overwhelming need for more data to best understand optimal management strategies. The focus should be individual patient-level prognostication, how and when to initiate and manage PH-specific therapy, and appropriate triage with regard to the timing of lung (or heart-lung) transplantation.