Venous retrograde approach for endovascular angioplasty in chronic total pulmonary vein occlusion -a case report.

INTRODUCTION: Fibrosing mediastinitis (FM) is a rare disease characterized by excessive proliferation of fibrous tissue in the mediastinum and can cause bronchial stenosis, superior vena cava obstruction, pulmonary artery and vein stenosis, etc. CASE PRESENTATION: An aging patient with intermittent chest tightness and shortness of breath was diagnosed with FM associated pulmonary hypertension (FM-PH) by echocardiography and enhanced CT of the chest, and CT pulmonary artery (PA)/ pulmonary vein (PV) imaging revealed PA and PV stenosis. Selective angiography revealed complete occlusion of the right upper PV, and we performed endovascular intervention of the total occluded PV. After failure of the antegrade approach, the angiogram revealed well-developed collaterals of the occluded RSPV-V2b, so we chose to proceed via the retrograde approach. We successfully opened the occluded right upper PV and implanted a stent. CONCLUSIONS: This report may provide new management ideas for the interventional treatment of PV occlusion.

Pulmonary Arterial Hypertension with Features of Venous Involvement: A Detective's Task. / Hipertensão Arterial Pulmonar com Características de Envolvimento Venoso: Um Trabalho Investigativo.

Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis are rare types of histopathological substrates within the spectrum of pulmonary arterial hypertension (PAH) with a very poor prognosis. They are characterized by a widespread fibroproliferative process of the small caliber veins and/or capillaries with sparing of the larger veins, resulting in a pre-capillary pulmonary hypertension phenotype. Clinical presentation is unspecific and similar to other PAH etiologies. Definitive diagnosis is obtained through histological analysis, although lung biopsy is not advised due to a higher risk of complications. However, some additional findings may allow a presumptive clinical diagnosis of PVOD, particularly a history of smoking, chemotherapy drug use, exposure to organic solvents (particularly trichloroethylene), low diffusing capacity for carbon monoxide (DLCO), exercise induced desaturation, and evidence of venous congestion without left heart disease on imaging, manifested by a classical triad of ground glass opacities, septal lines, and lymphadenopathies. Lung transplant is the only effective treatment, and patients should be referred at the time of diagnosis due to the rapid progression of the disease and associated poor prognosis. We present a case of a 58-year-old man with PAH with features of venous/capillary involvement in which clinical suspicion, prompt diagnosis, and early referral for lung transplantation were determinant factors for the successful outcome.

A doença veno-oclusiva pulmonar (DVOP) e a hemangiomatose capilar pulmonar são tipos raros de substratos histopatológicos dentro do espectro da hipertensão arterial pulmonar (HAP) com prognóstico muito ruim. Caracterizam-se por um processo fibroproliferativo generalizado das veias e/ou capilares de pequeno calibre com preservação das veias maiores, resultando em um fenótipo de hipertensão pulmonar pré-capilar. A apresentação clínica é inespecífica e semelhante a outras etiologias de HAP. O diagnóstico definitivo é obtido por meio de análise histológica, embora a biópsia pulmonar não seja aconselhada devido ao maior risco de complicações. No entanto, alguns achados adicionais podem permitir um diagnóstico clínico presuntivo de DVOP, especialmente história de tabagismo, uso de drogas quimioterápicas, exposição a solventes orgânicos (particularmente tricloroetileno), baixa capacidade de difusão do monóxido de carbono (DLCO), dessaturação ao esforço e evidências de doença venosa sem doença cardíaca esquerda no exame de imagem, manifestada por uma tríade clássica de opacidades em vidro fosco, linhas septais, e linfadenopatias. O transplante pulmonar é o único tratamento eficaz e os pacientes devem ser encaminhados no momento do diagnóstico, devido à rápida progressão da doença e ao prognóstico ruim. Apresentamos o caso de um homem de 58 anos com HAP com características de envolvimento venoso/capilar em que a suspeita clínica, o pronto diagnóstico e o encaminhamento precoce para transplante pulmonar foram determinantes para um bom desfecho.

Congenital Pulmonary Lymphangiectasia Masked by Postoperative Pulmonary Venous Obstruction in an Infant with Total Anomalous Pulmonary Venous Connection.

Congenital pulmonary lymphangiectasia (CPL) is associated with fetal pulmonary venous obstructive physiology. The precise morbidity of CPL is unknown as CPL is generally fatal in neonates. Here, we report an infant with secondary CPL in total anomalous pulmonary venous connection (TAPVC). He developed severe pulmonary hypertension (PH) after corrective surgery for TAPVC. However, cardiac catheterization showed mild left pulmonary venous obstruction (PVO), which was deemed unnecessary for re-intervention. He died at 11 months-old due to an exacerbation of PH. Autopsy revealed medial hypertrophy of the pulmonary arteries, mild left PVO, and marked dilatation and proliferation of the pulmonary lymphatics which might have been involved in the PH, although CPL was not conclusively identified based on the previous biopsy findings. We should be aware of the possibility of CPL in addition to postoperative PVO when encountering patients with fetal pulmonary venous obstructive physiology. Furthermore, a cautious approach to the interpretation of lung biopsy results is warranted.

Pulmonary veno-occlusive disease: illustrative cases and literature review.

Pulmonary veno-occlusive disease (PVOD), also known as "pulmonary arterial hypertension (PAH) with overt features of venous/capillary involvement", is a rare cause of PAH characterised by substantial small pulmonary vein and capillary involvement, leading to increased pulmonary vascular resistance and right ventricular failure. Environmental risk factors have been associated with the development of PVOD, such as occupational exposure to organic solvents and chemotherapy, notably mitomycin. PVOD may also be associated with a mutation in the EIF2AK4 gene in heritable forms of disease. Distinguishing PVOD from PAH is critical for guiding appropriate management. Chest computed tomography typically displays interlobular septal thickening, ground-glass opacities and mediastinal lymphadenopathy. Life-threatening pulmonary oedema is a complication of pulmonary vasodilator therapy that can occur with any class of PAH drugs in PVOD. Early referral to a lung transplant centre is essential due to the poor response to therapy when compared with other forms of PAH. Histopathological analysis of lung explants reveals microvascular remodelling with typical fibrous veno-occlusive lesions. This review covers the main features distinguishing PVOD from PAH and two clinical cases that illustrate the challenges of PVOD management.

Lung transplantation in primary pulmonary arterial hypertension and pulmonary venous hypertension.

OBJECTIVES: End-stage lung disease from primary pulmonary hypertension (PPHTN) and pulmonary venous-occlusive disease (PVOD) may require lung transplantation (LT). While medical therapies exist for the palliation of PPHTN, no therapies exist for PVOD. The study's objective is to compare outcomes of LT in these patients. METHODS: Patients with PPHTN and PVOD who had undergone LT were identified in the UNOS database (2005-2022). Univariable analyses compared differences between groups in demographic, clinical, and post-transplant outcomes. Multivariable logistic regression examined the association between the diagnosis group and survival. Overall survival time between groups was compared using the Kaplan-Meier method. RESULTS: Six hundred and ninety-six PPHTN and 78 PVOD patients underwent LT during the study period. Patients with PVOD had lower pulmonary artery mean pressure (47 vs. 53 mmHg, p < .001), but higher cardiac output (4.51 vs. 4.31 L/min, p = .04). PVOD patients were more likely to receive lungs from donation after cardiac death donors (7.7 vs. 2.9%, p = .04). There were no differences in postoperative complications or length of stay. PVOD was associated with superior survival at 30-day (100 vs. 93%, p = .02) and 90-day post-transplant (93 vs. 83%, p = .03), but not at later time points. In multivariable analyses, PVOD and brain death donor use were associated with better survival up to 90-day mark. CONCLUSIONS: Patients undergoing LT for PVOD had better initial survival, which disappeared after 1 year of transplantation. Donation after circulatory death donor use had a short-term survival disadvantage.

[Genetic diagnostics and molecular approaches in pulmonary arterial hypertension]. / Genetische Diagnostik und molekulare Ansätze bei pulmonalarterieller Hypertonie.

The recently published new European guidelines for diagnosis and treatment of pulmonary hypertension now offer the so far most extensive description of genetic testing and counselling for pulmonary arterial hypertension patients. In addition, the importance of a clinical screening of healthy mutation carriers is highlighted as well as the genetic testing of patients with a suspicion of pulmonary veno-occlusive disease. We frame the respective parts of the guidelines on genetic testing and counselling in the context of recent data and provide comments. Finally, we give an outlook on novel molecular approaches starting from Sotatercept, addressing ion channels and novel therapeutic developments.

Home-inhaled nitric oxide in a child with pulmonary arterial hypertension associated with post-operative pulmonary venous obstruction.

Home-inhaled nitric oxide therapy was effective and feasible in the patients with intractable pulmonary arterial hypertension. We present the case of a child with severe pulmonary arterial hypertension associated with post-operative pulmonary venous obstruction who was treated with home-inhaled nitric oxide therapy.

Diagnosis and management of pulmonary veno-occlusive disease.

INTRODUCTION: Pulmonary veno-occlusive disease (PVOD) is an orphan disease and uncommon etiology of pulmonary arterial hypertension (PAH) characterized by substantial small pulmonary vein and capillary involvement. AREAS COVERED: PVOD, also known as 'PAH with features of venous/capillary involvement' in the current ESC/ERS classification. EXPERT OPINION: In recent years, particular risk factors for PVOD have been recognized, including genetic susceptibilities and environmental factors (such as exposure to occupational organic solvents, chemotherapy, and potentially tobacco). The discovery of biallelic mutations in the EIF2AK4 gene as the cause of heritable PVOD has been a breakthrough in understanding the molecular basis of PVOD. Venous and capillary involvement (PVOD-like) has also been reported to be relatively common in connective tissue disease-associated PAH (especially systemic sclerosis), and in rare pulmonary diseases like sarcoidosis and pulmonary Langerhans cell granulomatosis. Although PVOD and pulmonary arterial hypertension (PAH) exhibit similarities, including severe precapillary PH, it is essential to differentiate between them since PVOD has a worse prognosis and requires specific management. Indeed, PVOD patients are characterized by poor response to PAH-approved drugs, which can lead to pulmonary edema and clinical deterioration. Due to the lack of effective treatments, early referral to a lung transplantation center is crucial.

Stiff left atrial syndrome with pulmonary veins occlusion after percutaneous radiofrequency ablation: a life-long complication that can lead to heart transplantation.

BACKGROUND: Stiff left atrial syndrome (SLAS) and pulmonary vein (PV) occlusion are rare yet potentially major life-long complications after radiofrequency ablation for atrial fibrillation. While mostly controlled by medical management, SLAS can progress to refractory congestive heart failure. Treatment of PV stenosis and occlusion remains a challenging problem with ongoing risk for recurrence regardless of techniques employed. Herein we present the case of a now 51-year-old male with acquired PV occlusion and SLAS who, over the course of eleven years, despite multiple interventions, ultimately required heart transplantation. CASE PRESENTATION: After undergoing three radiofrequency catheter procedures for paroxysmal atrial fibrillation (AF), a hybrid ablation was planned due to reappearance of symptomatic AF. Preoperative echocardiography and chest computed tomography (CT) revealed an occlusion of both left PVs. Furthermore, left atrial dysfunction, high pulmonary artery and pulmonary wedge pressures were diagnosed as well as an important reduction of the left atrial volume. The diagnosis of stiff left atrial syndrome was made. Primary surgical repair of the left-sided PVs was performed using a pericardial patch as a tubular neo-vein, combined with cryoablation in the left and right atrium to treat the patient's arrhythmia. Initial results were favorable, however, after two years the patient experienced progressive restenosis with hemoptysis. Therefore, stenting of the common left PV was performed. Over the years, progressive right heart failure with severe tricuspid regurgitation developed, despite maximal medical therapy, which led to the need for heart transplantation. CONCLUSION: The impact of PV occlusion and SLAS after percutaneous radiofrequency ablation can be lifelong and devastating for the clinical course of the patient. Since the presence of a small left atrium could be an important predictor for SLAS in case of redo ablation, preprocedural imaging should guide the operator to an algorithm of a decision-making containing lesion set, energy source, and safety of re-ablation.

Clinical and Hemodynamic Responses to Imatinib in Pulmonary Veno-Occlusive Disease/Pulmonary Capillary Hemangiomatosis: A Retrospective Pilot Study of Five Cases and Review of the Literature.

BACKGROUND: Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) are rare types of pulmonary arterial hypertension with dismal prognoses; there is no established medical treatment for these conditions. Possible efficacy of imatinib against these conditions has been reported in 15 cases; however, how and in whom imatinib is effective remain unknown. METHODS: We retrospectively evaluated clinical data from consecutive patients with PVOD/PCH treated with imatinib at our institution. The diagnosis of PVOD/PCH was established using the following criteria: pre-capillary pulmonary hypertension; diffusion capacity of the lung for carbon monoxide < 60%; and two or more high-resolution computed tomography findings of interlobular septal thickening, centrilobular opacities, and mediastinal lymphadenopathy. The dose of pulmonary vasodilators remained unchanged during the assessment of imatinib. RESULTS: The medical records of five patients with PVOD/PCH were reviewed. The patients were aged 67 ± 13 years, their diffusion capacity of the lung for carbon monoxide was 29 ± 8%, and their mean pulmonary artery pressure was 40 ± 7 mmHg. Imatinib was administered at 50-100 mg/day; consequently, the World Health Organization functional class improved in one patient. In addition, imatinib improved the arterial oxygen partial pressure in this and another patient (these two also experienced a decreased mean pulmonary artery pressure and pulmonary vascular resistance after imatinib usage). CONCLUSIONS: This study indicated that imatinib improves the clinical condition, including pulmonary hemodynamics, of some patients with PVOD/PCH. In addition, patients with a certain high-resolution computed tomography pattern or PCH-dominant vasculopathy may respond favorably to imatinib.

T-cell dysregulation and inflammatory process in Gcn2 (Eif2ak4-/-)-deficient rats in basal and stress conditions.

Hereditary pulmonary veno-occlusive disease (hPVOD) is a severe form of autosomal recessive pulmonary hypertension and is due to biallelic loss of function of the EIF2AK4 gene (alias GCN2) coding for GCN2. GCN2 is a stress kinase that belongs to the integrated stress response pathway (ISR). Three rat lines carrying biallelic Gcn2 mutation were generated and found phenotypically normal and did not spontaneously develop a PVOD-related disease. We submitted these rats to amino acid deprivation to document the molecular and cellular response of the lungs and to identify phenotypic changes that could be involved in PVOD pathophysiology. Gcn2-/- rat lungs were analyzed under basal conditions and 3 days after a single administration of PEG-asparaginase (ASNase). Lung mRNAs were analyzed by RNAseq and single-cell RNAseq (scRNA-seq), flow cytometry, tissue imaging, and Western blots. The ISR was not activated after ASNase treatment in Gcn2-/- rat lungs, and apoptosis was increased. Several proinflammatory and innate immunity genes were overexpressed, and inflammatory cells infiltration was also observed in the perivascular area. Under basal conditions, scRNA-seq analysis of Gcn2-/- rat lungs revealed increases in two T-cell populations, a LAG3+ T-cell population and a proliferative T-cell population. Following ASNase administration, we observed an increase in calprotectin expression involved in TLR pathway activation and neutrophil infiltration. In conclusion, under basal and asparagine and glutamine deprivation induced by asparaginase administration, Gcn2-/- rats display molecular and cellular signatures in the lungs that may indicate a role for Gcn2 in immune homeostasis and provide further clues to the mechanisms of hPVOD development.

Supracardiac total anomalous pulmonary venous connection type Ib: Morphology and outcomes.

BACKGROUND: Supracardiac total anomalous pulmonary venous connection is the most common subtype of total anomalous pulmonary venous connection. We aimed to describe the morphological spectrum of supracardiac total anomalous pulmonary venous connection and to identify risk factors for death and postoperative pulmonary venous obstruction. METHODS: From February 2009 to June 2019, 241 patients diagnosed with supracardiac-Ia (left-sided vertical vein, n = 185) or supracardiac-Ib (right-sided connection directly to superior vena cava, n = 56) total anomalous pulmonary venous connection underwent initial surgical repair at our institute. Cases with functionally univentricular circulations or atrial isomerism were excluded. Patients' postoperative survival was described by Kaplan-Meier curves. Cox proportional hazards models and competing risk regression models were used to identify clinical risk factors for death and postoperative pulmonary venous obstruction. RESULTS: There were 8 early deaths and 4 late deaths. The overall survivals at 30 days, 1 year, and 10 years were 97.1%, 94.8%, and 94.8%, respectively, in the supracardiac-Ia group (2.7%, 5/185) (hazard ratio, 4.8; P = .003). Five patients required reoperation for pulmonary venous obstruction, including 2 patients who required reintervention for superior vena cava syndromes (all in the supracardiac-Ib group). One patient required superior vena cava balloon dilation for superior vena cava syndromes. Multivariable analysis showed that the supracardiac-Ib group (12.5%, 7/56) had a significantly higher mortality rate than the supracardiac-Ia group (adjusted hazard ratio, 8.5, P = .008). Surgical weight less than 2.5 kg (adjusted hazard ratio, 10.8, P = .023), longer duration of cardiopulmonary bypass (adjusted hazard ratio, 1.15 per 10 minutes, P = .012), and supracardiac-Ib subtype (adjusted hazard ratio, 4.7, P = .037) were independent risk factors associated with death. The supracardiac-Ib subtype (adjusted hazard ratio, 4.8, P = .003) was an incremental risk factor associated with postoperative pulmonary venous obstruction. CONCLUSIONS: Morphological features of supracardiac total anomalous pulmonary venous connection, especially the supracardiac-Ib subtype, were risk factors associated with postoperative pulmonary venous obstruction and survival. Patients with unique anatomic subtypes might require more individualized surgical planning.

Recanalization of a Chronic Total Pulmonary Vein Occlusion Occurring after Transcatheter Atrial Fibrillation Ablation.

Pulmonary vein occlusion (PVO) is a known complication of radiofrequency ablation for atrial fibrillation. We present a case with delayed presentation leading to chronic total PVO. Computed Tomography (CT) imaging did not predict the presence of residual flow. Despite this, the occlusion was successfully stented using wire escalation techniques adapted from chronic total occlusion coronary angioplasty, with resolution of symptoms. This emphasises the importance of combining CT with invasive angiography for patient selection and interventional strategy. Innovative angioplasty techniques used to overcome PVO need to be balanced against additional risk of perforation when dealing with extra-cardiac structures.

Assessment of left atrial deformation in patients with total anomalous pulmonary venous connection by two-dimensional speckle-tracking echocardiography.

BACKGROUND: Total anomalous pulmonary venous connection (TAPVC) is a rare congenital heart disease of newborns characterized by impaired left ventricle growth and diastolic dysfunction. We hypothesized that the patients with TAPVC reduced blood flow into the left heart prenatally could affect left atrium (LA) not just growth but function. We compared the age-related changes in LA deformation using two-dimensional speckle-tracking echocardiography (2DSTE) in Patients with TAPVC. METHOD: This single-center, retrospective cohort study was conducted on consecutive isolated TAPVC patients who underwent neonatal surgery between January 1, 2009 and January 1, 2022. The LA datasets in TAPVC patients were analyzed before surgery (n = 28) and follow-ups at 1-2 (n = 24) and 5-7 years of age (n = 13) and compared with those of age-matched healthy controls (January 2009-2022). The LA strain (ε), indicating LA function, was analyzed using QLAB represented by reservoir (εR), conduit (εCD), and contractile (εCT) strains. LA pressure was evaluated by periodic follow-up catheterization after repair. RESULTS: Compared to the controls, the TAPVC patients had significantly smaller LA maximum volume preoperatively, and with age, the LA maximal volumes reached normal levels, while the LA minimal volumes were larger. All 2DSTE-determined LA strains showed significant reductions at all time points in the TAPVC group compared to those in the control (median εR, εCD, and εCT; before surgery: 17.0% vs. 26.0%, 12.9% vs. 15.9%, and 6.3% vs. 10.4%; follow-up at 1-2 years: 30.0% vs. 45.7%, 23.2% vs. 29.6%, and 6.1% vs. 16.3%; follow-up at 5-7 years: 31.2% vs. 43.1%, 25.0% vs. 31.2%, and 5.2% vs. 10.8%, respectively; p < 0.05). Only εCT did not represented a significant change over time even though after correction of blood flow (median εCT: 6.0% → 5.9%). Patients with pulmonary venous obstruction (PVO) at birth showed significantly decreased εR and εCD and higher LA pressure compared to those without PVO. CONCLUSION: This study showed that nevertheless maximum volume of LA was recovered within the normal range, reduced LA strains, especially contractile function lasted from birth even after repair in Patients with TAPVC.

Endovascular transatrial stenting of pulmonary vein stenosis after lung transplantation.

Pulmonary vein stenosis (PVS) and pulmonary vein occlusion (PVO) represent rare complications after lung transplantation (LTx), with limited therapeutic options and a high risk of graft loss. We present 2 cases of successful endovascular transatrial stenting following double LTx. A 60-year-old woman with chronic obstructive pulmonary disease who underwent double lobar LTx was diagnosed at postoperative day 72 with a high-grade PVS on the left side. A 22-year-old woman with idiopathic pulmonary arterial hypertension who underwent double LTx was diagnosed 9 days later with PVO of the left upper lobe vein. To avoid surgical reintervention, endovascular transatrial dilatation and stenting were performed successfully in both cases. Transatrial endovascular stenting of PVS or PVO after LTx seems an effective and safe treatment option that should be considered for these life-threatening complications and executed with care.