Clinical phenotypes and outcomes of pulmonary veno-occlusive disease in carriers of bi-allelicEIF2AK4mutations

Abstract

BACKGROUND: Bi-allelic EIF2AK4 mutations predispose to the development of pulmonary veno-occlusive disease (PVOD). AIMS OF THE STUDY: To describe phenotype and outcomes of PVOD patients according to EIF2AK4 mutations status. RESULTS: 85 PVOD patients (25 mutations carriers and 60 non-carriers) were identified in the French referral centre for pulmonary hypertension. At diagnosis, EIF2AK4 mutations carriers were significantly younger than non-carriers. PVOD in non-carriers was characterized by male predominance and organic solvents exposure. No difference was observed in NYHA functional class, 6-MWD and hemodynamic characteristics except for pulmonary vascular resistances. 77 PVOD patients (21 EIF2AK4 mutation carriers and 56 non-carriers) received specific PAH therapy and 13 patients (16.8%) experienced drug-induced pulmonary edema. In the 53 patients reassessed within 8 months, mild clinical, functional and hemodynamic improvements were observed. During follow-up, 29 patients were transplanted and 43 patients died. Event-free survival (death or transplantation) at 1, 2 and 3 years was 64%, 56% and 34% in EIF2AK4 mutations carriers and 78%, 47% and 36% in non-carriers. CONCLUSION: PVOD patients carrying bi-allelic EIF2AK4 mutations are characterized by a younger age, severe clinical, functional and hemodynamic impairment and poor outcomes.