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We herein report a case of pulmonary veno-occlusive disease (PVOD) induced by allo-hematopoietic stem cell transplantation (HSCT) in a 48-year-old man who was diagnosed with acute myeloid leukemia. Five months after transplantation, he developed dyspnea and was diagnosed with pulmonary hypertension based on right heart catheterization. Although he received treatment with pulmonary vasodilators, diuretics, and corticosteroids, his pulmonary artery pressure did not decrease, and his pulmonary edema worsened. Based on the clinical course, hypoxemia, diffusion impairment, and computed tomography findings, the patient was diagnosed with HSCT-related PVOD. Critical attention should be paid to dyspnea after HSCT for the early diagnosis of PVOD.

Prostacyclin (PGI2) and its mimetics (iloprost, treprostinil, beraprost and MRE-269) are potent vasodilators (via IP-receptor activation) and a major therapeutic intervention for pulmonary hypertension (PH). These PGI2 mimetics have anti-proliferative and potent vasodilator effects on pulmonary vessels. We compared the relaxant effects induced by these recognized IP-agonists in isolated human pulmonary arteries (HPA) and veins (HPV). In addition, using selective antagonists, the possible activation of other prostanoid relaxant receptors (DP, EP4) was investigated. Iloprost and treprostinil were the more potent relaxant agonists when both vessels were analyzed. HPA were significantly more sensitive to iloprost than to treprostinil, pEC50 values: 7.94±0.06 (n =23) and 6.73±0.08 (n =33), respectively. In contrast, in HPV these agonists were equipotent. The relaxations induced by treprostinil were completely or partially inhibited by IP-antagonists in HPA or HPV, respectively. The effects of the IP-agonists were not significantly modified by the EP4 antagonist. Finally, DP-antagonists inhibited the relaxations induced by treprostinil in HPV, suggesting that the DP-receptor plays a role in treprostinil-induced relaxation in the HPV. These data suggest that iloprost and treprostinil should be the most effective clinically available agonists to decrease pulmonary vascular resistance and to prevent oedema formation (by similar decrease in HPA and HPV resistance) in PH patients. [ABSTRACT FROM AUTHOR]

Pulmonary veno-occlusive disease (PVOD) is a rare disease leading to pulmonary hypertension and potentially death related to right heart failure and/or respiratory insufficiency. Clinical symptoms are heterogenous and nonspecific: fatigue, decreased exercise tolerance, shortness of breath on exertion, cough, dizziness, chest pain with exercise, palpitations, syncope, as well as nonspecific symptoms such as headache, poor appetite, pallor or perioral cyanosis. Mutations in the EIF2AK4 (eukaryotic translation initiation factor 2-alpha kinase 4) have been recently described, other risk factors include exposure to organic solvent and trichloroethylene, tobacco exposure and chemotherapy. Echocardiography helps to estimate right ventricular systemic pressure, but further diagnostic workup includes cardiac catheterization to confirm pulmonary hypertension and increased pulmonary vascular resistance. High-resolution computed tomography reveals typical findings: centrilobular ground-glass nodules or opacities, septal lines, thickened interlobular septa, mosaic perfusion, and lymphadenopathy. Histology remains the gold standard, but carries risks for the patient. Proper workup is essential in order to avoid incorrect diagnosis. Pulmonary hypertension targeted treatment has been used in patients with PVOD, however, experience is limited, vasodilatory effects on pulmonary vasculature may lead to deterioration of the patients and should be used with great caution. Lung transplantation is currently the only valid treatment option for patients with PVOD. With prolonged waiting time and progression of the disease mechanical support could be considered., Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/cdt-20-320). The series “Pediatric Pulmonary Hypertension” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2021 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Pulmonary arterial hypertension (PAH), whether idiopathic PAH (IPAH), heritable PAH, or associated with other conditions, is a rare and potentially lethal disease characterized by progressive vascular changes. To date, there is limited data on the genetic basis of PAH in the Arab region, and none from Saudi Arabian patients. This study aims to identify genetic variations and to evaluate the frequency of risk genes associated to PAH, in Saudi Arabian patients. Adult PAH patients, diagnosed with IPAH and pulmonary veno-occlusive disease, of Saudi Arabian origin, were enrolled in this study. Forty-eight patients were subjected to whole-exome sequencing, with screening of 26 genes suggested to be associated with the disease. The median age at diagnosis was 29.5 years of age, with females accounting for 89.5% of our cohort population. Overall, we identified variations in nine genes previously associated with PAH, in 16 patients. Fourteen of these variants have not been described before. Plausible deleterious variants in risk genes were identified in 33.3% (n = 16/48) of our entire cohort and 25% of these cases carried variants in BMPR2 (n = 4/16). Our results highlight the genetic etiology of PAH in Saudi Arabia patients and provides new insights for the genetic diagnosis of familial and IPAH as well as for the identification of the biological pathways of the disease. This will enable the development of new target therapeutic strategies, for a disease with a high rate of morbidity and mortality., (© The Author(s) 2021.)

Pulmonary capillary hemangiomatosis (PCH) is a very rare and refractory disease characterized by capillary angioproliferation. The updated classification of pulmonary hypertension categorizes PCH into a subgroup of pulmonary arterial hypertension (PAH) alongside pulmonary veno-occlusive disease (PVOD). However, the definitive diagnosis of PCH only with noninvasive tools remains difficult. The aim of this study was to elucidate the radiological and physiological characteristics of PCH. We searched for cases of pathologically confirmed PCH in the English literature published between 2000 and 2018. We identified 26 cases among 39 studies. Then, we extracted and evaluated the relevant clinical information in all cases with available data. On chest computed tomography (CT), ground-glass opacities (GGOs) were observed in 92% of the cases, in which poorly defined nodular pattern was the most common (88%). GGOs in a bat-wing distribution were observed in one case. Septal lines and lymph node enlargement were observed less frequently (each 19%, 12%). Seven cases (27%) had overlapping abnormalities. Diffusing capacity of the lung for carbon monoxide (DL CO ) was remarkably decreased. Alveolar hemorrhage by histological findings or bronchoalveolar lavage (BAL) was observed in seven cases. The present study showed that the most characteristic findings of CT in PCH was centrilobular GGOs with a poorly defined nodular pattern, and septal lines and lymph node enlargement were seen less frequently. Alveolar hemorrhage detected by BAL and decreased DL CO may also be helpful to recognize the possibility of PCH like PVOD., (© The Author(s) 2019.)

In early 2019, the 6th World Symposium on Pulmonary Hypertension (WSPH) released an updated document highlighting the advances in the last five years. During the quinquennial event many experts worked together to suggest new changes in the disease diagnosis and management. Since inception of the WSPH in 1973, this is the first time when the hemodynamic definition of pulmonary hypertension (PH) has been updated. These proceedings have re-defined the different hemodynamic types of PH that occur with the left heart disease along with introduction to the genetic testing as part of pulmonary arterial hypertension (PAH) evaluation. Objective of this review is to highlight the evaluation and diagnosis of PAH based on the proceedings of the 6th WSPH. Accurate early diagnosis and subsequent management of PH is necessary, as despite of treatment advances, survival remains suboptimal., Competing Interests: Conflicts of Interest: The author serves on the speaker panel for Actelion pharmaceuticals, Bayer and United therapeutics; has received honoraria from these entities for consultancy and speaking engagements. Member of a data safety and monitoring board for an industry sponsored FDA approved study. The author is PI or Sub I on multiple clinical trials sponsored by Actelion and United therapeutics., (2019 Journal of Thoracic Disease. All rights reserved.)

Pulmonary veno-occlusive disease (PVOD) is a rare disease in the subgroup of conditions known as pulmonary arterial hypertension. Although a histological examination is needed for a definitive diagnosis, a non-invasive diagnosis is required for patients with pulmonary hypertension because a lung biopsy is deemed risky. We herein report a 32-year-old woman diagnosed with PVOD via a surgical lung biopsy and autopsy whose disease showed radiological findings mimicking those of hypersensitivity pneumonitis (pneumonia) at the time of the transbronchial lung biopsy, without obvious pulmonary hypertension on admission. When clinicians encounter patients with interstitial lung disease, they should not forget the possibility of PVOD and should be alert for emerging pulmonary hypertension.

Pulmonary arterial hypertension (PAH) includes various forms of pulmonary hypertension of different etiology but similar clinical presentation and functional derangement. Histopathological vascular changes in all forms of PAH are qualitatively similar but with quantitative differences in the distribution and prevalence of pathological changes in various portions of the pulmonary vascular bed. The documentation of these topographic variations in the response of the pulmonary vasculature to injury may be important to understand the pathogenesis of the various subsets of PAH. To standardize the precise histopathological documentation of the pulmonary vasculopathy in PAH we propose a histopathological classification that includes both the predominant segment of the pulmonary vasculature affected and the possible coexistence of pathological changes in other vascular segments. [Copyright &y& Elsevier]

In 1998, during the Second World Symposium on Pulmonary Hypertension (PH) held in Evian, France, a clinical classification of PH was proposed. The aim of the Evian classification was to individualize different categories sharing similarities in pathophysiological mechanisms, clinical presentation, and therapeutic options. The Evian classification is now well accepted and widely used in clinical practice, especially in specialized centers. In addition, this classification has been used by the U.S. Food and Drug Administration and the European Agency for Drug Evaluation for the labeling of newly approved medications in PH. In 2003, during the Third World Symposium on Pulmonary Arterial Hypertension held in Venice, Italy, it was decided to maintain the general architecture and philosophy of the Evian classification. However, some modifications have been proposed, mainly to abandon the term “primary pulmonary hypertension” and to replace it with “idiopathic pulmonary hypertension”; to reclassify pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis; to update risk factors and associated conditions for pulmonary arterial hypertension and to propose guidelines in order to improve the classification of congenital systemic-to-pulmonary shunts. [Copyright &y& Elsevier]