Proximal Pulmonary Artery Research Articles

Longitudinal Evolution of Pulmonary Artery Wall Shear Stress in a Swine Model of Pulmonary Artery Stenosis and Stent Interventions.

Branch pulmonary artery stenosis (PAS) commonly occurs in congenital heart disease and it has previously been hypothesized that in branch PAS the pulmonary arteries (PAs) remodel their lumen diameter to maintain constant wall shear stress (WSS). We quantified the longitudinal progression of PA WSS in a swine model of unilateral PAS and two different intervention time courses to test this hypothesis. To quantify WSS in the entire pulmonary tree we used 4D Flow MRI for the large-proximal PAs and a structured tree model for the small-distal PAs. Our results only partially supported the hypothesis that in branch PAS the PAs remodel their lumen diameter to maintain WSS homeostasis. Proximal PA WSS was similar between groups at the final study time-point but WSS of mid-sized (5mm to 500μm) PA segments was found to be different between the sham and LPAS groups. This suggests that WSS homeostasis may only be achieved for the large-proximal PAs. Additionally, our results do not show WSS homeostasis being achieved over shorter periods of time suggesting that any potential WSS dependent changes in PA lumen diameter were a long-term remodeling response rather than a short-term vasodilation response. Future studies should confirm if these findings hold true in humans and investigate the impacts of WSS at different levels of the pulmonary tree on growth.

ERS statement on chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism, either symptomatic or not. The occlusion of proximal pulmonary arteries by fibrotic intravascular material, in combination with a secondary microvasculopathy of vessels <500 µm, leads to increased pulmonary vascular resistance and progressive right heart failure. The mechanism responsible for the transformation of red clots into fibrotic material remnants has not yet been elucidated. In patients with pulmonary hypertension, the diagnosis is suspected when a ventilation/perfusion lung scan shows mismatched perfusion defects, and confirmed by right heart catheterisation and vascular imaging. Today, in addition to lifelong anticoagulation, treatment modalities include surgery, angioplasty and medical treatment according to the localisation and characteristics of the lesions.This statement outlines a review of the literature and current practice concerning diagnosis and management of CTEPH. It covers the definitions, diagnosis, epidemiology, follow-up after acute pulmonary embolism, pathophysiology, treatment by pulmonary endarterectomy, balloon pulmonary angioplasty, drugs and their combination, rehabilitation and new lines of research in CTEPH.It represents the first collaboration of the European Respiratory Society, the International CTEPH Association and the European Reference Network-Lung in the pulmonary hypertension domain. The statement summarises current knowledge, but does not make formal recommendations for clinical practice.

Chronic Hypoxia Decreases Endothelial Connexin 40, Attenuates Endothelium-Dependent Hyperpolarization-Mediated Relaxation in Small Distal Pulmonary Arteries, and Leads to Pulmonary Hypertension.

BackgroundAbnormal endothelial function in the lungs is implicated in the development of pulmonary hypertension; however, there is little information about the difference of endothelial function between small distal pulmonary artery (PA) and large proximal PA and their contribution to the development of pulmonary hypertension. Herein, we investigate endothelium‐dependent relaxation in different orders of PAs and examine the molecular mechanisms by which chronic hypoxia attenuates endothelium‐dependent pulmonary vasodilation, leading to pulmonary hypertension.Methods and ResultsEndothelium‐dependent relaxation in large proximal PAs (second order) was primarily caused by releasing NO from the endothelium, whereas endothelium‐dependent hyperpolarization (EDH)–mediated vasodilation was prominent in small distal PAs (fourth–fifth order). Chronic hypoxia abolished EDH‐mediated relaxation in small distal PAs without affecting smooth muscle–dependent relaxation. RNA‐sequencing data revealed that, among genes related to EDH, the levels of Cx37, Cx40, Cx43, and IK were altered in mouse pulmonary endothelial cells isolated from chronically hypoxic mice in comparison to mouse pulmonary endothelial cells from normoxic control mice. The protein levels were significantly lower for connexin 40 (Cx40) and higher for connexin 37 in mouse pulmonary endothelial cells from hypoxic mice than normoxic mice. Cx40 knockout mice exhibited significant attenuation of EDH‐mediated relaxation and marked increase in right ventricular systolic pressure. Interestingly, chronic hypoxia led to a further increase in right ventricular systolic pressure in Cx40 knockout mice without altering EDH‐mediated relaxation. Furthermore, overexpression of Cx40 significantly decreased right ventricular systolic pressure in chronically hypoxic mice.ConclusionsThese data suggest that chronic hypoxia‐induced downregulation of endothelial Cx40 results in impaired EDH‐mediated relaxation in small distal PAs and contributes to the development of pulmonary hypertension.

Feasibility of ultra-central stereotactic ablative irradiation in lung cancer undergoing nivolumab: a case report

: Oligometastatic disease represent a subgroup of cancer patients characterized by a low burden of metastatic disease potentially amenable for local treatments, aimed at achieving long-term remission. At the same time, in a percentage of the patient the localization of oligometastases can be challenging. In particular, ultracentral localization are characterized by the overlapping of the target volumes with critical structures such as proximal bronchial tree, trachea, esophagus, pulmonary vein or pulmonary artery. For this subset of localizations, the optimal dose and fractionation, as well as the safety of a radiotherapy approach, is still unknown. We report a case of an oligometastatic lung cancer patient undergoing therapy with Nivolumab that was successfully treated with thoracic stereotactic ablative radiation therapy (SABR) for a subcarinal lymph node metastasis. The patient began the radiation treatment concurrent with immunotherapy and reported no acute toxicity. The computed tomography (CT) scan 60 days after radiotherapy showed partial response and no acute toxicity. The subsequent positron emission tomography (PET)/CT scan performed 6 months after radiotherapy showed, conversely, a complete response of the irradiated lesion. The patient is still undergoing immunotherapy and show no signs of recurrence of disease. The association between immunotherapy and SABR seems to be useful in terms of outcomes, although at the present time we need more data on the safety of this combined approach in the subset of ultra-central localizations.

Abstract 14367: Abnormal Pulmonary Flow is Associated With Impaired Right Ventricular Coupling in Patients With COPD

Introduction: Cor Pulmonale or right ventricular (RV) dysfunction due to pulmonary disease is an expected complication of COPD resulting from increased afterload mediated by hypoxic pulmonary vasoconstriction as well as the destruction of the pulmonary vascular bed. Early detection of elevated RV afterload has been previously demonstrated by visualization of abnormal flow patterns in the proximal pulmonary arteries. Prior quantitative analysis of helicity in the pulmonary arteries of pulmonary hypertension patients has demonstrated a strong association between helicity and increased RV afterload. Hypothesis: Patients with COPD will have abnormal pulmonary flow as evaluated by 4D-Flow MRI and associated with RV function and pulmonary arterial stiffness. Methods: Patients with COPD (n=15) (65yrs ± 6) and controls (n=10) (58yrs ± 9) underwent 4D-Flow MRI to calculate helicity (Figure 1A). The helicity was calculated in 2 segments: 1) the main pulmonary artery (MPA) and 2) along the RV outflow tract (RVOT) - MPA axis. Main pulmonary arterial stiffness was measured using the relative area change (RAC). Results: COPD patients had decreased helicity relative to healthy controls in the MPA (19.4±7.8 vs 32.8±15.9 s -2 , P=0.007) (Figure 1B). Additionally, COPD patients had reduced helicity along the RVOT-MPA axis (33.2±9.0 vs 43.5±8.3 s -2 , P=0.010). The helicity measured in the MPA was associated with RV end-systolic volume (R=0.59, P = 0.002), RVEF (R=0.631, P&lt;0.001), RAC (R=-0.61, P=0.001). e combined helicity along the MPA-RVOT axis was associated with RVEF (R=0.74, P&lt;0.001), RVESV (R=-0.57, P=0.004), and RAC (R=0.42, P=0.005). Conclusion: Patients with COPD show quantitatively abnormal flow hemodynamics, when compared with healthy controls, as assessed by 4D-Flow MRI. A strong association between helicity along the MPA-RV outflow tract axis and RV function suggests that 4D-Flow MRI might be a sensitive tool in evaluating RV - pulmonary arterial coupling in COPD.

PATIENT-SPECIFIC 3-D LUNG MODELING: THE FUTURE OF PRECISION LUNG CANCER SURGERY?

SESSION TITLE: Fellows Lung Cancer Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Reconstruction software based on mathematical algorithms and machine learning are beginning to allow the processing of chest CT scans to generate highly specific 3D lung models. We describe our initial experience using this technology for simulation and planning of lung cancer resection. CASE PRESENTATION: DICOM data from patient CT scans was processed (IQQA-Lung, EDDA Technology, Princeton, NJ, USA) to generate 3D maps of patient's airways and vasculature as well as obtain information on lung volumes (cm3), tumor volume and volumes of individual lung lobes. Case 1: The model [Figure 1(A-G), Gif 1] generated demonstrated a 2.2 cm x 2.2 cm x 1.7 cm lesion in the left upper lobe (LUL). The lesion had a total volume of 3.39 cm3. Total lung volume (TLV), right lung volume (RLV) and left lung volume (LLV) were 4029.54 cm3, 2369.08 (58.79%) cm3 and 1660.46 (41.21%) cm3 respectively. LUL and left lower lobe (LLL) had volumes of 951.02 cm3 (57.27%) and 709.45 cm3 (42.73%) respectively. While the lesion appeared to be located in the lingular segment, our model showed that it crossed into the adjacent segments and a segmentectomy would have led to a close or positive margin. This was confirmed in the operating room. Case 2: The model [Figure 1(H-N), Gif 2] generated demonstrated a 2.6 cm x 2.3 cm x 1.3 cm lesion in the right lower lobe (RLL). The lesion had a total volume of 4.72 cm3. TLV, RLV and LLV were 2948.46 cm3, 1579.84 (53.58%) and 1368.62 (46.42%) cm3 respectively. Right upper lobe (RUL), right middle lobe (RML) and RLL had volumes of 738.09 cm3 (46.72%), 178.57 cm3 (11.3%) and 663.18 cm3 (41.98%) respectively. While the lesion appeared to be located in the superior segment, interplanar analysis showed that a segmentectomy would have led to a close or positive margin. This was confirmed intraoperatively. In addition, a small proximal pulmonary artery was identified preoperatively that informed on the need for extra vigilance during dissection of the PA. DISCUSSION: Highly accurate patient-specific lung models provide extensive detail on pulmonary vasculature and intersegmental planes, allowing for preoperative recognition of anatomic variations and guiding the extent of an ideal oncologic resection. The ability to get high-resolution images without the need for IV contrast is an added benefit. These models also provide an accurate measurement of postoperative residual lung volumes hence providing a surrogate marker for postoperative residual lung function and quality of life. These models also carry teaching value for residents and medical students. CONCLUSIONS: Highly accurate 3D lung models give detailed information on patient-specific anatomy as well as preoperative and postoperative lung volumes. These platforms should be utilized to obtain a better understanding of patient anatomy in order to make lung operations safer, more efficient and allow appropriate lung conservation surgery. Reference #1: Nakada, T., Akiba, T., Inagaki, T. and Morikawa, T., 2014. Thoracoscopic anatomical subsegmentectomy of the right S2b + S3 using a 3D printing model with rapid prototyping. Interact Cardiovasc Thorac Surg, 19(4), pp.696-698. Reference #2: Akiba T, Nakada T, Inagaki T. Three-Dimensional Pulmonary Model Using Rapid-Prototyping in Patient with Lung Cancer Requiring Segmentectomy. Annals of Thoracic and Cardiovascular Surgery. 2014;20(Supplement):490-492. DISCLOSURES: No relevant relationships by Mirza Zain Baig, source=Web Response No relevant relationships by Faiz Bhora, source=Web Response No relevant relationships by Zaid Muslim, source=Web Response

Computed Tomography Angiography-Based Pulmonary Artery Volumetry as a Diagnostic Tool for Pulmonary Hypertension.

We evaluated use of three-dimensional pulmonary artery volumes derived from computed tomography pulmonary angiography (CTPA) in a group with pulmonary hypertension (PH) compared with healthy controls as a tool for the diagnosis of PH. Retrospective analysis was performed of 40 CTPA scans obtained within 90 days of right heart catheterization demonstrating PH. The CTPA scans of 40 age- and sex-matched patients without cardiopulmonary disease were used as comparison. Diameters and volumes of the pulmonary arteries were compared. Adjusted total volume of the main, right, and left proximal pulmonary arteries (PAvol) demonstrated area under the curve of 0.918 (95% confidence interval, 0.860-0.975) for detection of PH, comparable to main pulmonary artery diameter measurement. Area under the curve values for PAvol were higher in subgroups divided by sex and PH severity. Volumetric analysis of the proximal pulmonary arteries using CTPA is a promising diagnostic tool for PH in a real-world cohort.

Virtual Histology to Evaluate Mechanisms of Pulmonary Artery Lumen Enlargement in Response to Balloon Pulmonary Angioplasty in Chronic Thromboembolic Pulmonary Hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) results from an obstruction of pulmonary arteries (PAs) by organized thrombi. The stenosed PAs are targeted during balloon pulmonary angioplasty (BPA). We aimed to evaluate the mechanism of BPA in inoperable patients with CTEPH. We analyzed stenosed PAs with intravascular grey-scale ultrasound (IVUS) to determine the cross-sectional area (CSA) of arterial lumen and of organized thrombi. The composition of organized thrombi was assessed using virtual histology. We distinguished two mechanisms of BPA: Type A with dominant vessel stretching, and type B with dominant thrombus compression. PAs were assessed before (n = 159) and after (n = 98) BPA in 20 consecutive patients. Organized thrombi were composed of dark-green (57.1 (48.0–64.0)%), light-green (34.0 (21.4–46.4)%), red (6.4 (2.9–11.7)%;) and white (0.2 (0.0–0.9)%) components. The mechanism type depended on vessel diameter (OR = 1.09(1.01–1.17); p = 0.03). In type B mechanism, decrease in the amount of light-green component positively correlated with an increase in lumen area after BPA (r = 0.50; p = 0.001). The mechanism of BPA depends on the diameter of the vessel. Dilation of more proximal PAs depends mainly on stretching of the vessel wall while dilation of smaller PAs depends on compression of the organized thrombi. The composition of the organized thrombi contributes to the effect of BPA.

The Effects of Inhaled Sodium Nitrite on Pulmonary Vascular Impedance in Patients With Pulmonary Hypertension Associated with Heart Failure With Preserved Ejection Fraction

BackgroundThe severity of pulmonary hypertension (PH) is monitored by measuring pulmonary vascular resistance, which is a steady-state measurement and ignores the pulsatile load encountered by the right ventricle (RV). Pulmonary vascular impedance (PVZ) can depict both steady-state and pulsatile forces, and thus may better predict clinical outcomes. We sought to calculate PVZ in patients with PH associated with heart failure with preserved ejection fraction who were administered inhaled sodium nitrite to better understand the acute effects on afterload. Methods and ResultsFourteen patients with PH associated with heart failure with preserved ejection fraction underwent right heart catherization and were administered inhaled sodium nitrite. A Fourier transform was used to calculate PVZ for both before and after nitrite for comparison. Inhaled sodium nitrite decreased characteristic impedance (inversely related to proximal pulmonary artery compliance) and total work performed by the RV. RV efficiency improved, defined by a reduction in the total work divided by cardiac output. There was a mild decrease in pulmonary steady-state resistance after the administration of inhaled sodium nitrite, but this effect was not significant. ConclusionsPVZ analysis showed administration of inhaled sodium nitrite was associated with an improvement in pulmonary vascular compliance via a decrease in characteristic impedance, more so than pulmonary steady-state resistance. This effect was associated with improved RV efficiency and total work.

Pulmonary ductal coarctation and left pulmonary artery interruption; pathology and role of neural crest and second heart field during development.

ObjectivesIn congenital heart malformations with pulmonary stenosis to atresia an abnormal lateral ductus arteriosus to left pulmonary artery connection can lead to a localised narrowing (pulmonary ductal coarctation) or even interruption We investigated embryonic remodelling and pathogenesis of this area.Material and methodsNormal development was studied in WntCre reporter mice (E10.0–12.5) for neural crest cells and Nkx2.5 immunostaining for second heart field cells. Data were compared to stage matched human embryos and a VEGF120/120 mutant mouse strain developing pulmonary atresia.ResultsNormal mouse and human embryos showed that the mid-pharyngeal endothelial plexus, connected side-ways to the 6th pharyngeal arch artery. The ventral segment formed the proximal pulmonary artery. The dorsal segment (future DA) was solely surrounded by neural crest cells. The ventral segment had a dual outer lining with neural crest and second heart field cells, while the distal pulmonary artery was covered by none of these cells. The asymmetric contribution of second heart field to the future pulmonary trunk on the left side of the aortic sac (so-called pulmonary push) was evident. The ventral segment became incorporated into the pulmonary trunk leading to a separate connection of the left and right pulmonary arteries. The VEGF120/120 embryos showed a stunted pulmonary push and a variety of vascular anomalies.SummarySide-way connection of the DA to the left pulmonary artery is a congenital anomaly. The primary problem is a stunted development of the pulmonary push leading to pulmonary stenosis/atresia and a subsequent lack of proper incorporation of the ventral segment into the aortic sac. Clinically, the aberrant smooth muscle tissue of the ductus arteriosus should be addressed to prohibit development of severe pulmonary ductal coarctation or even interruption of the left pulmonary artery.

Cardiac Neural Crest Cells: Their Rhombomeric Specification, Migration, and Association with Heart and Great Vessel Anomalies.

Outflow tract abnormalities are the most frequent congenital heart defects. These are due to the absence or dysfunction of the two main cell types, i.e., neural crest cells and secondary heart field cells that migrate in opposite directions at the same stage of development. These cells directly govern aortic arch patterning and development, ascending aorta dilatation, semi-valvular and coronary artery development, aortopulmonary septation abnormalities, persistence of the ductus arteriosus, trunk and proximal pulmonary arteries, sub-valvular conal ventricular septal/rotational defects, and non-compaction of the left ventricle. In some cases, depending on the functional defects of these cells, additional malformations are found in the expected spatial migratory area of the cells, namely in the pharyngeal arch derivatives and cervico-facial structures. Associated non-cardiovascular anomalies are often underestimated, since the multipotency and functional alteration of these cells can result in the modification of multiple neural, epidermal, and cervical structures at different levels. In most cases, patients do not display the full phenotype of abnormalities, but congenital cardiac defects involving the ventricular outflow tract, ascending aorta, aortic arch and supra-aortic trunks should be considered as markers for possible impaired function of these cells. Neural crest cells should not be considered as a unique cell population but on the basis of their cervical rhombomere origins R3-R5 or R6-R7-R8 and specific migration patterns: R3-R4 towards arch II, R5-R6 arch III and R7-R8 arch IV and VI. A better understanding of their development may lead to the discovery of unknown associated abnormalities, thereby enabling potential improvements to be made to the therapeutic approach.

Quantification of Cardiac Output with Phase Contrast Magnetic Resonance Imaging in Patients with Pulmonary Hypertension.

Objective:The purpose of the study is to compare phase contrast (PC) imaging with invasive measurements of cardiac output (CO) in patients with pulmonary hypertension (PH).Materials and Methods:We analyzed 81 cases with PH who underwent cardiac magnetic resonance imaging and right heart catheterization (RHC). Measurement of CO and stroke volume (SV) by cardiac magnetic resonance (CMR) was performed by PC imaging of the proximal aorta (Ao) and pulmonary artery (Pa) and by RHC using the Fick and thermodilution (TD) methods.Results:There was good correlation in CO measurements between PC and RHC; however, there was better correlation with SV measurements; Fick-TD (r=0.85), PC-TD (Ao r=0.77, Pa r=0.79), and PC-Fick (Ao r = 0.73, Pa r = 0.78). Bland-Altman analysis of SV showed that Pa PC had slightly lower standard deviation than Ao PC; PC-Fick (Pa SD = 15.11 vs. Ao SD = 16.4 ml) and PC-TD (Pa SD = 16.99 ml vs. Ao SD = 17.4 ml) while Fick-TD had the lowest (SD = 14.4 ml). Compared to Fick, measurement of SV with Ao PC (‒4.12 ml) and Pa PC (0.22 ml) both had lower mean difference than TD (‒11.1 ml).Conclusion:Non-invasive measurement of CO and SV using PC-CMR correlates well with invasive measurement using RHC. Our study showed that PC-CMR had high accuracy and precision when compared to Fick. Among all the modalities, PC-CMR contributed the least amount of variation in measurements.

Single Cell RNA Sequencing of Human Pulmonary Endarterectomy Specimen Reveals Distinct Cell Populations and Gene Profiles

Chronic thromboembolic pulmonary hypertension (CTEPH), is a progressive condition characterized by persistent elevation in pulmonary artery pressure due to thromboembolic occlusion of the pulmonary arteries. Little is known about the cells that make up the cast of pulmonary endarterectomy (PEA) and its immune microenvironment. Here we report a map of the cellular landscape of the human PEA specimen using single-cell RNA sequencing. Five human PEA specimen from the proximal pulmonary arteries were collected from CTEPH patients who underwent PEA surgery. The protocol was approved (University Health Network, REB# 18-5892). 10x sample processing and cDNA library preparation was prepared using the 10x Genomics Single Cell Reagent Kit. Molecular analysis, Western blot, and immunohistochemistry were also performed. The transcriptional profiles of 12598 cells obtained by fractionating fresh tissues from five CTEPH patients after PEA are presented in Figure 1. Using gene expression patterns and immunohistochemical examinations, we identified 18 discrete cell populations with distinct endothelial cell, smooth muscle cell, monocyte/macrophage, T cell, B cell, and NK-like cell characteristics. Transcription of endothelin-1 was observed in endothelial cells from every patient. The expression of endothelin-1 was confirmed by Western blot and immunohistochemistry in the PEA specimen from an additional 14 CTEPH patients undergoing surgery. Single cell RNA sequencing demonstrates a large population of inflammatory cells combined with endothelial cells and smooth muscle cell in the cast of PEA. Endothelin-1 expression by endothelial cells may contribute to the development of PH in patients with CTEPH.

P1323 From a suspicion of pulmonary arterial hypertension to a rare form of Takayasu disease

Abstract A 27-year-old female with a history of glomerulonephritis,with diagnosed systemic lupus and retroperitoneal fibrosis was admitted due to fast worsening dyspnoea(NYHA class IV) over the prior four weeks with suspicion for PA hypertension. In 2015, retroperitoneal fibrosis was diagnosed based on MR examination. With the methylprednisolone treatment a regression of changes was obtained. The patient was chronically treated with prednisone 7.5mg/day and mycophenolate mofetil 2g/d. When admitted to the ward, the patient was in a severe condition, with symptoms of resting dyspnea and blood oxygen saturation up to 80%. A loud systolic murmur was audible over the entire chest. In laboratory tests, the NT-proBNP values (11,000 pg/ml) were significantly elevated, arterial blood gases showed tendency to alkalosis, hypoxemia (PO2 45mmHg)with hypocapnia. Parameters of inflammation were moderately elevated (CRP 25mg/l, WBC 12,000/ul), with normal serum IgG4 concentrations. In TTE, significant dilatation of the right ventricle with left chamber compression were observed. Tricuspid ring dilation with no leaflets coaptation and a severe tricuspid regurgitation (Vmax 5m/s, RVSP 100mmHg) were found. In addition, the critical proximal pulmonary artery (PA) stenosis was revealed (left PA Vmax 3.3m/s, Pmax 42mmHg, right PA Vmax 5.2 m/s, Pmax 110mmHg). Angio-CT confirmed critical proximal constriction of both PAs with a flow channelup to 4 mm. Based on angio-CT and cardiac MR study the inflammatory etiology of stenoses was suspected and an empiric diagnosis of the Takayahu disease of pulmonary arteries was made. The patient was qualified for conservative treatment using prednisone and cyclophosphamide. Over the course of two months,2.8 g of cyclophosphamide were administered intravenously in three cycles with good response to the treatment. It resulted in regression of dyspnea and a improvement in exercise tolerance - to the NYHA class II, normalization of saturation. Laboratory tests showed reduction of NT-proBNP (1300 pg/ml). Control TTE revealed reduction in the size of the right ventricle and regression of PAs stenoses (left PA 11mm, right PA 7mm), also reduction of systolic flow gradients (left PA Vmax 3.1 m / s, Pmax 39 mmHg, right PA 4.1 m/s, Pmax 68 mmHg). Because of the significant improvement in patient’s condition,it was decided to continue the treatment. Legend for the Fig.1 A angio-CT, critical proximal constriction of both PA B TTE, parasternal short axis view, imflammatory infiltration C TTE, continuous wave doppler, flow velocity pattern in the PA stenosis D TTE PLAX, dilatation of the right ventricle with left chamber compression fig. 1 Abstract P1323 Figure. Fig.1 artety pulmonary stenosis

P1449 CMR-driven computational modeling of right ventricular flow dynamics

Abstract Introduction The analysis of intracardiac blood flow patterns can significantly contribute to improve the understanding and treatment of cardiovascular disease. In contrast to the substantial literature on the left side of the heart, there is currently a significant lack of knowledge about the fluid mechanics of the right heart – pulmonary circulation unit (RH-PCU), both in healthy and diseased conditions. Purpose It is conjectured that computational modeling can be a key element to enhance current imaging techniques and provide quantitative insights into the unique RH-PCU biomechanics. Here we present a novel methodology that allows personalized numerical simulations of right heart flows, through a proper combination of cardiac magnetic resonance (CMR) with computational fluid dynamics (CFD). Methods and results We developed a patient-specific pipeline from medical images to computational models, as depicted in the figure. First, the RV geometry is reconstructed from time-resolved CMR cine images, comprising short-axis and longitudinal slices of the heart, where feature-tracking techniques are used to extract the motion of the RV endocardium contours. A time-continuous description of the moving geometry is obtained through an image-registration algorithm based on diffeomorphic mappings. The moving model of the RV, including the outflow tract and proximal pulmonary arteries, is finally fed to a dedicated CFD solver. The tool is able to provide a detailed description of the velocity and pressure fields inside the right ventricle and proximal pulmonary arteries during all phases of the cardiac cycle. From these fields, global hemodynamic quantities such as vortex properties, kinetic energy, pressure gradients and hemodynamic forces can be computed. Conclusions CMR-driven computational modeling of intra-ventricular flow enables a promising approach for understanding and evaluating the biomechanical environment of the right heart. This high-fidelity framework can be applied to investigate the RV response and adaptation to abnormal pressure and/or volume load conditions. It can also be used to reproduce the virtual flow that would realize in hypothetical conditions, and therefore adds predictive capabilities to modern flow imaging. The analysis may allow to determine an association between blood flow patterns and disease progression, and ultimately lead to derive and validate imaging biomarkers of clinical significance. Abstract P1449 Figure. Pipeline for patient-specific modeling

P684 Paradoxical cerebral infarction due to massive pulmonary embolism in extracorporeal cardiopulmonary resuscitation and surgical embolectomy

Abstract Introduction Paradoxical cerebral infarction is a mechanism of acute ischemic stroke; however, definitive images to diagnose paradoxical embolism are not often obtained. We report a case of paradoxical cerebral embolism complicated with cardiac arrest due to massive pulmonary embolism. Case report A 40-year-old man presented due to sudden-onset chest pain, and was admitted to our hospital. He was restless and had cold sweat; we could not measure blood pressure. Electrocardiography showed wide QRS complex with right bundle branch block, and T wave inversion in leads V1 and III. Transthoracic echocardiography showed diffuse severe left ventricular hypokinesis, with slightly better inferior wall motion compared to other segments. Few minutes after arriving, he experienced cardiac arrest; chest compression was initiated. He was transported to the catheter laboratory, and veno-arterial extracorporeal membrane oxygenation was initiated subsequently. To diagnose the cause of arrest, we performed coronary angiography, which revealed no occluded coronary artery. Pulmonary angiograms showed bilateral proximal pulmonary artery occlusion with massive thrombi (panel A). Surgical embolectomy was performed after cardiac team discussion. After ICU admission post-surgery, pericardial effusion was increased, and the blood drained continuously from the chest tube; a large amount of blood transfusion was required. Reopen chest haemostasis was utilised. After the second ICU admission, anisocoria was observed; subsequent computed tomography showed low density and midline shift in almost the entire left cerebral hemisphere (Panel B). Carotid duplex ultrasound revealed a large thrombus saddled at the left carotid artery bifurcation (Panel C and D). We rechecked the transthoracic echocardiogram at arrival to reveal the cause of the cerebral infarction, which showed the thrombus to be at the ascending aorta (Panel E). We thought that the thrombi had moved from the lower limb to the right atrium. The massive pulmonary embolism increased the pulmonary artery and right atrial pressure, resulting in the lower pressure of the left atrium compared to that of the right atrium. The thrombi passed through the patent foramen ovale into the left atrium, moved into the left ventricle, and embolised the left internal carotid artery (Panel F). He expired due to severe neurologic injury from brain herniation. Conclusion In this case, although the pulmonary embolism was massive and led to cardiac arrest, the deteriorated haemodynamics improved by extracorporeal cardiopulmonary resuscitation and surgical embolectomy. However, we could not rescue the patient because of the severe neurological injury due to paradoxical embolism. Paradoxical cerebral infarction in pulmonary embolism is rare; however, we should pay careful attention to early detection of paradoxical cerebral infarction in pulmonary embolism and treatment for return of the patient to the former lifestyle. Abstract P684 figure

P4678The hemodynamic improvement with balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension depends on the lesion location

Abstract Background Pulmonary endarterectomy (PEA) is a treatment of choice for patients with chronic thromboembolic pulmonary hypertension (CTEPH). Patients with proximal pulmonary artery disease are considered to be good candidates for PEA because of their generally excellent outcomes. However, not all patients can be operated because of patients' advanced age, comorbidities and poor general condition. Balloon pulmonary angioplasty (BPA) has become an alternative treatment for CTEPH patients especially whose lesions locate in the distal site. The effectiveness of BPA in patients who have lesions in the proximal pulmonary arteries but cannot be a candidate for PEA remains unclear. Purpose The aim of this study was to investigate the outcome of BPA in CTEPH patients whose lesions appears operable but ineligible for PEA. Methods A total of 370 patients who underwent BPA in our institute from November 2004 to January 2018 were enrolled. All the patients were divided into operable group and inoperable group according to the difference of lesion location based on the findings of perfusion scintigraphy, computed tomography and pulmonary angiography. Hemodynamic effects of BPA in both groups were investigated. We also conducted survival analyses using the Kaplan-Meier method with the log-rank test. Results Among 370 patients, 90 patients deemed operable. The main reasons why not operated in the PEA operable group were patient's refusal (44%), advanced age (14%), and comorbidities (27%). There were no baseline characteristic differences between two groups except for the history of acute pulmonary embolism. Mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) equally improved after BPA in both groups (operable: 38.2±10.8 mmHg to 21.5±4.7mmHg, inoperable: 42.4±11.3 mmHg to 21.8±4.8 mmHg, p&lt;0.001, operable: 8.0±4.2 wood unit to 3.5±1.5 wood unit, inoperable: 9.1±4.6 wood unit to 3.4±1.3 wood unit, p&lt;0.001). Furthermore, five-year cumulative survival rates were not different between two groups (inoperable vs. operable: 93% vs. 88%, p=0.23, median follow-up period was 23.0 months (range: 5–136 months)). Meanwhile, the absolute change of mPAP and PVR in inoperable group were greater than those in operable group (inoperable: 20.7±11.2 mmHg, operable: 16.6±11.0 mmHg, p=0.010, inoperable: 5.6±4.4 wood unit, operable: 4.5±3.9 wood unit, p=0.015). Conclusions Although the outcome of BPA for CTEPH patients with operable lesions appears acceptable, absolute change in hemodynamics was lower than that of the patients with inoperable lesions. CTEPH with proximal lesions should be treated with PEA rather than BPA.

SARCOMA OF THE GREAT VESSELS MASQUERADING AS PULMONARY EMBOLISM

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Soft tissue sarcomas originating in the heart or great vessels are extremely rare and have a very poor prognosis. We present a case of a sarcoma of the great vessels originally identified as a pulmonary embolism. CASE PRESENTATION: A 74 year old male with a history of chronic obstructive pulmonary disease and sarcoidosis originally presented with hemoptysis, cough, and dyspnea on exertion. A computed tomography angiography of his chest was obtained and showed a 3 cm thrombus present in the right ventricular outflow tract extending into the proximal main pulmonary artery consistent with pulmonary embolism, along with two new centrally located masses in the right lung. Patient was subsequently admitted to the hospital and started on unfractionated heparin. Follow up echocardiogram failed to show right ventricular outflow tract obstruction along with normal bilateral ventricular function. Further imaging with cardiac magnetic resonance imaging showed a 2.5 x 16.6 cm solid mass lesion attached to the anterolateral aspect of the right ventricle prolapsing toward the pulmonic valve. Positron emission tomography–computed tomography did not show increased metabolic activity of this lesion although the right lung lesions were noted to have increased radiotracer uptake. Biopsy of one of the right lung lesions showed high-grade undifferentiated sarcoma of the great vessels with pulmonary metastasis. During his admission, the patient developed ongoing hemoptysis due to anticoagulation which was held on discharge. He was referred to a sarcoma specialist and was started on adriamycin and olaratumab after being deemed a non-surgical candidate. Following a poor response to chemotherapy he was started on local radiation. DISCUSSION: Soft tissue sarcomas originating in the heart or great vessels are very rare and only make up an estimated 1% of all sarcomas. Only a few cases are described in mainly case reports and case series. Given their rarity, they are often misidentified as pulmonary emboli given their location and clinical symptoms.. Mis-identification can lead to delay in treatment which is critical given the poor prognosis. Ideally the first step of treatment is referral to specialized sarcoma centers followed by surgical resection when possible as this is the only definitive therapy. However, in advanced disease, such as our patient, this is not feasible. Therefore, other treatment modalities such as chemotherapy and/or radiotherapy are used. Typically, these therapies are used for palliation or as a neo-adjuvant prior to possible resection. CONCLUSIONS: This case illustrates a very rare cause of primary cardiac tumor, its diagnosis, and management. Furthermore, when these tumors are located in or near the pulmonary artery, they are commonly misidentified as pulmonary embolism. Reference #1: Von Falck C, Meyer B, Fegbeutel C, Langer F, Bengel F, Wacker F, et al. Imaging features of primary sarcomas of the great vessels in CT, MRI and PET/CT: a single-center experience. BMC Med Imaging. 2013;13:25 Reference #2: Nicolas Girard, Jacques Cadranel, Elisabeth Brambilla, and Jean-François Cordier. Rare Primary Lung Tumors. Murray and Nadel's Textbook of Respiratory Medicine, 54, 965-980.e29 Reference #3: Mayer F, Aebert H, Rudert M, Konigsrainer A, Horger M, Kanz L, et al. Primary malignant sarcomas of the heart and great vessels in adult patients–a single-center experience. Oncologist 2007;12:1134–1142. DISCLOSURES: No relevant relationships by Johnathan Fagg, source=Web Response No relevant relationships by Thamer Sartawi, source=Web Response No relevant relationships by Taylor Stone, source=Web Response No relevant relationships by Tareq Zaza, source=Web Response

Abnormal Pulmonary Artery Bending Correlates With Increased Right Ventricular Afterload Following the Arterial Switch Operation.

In transposition of great arteries, increased right ventricular (RV) afterload is observed following arterial switch operation (ASO), which is not always related to pulmonary artery (PA) stenosis. We hypothesize that abnormal PA bending from the Lecompte maneuver may affect RV afterload in the absence of stenosis. Thus, we sought to identify novel measurements of three-dimensional cardiac magnetic resonance (CMR) images of the pulmonary arteries and compare with conventional measurements in their ability to predict RV afterload. Conventional measurements and novel measurements of the pulmonary arteries were performed using CMR data from 42 ASO patients and 13 age-matched controls. Novel measurements included bending angle, normalized radius of curvature (Rc), and normalized weighted radius of curvature (Rc-w). Right ventricular systolic pressures (as the surrogate for RV afterload) were measured by either recent echocardiogram or cardiac catheterization. Conventional measurements of proximal PA size correlated with differential pulmonary blood flow (r = 0.49, P = .001), but not with RV peak systolic pressures (r = -0.26, P = .18). In ASO patients, Rc-w correlated with higher RV systolic pressures (r = -0.57, P = .002). Larger neoaortic areas and rightward bending angles correlated with smaller right pulmonary artery Rc (r = -0.48, P = .001; r = 0.41, P = .01, respectively). Finally, both pulmonary arteries had significantly smaller Rc compared to normal controls. Pulmonary arteries exhibit abnormal bends following ASO that correlate with increased RV afterload, independent of PA stenosis. Future work should focus on clinical and hemodynamic contributions of these shape parameters.

Precapillary pulmonary gas exchange is similar for oxygen and inert gases.

Precapillary gas exchange for oxygen has been documented in both humans and animals. It has been suggested that, if precapillary gas exchange occurs to a greater extent for inert gases than for oxygen, shunt and its effects on arterial oxygenation may be underestimated by the multiple inert gas elimination technique (MIGET). We evaluated fractional precapillary gas exchange in canines for O2 and two inert gases, sulphur hexafluoride and ethane, by measuring these gases in the proximal pulmonary artery, distal pulmonary artery (1cm proximal to the wedge position) and systemic artery. Some 12-19% of pulmonary gas exchange occurred within small (1.7mm in diameter or larger) pulmonary arteries and this was quantitatively similar for oxygen, sulphur hexafluoride and ethane. Under these experimental conditions, this suggests only minor effects of precapillary gas exchange on the magnitude of calculated shunt and the associated effect on pulmonary gas exchange estimated by MIGET. Some pulmonary gas exchange is known to occur proximal to the pulmonary capillary, although the magnitude of this gas exchange is uncertain, and it is unclear whether oxygen and inert gases are similarly affected. This has implications for measuring shunt and associated gas exchange consequences. By measuring respiratory and inert gas levels in the proximal pulmonary artery (P), a distal pulmonary artery 1cm proximal to the wedge position (using a 5-F catheter) (D) and a systemic artery (A), we evaluated precapillary gas exchange in 27 paired samples from seven anaesthetized, ventilated canines. Fractional precapillary gas exchange (F) was quantified for each gas as F=(P-D)/(P-A). The lowest solubility inert gases, sulphur hexafluoride (SF6 ) and ethane were used because, with higher solubility gases, the P-A difference is sufficiently small that experimental error prevents accurate assessment of F. Distal samples (n=12) with oxygen (O2 ) saturation values that were (within experimental error) equal to or above systemic arterial values, suggestive of retrograde capillary blood aspiration, were discarded, leaving 15 for analysis. D was significantly lower than P for SF6 (D/P=88.6±18.1%; P=0.03) and ethane (D/P=90.6±16.0%; P=0.04), indicating partial excretion of inert gas across small pulmonary arteries. Distal pulmonary arterial O2 saturation was significantly higher than proximal (74.1±6.8% vs. 69.0±4.9%; P=0.03). Fractional precapillary gas exchange was similar for SF6 , ethane and O2 (0.12±0.19, 0.12±0.20 and 0.19±0.26, respectively; P=0.54). Under these experimental conditions, 12-19% of pulmonary gas exchange occurs within the small pulmonary arteries and the extent is similar between oxygen and inert gases.