Background/Purpose: Pulmonary arterial hypertension associated with systemic sclerosis (SSc-PAH) is a life-threatening condition with obliterative pulmonary vascular remodeling, right ventricular (RV) dysfunction, and poor prognosis. Despite therapeutic advances, SSc-PAH remains a critical unmet clinical need due to its complex pathophysiology and lack of effective treatments. Chronic inflammation and immune dysregulation are believed to play a pivotal role in disease progression, but specific immune mechanisms remain poorly understood. Early detection of pulmonary hypertension (PH) and RV dysfunction is also a major challenge in clinical practice. To address this, we employed exercise echocardiography to unmask early RV dysfunction and PH and sought to elucidate the relationship between circulating immune subsets and PH and RV dysfunction severity in patients with SSc.

Methods: We prospectively enrolled 96 participants: 41 SSc-PH patients, 23 SSc-nonPH patients, 15 idiopathic PAH patients, and 17 age- and sex-matched controls. All participants underwent resting and exercise echocardiography, 6-minute walk test, electrocardiography, clinical assessments, and blood tests. We evaluated associations between immune cell subsets in peripheral blood and echocardiographic parameters of PH severity and RV function both at rest and during exercise, using univariate and multivariate linear regression models adjusted for age, sex, SSc subtype, and disease duration.

Results: Immune cell subset distributions did not differ significantly among the groups. However, increased monocyte percentage in SSc patients was associated with greater RV end-diastolic area, higher tricuspid regurgitation velocity peak velocity (TRV)/RV outflow tract velocity time integral (RVOT-VTI) which is an echo estimate of total pulmonary resistance, and reduced tricuspid annular plane systolic excursion (TAPSE)/TRV ratio which is an indicator of worse RV-pulmonary arterial coupling (Figure 1). These associations remained significant after adjustment for covariates. Exercise echocardiography revealed that most SSc patients (81%) had RV dysfunction, including subclinical RV dysfunction (change in absolute RV strain from rest to exercise [ΔRV strain ] < 0) or clinical RV dysfunction (absolute resting RV strain < 20%) (Figure 2). Notably, higher monocyte percentage was associated with worse RV contractile reserve (ΔRV strain from rest to 25W exercise): multivariable β = -1.71, 95% CI: -3.31 to -0.113, p = 0.037.

Conclusion: Increased levels of circulating monocytes are associated with greater PH severity and RV dysfunction in SSc. Dysregulation of the innate immune system potentially links cardiopulmonary dysfunction/remodeling in SSc.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/circulating-monocyte-level-is-associated-with-pulmonary-vascular-disease-and-right-ventricular-dysfunction-in-systemic-sclerosis/