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.

Lumped-Parameter Circuit Platform for Simulating Typical Cases of Pulmonary Hypertensions from Point of Hemodynamics.

Pulmonary hypertension (PH) presents unusual hemodynamic states characterized by abnormal high blood pressure in pulmonary artery. The objective of this study is to simulate how the hemodynamics develops in typical PH cases without treatment. A lumped-parameter circuit platform of human circulation system is set up to simulate hemodynamic abnormalities of PH in different etiologies and pathogenesis. Four typical cases are considered, which are distal pulmonary artery stenosis, left ventricular diastolic dysfunction, ventricular septal defect, and mitral stenosis. The authors propose regulation laws for chambers and vessels to adapt the abnormal hemodynamic conditions for each PH case. The occurrence and development of each PH case are simulated over time using the lumped-parameter circuit platform. The blood pressure, blood flow, pressure-volume relations for chambers and vessels are numerically calculated for each case of PH progression. The model results could be a quite helpful to understand the hemodynamic mechanism of typical PHs. Graphical Abstract.

Pneumonectomy is necessary following delayed detection of pulmonary artery compromise.

It has been previously suggested that lung tissue remains viable without blood supply from the pulmonary artery (PA). However, our experience demonstrates otherwise. We present 2 cases of accidental left lower lobe PA occlusion during upper lobectomy causing ischaemic changes to the remaining lung tissue. Both patients became septic secondary to necrosis of infarcted lung and required completion pneumonectomy. Development of collateral circulation to bypass the occluded PA may occur but is often insufficient to support the affected lung tissue. Unless the patient is medically unfit, resection of the ischaemic lung should be undertaken.

Pulmonary vascular involvement of IgG4-related disease: Case series with a PRISMA-compliant systemic review.

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized, immune-mediated chronic fibrotic inflammation that can involve almost all organs, causing tumefaction and dysfunction. Its presence in pulmonary circulation is underestimated and has not yet been investigated. OBJECTIVES: We describe a representative IgG4-RD patient with pulmonary artery stenosis and pulmonary embolism, leading to reversible pulmonary hypertension. Literature review of IgG4-RD with pulmonary circulation involvement was conducted. DATA SOURCES: References for this review were identified through searches via PubMed, EBSCO, and Web of Science for published articles before November 2016. RESULTS: There were 15 published cases of IgG4-RD with pulmonary vascular involvement, 3 with pulmonary arteritis, 2 with pulmonary artery aneurysm, 3 with pulmonary artery stenosis, 1 with obliterative phlebitis, and 1 with pulmonary embolism. Possible immunity and inflammation mechanisms were summarized. CONCLUSIONS: IgG4-RD with pulmonary vascular involvement is rare. Echocardiogram and contrast-enhanced chest CT are helpful to screen the disease. Clinical manifestations were found from asymptomatic to dyspnea or even syncope. And nearly all cases had more than 1 organ affected, with significantly increased serum IgG4 levels. PET/CT aided in identifying affected organs and determining candidate biopsy sites. More awareness is urged to evaluate the pulmonary vascular manifestations of this disease.

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.

Successful living donor liver transplantation after stent implantation in a patient with Alagille syndrome and severe bilateral pulmonary artery stenosis.

Severe pulmonary hypertension is a contraindication for liver transplantation owing to high mortality. However, decision-making regarding the treatment approach for patients with bilateral peripheral pulmonary artery stenosis, typically complicated by elevated main pulmonary artery and right ventricle pressures, can be challenging. Here, we report successful living donor liver transplantation after bilateral pulmonary artery stent implantation in a patient with Alagille syndrome, severe bilateral peripheral pulmonary artery stenosis, and extremely high main pulmonary artery and right ventricle pressures.

Pulmonary Perfusion Using Intrabronchial Capnography in Pulmonary Artery Stenosis.

Stenting at the flow-limiting segment can improve the ventilation-perfusion ratio in patients with central airway stenosis. However, there is no quantitative examination for assessing the perfusion status during interventional bronchoscopy. Intrabronchial capnography can estimate regional gas exchange by measuring carbon dioxide concentration. We herein report a case of bilateral bronchial stenosis where stenting was able to improve ventilation-perfusion ratio using intrabronchial capnography. A 44-year-old man was admitted to our institution with orthopnea. Chest computed tomography showed an extrinsic compression at the bilateral main bronchus and right pulmonary artery due to a mediastinal mass. After introduction of general anesthesia, arterial oxygen tension suddenly decreased in the supine position. After initial stenting, an increase was seen in ventilation at the right lung; however, a ventilation-perfusion mismatch occurred due to an increase in dead-space ventilation at the right pulmonary artery stenosis. Intrabronchial capnography was an effective modality to confirm the regional perfusion status during interventional bronchoscopy in real time.

Vessel Stretching Is a Cause of Lumen Enlargement Immediately After Balloon Pulmonary Angioplasty: Intravascular Ultrasound Analysis in Patients With Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Balloon pulmonary angioplasty (BPA) has become an alternative therapy for patients with chronic thromboembolic pulmonary hypertension who are ineligible for pulmonary endarterectomy. We retrospectively investigated intravascular ultrasound measurements to elucidate how the lumen enlarges immediately after BPA. METHODS AND RESULTS: A total of 326 lesions in 71 patients with chronic thromboembolic pulmonary hypertension were analyzed. The cross-sectional areas (CSAs) of the external elastic membrane and lumen measured by intravascular ultrasound before and after BPA were assessed for each lesion type (type A, ring-like stenosis lesions; type B, web lesions; type C, subtotal occlusion lesions). Comparing the lesion types, the proportion of the area occupied by fibrous tissue was smallest in the type A lesions and largest in the type C lesions. The mean lesion lumen CSA was increased after BPA because of an increase in external elastic membrane CSA (from 23.2±12.9 to 27.2±14.3 mm2; P<0.001) with a slight decrease in fibrous tissue plus media CSA (from 17.7±11.7 to 17.3±11.1 mm2; P<0.001). The change in lumen CSA correlated strongly with the change in external elastic membrane CSA (r2=0.762; P<0.001). CONCLUSIONS: Lumen enlargement immediately after BPA was obtained by the overall vessel expansion induced by a stretch of the arterial wall. In addition, the amount of fibrous tissue depended on each lesion type. Thus, it might be beneficial to change the balloon size to correspond with the lesion type.

The Structure of a Chronic Total Occlusion and Its Safe Treatment in a Patient with Chronic Thromboembolic Pulmonary Hypertension.

A pouching defect, which is a type of angiographic classification in chronic thromboembolic pulmonary hypertension (CTEPH), is equivalent to a chronic total occlusion (CTO). Thus far, treating CTO involves high risk of the lung bleeding and is difficult because the structure and treating strategy have not been clarified, yet treating it has great potential to improve hemodynamic status and ventilation perfusion mismatch. Here, we describe a case of successfully treated the CTO. In this case, we treated it safely by two balloon pulmonary angiography (BPA) sessions. In first session, the surface of the CTO was partially broken by the catheter. However, the distal vessels of it were not observed. Pulmonary angiogram was performed 4 months later, the distal vessels of CTO were observed. This lesion was no longer the CTO, we performed BPA safely and pulmonary arterial pressure was improved dramatically. Furthermore, pulmonary angiogram revealed the surface of the CTO has a cap which is comprised of cross-aggregation of organized thrombi. Partial breakage of the cap is a key to recanalization of the CTO, even if the distal vessels were not seen in same BPA session.

Lung Abscess as Delayed Manifestation of Pulmonary Arterial Narrowing After Sleeve Resection.

A patient who had undergone right upper bilobectomy because of a carcinoid experienced lung abscesses 17 months after operation. After recurrences, despite different antibiotic agents, dual-energy computed tomography showed subtotal stenosis of the right lower lobe pulmonary artery with marked pulmonary perfusion-reduction. Rare causes of lung-abscesses should be considered.

Dehiscence of a pulmonary bioprosthesis with a focal dissection of the pulmonary artery in a patient with congenital pulmonic stenosis.

Pulmonary valve replacement (PVR) is the most common adult congenital cardiac operation performed. Valve degeneration leading to prosthetic stenosis and/or regurgitation is a long-term risk in this population and may be associated with paravalvular leak (PVL). Complications involving the proximal pulmonary artery, including dissection, are less clearly defined. Herein, we report the case of a 30-year-old patient with a history of multiple pulmonary valve interventions secondary to congenital pulmonic stenosis, who developed dehiscence of a bioprosthetic PVR associated with significant paravalvular leak (PVL) and further complicated by a focal dissection of the proximal pulmonary artery.

Generalized Arterial Calcification in a Recipient Twin: Discordant Fetal Hemodynamics Result in Differing Phenotypes in Monozygotic Twins with an ABCC6 Mutation.

Recipients of the twin-twin transfusion syndrome (TTTS) often develop cardiac manifestations, but arterial calcification has rarely been reported. Generalized arterial calcification of infancy (GACI) is a genetic disorder with high infantile mortality. We report the case of a TTTS recipient with moderate cardiomyopathy at diagnosis who developed progressive calcification of the pulmonary arteries and aorta after successful in utero laser therapy. Postnatally, both twins were diagnosed with a heterozygous ABCC6 gene mutation associated with GACI. The recipient had progressive supravalvular pulmonary and aortic stenosis, was treated with bisphosphonate therapy, and successfully underwent cardiac surgery at 4 months of age. The donor twin with the same mutation remained phenotypically normal at 15 months of age. This case illustrates monozygotic fetuses with discordant in utero hemodynamics, with subsequent development of phenotypic differences. TTTS recipients with arterial calcifications should undergo genetic testing for GACI.

Arteritis de Takayasu con pulmonares estenosis severa de ramas principales / Takayasu's arteritis with severe stenosis of main pulmonary artery branches

A 40-year-old woman consulted for progressive dyspnea. Physical examination revealed systolic murmurs in the upper thoracic area and asymmetric pulses in the upper extremities. Echocardiography revealed a 117-mmHg systolic gradient across the tricuspid valve and CT angiography revealed severe stenosis of pulmonary artery branches. A discussion of the disease is included.

Effects of Proximal Pulmonary Artery Occlusion on Pulsatile Right Ventricular Afterload in Rats.

BACKGROUND: In patients with proximal pulmonary artery (PA) thromboembolism, an increased PA resistance contributes to abnormal right ventricular (RV) afterload. However, the effects of proximal thromboembolism on the dynamic properties of RV afterload, which is determined by PA impedance, have not been analyzed quantitatively. The present study aimed to identify changes in PA impedance after the pulmonary perfusion volume was greatly reduced by unilateral proximal PA occlusion. METHODS AND RESULTS: Ten male Sprague-Dawley rats were used. PA flow and pressure waveforms were recorded during irregular pacing, before and 10 min after left PA occlusion. PA impedance was parameterized by using a three-element Windkessel model consisting of peripheral resistance (RP), arterial compliance (CP) and characteristic impedance (ZC). After proximal PA occlusion, PA impedance modulus increased over a frequency range of interest.ZCincreased significantly (after PA occlusion vs. baseline: 0.128±0.016 vs. 0.074±0.010 mmHg·min/ml, P<0.001), whereasCPandRPdid not change significantly. CONCLUSIONS: Proximal PA occlusion increasedZCwith the attenuation ofRPincrease andCPdecrease predicted from the decreased pulmonary perfusion volume. The insignificant changes inRPandCPindicate that a recruitment phenomenon may result in this attenuation. The existence of compensation by a recruitment mechanism suggests the relative importance of increasedZCin defining abnormal RV afterload in patients with proximal PA thromboembolism. (Circ J 2016; 80: 2010-2018).

CT-defined phenotype of pulmonary artery stenoses in Alagille syndrome.

BACKGROUND: Alagille syndrome is a rare disorder commonly associated with pulmonary artery stenosis. Studies exist discussing the cardiovascular sequela but no consistent phenotype, or pattern of pulmonary artery stenosis, has been described. OBJECTIVE: The objective of this study was to characterize the distribution and severity of pulmonary artery stenosis in patients with Alagille syndrome based on computed tomography angiography. MATERIALS AND METHODS: A retrospective chart review identified patients with Alagille syndrome who had undergone CT angiography. Pulmonary trunk (MPA), left main pulmonary artery (LPA) and right main pulmonary artery (RPA) diameters in Alagille patients were compared with those from matched control subjects. Stenoses at lobar and segmental pulmonary arteries were categorized as: Grade 1 (<33% stenosis), Grade 2 (33-66% stenosis) or Grade 3 (>66% stenosis). Involvement among the different lung regions was then compared. RESULTS: Fifteen patients ages 6 months to 17 years were identified; one had surgical augmentation of the central pulmonary arteries and was excluded from the central (main, right and left) pulmonary artery analysis. The proximal LPA and RPA, but not the MPA, were significantly smaller than those of the control subjects (P<0.01). The proximal LPA was significantly smaller than the proximal RPA (P<0.01) in the Alagille group (0.55 LPA:RPA ratio). Within the Alagille group, 75% of the lobar and segmental branches showed mild or no stenoses (Grade 1), 17% showed moderate stenosis (Grade 2) and 8% showed severe stenosis (Grade 3). While not statistically significant, the right lung demonstrated a greater percentage of Grades 2 and 3 stenoses (28%, right vs. 20% left, P=0.1). The right middle and lingula lobes of both lungs showed more Grade 2 and 3 stenoses (33% upper/middle vs. 18% lower, P<0.01). CONCLUSION: We describe a common pattern pulmonary artery stenosis in Alagille patients consisting of severe proximal LPA stenosis, heavy involvement of the lobar and segmental branches (more often right than left), and a greater involvement of the upper lobes. Knowledge of this phenotypic pattern can help in the diagnosis of Alagille syndrome in patients presenting with pulmonary artery stenosis.