Background/Purpose: Pulmonary arterial hypertension (PAH) is a severe complication of systemic sclerosis (SSc), and its diagnosis requires right heart catheterization (RHC). The DETECT study developed an algorithm to select SSc patients with high suspicion of PAH for referral to RHC, identifying patients with early stage PAH and minimizing missed diagnoses. In this longitudinal follow up study, we aimed to identify factors associated with PAH progression in the DETECT cohort.

Methods: DETECT enrolled patients with SSc fulfilling the 1980 ACR classification criteria with a disease duration <3 years since the first non-Raynaud symptom, and who had a pulmonary diffusing capacity for carbon monoxide (DLCO) < 60% of the predicted value. Patients who had been previously diagnosed with pulmonary hypertension (PH) by RHC, who received treatment for PH, and who were at risk for developing PH other than PAH were excluded. A broad range of clinical and laboratory parameters potentially associated with PAH were assessed and RHC was performed in all patients at baseline. Patients diagnosed with PAH at baseline were followed up for up to 3 years in centers that agreed for the longitudinal part of the DETECT study, collecting data on survival, World Health Organization (WHO) Functional Class (FC), hospitalization, and PAH-specific treatment. Disease progression was defined as the occurrence of any of the following: WHO-FC worsening, PAH therapy with a drug combination, PAH-related hospitalization, or death. Associations between baseline variables and disease progression were assessed by univariable logistic regression.

Results: Of the 145 SSc patients with PH enrolled in the DETECT study, 87 patients were diagnosed with group I PH (PAH), of whom 57 participated in the longitudinal follow up study (median follow-up time 12.6 months, interquartile range 10.7-21.7 months). Among these 57 patients, 33 (57.9%) had mild PAH, in WHO FC I or II, and 52 received PAH-specific therapy. During follow-up, 25/57 (43.9%) patients had disease progression (4 deaths, 11 hospitalizations for PAH, 14 with worsening in WHO FC, and 8 received PAH-specific combination treatment), with a 1-year survival rate of 93%. The following factors [odds ratio, (95% confidence interval, CI)] were associated with disease progression: male gender [4.1 (1.1-14.1)], high Forced Vital Capacity (FVC) % predicted/ DLCO % predicted ratio [3.6 (1.2-10.7)], and high Borg dyspnoea index [1.7 (1.1-2.6)]. Low DLCO (% predicted) was also significantly associated with progression [area under the curve (95% CI) 0.8 (0.6-0.9)], but the relationship was not linear. A sensitivity analysis, excluding 4 patients with missing outcome data, was also performed and found similar results.

Conclusion: Although the large majority of these patients with early-diagnosed SSc-PAH were treated with PAH-specific drugs, more than 40% had disease progression during a rather short follow-up time, with male gender, functional capacity, and pulmonary function tests (low DLCO, high FVC%/DLCO % predicted ratio) at PAH diagnosis being associated with progression. This suggests that even mild and early detected PAH should be regarded as a high-risk complication of SSc.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/factors-associated-with-disease-progression-in-early-diagnosed-pulmonary-arterial-hypertension-associated-with-systemic-sclerosis/