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.

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.

Pulmonary Veno-occlusive Disease that Developed Following Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia.

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.

Atrial Fibrillation Ablation-induced Pulmonary Venous Occlusion Requiring Pneumonectomy.

A 71-year-old woman with a history of atrial fibrillation underwent a catheter-based ablation procedure. Months later, she presented with dyspnea and a left-sided pleural effusion. Diagnostic evaluation revealed left-sided pulmonary venous occlusion, with essentially absent left lung perfusion. The patient underwent left pneumonectomy, with left atrial appendage occlusion. Although lobectomy for pulmonary venous occlusion of a single vein after pulmonary vein isolation has been described, this appears to be a novel report of occluded pulmonary venous drainage of an entire lung necessitating pneumonectomy.

Anatomical attention-based prediction of postoperative pulmonary venous obstruction via CTA images.

Total anomalous pulmonary venous connection (TAPVC) is a rare congenital heart disease, with which some patients suffer from postoperative pulmonary venous obstruction (PPVO), requiring particular follow-up strategies and treatments. PPVO prediction has important clinical significance, while building a PPVO prediction model is challenging due to limited data and class imbalance distribution. Inspired by the anatomical evidence of PPVO, which is related to the structure of the left atrium (LA) and pulmonary vein (PV), we design an effective multi-task network for PPVO classification. The proposed method incorporates clinical priors and merits of the segmentation-based network into the classification task. The features learned from segmenting LA and PV are concatenated into the PPVO classification branch to constrain the learning of discriminative features. Anatomical-guided attention is applied in the aggregation of these features to restrict them focusing on TAPVC-related regions. To deal with the imbalance classification problem of PPVO, a novel classification loss derived by masked class activation map (MCAM) is designed to improve the classification performance. Computed tomography angiography (CTA) images of 146 patients diagnosed with supracardiac TAPVC in Shanghai Children's Medical Center and Guangdong Provincial People's Hospital were enrolled in this work. The comprehensive experiments demonstrate the effectiveness and generalization of our proposed method. The automatic PPVO prediction model shows the potential application in helping clinicians develop follow-up strategies, thereby improving the survival rate of TAPVC patients.

Pediatric pulmonary veno-occlusive disease associated with a novel BMPR2 variant.

Pulmonary veno-occlusive disease (PVOD) and idiopathic/heritable pulmonary arterial hypertension (I/HPAH) cause progressive PH on the distinct genetic impact. A 29-month-old boy presented with a loss of consciousness. He had severe PH refractory to pulmonary vasodilators. Hypoxemia and ground-glass opacity on the chest computed tomography were present, and significant pulmonary edema developed after the introduction of continuous intravenous prostaglandin I2 . Based on the clinical diagnosis of PVOD, he underwent a single living-donor lobar lung transplantation with the right lower lobe of his mother. The pathological findings of his explanted lung showed intimal thickening and luminal narrowing of the pulmonary vein. A genetic test revealed a novel heterozygous splice acceptor variant (c.77-2A>C) in BMPR2, which is typically associated with I/HPAH. This is the first pediatric case of PVOD with BMPR2 variant, supporting the concept that I/HPAH and PVOD are part of a spectrum of pulmonary vascular disease.

Dual-energy CT lung perfusion characteristics in pulmonary arterial hypertension (PAH) and pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis (PVOD/PCH): preliminary experience in 63 patients.

BACKGROUND: In the stratification of potential causes of PH, current guidelines recommend performing V/Q lung scintigraphy to screen for CTEPH. The recognition of CTEPH is based on the identification of lung segments or sub-segments without perfusion but preserved ventilation. The presence of mismatched perfusion defects has also been described in a small proportion of idiopathic pulmonary arterial hypertension (PAH) and pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis (PVOD/PCH). Dual-energy CT lung perfusion changes have not been specifically investigated in these two entities. PURPOSE: To compare dual-energy CT (DECT) perfusion characteristics in PAH and PVOD/PCH, with specific interest in PE-type perfusion defects. MATERIALS AND METHODS: Sixty-three patients with idiopathic or heritable PAH (group A; n = 51) and PVOD/PCH (group B; n = 12) were investigated with DECT angiography with reconstruction of morphologic and perfusion images. RESULTS: The number of patients with abnormal perfusion did not differ between group A (35/51; 68.6%) and group B (6/12; 50%) (p = 0.31) nor did the mean number of segments with abnormal perfusion per patient (group A: 17.9 ± 4.9; group B: 18.3 ± 4.1; p = 0.91). The most frequent finding was the presence of patchy defects in group A (15/35; 42.9%) and a variable association of perfusion abnormalities in group B (4/6; 66.7%). The median percentage of segments with PE-type defects per patient was significantly higher in group B than in group A (p = 0.041). Two types of PE-type defects were depicted in 8 patients (group A: 5/51; 9.8%; group B: 3/12; 25%), superimposed on PH-related lung abnormalities (7/8) or normal lung (1/8). The iodine concentration was significantly lower in patients with abnormal perfusion (p < 0.001) but did not differ between groups. CONCLUSION: Perfusion abnormalities did not differ between the two groups at the exception of a higher median percentage of segments with PE-type defects in patients with PVOD/PCH. KEY POINTS: • Patchy perfusion defect was the most frequent pattern in PAH. • A variable association of perfusion abnormalities was seen in PVOD/PCH. • Lobular and PE-type perfusion defects larger than a sub-segment were depicted in both PAH and PVOD/PCH patients.

Total anomalous pulmonary venous connection: Influence of heterotaxy and venous obstruction on outcomes.

BACKGROUND: Previous studies have demonstrated increased early mortality and pulmonary vein reintervention for patients with total anomalous pulmonary venous connection (TAPVC) and heterotaxy syndrome (HTX+) compared with patients with TAPVC without heterotaxy syndrome (HTX-). We aimed to evaluate the longitudinal risk of pulmonary vein reintervention and mortality in HTX + patients. METHODS: A retrospective review was performed to identify longitudinal interventions in patients with TAPVC seen at a single center from 1995 to 2019. The mean cumulative interventions were described for all patients using the Nelson-Aalen estimator. Survival with TAPVC was described using Kaplan-Meier estimates. RESULTS: A total of 336 patients were identified with TAPVC, of whom 118 (35%) had heterotaxy syndrome. Functional single ventricles were identified in 106 of these 118 HTX + patients (90%) and in 14 of 218 HTX- patients (6%) (P < .001). Obstructed TAPVC (OBS+) was present in 49 of 118 HTX + patients (42%) and in 87 of 218 HTX- patients (40%) (P = .89). The median duration of follow-up was 6.5 years. Five-year survival was 69% for HTX+/OBS + patients, 72% for HTX+/OBS- patients, 86% for HTX-/OBS + patients, and 95% for HTX-/OBS- patients (P < .0001, log-rank test). The mean number of pulmonary vein interventions at the median follow-up time was greater in the HTX+/OBS + patients compared with HTX+/OBS- patients (mean, 2.0 vs 1.1; P = .030), HTX-/OBS + patients (mean, 1.3; P = .033), and HTX-/OBS- patients (mean, 1.3; P = .029). CONCLUSIONS: Among the 4 cohorts, HTX+ was associated with a higher rate of mortality, and HTX+/OBS+ was associated with a greater number of pulmonary vein interventions. This may be due in part to the high prevalence of single ventricle physiology in the HTX + cohort.

Dyspnoea and diffuse pulmonary nodules in a patient with pulmonary veno-occlusive disease: a case report and literature review.

Pulmonary veno-occlusive disease (PVOD) is a rare type of pulmonary hypertension characterized by capillary damage or arterial pulmonary hypertension. Early lung transplantation is the only effective treatment for PVOD because of the lack of specificity in its clinical manifestations and its rapid progression and poor prognosis. A 28-year-old woman presented with exertional dyspnoea. A chest computed tomography scan revealed diffuse centrilobular ground glass opacities in both lungs, a ratio of the transverse diameter of the main pulmonary trunk to the ascending aorta of >1, and enlargement of the right ventricle and right atrium. A right atrial floating catheter test showed right ventricular pressure of 82/0/4 mmHg, mean pulmonary artery pressure of 83/34/53 mmHg, and pulmonary artery wedge pressure of 15/8/12 mmHg. A mutation was found in the eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) gene. Thus, the patient was diagnosed with PVOD and subsequently given standard bosentan treatment (62.5 mg twice a day). However, after 6 months of follow-up, there was no significant improvement in the pulmonary artery pressure or activity tolerance (6-minute walking test). Therefore, cardiopulmonary transplantation was performed. Early diagnosis and timely treatment of PVOD may improve the patient's prognosis.

Recurrent pulmonary vein stenosis after successful intervention: Prognosis and management of restenosis.

OBJECTIVES: The aim of this study was to describe management of recurrent pulmonary vein stenosis (PVS) and determine if stenting is superior to balloon angioplasty (BA) in preventing subsequent restenosis. BACKGROUND: PVS is a serious complication of atrial fibrillation ablation. BA and stenting are effective therapies; however, restenosis frequently occurs. Here we report management of recurrent stenosis. METHODS: This was a prospective observational study performed from 2000 to 2014. RESULTS: One hundred and thirteen patients with severe PVS underwent intervention in 88 veins treated with BA and 81 treated with stenting. Forty-two patients experienced restenosis. Restenosis was more common in veins treated with BA (RRR 53% [95% CI 32-70%, p = .008]). A second intervention was performed in 41 patients. In the 34 vessels treated with initial BA, 24 were treated for restenosis with a stent and 10 were treated with a second BA. The recurrence rate was 46% in those treated with BA followed by stenting and 50% in those treated with two BA procedures. In the 22 veins treated with initial stenting, 9 were treated with another stent and 13 were treated with BA. The recurrence rate was 44% in those treated with a second stent and 46% for those treated with a stent followed by BA. The risk of a third stenosis was the same among all groups (Analysis of variance [ANOVA] p = .99). Limited sample size precluded analysis of outcome by stent size. CONCLUSIONS: Restenosis occurred in 44% of patients overall. Management is challenging; stenting does not appear to be superior to BA.

Long-term outcome of percutaneous intervention for pulmonary vein stenosis after pulmonary vein isolation procedure.

OBJECTIVES: Report long-term outcomes of percutaneous intervention in patients with pulmonary vein stenosis (PVS) after pulmonary vein isolation (PVI) from a single center over 16 years. BACKGROUND: Outcome reports of percutaneous intervention for PVS resulting from PVI are limited. METHODS: Retrospective review of all patients with PVS after PVI who underwent percutaneous intervention at the Cleveland Clinic Foundation between January 2000 and December 2016. RESULTS: A total of 205 patients underwent cardiac catheterization for PVS during the study period. Completely occluded veins which could not be recanalized occurred in six patients. Of the remaining 199 patients, 27 (14%) were lost to follow-up, leaving 172 patients with 276 veins for analysis. Balloon angioplasty was performed in 62 veins and stent implantation in 250 (primary in 214, to treat postdilation restenosis in 36). Re-intervention occurred in 45/62 (73%) balloon-dilated veins and 45/250 (18%) stented veins. Freedom from re-intervention at 1 and 5 years was 90 and 73% following stenting versus 40 and 23% following balloon dilation (p < .001, Hazard ratio (HR) = 5.7). Veins with stent diameter ≥7 mm (n = 231) had greater freedom from re-intervention (95% at 1 year, 79% at 5 years) than veins with stents <7 mm (43% at 1 year, 9% at 5 years), p < .001. There was clear symptomatic improvement after intervention and no procedural mortality. CONCLUSIONS: Stent implantation at ≥7 mm for PVS after PVI is associated with low rates of re-intervention, in contrast to balloon dilation and stenting with small conventional stents.

Computed tomographic and clinical features of pulmonary veno-occlusive disease: raising the radiologist's awareness.

Pulmonary veno-occlusive disease (PVOD) is a rare subtype of pulmonary arterial hypertension (PAH) characterised by preferential remodelling of the pulmonary venules. Differentiation from other subtypes of PAH is essential as the management can differ significantly; for example, initiation of vasodilator therapy may cause fatal pulmonary oedema in a patient with PVOD misdiagnosed with idiopathic PAH. PVOD also carries a substantially worse prognosis. Lung biopsy is required for definitive diagnosis, but this is hazardous, and ideally, should be avoided in pulmonary hypertension. Computed tomography (CT) may suggest the diagnosis, directing the patient towards specialist review. Potential distinguishing CT features between PVOD and other subtypes of PAH include interlobular septal thickening, mediastinal lymphadenopathy, and centrilobular ground-glass opacities. No evidence-based medical therapy exists for PVOD at present and lung transplantation remains the definitive treatment for eligible patients. Therefore, early radiological identification of this challenging diagnosis facilitates timely referral for transplant.