Pulmonary Hypertension Phenotypes in Systemic Sclerosis: The Right Diagnosis for the Right Treatment

Abstract

Systemic sclerosis is an auto-immune disease characterized by skin involvement that often affects multiple organ systems. Pulmonary hypertension is a common finding that can significantly impact prognosis. Molecular pathophysiological mechanisms underlying pulmonary hypertension in systemic sclerosis can be extremely heterogeneous, leading to distinct clinical phenotypes. In addition, different causes of pulmonary hypertension may overlap within the same patient. Since pulmonary hypertension treatment is very different for each phenotype, it is fundamental to perform an adequate diagnostic work-up to properly and promptly identify the prevalent mechanism underlying pulmonary hypertension in order to start the right therapies. When pulmonary hypertension is caused by a primary vasculopathy of the small pulmonary arteries, treatment with pulmonary vasodilators, often in an initial double-combination regimen, is indicated, aimed at reducing the mortality risk profile. In this review, we describe the different clinical phenotypes of pulmonary hypertension in the scleroderma population and discuss the utility of clinical tools to identify the presence of pulmonary vascular disease. Furthermore, we focus on systemic sclerosis-associated pulmonary arterial hypertension, highlighting the advances in the knowledge of right ventricular dysfunction in this setting and the latest updates in terms of treatment with pulmonary vasodilator drugs.

Keywords: pulmonary hypertension; pulmonary vascular disease; pulmonary vasodilators; risk stratification; systemic sclerosis.

Figure 1

Different phenotypes of pulmonary hypertension in patients with systemic sclerosis. Abbreviations: PAH: pulmonary arterial hypertension; SSc, systemic sclerosis; RV, right ventricle; PVOD, pulmonary veno-occlusive disease; PH, pulmonary hypertension; CAD, coronary artery disease; HFpEF, Heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; CTEPH, chronic thromboembolic pulmonary hypertension; ILD, interstitial lung disease; HRCT, high resolution computed tomography; FVC, forced vital capacity.

Figure 2

Summary of the investigation tools required to properly categorize different systemic sclerosis–pulmonary hypertension (SSc–PH) phenotypes. Abbreviations: PH: pulmonary hypertension; PAH: pulmonary arterial hypertension; RHC: right heart cathetherization; mPAP: mean pulmonary artery oressure; PAWC: pulmonary artery wedge pressure; PVR: pulmonary vascular resistance; WU: wood units; RV: right ventricle; STE: speckle-tracking echocardiography; PVOD: pulmonary veno-occlusive disease; HRCT: high-resolution computed tomogrphy; PFT: pulmonary function tests; DLCO: diffusion lung CO; V/Q: ventilation/perfusion; EKG: elettrocardiogram; CMR: cardiac magnetic resonance; ILD; interstitial lung disease; FVC: forced vital capacity; CTEPH: chronic thromboembolic pulmonary hypertension; CT computer tomography.