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

Abstract

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 20mg 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.

A rare compound heterozygous EIF2AK4 mutation in pulmonary veno-occlusive disease

“…In 2021, our group reported two cases of PVOD that were initially misdiagnosed as idiopathic pulmonary arterial hypertension owing to the lack of typical findings [ 3 ]. Both patients responded well to PAH-targeted therapy.…”

Efficacy and safety of oral pulmonary vasodilators in pulmonary veno‐occlusive disease

“…15 However, the survival has improved according to more recent studies. 7 , 9 , 10 , 14 For example, the 1‐year survival rate was approximately 70% in 94 PVOD/PCH cases. 4 In our study, the 1‐year survival rate was 93%, and mean survival time was 3.9 years; these findings are better than those in early reports and at least comparable to those in recent studies.…”

“…In previous reports, oral calcium channel blockers or intravenous prostaglandin I 2 were primarily used, 3 , 15 whereas in recent reports, current oral pulmonary vasodilators have been more prevalent. 4 , 9 , 10 Finally, the involvement of reporting/publication bias should be considered. Taken together, more information is needed to determine whether the prognosis of PVOD/PCH has indeed improved in recent years, and if so, what factors were involved.…”

“… 3 , 4 , 7 , 8 However, oral drugs for pulmonary arterial hypertension have made significant progress in recent years, and there have been some reports of their efficacy in PVOD/PCH. 9 , 10 In contrast to studies of early‐phase drugs such as intravenous prostaglandin I 2 and calcium channel blockers, these reports have been limited to a small number of cases, and detailed data on their efficacy and safety are lacking.…”

“…Lung transplantation is the only definitive treatment for PVOD/PCH, 1,5 and although PVOD/PCH is classified as a form of pulmonary arterial hypertension, 6 the use of pulmonary vasodilators for pulmonary arterial hypertension has not been proven to be effective and causes pulmonary edema in some cases 3,4,7,8 . However, oral drugs for pulmonary arterial hypertension have made significant progress in recent years, and there have been some reports of their efficacy in PVOD/PCH 9,10 . In contrast to studies of early‐phase drugs such as intravenous prostaglandin I 2 and calcium channel blockers, these reports have been limited to a small number of cases, and detailed data on their efficacy and safety are lacking.…”