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.

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.

Stent interventions for pulmonary artery stenosis improve bi-ventricular flow efficiency in a swine model.

BACKGROUND: Branch pulmonary artery (PA) stenosis (PAS) commonly occurs in patients with congenital heart disease (CHD). Prior studies have documented technical success and clinical outcomes of PA stent interventions for PAS but the impact of PA stent interventions on ventricular function is unknown. The objective of this study was to utilize 4D flow cardiovascular magnetic resonance (CMR) to better understand the impact of PAS and PA stenting on ventricular contraction and ventricular flow in a swine model of unilateral branch PA stenosis. METHODS: 18 swine (4 sham, 4 untreated left PAS, 10 PAS stent intervention) underwent right heart catheterization and CMR at 20 weeks age (55 kg). CMR included ventricular strain analysis and 4D flow CMR. RESULTS: 4D flow CMR measured inefficient right ventricular (RV) and left ventricular (LV) flow patterns in the PAS group (RV non-dimensional (n.d.) vorticity: sham 82 ± 47, PAS 120 ± 47; LV n.d. vorticity: sham 57 ± 5, PAS 78 ± 15 p < 0.01) despite the PAS group having normal heart rate, ejection fraction and end-diastolic volume. The intervention group demonstrated increased ejection fraction that resulted in more efficient ventricular flow compared to untreated PAS (RV n.d. vorticity: 59 ± 12 p < 0.01; LV n.d. vorticity: 41 ± 7 p < 0.001). CONCLUSION: These results describe previously unknown consequences of PAS on ventricular function in an animal model of unilateral PA stenosis and show that PA stent interventions improve ventricular flow efficiency. This study also highlights the sensitivity of 4D flow CMR biomarkers to detect earlier ventricular dysfunction assisting in identification of patients who may benefit from PAS interventions.

Autologous skeletal myoblast patch implantation prevents the deterioration of myocardial ischemia and right heart dysfunction in a pressure-overloaded right heart porcine model.

Right ventricular dysfunction is a predictor for worse outcomes in patients with congenital heart disease. Myocardial ischemia is primarily associated with right ventricular dysfunction in patients with congenital heart disease and may be a therapeutic target for right ventricular dysfunction. Previously, autologous skeletal myoblast patch therapy showed an angiogenic effect for left ventricular dysfunction through cytokine paracrine effects; however, its efficacy in right ventricular dysfunction has not been evaluated. Thus, this study aimed to evaluate the angiogenic effect of autologous skeletal myoblast patch therapy and amelioration of metabolic and functional dysfunction, in a pressure-overloaded right heart porcine model. Pulmonary artery stenosis was induced by a vascular occluder in minipigs; after two months, autologous skeletal myoblast patch implantation on the right ventricular free wall was performed (n = 6). The control minipigs underwent a sham operation (n = 6). The autologous skeletal myoblast patch therapy alleviated right ventricular dilatation and ameliorated right ventricular systolic and diastolic dysfunction. 11C-acetate kinetic analysis using positron emission tomography showed improvement in myocardial oxidative metabolism and myocardial flow reserve after cell patch implantation. On histopathology, a higher capillary density and vascular maturity with reduction of myocardial ischemia were observed after patch implantation. Furthermore, analysis of mRNA expression revealed that the angiogenic markers were upregulated, and ischemic markers were downregulated after patch implantation. Thus, autologous skeletal myoblast patch therapy ameliorated metabolic and functional dysfunction in a pressure-overloaded right heart porcine model, by alleviating myocardial ischemia through angiogenesis.

Transcatheter Intervention for Congenital Defects Involving the Great Vessels: JACC Review Topic of the Week.

Since the development of balloon angioplasty and balloon-expandable endovascular stent technology in the 1970s and 1980s, percutaneous transcatheter intervention has emerged as a mainstay of therapy for congenital heart disease (CHD) lesions throughout the systemic and pulmonary vascular beds. Congenital lesions of the great vessels, including the aorta, pulmonary arteries, and patent ductus arteriosus, are each amenable to transcatheter intervention throughout the lifespan, from neonate to adult. In many cases, on-label devices now exist to facilitate these therapies. In this review, we seek to describe the contemporary approach to and outcomes from transcatheter management of major CHD lesions of the great vessels, with a focus on coarctation of the aorta, single- or multiple-branch pulmonary artery stenoses, and persistent patent ductus arteriosus. We further comment on the future of transcatheter therapies for these CHD lesions.

Treatment approach to unilateral branch pulmonary artery stenosis.

Unilateral proximal pulmonary artery stenosis is often seen in the setting of postoperative congenital heart disease. Accurate assessment of the hemodynamic significance of such a lesion is important so as to determine "When to intervene?" A thorough evaluation should include symptom assessment, anatomical assessment through detailed imaging, functional assessment using differential pulmonary blood flow measurement and cardiopulmonary exercise testing. Symptoms of exertional dyspnea or intolerance, decreased pulmonary blood flow to stenosed lung, and abnormal exertional performance would be factors to pursue therapy in the setting of significant anatomical narrowing. Safe and effective therapy can be offered through transcatheter or surgical techniques and has been shown to improve exertional performance.

Comparison of pulmonary artery dimensions in swine obtained from catheter angiography, multi-slice computed tomography, 3D-rotational angiography and phase-contrast magnetic resonance angiography.

Accurate pulmonary artery (PA) imaging is necessary for management of patients with complex congenital heart disease (CHD). The ability of newer imaging modalities such as 3D rotational angiography (3DRA) or phase-contrast magnetic resonance angiography (PC-MRA) to measure PA diameters has not been compared to established angiography techniques. Measurements of PA diameters (including PA stenosis and PA stents) from 3DRA and non-contrast-enhanced PC-MRA were compared to 2D catheter angiography (CA) and multi-slice computed tomography (MSCT) in a swine CHD model (n = 18). For all PA segments 3DRA had excellent agreement with CA and MSCT (ICC = 0.94[0.91-0.95] and 0.92[0.89-0.94]). 3DRA PA stenosis measures were similar to CA and MSCT and 3DRA was on average within 5% of 10.8 ± 1.3 mm PA stent diameters from CA and MSCT. For compliant PA segments, 3DRA was on average 3-12% less than CA (p < 0.05) and MSCT (p < 0.01) for 6-14 mm vessels. PC-MRA could not reliably visualize stents and distal PA vessels and only identified 34% of all assigned measurement sites. For measured PA segments, PC-MRA had good agreement to CA and MSCT (ICC = 0.87[0.77-0.92] and 0.83[0.72-0.90]) but PC-MRA overestimated stenosis diameters and underestimated compliant PA diameters. Excellent CA-MSCT PA diameter agreement (ICC = 0.95[0.93-0.96]) confirmed previous data in CHD patients. There was little bias in PA measurements between 3DRA, CA and MSCT in stenotic and stented PAs but 3DRA underestimates measurements of compliant PA regions. Accurate PC-MRA imaging was limited to unstented proximal PA anatomy.

Long-term evolution of stents implanted in branch pulmonary arteries.

BACKGROUND: Branch pulmonary artery stenosis complicates the management of congenital heart diseases. Surgical branch pulmonary artery angioplasty is associated with a high reintervention rate. As an alternative, percutaneous or intraoperative branch pulmonary artery stents have been implanted to improve efficiency, but long-term evaluations are limited. AIM: To describe the long-term evolution of branch pulmonary artery stents. METHODS: We conducted a retrospective cohort study at Tours University Hospital. All stents implanted by surgery or catheterization in branch pulmonary arteries with a minimum follow-up of 12 months and at least one catheterization control were included. The primary endpoint combined cardiovascular mortality, surgical or percutaneous reintervention for stent complication or new stent implantation. RESULTS: Between 2007 and 2017, 76 stents in 51 patients were included (62 stents implanted by surgery, 14 by catheterization). At implantation, the patients' mean age and weight were 4.7years (interquartile range 4.2years) and 17.3kg (interquartile range 11.0kg), respectively. Mean branch pulmonary artery minimum diameter was 4.1±2.1mm (mean Z-score-4.9±2.9), and mean initial stent diameter was 9.1±3.1mm. During a follow-up of 5.3years (range 0-11.2 years), freedom from primary endpoint was 86.8% (95% confidence interval 79.6-94.8%) at 1 year, 71.5% (95% confidence interval 61.9-82.7%) at 5years and 69.6% (95% confidence interval 59.6-81.2%) at 10 years. We did not identify any factors associated with major adverse cardiovascular events. Among stents without major adverse cardiovascular events, the mean branch pulmonary artery diameter Z-score at last evaluation had increased by +4.8±3.2 compared with the initial diameter (P<0.001). After stent implantation, a median of 2 re-expansions were performed for each stent (range 0-7). CONCLUSIONS: Stent implantation should offer a good long-term solution for branch pulmonary artery stenosis, although iterative re-expansions are required.

Pulmonary artery and lung parenchymal growth following early versus delayed stent interventions in a swine pulmonary artery stenosis model.

OBJECTIVES: Compare lung parenchymal and pulmonary artery (PA) growth and hemodynamics following early and delayed PA stent interventions for treatment of unilateral branch PA stenosis (PAS) in swine. BACKGROUND: How the pulmonary circulation remodels in response to different durations of hypoperfusion and how much growth and function can be recovered with catheter directed interventions at differing time periods of lung development is not understood. METHODS: A total of 18 swine were assigned to four groups: Sham (n = 4), untreated left PAS (LPAS) (n = 4), early intervention (EI) (n = 5), and delayed intervention (DI) (n = 5). EI had left pulmonary artery (LPA) stenting at 5 weeks (6 kg) with redilation at 10 weeks. DI had stenting at 10 weeks. All underwent right heart catheterization, computed tomography, magnetic resonance imaging, and histology at 20 weeks (55 kg). RESULTS: EI decreased the extent of histologic changes in the left lung as DI had marked alveolar septal and bronchovascular abnormalities (p = .05 and p < .05 vs. sham) that were less prevalent in EI. EI also increased left lung volumes and alveolar counts compared to DI. EI and DI equally restored LPA pulsatility, R heart pressures, and distal LPA growth. EI and DI improved, but did not normalize LPA stenosis diameter (LPA/DAo ratio: Sham 1.27 ± 0.11 mm/mm, DI 0.88 ± 0.10 mm/mm, EI 1.01 ± 0.09 mm/mm) and pulmonary blood flow distributions (LPA-flow%: Sham 52 ± 5%, LPAS 7 ± 2%, DI 44 ± 3%, EI 40 ± 2%). CONCLUSION: In this surgically created PAS model, EI was associated with improved lung parenchymal development compared to DI. Longer durations of L lung hypoperfusion did not detrimentally affect PA growth and R heart hemodynamics. Functional and anatomical discrepancies persist despite successful stent interventions that warrant additional investigation.

First in man study of a new semi-open cell design Zephyr cobalt-chromium stent in large vessels and conduits.

OBJECTIVES: We present a first-in-man clinical use of a new hybrid design stent in stenosed large vessels. Its unique C and S polylinks prevent foreshortening without compromising its strength. Its thin profile permits use of smaller introducer sheaths. BACKGROUND: Stent angioplasty is widely employed in large vessel and conduit stenosis. These procedures are associated with difficulties due to large stent profiles, stent fractures, foreshortening and recoil. Cobalt chromium stents have high tensile strengths compared to stainless steel stents. METHODS: A retrospective analysis of feasibility and safety of a new Cobalt chromium stent in large vessels namely aorta, pulmonary arteries and outflow conduits was done from two institutions. Demographic patient details, procedural results, complications and medium term follow-up were analyzed. Stent recoil, foreshortening, fractures were assessed. RESULTS: Twenty patients including three with aortic coarctations, seven with stenosed conduits and 10 with pulmonary artery stenosis underwent stent angioplasty using 23 stents. Three stents were deployed to expand further a previously implanted stent. Procedure was successful in all patients, lumen increased by 150-300%, gradients reduced in all patients. There was no stent recoil, foreshortening or fractures. There were no complications. At a follow up of 3-27 months, there were no stent related complications and the gradients remained stable. CONCLUSIONS: The new Zephyr stent was useful in a wide variety of stenotic lesions involving large vessels including those that were previously stented. Lack of stent recoil and foreshortening seems to be an advantage for this new stent that needs validation in larger multicenter studies.

Utility of the Medtronic microvascular plug™ as a transcatheter implantable and explantable pulmonary artery flow restrictor in a swine model.

BACKGROUND: A surgical pulmonary artery band (PAB) is used to control excessive pulmonary blood flow for certain congenital heart diseases. Previous attempts have been made to develop a transcatheter, implantable pulmonary flow restrictor (PFR) without great success. We modified a microvascular plug (MVP) to be used as a PFR. The objectives of this study were to demonstrate feasibility of transcatheter implantation and retrieval of the modified MVP as a PFR, and compare PA growth while using the PFR versus PAB. METHODS AND RESULTS: The PFR was implanted in eight newborn piglets in bilateral branch pulmonary arteries (PAs). Immediately post-PFR implantation, the right ventricular systolic pressure increased from a median of 20-51 mmHg. Transcatheter retrieval of PFR was 100% successful at 3, 6, and 9 weeks and 50% at 12-weeks post-implant. A left PAB was placed via thoracotomy in four other newborn piglets. Debanding was performed 6-weeks later via balloon angioplasty. On follow-up, the proximal left PA diameters in the PFR and the PAB groups were similar (median 8 vs. 7.1 mm; p = 0.11); albeit the surgical band sites required repeat balloon angioplasty secondary to recurrent stenosis. By histopathology, there was grade II vessel injury in two pigs immediately post-retrieval of PFR that healed by 12 weeks. CONCLUSIONS: Transcatheter implantation and retrieval of the MVP as a PFR is feasible. PA growth is comparable to surgical PAB, which is likely to require reinterventions. The use of the MVP as a PFR in humans has to be trialed before recommending its routine use.

Catheter based treatments for fibrosing mediastinitis.

Fibrosing mediastinitis is a rare, often debilitating and potentially lethal disease characterized by an exuberant fibroinflammatory response within the mediastinum. Patients typically present with insidious symptoms related to compression of adjacent structures including the esophagus, heart, airways, and cardiac vessels. Fibrosing mediastinitis is most often triggered by Histoplasmosis infection; however, antifungal and anti-inflammatory therapies are largely ineffective. While structural interventions aimed at alleviating obstruction can provide significant palliation, surgical interventions are challenging with high mortality and clinical experience with percutaneous interventions is limited. Here, we will review the presentation, natural history, and treatment of fibrosing mediastinitis, placing particular emphasis on catheter-based therapies.

Balloon Angioplasty and Stenting for Unilateral Branch Pulmonary Artery Stenosis Improve Exertional Performance.

OBJECTIVES: This study sought to determine whether pulmonary artery intervention in patients with unilateral proximal pulmonary artery stenosis (PAS) improves exercise capacity, abnormal ventilatory response to exercise, and symptoms. BACKGROUND: Stenosis of the branch pulmonary arteries results in pulmonary blood flow maldistribution (PBFM). The resulting ventilation-perfusion mismatch is associated with an increased ventilatory response to exercise and decreased exercise capacity. It is unclear if technical success in relieving branch PAS translates to clinical improvement in exercise capacity and ventilatory response. METHODS: Twenty patients with biventricular circulation and a minimum 10% PBFM who underwent transcatheter relief of PAS were enrolled in a multi-institutional prospective cohort study. Pre- and post-procedure assessment of the degree of PBFM, exercise capacity, ventilatory response to exercise, and subjective assessment of breathlessness were collected and analyzed. RESULTS: Technical success was achieved in all patients with significant angiographic improvement in minimal lumen diameter (p = 0.001) and peak gradient (p = 0.001). Median PBFM improved (19.5% [range 12.0% to 31.0%] before vs. 7.0% [range 0% to 33.0%] after; p = 0.003). Exercise capacity was low at baseline and improved significantly post-intervention; percent predicted peak oxygen consumption improved from 70% (range 45% to 96%) to 83% (range 47% to 121%) (p = 0.02). Percent predicted oxygen pulse improved (p = 0.02). Ventilatory response to exercise improved; ventilatory equivalent of carbon dioxide slope post-intervention decreased to 29.3 versus 32.5 pre-intervention (p = 0.01). Subjective assessment of dyspnea improved. Five patients with minimal improvement in PBFM also showed minimal improvement in exercise parameters. CONCLUSIONS: Successful relief of unilateral branch PAS results in significant improvements in exercise capacity, ventilatory efficiency, and symptoms.