Phenotype and Outcomes of Pulmonary Hypertension Associated with Neurofibromatosis Type 1

Rationale: Pulmonary hypertension associated with neurofibromatosis type 1 (PH-NF1) is a rare and largely unknown complication of NF1.

Objectives: To describe characteristics and outcomes of PH-NF1.

Methods: We reported the clinical, functional, radiologic, histologic and hemodynamic characteristics, response to pulmonary arterial hypertension (PAH)-approved drugs and transplant-free survival of patients with PH-NF1 from the French PH registry.

Results: We identified 49 PH-NF1 cases, characterized by a female/male ratio of 3.9 and a median age at diagnosis of 62 [18-82] years. At diagnosis, 92% were in New York Heart Association (NYHA) functional class III or IV. The 6-minute walk distance was 211 [0-460] m. Pulmonary function tests showed low diffusing capacity of the lung for carbon monoxide (DLCO) (30 [12-79] %) and severe hypoxemia (PaO2 56 [38-99] mmHg). Right heart catheterization showed severe precapillary pulmonary hypertension (PH) with a mean pulmonary artery pressure of 45 (10) mmHg and a pulmonary vascular resistance of 10.7 (4.2) WU. High-resolution computed tomography revealed cysts (76%), ground glass opacities (73%), emphysema (49%) and reticulations (39%). Forty patients received PAH-approved drugs with a significant improvement in functional class and hemodynamic parameters. Transplant-free survival at 1, 3 and 5 years was 87%, 54% and 42%, respectively, and 4 patients were transplanted. Pathologic assessment showed nonspecific interstitial pneumonia and major pulmonary vascular remodeling.

Conclusions: PH-NF1 is characterized by a female predominance, a low DLCO and severe functional and hemodynamic impairment. Despite a potential benefit of PAH treatment, prognosis remains poor, and double-lung transplantation is an option for eligible patients.

Keywords: Interstitial lung disease; Neurofibromatosis type 1; Outcomes; Pulmonary hypertension.