Sarcoidosis-associated pulmonary hypertension due to pulmonary arteries stenosis - a case report.

BACKGROUND: Sarcoidosis-associated pulmonary hypertension (SAPH) is listed in Group 5 of the clinical classification of pulmonary hypertension, due to its complex and multifactorial pathophysiology. The most common cause of SAPH development is advanced lung fibrosis with the associated destruction of the vascular bed, and/or alveolar hypoxia. However, a substantial proportion of SAPH patients (up to 30%) do not have significant fibrosis on chest imaging. In such cases, the development of pulmonary hypertension may be due to the lesions directly affecting the pulmonary vasculature, such as granulomatous angiitis, pulmonary veno-occlusive disease, chronic thromboembolism or external compression of vessels by enlarged lymph nodes. Based on the case of a 69-year-old female who developed SAPH due to pulmonary arteries stenosis, diagnostic difficulties and therapeutic management are discussed. CASE PRESENTATION: The patient, non-smoking female, diagnosed with stage II sarcoidosis twelve years earlier, presented with progressive dyspnoea on exertion, dry cough, minor haemoptysis and increasing oedema of the lower limbs. Computed tomography pulmonary angiography (CTPA) showed complete occlusion of the right upper lobe artery and narrowing of the left lower lobe artery, with post-stenotic dilatation of the arteries of the basal segments. The vascular pathology was caused by adjacent, enlarged lymph nodes with calcifications and fibrotic tissue surrounding the vessels. Pulmonary artery thrombi were not found. The patient was treated with systemic corticosteroid therapy and subsequently with balloon pulmonary angioplasty. Partial improvement in clinical status and hemodynamic parameters has been achieved. CONCLUSIONS: An appropriate screening strategy is required for early detection of pulmonary hypertension in sarcoidosis patients. Once SAPH diagnosis is confirmed, it is crucial to determine the appropriate phenotype of pulmonary hypertension and provide the most effective treatment plan. Although determining SAPH phenotype is challenging, one should remember about the possibility of pulmonary arteries occlusion.

Results of the multicenter early feasibility study (EFS) of the Renata Minima stent as treatment for branch pulmonary artery stenosis and coarctation of aorta in infants.

BACKGROUND: Stent implantation has become standard of care in older children and adults for treatment of branch pulmonary artery stenosis (BPAS) and coarctation aorta (CoAo). There are no stents approved or available for infants that have the potential to be dilated to adult diameters. The Minima stent was designed to fulfill this unmet need. METHODS: Multicenter, prospective, nonrandomized early feasibility study evaluating safety and effectiveness of the Minima stent for treatment of BPAS and CoAo. Primary endpoints included: (1) successful deployment across lesion, (2) stenosis relief defined by an increase in angiographic diameter of >50% and (3) freedom from stent explant, embolization or migration at 30 days and 6 months. RESULTS: Between 2/2022 and 5/2022, 10 pts underwent Minima stent implantation with a median age and weight of 9 months (4-43 months) and 7.6 kg (5.1-16.9 kg). Procedural success and predefined stenosis relief was achieved in all cases (CoAo [n = 4], BPAS [n = 6]). Adverse events occurred in 3 pts: transient diminished lower extremity pulse (n = 2), distal stent on-balloon displacement successfully managed in the catheterization suite (n = 1). There were no deaths or major adverse events. All patients were free from stent explant and migration at 30 days and 6 months with no evidence for significant restenosis at latest follow-up. CONCLUSIONS: Implantation of the Renata Minima stent was safe and effective for the treatment of BPAS and CoAo in this small cohort of infants and young children during early follow-up. Based on these early results, an expanded study with longer follow-up is warranted.

The impact of unilateral pulmonary artery stenosis on right ventricular to pulmonary arterial coupling in patients with transposition of the great arteries.

BACKGROUND: Unilateral pulmonary artery (PA) stenosis is common in the transposition of the great arteries (TGA) after arterial switch operation (ASO) but the effects on the right ventricle (RV) remain unclear. AIMS: To assess the effects of unilateral PA stenosis on RV afterload and function in pediatric patients with TGA-ASO. METHODS: In this retrospective study, eight TGA patients with unilateral PA stenosis underwent heart catheterization and cardiac magnetic resonance (CMR) imaging. RV pressures, RV afterload (arterial elastance [Ea]), PA compliance, RV contractility (end-systolic elastance [Ees]), RV-to-PA (RV-PA) coupling (Ees/Ea), and RV diastolic stiffness (end-diastolic elastance [Eed]) were analyzed and compared to normal values from the literature. RESULTS: In all TGA patients (mean age 12 ± 3 years), RV afterload (Ea) and RV pressures were increased whereas PA compliance was reduced. RV contractility (Ees) was decreased resulting in RV-PA uncoupling. RV diastolic stiffness (Eed) was increased. CMR-derived RV volumes, mass, and ejection fraction were preserved. CONCLUSION: Unilateral PA stenosis results in an increased RV afterload in TGA patients after ASO. RV remodeling and function remain within normal limits when analyzed by CMR but RV pressure-volume loop analysis shows impaired RV diastolic stiffness and RV contractility leading to RV-PA uncoupling.

Adult-onset idiopathic peripheral pulmonary artery stenosis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Chronic inflammatory pulmonary artery lesion causing right pulmonary artery stenosis 15 years post Blalock-Taussig shunt ligation.

Discrete central endovascular pulmonary arterial lesions raise clinical concern for malignancy such as primary pulmonary artery sarcoma. We present a case of a female in her late teens who had an obstructive mid right pulmonary artery lesion found on follow-up imaging 15 years after Tetralogy of Fallot repair. The lesion was in the vicinity of a previously ligated Blalock-Taussig shunt and causing right PA stenosis with delayed perfusion to the right lung, and a flow-related distal left PA aneurysm. The lesion was excised and confirmed histologically to be inflammatory in nature. Intraoperative microbiology demonstrated growth of the Kytococcus species, and she was managed with 6 weeks of intravenous antibiotics, with a full recovery.

Numerical simulation of hemodynamics in patient-specific pulmonary artery stenosis.

BACKGROUND: The incidence rate of pulmonary artery stenosis is increasing year by year and its numerical simulation has become a key project of biomedical engineering. OBJECTIVE: The purpose of this work is to study the changes of hemodynamic parameters in patient-specific pulmonary artery stenosis. METHODS: A pulmonary artery stenosis model is established based on patient-specific computed tomography (CT) images. According to the actual anatomy of patient-specific pulmonary artery stenosis, the stenosis area is simulated using a porous medium to study its hemodynamic changes. The computational fluid dynamics (CFD) method is used to simulate the hemodynamic changes of pulmonary artery stenosis, and to explore the mechanical characteristics between blood flow and vessel wall. RESULTS: The results suggest that the blood pressures of arterial branches increase and the pressure drop at both ends of the stenosis is higher. There is a high flow rate and wall shear stress at the stenosis. CONCLUSION: This study shows that the hemodynamic model of pulmonary artery stenosis can be accurately reconstructed by achieving numerical simulation of the local stenosis through CT images, and this work has important implications for improving the confidence of clinical diagnosis and treatment of pulmonary artery diseases.

Comparison of long-term survival after endovascular treatment versus medical therapy in patients with Takayasu's arteritis and pulmonary artery stenosis.

OBJECTIVES: There is currently no unanimous consensus on the treatment of Takayasu's arteritis (TAK) involving the pulmonary artery, and there are very few related studies that compare the efficacies of drug-based therapy and revascularization. This study aimed to compare the long-term survival outcomes after endovascular treatment and medical therapy in TAK patients with pulmonary artery stenosis (PAS) and pulmonary hypertension (PH). METHODS: A total of 129 TAK patients with PAS and PH (women, 101; men, 28; mean age, 40.5 years) were retrospectively enrolled in this study. Data on clinical features, treatment regimens, and mortality, were collected. Patients were categorised into medical treatment (n=75) and percutaneous transluminal pulmonary angioplasty (PTPA; n=54: 52 with PTPA and 2 with stent implantation) groups. The primary endpoint was cardiac mortality. The median follow-up time was 54 (40.5, 58.5) months. RESULTS: There were no significant differences in sex, age, comorbidities, disease activity, World Health Organization (WHO) function classification, and 6-min walk distance (6MWD) between the two groups at baseline. Compared with the conservative treatment group, cardiac mortality, WHO functional class, and 6MWD were significantly improved in the PTPA group (p=0.031, p<0.001, and p=0.004, respectively). CONCLUSIONS: Under basic medicine, PTPA therapy improves the long-term survival of TAK patients with PAS and PH compared to medical treatment alone. PTPA may be a promising modality for the TAK patients with PAS and PH.

Long-Term Outcomes After Percutaneous Transluminal Pulmonary Angioplasty in Patients With Takayasu Arteritis and Pulmonary Hypertension.

Objective: To investigate the long-term efficacy of percutaneous transluminal pulmonary angioplasty (PTPA) in patients with Takayasu arteritis (TA) and pulmonary artery stenosis and pulmonary hypertension (PH). Methods: Data from 183 lesions from 79 surgeries performed on 32 patients with TA and PH were analyzed. Symptoms, laboratory investigation results, World Health Organization (WHO) functional class, 6-min walk distance (6 MWD), hemodynamic parameters, and prognosis were analyzed at baseline and follow-up. Results: The mean (± SD) age of the 32 patients (28 female, 4 male) was 42.8 ± 11.9 years, and the median follow-up was 49.5 months (interquartile range, 26-71 months). Compared with baseline, changes in total bilirubin, N-terminal pro-brain natriuretic peptide (NT-proBNP) level, 6 MWD, and WHO score functional class demonstrated significant differences (P<0.001). Echocardiography findings, right and left ventricular diameter, tricuspid annular plane systolic excursion, and estimated pulmonary artery systolic pressure were all improved (P=0.016, P<0.001, P<0.001, and P=0.005, respectively). Importantly, repeat right heart catheterization revealed that mean pulmonary artery pressure, pulmonary vascular resistance, and cardiac index also improved significantly at follow-up (P<0.001, P<0.001, and P=0.011, respectively). Pulmonary angiography revealed post-procedure restenosis in 64 (35.0%) lesions underwent PTPA within three to six months. Among three patients who underwent stent implantation, one experienced restenosis. Two patients died during the follow-up period, one from aggravation of right heart failure after lung infection, and the other in a traffic accident. Conclusions: Results of this study indicated that PTPA significantly improved clinical symptoms, exercise tolerance, and hemodynamic parameters in patients with TA pulmonary artery stenosis and PH. More importantly, reperfusion pulmonary edema significantly decreased, and no patient died of PTPA-related complications with guidance from the pressure wire.

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

Background Despite 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 Results Isolated 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. Conclusions In 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.

Two Siblings With Peripheral Pulmonary Arterial Stenosis: Pulmonary Angiography of Advanced and Early Stages.

Peripheral pulmonary arterial stenosis (PPAS) is known to cause pulmonary hypertension (PH). Although adult patients at advanced stage have been increasingly reported, there are few reports on clinical characteristics and pulmonary angiography (PAG) findings of early stage PPAS. We present two Japanese siblings with PPAS with homozygosity of RNF213 p.Arg4810Lys-one with advanced stage and the other with early stage. The latter case was an asymptomatic 37-year-old woman with mild PH. Notably, her PAG demonstrated nonthrombotic stenosis in the subsegmental branches of the pulmonary arteries with varying degrees of stenosis among lung segments. Taken together with a family history, genetic analysis, and cerebral angiography, the obtained images were considered as showing PPAS with early stage. This result is clinically informative to diagnose PPAS at an early stage and is also important to understand the pathogenesis of PPAS.

Echocardiographic Predictors of Ductal Tissue-Related Branch Pulmonary Artery Stenosis in Pulmonary Atresia.

Branch pulmonary artery (PA) stenosis due to ductus arteriosus (DA) tissue (DA-PS) contributes to the morbidity associated with pulmonary atresia (PAtr). We sought to identify preoperative echocardiographic features predictive of DA-PS. Patients consecutively encountered with PAtr and a DA-dependent pulmonary circulation at birth who underwent intervention in our program over a 5-year period were identified and records reviewed. Preoperative echocardiograms were reviewed to identify features that predicted postoperative DA-PS. Seventy patients with PAtr met inclusion criteria and 36 (51%) had DA-PS. At preoperative echocardiography, the proximal diameter of the PA ipsilateral to the DA was smaller in those with versus without DA-PS (Z-score - 4.8 ± 1.7 vs - 1.1 ± 1.7, respectively p < 0.001). PA origins could not be imaged on the same axial plane in 21/36 (58%) with versus 2/34 (6%) without DA-PS. Patients with DA-PS had an obtuse posterior angle of the PA bifurcation compared to those without (128 ± 17° and 87 ± 21°, p < 0.001), and a posterior angle of > 100° best predicted DA-PS with a sensitivity of 97% and specificity of 76%. An abnormal PA relationship and/or an obtuse posterior bifurcation angle had a sensitivity, specificity, positive and negative predictive value for DA-PS of 78%, 94%, 90% and 86%, respectively. Finally, DA insertion was into the ipsilateral PA in 26/36 (72%) of cases with DA-PS. A smaller proximal ipsilateral PA diameter, inability to image the PAs in the same plane, a posterior PA bifurcation angle of > 100°, and insertion of the DA in the ipsilateral PA demonstrated by echo are useful in identifying patients at risk for DA-PS.

A Personalized Pulmonary Circulation Model to Non-Invasively Calculate Fractional Flow Reserve for Artery Stenosis Detection.

OBJECTIVE: Fractional Flow Reserve (FFR) is regarded as a fundamental index to assess pulmonary artery stenosis. The application of FFR can increase the accuracy of detection of pulmonary artery stenosis. However, the invasive examination may carry a number of physiological risks for patients. Therefore, we propose a personalized pulmonary circulation model to non-invasively calculate FFR of pulmonary artery stenosis. METHODOLOGY: We have employed a personalized pulmonary circulation model to non-invasively calculate FFR. This model combines boundary condition estimation and 3D pulmonary artery morphology reconstruction for CFD simulation. Firstly, we obtain patient-specific boundary conditions by matching cardiac output and main pulmonary artery pressure. Secondly, the 3D pulmonary artery morphology is reconstructed by semi-automatic segmentation. The CFD simulation is performed to obtain the pressure distribution in the entire pulmonary artery. Finally, the FFR in pulmonary artery stenosis is calculated as the ratio of distal pressure and proximal pressure. RESULTS: To validate our model, we compare the simulated FFR with the measured FFR by pressure guide wires examination of 20 patients. The FFR simulated by our model shows a good agreement with the measured FFR by pressure guide wires examination ( r= 0.989, 0.001). CONCLUSION: Our proposed personalized pulmonary circulation model is shown to be capable of non-invasively calculating FFR with sufficient accuracy. SIGNIFICANCE: The FFR calculated by our personalized circulation model may effectively contribute to non-invasive detection of pulmonary artery stenosis and to a comprehensive evaluation of the entire pulmonary artery vascular tree.

Identification and characterization of a novel ELN mutation in congenital heart disease with pulmonary artery stenosis.

Congenital heart defects, one of the most common birth defects, affect approximately 1% of live birth globally and remain the leading cause of infant mortality in developed countries. Utilizing the pathogenicity score and inheritance mode from whole exome sequencing results, a heterozygous mutation (NM_001278939.1: c.1939G>T, p.Gly647Ter) in elastin (ELN) was identified among 6,440 variants in a female proband born with an atrial septal defect accompanied by pulmonary artery stenosis. Results of RT-PCR showed that the mutation (NM_001278939.1: c.1939G>T, p.Gly647Ter) did not affect the expression levels of ELN mRNA but increased protein level. The content of ELN truncate (functional component) was significantly lower in both the intracellular and extracellular compartments after mutation. These results indicate that the ELN mutation (NM_001278939.1: c.1939G>T, p.Gly647Ter) affected the protein truncate, which may be a functional component of ELN and play crucial roles for this pedigree. Here we report of an ELN heterozygous variant associated with congenital heart disease accompanied with pulmonary artery stenosis, which is less common. Based on our results, we speculate that this may be the main molecular mechanism underlying the mutation-led functional changes, and propose that the decrease of ELN protein level may cause this pedigree vascular abnormality, especially pulmonary artery stenosis, and reinforce the view that ELN insufficiency is the primary cause of these vascular lesions. This may be the main molecular mechanism underlying the mutation-led functional changes. Thus, systematic analysis not only enables us to better understand the etiology of this disease but also contributes to clinical and prenatal diagnosis.

Cutting balloon angioplasty on branch pulmonary artery stenosis in pediatric patients.

OBJECTIVES: To identify medium-term results following cutting balloon angioplasty (CBA) for branch pulmonary artery stenosis (PAS) and predictors of successful intervention. BACKGROUND: CBA has emerged as a successful alternative therapy for PAS resistant to conventional balloon angioplasty techniques but there is little information on medium and long-term outcomes. METHODS: This is a descriptive, single center, retrospective chart review of pediatric patients who underwent CBA for PAS at Arkansas Children's Hospital between May 2005 and December 2020. We reviewed demographics, procedural specifics, and 30-day complications. RESULTS: Forty-four patients underwent pulmonary artery CBA on 114 pulmonary artery segments through 126 catheterization cases, totaling 148 CBA events. Thirty-three individual pulmonary arteries underwent repeat intervention. Average minimal luminal diameter increase from pre-CBA to end of follow-up was 57% (CI, 38%-75%). Absence of Tetralogy of Fallot with pulmonary atresia and major aortopulmonary collateral arteries (TOF/PA/MAPCAs) and the absence of Alagille Syndrome, Williams Syndrome, or Arterial Tortuosity Syndrome (ATS) were associated with increased odds of sustained success by 70% (CI, 0.11-0.79) and 91% (CI, 0.02-0.56), respectively. Increasing the cutting balloon diameter-to-minimal luminal diameter ratio by 0.5 increased odds of successful intervention by 2.37-fold (CI, 1.7-3.3). Seven patients had 30-day complications including one death. CONCLUSIONS: In the longest follow-up to date of children and adolescents who underwent CBA for branch PAS, we found that there was moderate medium-term success. Additionally, absence of TOF/PA/MAPCAs, absence of Alagille Syndrome, Williams Syndrome, or ATS, and high cutting balloon diameter-to-minimal luminal diameter ratio are predictors of sustained results.