Peripheral Pulmonary Artery Stenosis Research Articles

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.

Surgical repair of peripheral pulmonary artery stenosis: A 2-decade experience with 145 patients

BackgroundPeripheral pulmonary artery stenosis (PPAS) is a relatively rare form of congenital heart disease often associated with Williams syndrome, Alagille syndrome, and elastin arteriopathy. This disease is characterized by stenoses at nearly all lobar and segmental ostia and results in systemic-level right ventricular pressures. The current study summarizes our experience with the surgical treatment of PPAS. MethodsThis was a retrospective review of 145 patients who underwent surgical repair of PPAS. This included 43 patients with Williams syndrome, 39 with Alagille syndrome, and 21 with elastin arteriopathy. Other diagnoses include tetralogy of Fallot with PPAS (n = 21), truncus arteriosus (n = 5), transposition (n = 3), double-outlet right ventricle (n = 2), arterial tortuosity syndrome (n = 3), and other (n = 8). ResultsThe median preoperative right ventricle to aortic peak systolic pressure ratio was 1.01 (range, 0.50-1.60) which was reduced to 0.30 (range, 0.17-0.60) postoperatively. The median number of ostial repairs was 17 (range, 6-34) and median duration of cardiopulmonary bypass was 398 minutes (range, 92-844). There were 3 in-hospital deaths (2.1%). The median duration of follow-up was 26 months (range, 1-220) with 4 late deaths (2.9%). Eighty-two patients have subsequently undergone catheterization and 74 had a pressure ratio <0.50. ConclusionsThe surgical treatment of PPAS resulted in a 70% reduction in right ventricular pressures. At 3 years, freedom from death was 94% and 90% of those evaluated maintained low pressures. These results suggest that the surgical treatment of PPAS is highly effective in most patients.

Surgical Repair of Supravalvar Aortic Stenosis in Association With Transverse and Proximal Descending Aortic Abnormalities.

Supravalvar aortic stenosis (SVAS) may be an isolated defect of the proximal ascending aorta. However, more severe cases have extension of the arteriopathy into the transverse and proximal descending aorta. The purpose of this study was to review our experience with SVAS with and without aortic arch arteriopathy. This was a retrospective review of 58 patients who underwent surgical repair of SVAS. The median age at repair was 18 months. A total of 37 patients had Williams syndrome. A total of 31 (53%) patients had associated peripheral pulmonary artery stenosis and 23 (39%) had coronary artery ostial stenosis (CAOS). A total of 37 of 58 (64%) patients had surgical repair of SVAS without the need for arch intervention while 21 (36%) patients had repair of the distal aortic arch. There were 3 (5.2%) operative deaths, 2 of whom had aortic arch involvement and one without arch involvement. There were 2 deaths after discharge from the hospital. Patients who needed arch surgery were more likely to have severe arch gradients compared to those without arch involvement (71% vs 30%, P < .05), were more likely to undergo concomitant procedures for peripheral pulmonary artery stenosis or CAOS (90% vs 62%, P < .05), and to have Williams syndrome (86% vs 51%, P < .05). More than one-third of patients who had SVAS repair at our institution had procedures directed at the transverse or proximal descending aorta. Patients with arch involvement had more severe arch obstruction, required more concomitant procedures, and were more likely to have Williams syndrome.

RNF213-Associated Vascular Disease: A Concept Unifying Various Vasculopathies.

The ring finger protein 213 gene (RNF213) encodes a 590 kDa protein that is thought to be involved in angiogenesis. This gene was first recognized as a vasculopathy-susceptibility locus through genome-wide association studies undertaken in a Japanese population, demonstrating that heterozygotes for RNF213 p.Arg4810Lys (c.14429G>A, rs112735431) had a greatly increased risk of moyamoya disease. The association of RNF213 p.Arg4810Lys as a susceptibility variant of moyamoya disease was reproduced in Korean and Chinese individuals and, later, in Caucasians. Variants of the RNF213 gene have been linked to a number of vascular diseases such as moyamoya disease, intracranial major artery stenosis, pulmonary arterial hypertension, and peripheral pulmonary artery stenosis, and have also been associated with co-occurrent diseases and vascular disease in different organs. Based on the findings that we have reported to date, our paper proposes a new concept of “RNF213-associated vascular disease” to unify these conditions with the aim of capturing patients with multiple diseases but with a common genetic background. This concept will be highly desirable for clarifying all of the diseases in the RNF213-associated vascular disease category by means of global epidemiological investigations because of the possibility of such diseases appearing asymptomatically in some patients.

Virtual Transcatheter Interventions for Peripheral Pulmonary Artery Stenosis in Williams and Alagille Syndromes.

BackgroundDespite favorable outcomes of surgical pulmonary artery (PA) reconstruction, isolated proximal stenting of the central PAs is common clinical practice for patients with peripheral PA stenosis in association with Williams and Alagille syndromes. Given the technical challenges of PA reconstruction and the morbidities associated with transcatheter interventions, the hemodynamic consequences of all treatment strategies must be rigorously assessed. Our study aims to model, assess, and predict hemodynamic outcomes of transcatheter interventions in these patients.Methods and ResultsIsolated proximal and “extensive” interventions (stenting and/or balloon angioplasty of proximal and lobar vessels) were performed in silico on 6 patient‐specific PA models. Autoregulatory adaptation of the cardiac output and downstream arterial resistance was modeled in response to intervention‐induced hemodynamic perturbations. Postintervention computational fluid dynamics predictions were validated in 2 stented patients and quantitatively assessed in 4 surgical patients. Our computational methods accurately predicted postinterventional PA pressures, the primary indicators of success for treatment of peripheral PA stenosis. Proximal and extensive treatment achieved median reductions of 14% and 40% in main PA systolic pressure, 27% and 56% in pulmonary vascular resistance, and 10% and 45% in right ventricular stroke work, respectively.ConclusionsIn patients with Williams and Alagille syndromes, extensive transcatheter intervention is required to sufficiently reduce PA pressures and right ventricular stroke work. Transcatheter therapy was shown to be ineffective for long‐segment stenosis and pales hemodynamically in comparison with published outcomes of surgical reconstruction. Regardless of the chosen strategy, a virtual treatment planning platform could identify lesions most critical for optimizing right ventricular afterload.