Peripheral Pulmonary Artery Stenosis Research Articles

Clinical Care for Cardiovascular Disease in Patients With Williams-Beuren Syndrome.

Williams-Beuren syndrome (WBS) is a congenital multisystem disorder affecting the cardiovascular, central nervous, and musculoskeletal systems. Cardiovascular abnormalities, which consist principally of vascular stenoses, occur in approximately 80% of people with WBS and are the predominant cause of early morbidity and mortality. Supravalvar aortic stenosis and peripheral pulmonary artery stenosis are the most common stenotic lesions in WBS, though other stenoses often occur, including stenoses of the coronary arteries. Approximately one-third of people with WBS undergo cardiovascular interventions. The risk of sudden cardiac death is markedly higher than the general population, with most events occurring in the periprocedural period. Because of the rarity of WBS and the often-complex nature of the cardiovascular abnormalities, most physicians, including cardiologists, have limited experience in caring for patients with WBS. Further, heretofore, clinical cardiovascular management guidelines based on international expert consensus have not been available. This state-of-the-art review provides a comprehensive synopsis of the cardiovascular abnormalities in WBS and presents clinical management guidelines based on the authors' expert consensus.

Prevalence and Clinical Characteristics of Heterozygous RNF213 p.Arg4810Lys Variant Carriers Diagnosed With Chronic Thromboembolic Pulmonary Hypertension.

Ring finger protein 213 (RNF213) p.Arg4810Lys is a susceptibility gene for moyamoya disease, peripheral pulmonary artery stenosis (PPS), and other vascular diseases and thrombosis. We investigated the prevalence and clinical characteristics of RNF213 variant carriers diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH). We retrospectively analyzed the prevalence of the RNF213 p.Arg4810Lys variant in patients diagnosed with CTEPH (n=112) and PPS (n=10). Clinical and angiographic characteristics were evaluated between RNF213 variant carriers diagnosed with CTEPH and noncarriers with CTEPH and homozygous variant carriers with PPS. Eight heterozygous RNF213 p.Arg4810Lys variant carriers (7.1%) were identified among patients diagnosed with CTEPH, while 5 patients with PPS (50%) carried the homozygous variant. The clinical characteristics of heterozygous variant carriers with CTEPH were not remarkably different from those of noncarriers with CTEPH. All heterozygous variant carriers with CTEPH showed webs/bands lesions at the segmental/subsegmental level, with 75% showing distal tortuous vessels. None of the heterozygous variant carriers with CTEPH exhibited the string-of-beads pattern or elongated stenosis. Homozygous variant carriers with PPS showed the string-of-beads pattern, elongated stenosis, and distal tortuous vessels without webs/bands lesions. A subset of patients diagnosed with CTEPH (7.1%) carried the heterozygous RNF213 p.Arg4810Lys variant. Clinical and angiographic characteristics of heterozygous variant carriers were not remarkably different from those of noncarriers of CTEPH. However, both heterozygous variant carriers with CTEPH and homozygous variant carriers with PPS showed tortuous vessels on angiography.

Complex Pulmonary Artery Rehabilitation in Children with Alagille Syndrome: An Early Single-Center Experience of a Successful Collaborative Work.

Objective: In this paper, we share our single-center experience of successful multidisciplinary management of patients with Alagille syndrome. In addition, we aim to highlight the need for an Alagille program for effectively managing these patients, in general, and particularly peripheral pulmonary artery stenosis associated with this syndrome. Study Design: This is a retrospective review of six children with Alagille syndrome and advanced liver involvement who underwent pulmonary artery reconstruction between 2021 and 2022. Cardiac diagnosis, co-existing liver disease burdens, management approach, and short-term outcomes were analyzed. Results: All the patients underwent one-stage extensive bilateral branch pulmonary rehabilitation. Concomitant procedures included repair of tetralogy of Fallot in one patient and repair of supravalvar pulmonary artery stenosis in two. One patient had balloon pulmonary branch angioplasty before surgery. In all patients, there was a decrease in right ventricular systolic pressure post-operatively. Three patients underwent liver transplantation for pre-existing liver dysfunction. At a median 3-year follow-up, all the patients were alive with their right ventricular systolic pressure less than half of their systemic systolic pressure. One patient underwent balloon angioplasty due to new and recurrent left pulmonary artery stenosis 13 months after surgery. Conclusion: Pulmonary arteries can be successfully rehabilitated surgically in the presence of complex branch disease. Patients with advanced liver disease can undergo successful complex pulmonary artery reconstruction, which can facilitate their future liver transplantation course. A multidisciplinary team approach is a key for successful management of Alagille patients.

Endovascular Treatment for Peripheral Pulmonary Arterial Stenosis in RNF213-Related Vasculopathy

This brief report reviews the clinical, procedural, and imaging data of 7 patients with p.Arg4810Lys variant of the ring finger protein 213 (RNF213) gene–related peripheral pulmonary arterial stenosis who underwent percutaneous transluminal pulmonary angioplasties (PTPAs) for demographics, clinical presentation, indications for angioplasty, and procedural and clinical outcomes. During median follow-up of 64.4 months since the first confirmed diagnosis, PTPA was performed for 62 segmental pulmonary arteries with 38 sessions of the procedure in 7 patients. Vascular stent placement because of resistance to balloon dilation and immediate elastic recoil was performed in 48 of 62 procedures (77%). Except for 1 death, 6 patients showed an improvement in dyspnea and 5 patients showed a decrease in mean pulmonary arterial pressure (mean, 55.5–42.7 mm Hg) and increase in 6-minute walk distance (mean, 415.5–484.3 m). Reperfusion edema occurred in 4 of 7 patients (57%), which was 6 of 38 sessions (16%).

Effect of epoprostenol-induced thrombocytopaenia on lung transplantation for pulmonary arterial hypertension.

Preoperative intravenous epoprostenol therapy can cause thrombocytopaenia, which may increase the risk of perioperative bleeding during lung transplantation. This study aimed to determine whether lung transplantation can be safely performed in patients with epoprostenol-induced thrombocytopaenia. From June 2008 to July 2022, we performed 37 lung transplants in patients with pulmonary arterial hypertension (PAH), including idiopathic PAH (n = 26), congenital heart disease-associated PAH (n = 7), pulmonary veno-occlusive disease (n = 3) and peripheral pulmonary artery stenosis (n = 1) at our institution. Of these, 26 patients received intravenous epoprostenol therapy (EPO group), whereas 11 patients were treated with no epoprostenol (no-EPO group). We retrospectively analysed the preoperative and postoperative platelet counts and post-transplant outcomes in each group. Preoperative platelet counts were relatively lower in the EPO group than in the no-EPO group (median EPO: 127000 vs no-EPO: 176000/μl). However, blood loss during surgery was similar between the 2 groups (EPO: 2473 ml vs no-EPO: 2615 ml). The platelet counts significantly increased over 1 month after surgery, and both groups showed similar platelet counts (EPO: 298000 vs no-EPO: 284000/μl). In-hospital mortality (EPO: 3.9% vs no-EPO: 18.2%) and the 3-year survival rate (EPO: 91.4% vs no-EPO: 80.8%) were similar between the 2 groups. Patients with PAH treated with intravenous epoprostenol showed relatively lower platelet counts, which improved after lung transplantation with good post-transplant outcomes.

A probabilistic neural twin for treatment planning in peripheral pulmonary artery stenosis.

The substantial computational cost of high-fidelity models in numerical hemodynamics has, so far, relegated their use mainly to offline treatment planning. New breakthroughs in data-driven architectures and optimization techniques for fast surrogate modeling provide an exciting opportunity to overcome these limitations, enabling the use of such technology for time-critical decisions. We discuss an application to the repair of multiple stenosis in peripheral pulmonary artery disease through either transcatheter pulmonary artery rehabilitation or surgery, where it is of interest to achieve desired pressures and flows at specific locations in the pulmonary artery tree, while minimizing the risk for the patient. Since different degrees of success can be achieved in practice during treatment, we formulate the problem in probability, and solve it through a sample-based approach. We propose a new offline-online pipeline for probabilistic real-time treatment planning which combines offline assimilation of boundary conditions, model reduction, and training dataset generation with online estimation of marginal probabilities, possibly conditioned on the degree of augmentation observed in already repaired lesions. Moreover, we propose a new approach for the parametrization of arbitrarily shaped vascular repairs through iterative corrections of a zero-dimensional approximant. We demonstrate this pipeline for a diseased model of the pulmonary artery tree available through the Vascular Model Repository.

Flow pattern analysis of right ventricular outflow tract in repaired tetralogy of Fallot through 4D flow MRI.

Cardiac magnetic resonance imaging (CMR) often shows discrepancies between right ventricular outflow tract (RVOT) flow and left ventricular outflow tract flow in patients with late-stage repaired tetralogy of Fallot (rTOF), leading to potential errors in pulmonary regurgitation fraction (PRF) assessment. This study aimed to identify the conditions under which RVOT flow can be acutely evaluated using four-dimensional (4D) flow CMR. Twenty-seven consecutive patients with rTOF underwent both two-dimensional phase-contrast (2D PC) and 4D flow CMR between 2016 and 2018, excluding those with peripheral pulmonary artery stenosis, RVOT conduit replacement, unknown surgical method, and an aortic valve regurgitation greater than 20%. Seven healthy controls also underwent only 4D Flow CMR. All healthy controls and fifteen patients with rTOF showed laminar RVOT flow, while seven patients exhibited helical, and four patients exhibited vortical RVOT flow in 4D flow CMR visualization. Flow-volume concordance between the pulmonary artery and aortic flow was significantly lower in patients with rTOF and PRF > 40% in 2D PC CMR. This concordance rate in the suprapulmonary valve was high in both the TOF and control groups, comparing at five RVOT locations in 4D flow CMR. Regarding RVOT flow regurgitation in 4D flow, the whole bulk evaluation exhibited greater variation depending on the flow type compared to the whole pixel-wise evaluation. The study confirmed the flow volume at the upper section of the pulmonary valve as the most accurate correlate of aortic flow volume. Furthermore, the 4D flow CMR using the pixel-wise method demonstrated superior accuracy compared to the traditional bulk flow method.

Peripheral Pulmonary Artery Stenosis (PPAS) Mimicking Chronic Thromboembolic Pulmonary Hypertension (CTEPH) in SAPHO Syndrome: A Case Report and Review of the Literature

Peripheral Pulmonary Artery Stenosis (PPAS) Mimicking Chronic Thromboembolic Pulmonary Hypertension (CTEPH) in SAPHO Syndrome: A Case Report and Review of the Literature

Adult-onset idiopathic peripheral pulmonary artery stenosis.

Peripheral pulmonary artery stenosis (PPS) refers to stenosis of the pulmonary artery from the trunk to the peripheral arteries. Although paediatric PPS is well described, the clinical characteristics of adult-onset idiopathic PPS have not been established. Our objectives in this study were to characterise the disease profile of adult-onset PPS. We collected data in Japanese centres. This cohort included patients who underwent pulmonary angiography (PAG) and excluded patients with chronic thromboembolic pulmonary hypertension or Takayasu arteritis. Patient backgrounds, right heart catheterisation (RHC) findings, imaging findings and treatment profiles were collected. 44 patients (median (interquartile range) age 39 (29-57) years; 29 females (65.9%)) with PPS were enrolled from 20 centres. In PAG, stenosis of segmental and peripheral pulmonary arteries was observed in 41 (93.2%) and 36 patients (81.8%), respectively. 35 patients (79.5%) received medications approved for pulmonary arterial hypertension (PAH) and 22 patients (50.0%) received combination therapy. 25 patients (56.8%) underwent transcatheter pulmonary angioplasty. RHC data showed improvements in both mean pulmonary arterial pressure (44 versus 40 mmHg; p<0.001) and pulmonary vascular resistance (760 versus 514 dyn·s·cm-5; p<0.001) from baseline to final follow-up. The 3-, 5- and 10-year survival rates of patients with PPS were 97.5% (95% CI 83.5-99.6%), 89.0% (95% CI 68.9-96.4%) and 67.0% (95% CI 41.4-83.3%), respectively. In this study, patients with adult-onset idiopathic PPS presented with segmental and peripheral pulmonary artery stenosis. Although patients had severe pulmonary hypertension at baseline, they showed a favourable treatment response to PAH drugs combined with transcatheter pulmonary angioplasty.

Characteristics in patients with adult-onset idiopathic peripheral pulmonary artery stenosis

Abstract Background Peripheral pulmonary artery stenosis (PPS) refers to the obstruction of the pulmonary artery from the pulmonary artery trunk to the peripheral arteries. Although pediatric PPS is well described, the clinical characteristics of adult-onset idiopathic PPS have not been established. Purpose To establish the disease profile of adult-onset PPS, we characterized the clinical background, laboratory and imaging findings, treatment, and prognosis. Methods The nationwide survey in Japan, supported by the government, retrospectively collected clinical data on patients with idiopathic PPS from multiple centers. This cohort comprised individuals aged 15 years and above who had pulmonary arterial stenosis confirmed through pulmonary angiography, indeed patients with chronic thromboembolic pulmonary hypertension or Takayasu arteritis were excluded. Patient backgrounds, imaging findings, treatment profiles, right heart catheterization findings, and long-term prognosis were collected. A comparison was made between the data obtained from prior-treatment and post-treatment right heart catheterization. Results Forty-five patients (median age at diagnosis: 38 years [Q1–Q3:28–56]; 29 males [64.4%]) with idiopathic PPS were enrolled from 21 centers. The median period between diagnosis of PPS and the final follow-up was 60 months [Q1–Q3: 24–114 months]. Eight patients (17.8%) were associated with moyamoya disease. Pulmonary angiography was performed in all patients for a definite diagnosis, and stenosis of segmental and peripheral pulmonary arteries was observed in 41 (91.1%) and 36 patients (80.0%), respectively. Thirty-six patients (80.0%) received treatment with pulmonary arterial hypertension (PAH)-specific drugs, 23 patients (51.1%) received combination therapy, and 25 patients (55.6%) received transcatheter pulmonary angioplasty. Right heart catheterization data showed improvements in both the mean pulmonary artery pressure (46 vs. 41 mmHg; p&amp;lt;0.001) and pulmonary vascular resistance (738 vs. 506 dyn.s.cm-5; p&amp;lt;0.001) from baseline to the final follow-up. The 3-, 5-, and 10-year survival rates of patients with idiopathic PPS were 97.6% (95% confidence interval [CI]:83.9–99.7), 89.7% [95% CI:69.9–96.6), and 68.6% (95% CI:43.9–84.2), respectively. Conclusion In this study, the patients with adult-onset idiopathic PPS presented with segmental and peripheral pulmonary artery stenosis. Although patients had severe pulmonary hypertension at baseline, they showed a favorable treatment response to the PAH-specific drugs combined with transcatheter pulmonary angioplasty.

1226 The Role of Extracorporeal Membrane Oxygenation in William’s Syndrome Following Cardiac Surgery: A Case Report

Abstract Williams-Beuren Syndrome (WS) is a genetic syndrome seen in childhood, characterised by intellectual disabilities, outgoing personalities, elfin-like faces and cardiovascular complications. We report the story of a girl with WS who underwent complex cardiac surgery requiring extracorporeal membrane oxygenation (ECMO), to raise awareness of the perioperative challenges with WS. At 2 years old, a cardiac murmur was incidentally discovered. Further investigations revealed WS with cardiac manifestations including peripheral pulmonary artery stenosis (PPAS) and supravalvular aortic stenosis (SVAS). Isolated SVAS repair was feasible, however the severity of pulmonary artery hypoplasia deemed her inoperable. Her care was redirected to palliation. 18 months later, she remained in good clinical condition which prompted the multidisciplinary team (MDT) to change their decision and proceed with complex SVAS repair surgery (Brom technique) at the age of 5. Postoperatively, 3 failed attempts to wean from cardiopulmonary bypass preceded veno-arterial ECMO, which lasted 7 days. She stayed in intensive care for 17 days, and in hospital for 28 days. Frequent MDT decision making was crucial during her complex care. The patient is currently 15 years old, in good clinical condition, albeit exercise restrictions. WS patients have a known increased risk of perioperative sudden cardiac death and increasing use of paediatric ECMO, hence great attention and thorough preparation is required. Clear perioperative care guidelines for WS are essential to secure good outcomes in this patient population. This case demonstrated that MDT involvement and regular communication with the patient were key to deliver the appropriate care throughout her life.

Differential diagnosis of neonatal cholestasis by genetic testing: A case report

Alagille syndrome (ALGS) is a cholestasis disorder with multiple organ dysfunction, including heart and kidney. The causative genes of ALGS are JAG1 and NOTCH2. Dysregulation of Notch signaling leads to defects in the developmental mechanisms of the bile ducts. Sometimes extrahepatic bile duct hypoplasia makes it difficult to differentiate ALGS from biliary atresia. The Kasai procedure for ALGS is associated with poor liver and patient outcomes. Therefore, it is important to differentiate ALGS from biliary atresia correctly. A 2-day-old female neonate was admitted to the neonatal intensive care unit due to poor feeding; blood tests on day 7 showed elevated direct bilirubin and total bile acids. Right hydronephrosis, peripheral pulmonary artery stenosis, butterfly vertebra, and posterior embryotoxon were observed, and ALGS was suspected from these findings. Duodenal fluid tests and biliary scintigraphy showed no bile excretion from the liver into the intestinal tract. These findings suggested biliary atresia, and to distinguish ALGS from biliary atresia, rapid JAG1 and NOTCH2 sequencing was performed preoperatively. We found a heterozygous de novo single nucleotide insertion mutation c.192dupC p.(Lys65GlnfsX8). Operative cholangiography showed that the common bile duct was patent, but the common hepatic duct was barely open, a finding consistent with type III-a-o biliary atresia. Because of the preoperative diagnosis of ALGS, Kasai procedure was omitted. Neonates and early infants with cholestasis with extrahepatic symptoms should be carefully examined, with genetic syndromes and biliary atresia considered differential diagnoses. Advances in genetic analysis methods are expected to facilitate early diagnosis of ALGS.

Retroaortic Innominate Vein in Association With Pulmonary Atresia/Major Aortopulmonary Collaterals

BackgroundRetroaortic innominate vein (RAIV) is an extremely rare anomaly of systemic venous return. The prevalence of RAIV has been estimated to be 0.02% in individuals without congenital heart disease and 0.5% in those with congenital heart disease. Previous studies have demonstrated an association between RAIV and both conotruncal abnormalities and right aortic arch. Our center specializes in surgical procedures for patients with pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries (PA/VSD/MAPCAs), and we have frequently observed the presence of RAIV in these patients. The purpose of this study was to evaluate the prevalence and anatomic characteristics of RAIV. MethodsThis was a single-center retrospective review of medical records to identify patients with an RAIV. The study period was 2002 through 2022, with approximately 20,000 patients evaluated during this time frame. ResultsA total of 99 patients were identified with an RAIV. Of the 99 patients, 64 (65%) had PA/VSD/MAPCAs. Other diagnoses included tetralogy of Fallot (n = 16), tetralogy of Fallot with pulmonary atresia (n = 3), double outlet right ventricle (n = 4), peripheral pulmonary artery stenosis (n = 3), and other (n = 9). In the cohort of patients with PA/VSD/MAPCAs, 69% had a right aortic arch and 30% had completely absent central pulmonary arteries. ConclusionsThe overwhelming majority (90%) of patients with RAIV had conotruncal abnormalities, with PA/VSD/MAPCAs accounting for the preponderance of cases in our center.

A Large Turkish Cohort of Williams Syndrome: The Evaluation of Facial, Cardiovascular, and Neuropsychiatric Features.

Williams syndrome is caused by a microdeletion at 7q11.23 and is characterized by a distinctive face, cardiovascular disease, and intellectual disability with a specific cognitive and behavioral profile. This study aims to evaluate the clinical features and obtain important information that can guide early diagnoses and correct follow-up. The study included 78 patients whose diagnoses were confirmed by fluorescent in situ hybridization. Facial features, anthropometric measurements, and neurocognitive, endocrine, and urinary system evaluations were obtained from the medical records, and photographs of the patients were evaluated retrospectively. The most common complaints at admission were cardiovascular disease and atypical face. The mean age at admission was 39 ± 4.8 months. The mean age of patients presenting with atypical face was 41 ± 5.6 months, while it was 11 ± 3.1 months in patients presenting with cardiovascular disease. Short nose/bulbous nasal type with anteverted nares and periorbital fullness, which are diagnostic facial features, were present in all patients in the infantile/ early childhood period. 80% of the patients had cardiovascular disease; supravalvular aortic stenosis (53.8%) and peripheral pulmonary artery stenosis (41%) were the most common cardiac anomalies.Intel lectu al/de velop menta l disability was present in 75.6% of the patients. Behavioral disorders including autism spectrum disorder and attention deficit hyperactivity disorder were detected in 50% of our patients. Hypersensitivity to loud and/or sudden sounds was present in all patients. We highlighted that recognition of facial findings is important for early diagnosis, especially in patients without cardiovascular disease. The frequency of cardiovascular, endocrinological, renal anomalies, and intellectual disab ility /deve lopme ntal delay was described that provide valuable information in the follow-up of patients.

Analysis of risk factors associated with extracorporeal membrane oxygenation after surgical repair of peripheral pulmonary artery stenoses

ObjectiveAcute lung injury is a known complication of pulmonary artery reconstruction for peripheral pulmonary artery stenosis. Severe cases may require support with extracorporeal membrane oxygenation. The purpose of this study was to evaluate the characteristics of patients requiring extracorporeal membrane oxygenation after pulmonary artery reconstruction. MethodsThis was a retrospective study of 150 patients who underwent surgical repair of peripheral pulmonary artery stenosis at our institution from 2002 to 2022. Underlying diagnoses included Williams syndrome (n = 44), Alagille syndrome (n = 43), elastin arteriopathy (n = 21), tetralogy of Fallot (n = 21), and other (n = 21). Characteristics of patients who required extracorporeal membrane oxygenation were compared with those who did not require extracorporeal membrane oxygenation. ResultsEleven of the 150 patients undergoing pulmonary artery reconstruction (7.3%) required postoperative extracorporeal membrane oxygenation support (10 for acute lung injury and 1 for cardiac insufficiency). Four patients receiving extracorporeal membrane oxygenation had Williams syndrome, 3 patients had Alagille, and 4 patients had tetralogy of Fallot. Patients requiring extracorporeal membrane oxygenation had a higher preoperative right ventricle to aortic peak systolic pressure ratios (mean 1.14 vs 0.95), greater number of pulmonary artery ostial interventions (median, 23 vs 17), and longer duration of cardiopulmonary bypass (median, 597 vs 400 minutes). There were 3 in-hospital deaths (2.0%), 2 of whom required postoperative extracorporeal membrane oxygenation support. ConclusionsThe data demonstrate multiple differences between patients who did and did not require extracorporeal membrane oxygenation after surgical repair of peripheral pulmonary artery stenosis. These results suggest that the preoperative extent of disease may predispose to the development of acute lung injury requiring extracorporeal membrane oxygenation support.

Impact of liver dysfunction on outcomes in children with Alagille syndrome undergoing congenital heart surgery.

Children with Alagille syndrome often have complex forms of congenital heart defects with the majority having peripheral pulmonary artery stenosis (PPAS) and pulmonary valve atresia (PA) or stenosis (PS). Children with Alagille syndrome also have variable amounts of liver dysfunction. The purpose of this study was to evaluate the impact of liver dysfunction on outcomes in children with Alagille syndrome undergoing congenital heart surgery. This was a retrospective review of 69 patients with Alagille syndrome who underwent congenital heart surgery at our institution. The underlying diagnoses included PPAS (n=29), tetralogy of Fallot with PPAS (n=14), tetralogy with PA (n=3), PA with ventricular septal defect and major aortopulmonary collateral arteries (n=21), and one each with D-transposition and supravalvar aortic stenosis. The median age at surgery was 16 months (range 0-228 months). Procedures performed included PPAS repair (n=43), tetralogy with PA repair (n=3), unifocalization procedures (n=21), and other (n=2). Forty-two (61%) patients had mild or no liver dysfunction, while 26 (38%) had moderate or severe liver dysfunction. Median cardiopulmonary bypass time was 345 minutes (341with liver dysfunction, 345 without liver dysfunction). There were a total of 8 operative (12%) deaths and 3 late (4%) deaths. Six operative and two late deaths occurred in patients with liver dysfunction (combined 30.7%) versus two operative and one late death (combined 7.1%) for patients without liver dysfunction (p < 0.05). These results suggest that liver dysfunction has a profound impact on survival in children with Alagille syndrome undergoing congenital heart surgery.

Alagille Syndrome and Repeat Oxygenator Failure during Cardiopulmonary Bypass: A Word of Caution

Alagille syndrome is an autosomal dominant disorder that is caused by heterozygous mutation of JAG1 or NOTCH2 gene that impacts several multisystem organs including but may not be limited to the liver, heart, musculoskeletal, skin, and the eyes. The most common congenital heart defect associated with Alagille syndrome is multilevel right ventricular outflow tract obstruction with multiple central and peripheral branch pulmonary arterial stenoses occurring in up to two-thirds of these patients. We report two cases of Alagille syndrome who underwent extensive pulmonary arterial branch rehabilitation and experienced unusual oxygenator failure during cardiopulmonary bypass (CPB). We present lessons learned from these two cases and the changes that we implemented in our practice that facilitated smooth conduct of CPB in other cases that we performed subsequently.

Balloon Pulmonary Angioplasty for Takayasu Arteritis and Peripheral Pulmonary Artery Stenosis Mimicking Chronic Thromboembolic Pulmonary Hypertension.

Balloon pulmonary angioplasty (BPA) has been reported to be effective and safe to an acceptable level in patients with distal-type, inoperable chronic thromboembolic pulmonary hypertension (CTEPH), resulting in improved long-term survival. However, evidenced treatment options and strategy including medical therapy of antithrombotic therapy, glucocorticoids, immunosuppressants, and pulmonary hypertension (PH)-specific therapies are scarce in patients with significant PH and right heart failure associated with Takayasu arteritis and peripheral pulmonary artery stenosis, both of which mimic CTEPH. Moreover, there has been still concern on safety and lack of established methodology in performing BPA for these conditions. In this report, we would like to review recent publications including several case reports and discuss the efficacy, safety, and suitable methods of BPA in this population.

末梢型肺動脈狭窄症の遺伝的背景

末梢型肺動脈狭窄症の遺伝的背景

Pulmonary arterial angioplasty in peripheral pulmonary arterial stenosis in RNF213 vasculopathy: effective but high-risk treatment with reperfusion injury

Abstract Background p.Arg4810Lys variant of the ring finger protein 213 (RNF213) vasculopathy is a nonsyndromatic vasculopathy involving multisystemic organs including pulmonary arteries. Peripheral pulmonary arterial stenosis (PPAS) with diffuse stenosis and beaded appearance is a unique feature of this disease and no treatment option has been tried before. Methods We performed BPA for PPAS in RNF213 patients (n=7). Severity of pulmonary hypertension was assessed by echocardiography and right heart catheterization at the baseline. Several clinical and hemodynamic parameters were followed up after each BPA sessions. Results All of the patients had dyspnea on exertion. Right ventricular dysfunction was observed in six patients and NT-proBNP was elevated (949.2±1148.1 pg/mL). Baseline echocardiography showed severe pulmonary hypertension (70.1±19.2 mmHg). Pulmonary arterial ballooning was performed to all patients, but stenting (n=6) and cutting balloon (n=1) was necessary due to elastic recoil. Improvement of clinical and hemodynamic parameters was achieved in six patients after 5.3 sessions of BPA in average. Reperfusion edema was seen in four patients, eventually leading to death in one patient. Conclusions Pulmonary arterial angioplasty, when coupled with stenting, is an effective treatment for PPAS with RNF213 vasculopathy. Although reperfusion injury was common and fatal in a few cases, it is the only modality to improve the patient's symptom and hemodynamics till now. Careful selection of the target population should be preceded to perform the intervention. Funding Acknowledgement Type of funding sources: None.