Good response to pulmonary arterial hypertension-targeted therapy in 2 pulmonary veno-occlusive disease patients A case report

Rationale: Pulmonary veno-occlusive disease (PVOD) is a kind of rare and fatal pulmonary arterial hypertension (PAH). Different from other subtypes of PAH, PVOD patients have a very poor prognosis because of the progressive nature of pulmonary vascular involvement and fatal pulmonary edema induced by PAH-targeted drugs. Lung transplantation is the only choice for these patients. Patient concerns: We reported 2 cases of PVOD which was misdiagnosed as idiopathic pulmonary arterial hypertension initially due to the lack of typical findings of PVOD. Right heart catheterization was done. The results showed severe PAH with mean pulmonary artery pressure at 76 mmHg and 68 mmHg. Diagnosis: The diagnosis of idiopathic pulmonary arterial hypertension was corrected by eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) mutation screening. Biallelic mutations (c.1387delT (p. Arg463fs); c.989-990 delAA (p. Lys330fs)) were detected by next-generation sequencing for whole exome from blood sample. The presence of biallelic EIF2AK4 mutation was sufficient to confirm the diagnosis of PVOD. Interventions: The 2 patients had good response to PAH-targeted therapy (Ambrisentan 10 mg once a day and tadalafil 20 mg once a day) in the following 1 year. Outcomes: Because the patients had a good response to targeted drugs, the treatment of the 2 cases was unchanged. Over 1-year period, they still have a good response to PAH-targeted drugs. There was no sign of pulmonary edema. Lessons: All these results may indicate that PVOD is not so rare and typical findings of PVOD are lacking in some patients. EIF2AK4 mutation screening by next-generation sequencing maybe useful to differentiate PVOD from other PAH subtypes. PVOD is a heterogeneity population and different patients have different characteristics including response to PAH-targeted therapy. How to pick off this portion of patients timely is the core issue. Further study is necessary to answer this question.

Automated summary

The article reported two cases of PVOD initially misdiagnosed as idiopathic pulmonary arterial hypertension due to lack of typical findings, with subsequent correct diagnosis through EIF2AK4 mutation screening. This suggests that next-generation sequencing for EIF2AK4 mutation screening may be useful in differentiating PVOD from other PAH subtypes. PVOD is a heterogeneous population with different characteristics, including response to PAH-targeted therapy, highlighting the importance of timely identification of such patients and the need for further study.