Prevalence, Treatment, and Outcomes of Coexistent Pulmonary Hypertension and Interstitial Lung Disease in Systemic Sclerosis

Abstract

Objective: Systemic sclerosis (SSc) is associated with interstitial lung disease (ILD) and pulmonary hypertension (PH). This study was undertaken to determine the prevalence, characteristics, treatment, and outcomes of PH in a cohort of patients with SSc-associated ILD.

Methods: Patients with SSc-associated ILD on high-resolution computed tomography (HRCT) were included in a prospective observational cohort. Patients were screened for PH based on a standardized screening algorithm and underwent right-sided heart catheterization (RHC) if indicated. PH classification was based on hemodynamic findings and the extent of ILD on HRCT. Summary statistics and survival using the Kaplan-Meier method were calculated.

Results: Of the 93 patients with SSc-associated ILD included in the study, 76% were women and 65.6% had diffuse cutaneous SSc. The mean age was 54.9 years, and the mean SSc disease duration was 8 years. Twenty-nine patients (31.2%) had RHC-proven PH; of those 29 patients, 24.1% had PAH, 55.2% had World Health Organization (WHO) Group III PH, 34.5% had WHO Group III PH with pulmonary vascular resistance >3.0 Wood units, 48.3% had a PH diagnosis within 7 years of SSc onset, 82.8% received therapy for ILD, and 82.8% received therapy for PAH. The survival rate 3 years after SSc-associated ILD diagnosis for all patients was 97%. The survival rate 3 years after PH diagnosis for those with SSc-associated ILD and PH was 91%.

Conclusion: In a large cohort of patients with SSc-associated ILD, a significant proportion of patients had coexisting PH, which often occurs early after SSc diagnosis. Most patients were treated with ILD and PAH therapies, and survival was good. Patients with SSc-associated ILD should be evaluated for coexisting PH.

Figure 1.. Study Design and Characterization of PH in SSc-ILD Cohort

* Seven referred to cardiology, but no RHC as low likelihood of PH based on evidence; 2 refused RHC; 1 lost to follow up; 2 had negative RHC after data analysis; 2 had TTE findings normalize; 1 with stable lower DLCO, normal NTproBNP and no PAH findings on TTE. ^†Two underwent RHC due to severe symptoms, which was negative, and 1 underwent RHC due to decline in DLCO and had WHO Group III; none had variables required to calculate DETECT scores. ^‡ One subject also had combined post-capillary and pre-capillary PH (PCWP >15mmHg and diastolic PAP – PCWP ≥ 7mmHg) according to Vachiery et al [11] and had features of chronic thromboembolic disease based on pulmonary artery angiogram. ^§ SSc-ILD with PH due to ILD who have severe PH based on mPAP ≥ 35mmHg on RHC according to Seeger et al. [12]. PH-pulmonary hypertension; PAH –pulmonary arterial hypertension; SSc-systemic sclerosis; ILD-interstitial lung disease; SSc-ILD-systemic sclerosis associated interstitial lung disease; CTD-connective tissue disease; I/E –inclusion/exclusion; RHC –right heart catheterization; mPAP –mean pulmonary arterial pressure; PCWP-pulmonary capillary wedge pressure; WHO-World Health Organization; PVR –pulmonary vascular resistance; WU-woods units; DLCO-diffusing capacity for carbon monoxide.

Figure 2.. SSc-ILD and PH Change in WHO Functional Class

Histogram depicts FC prior to PH diagnosis for subjects with SSc-ILD and PH (WHO FC II, III, and IV) and the change in FC through time of data analysis. SSc-systemic sclerosis; ILD-interstitial lung disease; SSc-ILD-systemic sclerosis associated interstitial lung disease; PH-pulmonary hypertension; WHO-World Health Organization; FC-functional class