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.
EIF2AK4 mutation carriers (n=25) | Mutation non-carriers (n=60) | P | |
Age | 27.3 ± 9.6 | 59.7 ± 13.2 | <0.0001 |
Gender, F/M | 14/11 | 17/43 | 0.016 |
NYHA FC II/ III / IV | 3 /17 / 5 | 3 / 44 / 13 | 0.52 |
6-MWD, % theo | 49.3 ± 22.6 | 43.7 ± 28.3 | 0.40 |
mPAP, mmHg | 50 ± 13 | 45 ± 10 | 0.10 |
CI, L/min/m² | 2.51 ± 0.88 | 2.42 ± 0.66 | 0.60 |
PVR, WU | 11.7 ± 6.6 | 9.1 ± 3.5 | 0.02 |
DLCO, % pred | 30 ± 7 | 30 ± 10 | 0.78 |
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