Pulmonary Venous Vasculopathy in Connective Tissue Disease-Associated Pulmonary Arterial Hypertension With Reduced...

Connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) has a poorer prognosis than idiopathic PAH, potentially attributable to pulmonary veno-occlusive disease (PVOD)-like involvement. The diffusing capacity for carbon monoxide (DLco) may reflect small pulmonary venous obliteration. Whether severely reduced DLco reflects the severity of venous remodelling in CTD-PAH remains incompletely characterised, particularly with quantitative morphometric assessment. Thus, we evaluated the association of reduced DLco with clinical characteristics and venous vasculopathy in patients with CTD-PAH. We retrospectively reviewed patients with CTD-PAH without interstitial pneumonia. Patients were categorised into two groups based on %DLco (< 45%: severely reduced DLco or ≥ 45%: non-severely reduced DLco). Clinical characteristics and survival rates were compared. Histopathological characteristics of the pulmonary vasculature were analysed in eight autopsy cases. Of the 86 patients (mean age, 49.2 ± 16.8 years), 25 (29.1%) were classified into the severely reduced DLco group. They were older, showed a higher prevalence of systemic sclerosis, and exhibited lower arterial oxygen saturation and mean pulmonary arterial pressure compared with the other group. The severely reduced DLco group had a worse survival in unadjusted analysis (p = 0.048). Histopathological analysis revealed that the severity of small pulmonary venous stenosis was inversely correlated with %DLco (R ² = 0.537, p = 0.039; 95% CI, -0.69 to -0.03). Patients with CTD-PAH and a severely reduced DLco demonstrated a poorer prognosis than those without. Reduced DLco was associated with the severity of small pulmonary venous stenosis, consistent with a PVOD-like venous remodelling spectrum in CTD-PAH. DLco may serve as a clinically accessible marker of venous involvement within the PVOD-like spectrum of CTD-PAH.