Recent developments in connective tissue disease associated pulmonary arterial hypertension

Abstract

Connective tissue disease associated pulmonary arterial hypertension (CTD-PAH) has benefited from the major treatment advances that have occurred within pulmonary hypertension over the past three decades. Inclusion of CTD-PAH cases in pivotal clinical trials led to regulatory approval and drug availability. This has improved outcomes but there are additional challenges for management. First, the multifaceted co-morbidity related to the associated CTD needs treatment alongside PAH and may impact on diagnosis and evaluation of treatment response. Secondary, cardiac involvement, interstitial lung disease and predisposition to thromboembolism in CTD may lead to compound phenotypes where PH has multiple mechanisms as well as precapillary pulmonary vasculopathy of PAH. In general, especially for systemic sclerosis, CTD-PAH has worse long-term survival than idiopathic or familial PAH. However, CTD also present an opportunity for screening and early detection and treatment for associated PAH, and this may in the future be a major advantage over idiopathic disease where presentation inevitable only occurs at symptomatic stages and diagnosis may be delayed. This article reviews and summarises some of the recent developments in investigation and management of CTD-PAH.

Keywords: Connective tissue disease; Novel therapies; Pulmonary arterial hypertension; Screening; Systemic lupus erythematosus; Systemic sclerosis.

Fig. 1

Practical management of CTD-PAH. CTD: Connective tissue disease; SSc: systemic sclerosis; SLE: systemic lupus erythematosus; MCTD: mixed connective tissue disease; IIM: idiopathic inflammatory myopathies; pSS: primary Sjögren syndrome. *Warning signs include rapid progression of symptoms, severely reduced exercise capacity, syncope on mild exertion or pre-syncope, signs of right heart failure. Pulmonary hypertension in CTD needs to be considered in all relevant patients. SSc spectrum CTD require regular screening in line with current recommendations. The DETECT score, ASIG algorithm, or ESC/ERS algorithm can be applied to cases to stratify risk and determine need for RHC referral. Other CTD should be assessed according to clinical suspicion or screened similarly to SSc in case of high-risk phenotypes. All cases with suspected PH should be referred for assessment and management by a specialist PH centre and presence of warning signs should prompt early referral. Further evaluation after RHC will determine the predominant mechanism for PH and facilitate appropriate management according to latest ESC/ERC guidelines [1]. In PAH, treatment should be guided by risk stratification before and after therapy, using both clinical, biochemical, imaging and haemodynamic parameters [1].