Pulmonary Artery Thrombus Research Articles

Tocilizumab may not be a good option for vascular involvement due to Behçet's syndrome.

Tocilizumab has been increasingly reported as an alternative therapeutic agent in the management of Behçet's syndrome (BS) and it has been mostly tried in BS patients with neurological and eye involvement. As therapeutic responses to each drug may vary across different types of BS involvement, we aimed to report seven patients with large vessel involvement treated with tocilizumab. We enrolled seven BS patients with vascular involvement who were given tocilizumab at the Behçet's Disease Research Centre in Istanbul University-Cerrahpaşa between 2000 and 2022. Demographic information, BS features, types of vascular involvement, previous and concomitant medications, C-reactive protein (CRP) levels, imaging modality results, and outcomes were documented from the patients' medical records. Within a median of 6 months after the initiation of tocilizumab, 5 patients experienced vascular relapses. These relapses included the emergence of new bilateral pulmonary artery aneurysms, a new pulmonary artery thrombus, parenchymal lung involvement, deep vein thrombosis in the lower extremity, and pseudotumor cerebri in one patient each. CRP levels were normal in 4 of the 5 patients at the time of vascular relapse. One of these 5 patients and another patient with aortitis had an exacerbation of mucocutaneous symptoms. In the last patient, venous ulcers did not respond to tocilizumab and were complicated with infection. Tocilizumab could potentially exacerbate vascular manifestations, similar to what is observed with mucocutaneous lesions in BS patients. Furthermore, CRP levels appear to be ineffective in monitoring these patients.

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

BackgroundSarcoidosis-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 presentationThe 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.ConclusionsAn 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.

Living-donor lobar lung transplantation for pulmonary Langerhans cell histiocytosis complicated by extensive thrombi in central pulmonary arteries

BackgroundPulmonary Langerhans cell histiocytosis (PLCH) is a rare disorder characterized by the proliferation of Langerhans cells along the small airways, which causes nodular and cystic changes in the lung parenchyma. Lung transplantation can be a life-saving option for patients with severe respiratory failure or pulmonary hypertension. Herein, we present a case of successful lung transplantation in a patient with PLCH who developed unusually large thrombi in the central pulmonary artery.Case presentationA 47-year-old woman with 16-year history of PLCH with rapidly developing respiratory failure was admitted to our hospital for the evaluation of a lung transplant. Enhanced computed tomography revealed large thrombi in dilated central pulmonary arteries. Right heart catheterization revealed severe pulmonary hypertension, with a mean pulmonary artery pressure of 48 mmHg. The thrombi shrank markedly after 3 months of anticoagulation therapy. However, the respiratory status of the patient did not improve. We performed bilateral living-donor lobar lung transplantation with thrombectomy under extracorporeal membrane oxygenation for the remaining thrombi in the main pulmonary arteries. The dilated main pulmonary arteries of the recipient required direct plication for size mismatch. The patient survived in good condition for more than 2 years with no recurrence of thrombosis.ConclusionPreoperative anticoagulation therapy for massive thrombi in the pulmonary arteries was effective and led to safe lung transplantation.

Epidemio-Clinical and Paraclinical Aspects of Venous Thromboembolic Diseases in a Cardiology Department in Mali

<i>Introduction</i>: Venous thromboembolic diseases (VTED) include deep vein thrombosis of the lower limbs and pulmonary embolism (PE), which is its severe form due to its high mortality. The objective of our study was to determine the epidemio-clinical and paraclinical aspects of patients hospitalized for venous thromboembolic diseases. <i>Patients and method</i>: Cross-sectional study with prospective recruitment from patient records hospitalized for (VTED) from January to December 2023 in the cardiology department of the Mother-Child University Hospital in Bamako, Luxembourg. <i>Results</i>: We collected 55 out of 580 patient records hospitalized for (VTED), a hospital frequency of 9.48%. PE accounted for 58.20% of cases, 10.90% for deep vein thrombosis (DVT), and 30.90% for their association. The mean age of patients was 55.56 years ± 15.52 years. The majority of patients, 90%, were under 66 years of age. The predominance was female, 56%. In lower extremity DVT, calf pain and Homans' sign were present in 56% and 24% of patients. In pulmonary embolism, dyspnea and chest pain were present in 85.50% and 65.50% of patients. Etiological factors were dominated by neoplasia in 10.90%, contraception 5.45% and orthopedic surgery in 5.45% of cases. Cardiovascular risk factors were a sedentary lifestyle (50.90%), obesity (34.45%), high blood pressure (36.36%) and diabetes (21.81%). Laboratory abnormalities were elevation of troponin (46.87%), BNP (40.62%), D-Dimer (62.50%) and anemia (9.09%). Electrocardiographic abnormalities were tachycardia in 65.4% and S1Q3 in 21.81% of patients. Echocardiography showed dilation of the right cavities (47.27%), systolic pulmonary arterial hypertension (38.18%) and thrombus in the right cavitary (5.45%). On thoracic CT angiography, PE was proximal (36.40%), bilateral (61.80%) and massive (29.10%). On venous Doppler ultrasound, TVP was proximal in 65.21%. <i>Conclusion</i>: VETD was more common in women and younger subjects.

Retro-pancreatic pull-through reconstruction of the hypoplastic portal vein using the autologous mesosystemic shunt vessel in adult living donor liver transplantation: a case report

BackgroundIn liver transplant patients with hypoplastic portal vein (PV), when the narrowed segment is extended too deep into the dorsal side of the pancreas, it is difficult and dangerous to reconstruct the interposition graft from the upper part of the pancreas. Herein, we present a case of PV reconstruction with the autologous mesosystemic shunt vessel from the caudal side of the pancreas in a situation where the narrowed PV was deep, and we discuss the technical details.Case presentationA 25-year-old woman presented with cholestatic liver cirrhosis due to biliary atresia after Kasai procedure. Since her jaundice progressed, she was referred to our hospital for liver transplantation. Laboratory tests showed that her total bilirubin was elevated to 7.6 mg/dL. The Model for End-Stage Liver Disease score was 18, and the Child–Pugh score was 9 (Grade B). She underwent living donor liver transplantation (LDLT) using a right hemi-liver graft procured from her 54-year-old mother. The conventional approach from the cephalad side to the superior mesenteric vein (SMV) and splenic vein (SpV) confluence behind the pancreas was extremely difficult in this case because the confluence of SMV and SpV was close to the lower edge of the pancreas. Therefore, we decided to perform PV reconstruction from the caudal side. The main trunk of PV was documented as narrow (5 mm in diameter), for which retro-pancreatic pull-through PV reconstruction was successfully performed using her own mesosystemic shunt vessel. A contrast computed tomography (CT) scan was performed on postoperative day 5 because of an elevation of D-dimer and found a partial thrombus in the left pulmonary artery, as well as in the PV and left renal vein. Thereafter, thrombolytic therapy with low-molecular-weight heparin was started immediately and switched to a direct oral anticoagulant. The follow-up CT taken 3 months after liver transplantation revealed a patent PV without thrombus; therefore, anticoagulant therapy was discontinued. Currently, the patient has been well and active with a patent PV without anticoagulant therapy for 3 years after LDLT.ConclusionsRetro-pancreatic pull-through reconstruction of the hypoplastic PV is a feasible and effective method when conventional reconstruction is not indicated.

Simple and secure thrombectomy without circulatory arrest for acute pulmonary embolism

BackgroundSurgical pulmonary artery thrombectomy is a well-established emergency treatment for massive pulmonary embolism (PE) in which fibrinolysis or thrombolysis are not effective. However, surgery for massive PE that requires peripheral pulmonary artery thrombus removal remains challenging. We established a simple and secure pulmonary artery thrombectomy method using cardiopulmonary bypass and cardiac arrest. In this procedure, the surgical assistant arm, typically used for coronary artery bypass grafting, is used to obtain a feasible working space during thrombectomy.Case presentationWe present seven consecutive massive PE cases that were treated with the present surgical method and successfully weaned from cardiopulmonary bypass or extracorporeal membrane oxygenation postoperatively.ConclusionsThis procedure can be used to prevent right ventricular failure after surgery as surgeons can remove the peripheral thrombus with clear vision up to the second branch of the pulmonary artery.

A Saddle Pulmonary Embolism at Transthoracic Echocardiography: A Case Report

Acute Pulmonary embolism (PE) is a life-threatening disease and is considered the third major cause of cardiovascular death with higher incidence and mortality rates. Identifying a saddle PE between the left and the right pulmonary trunk in transthoracic echocardiography (TTE) is rare, and helps to make a rapid diagnosis to avoid complications. Clinical presentation, electrocardiogram, and X-ray guide the diagnosis but are not specific. TTE is helpful and confirms the diagnosis especially when the CT is not available or in other situations when it is not realizable. Visualizing a pulmonary artery thrombus in TTE is unusual. It can be identified in the right cardiac chambers in less than 5% of patients with PE. The severity of acute PE is determined by its hemodynamics, the sudden pulmonary hypertension, and the development of obstructive shock. Anticoagulation therapy is the cornerstone of PE management and should be initiated as soon as possible.

Exercise and pulsatile pulmonary vascular loading in chronic thromboembolic pulmonary disease.

Chronic thromboembolic pulmonary disease (CTEPD) is characterized by organized nonresolving thrombi in pulmonary arteries (PA). In CTEPD with pulmonary hypertension (PH), chronic thromboembolic PH (CTEPH), early wave reflection results in abnormalities of pulsatile afterload and augmented PA pressures. We hypothesized that exercise during right heart catheterization (RHC) would elicit more frequent elevations of pulsatile vascular afterload than resistive elevations in patients with CTEPD without PH. The interdependent physiology of pulmonary venous and PA hemodynamics was also evaluated. Consecutive patients with CTEPD without PH (resting mean PA pressure ≤20 mmHg) undergoing an exercise RHC were identified. Latent resistive and pulsatile abnormalities of pulmonary vascular afterload were defined as an exercise mean PA pressure/cardiac output >3 WU, and PA pulse pressure to PA wedge pressure (PA PP/PAWP) ratio >2.5, respectively. Forty-five patients (29% female, 53 ± 14 years) with CTEPD without PH were analyzed. With exercise, 19 patients had no abnormalities (ExNOR), 26 patients had abnormalities (ExABN) of pulsatile (20), resistive (2), or both (4) elements of pulmonary vascular afterload. Exercise elicited elevations of pulsatile afterload (53%) more commonly than resistive afterload (13%) (p < 0.001). ExABN patients had lower PA compliance and higher pulmonary vascular resistance at rest and exercise and prolonged resistance-compliance time product at rest. The physiological relationship between changes in PA pressures relative to PAWP was disrupted in the ExABN group. In CTEPD without PH, exercise RHC revealed latent pulmonary vascular afterload elevations in 58% of patients with more frequent augmentation of pulsatile than resistive pulmonary vascular afterload.

The significance of CD16+ monocytes in the occurrence and development of chronic thromboembolic pulmonary hypertension: insights from single-cell RNA sequencing.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious pulmonary vascular disease characterized by residual thrombi in the pulmonary arteries and distal pulmonary microvascular remodeling. The pathogenesis of CTEPH remains unclear, but many factors such as inflammation, immunity, coagulation and angiogenesis may be involved. Monocytes are important immune cells that can differentiate into macrophages and dendritic cells and play an important role in thrombus formation. However, the distribution, gene expression profile and differentiation trajectory of monocyte subsets in CTEPH patients have not been systematically studied. This study aims to reveal the characteristics and functions of monocytes in CTEPH patients using single-cell sequencing technology, and to provide new insights for the diagnosis and treatment of CTEPH. Single-cell RNA sequencing (scRNA-seq) were performed to analyze the transcriptomic features of peripheral blood mononuclear cells (PBMCs) from healthy controls, CTEPH patients and the tissues from CTEPH patients after the pulmonary endarterectomy (PEA). We established a CTEPH rat model with chronic pulmonary embolism caused by repeated injection of autologous thrombi through a central venous catheter, and used flow cytometry to detect the proportion changes of monocyte subsets in CTEPH patients and CTEPH rat model. We also observed the infiltration degree of macrophage subsets in thrombus tissue and their differentiation relationship with peripheral blood monocyte subsets by immunofluorescence staining. The results showed that the monocyte subsets in peripheral blood of CTEPH patients changed significantly, especially the proportion of CD16+ monocyte subset increased. This monocyte subset had unique functional features at the transcriptomic level, involving processes such as cell adhesion, T cell activation, coagulation response and platelet activation, which may play an important role in pulmonary artery thrombus formation and pulmonary artery intimal remodeling. In addition, we also found that the macrophage subsets in pulmonary endarterectomy tissue of CTEPH patients showed pro-inflammatory and lipid metabolism reprogramming features, which may be related to the persistence and insolubility of pulmonary artery thrombi and the development of pulmonary hypertension. Finally, we also observed that CD16+ monocyte subset in peripheral blood of CTEPH patients may be recruited to pulmonary artery intimal tissue and differentiate into macrophage subset with high expression of IL-1β, participating in disease progression. CD16+ monocytes subset had significant gene expression changes in CTEPH patients, related to platelet activation, coagulation response and inflammatory response. And we also found that these cells could migrate to the thrombus and differentiate into macrophages with high expression of IL-1β involved in CTEPH disease progression. We believe that CD16+ monocytes are important participants in CTEPH and potential therapeutic targets.

Pulmonary Embolism Successfully Treated with Tenecteplase: A case report

Acute pulmonary embolism is a life-threatening situation when presenting with hypotension is called high-risk (massive) pulmonary embolism (PE) which is associated with mortality, especially if there is hemodynamic instability, right ventricular dysfunction with thrombus. Thrombolytic therapy can be lifesaving and leads faster improvement in hemodynamics in patients with acute pulmonary embolism and cardiogenic shock which accelerates the resolution of thrombus, reduction of RV dilatation, mortality and recurrent PE. Only three fibrinolytic agents namely Recombinant tissue-type plasminogen activator (rtPA), Streptokinase and Urokinase have been approved in the treatment of PE. We report the case of a 64 years old Bangladeshi female with a history of immobilization due to unilateral cut injury of foot, who presented with shortness of breath and intermittent chest pain for a duration of 7 days during OPD visit. ECG showed sinus tachycardia (HR-120bpm, regular) and poor progression of R wave. Echocardiography revealed dilated RV, PA with RV dysfunction, presence of McConnell’s sign, RV apical &amp; PA thrombus, flattened IVS, PHT, and minimal pericardial effusion, normal LV systolic function which was reported as suspected pulmonary embolism. Urgent hospitalization and CT pulmonary angiogram (CTPA) was done for confirmatory diagnosis which revealed large pulmonary thrombus in both right and left pulmonary artery. Thrombolysis with Tenecteplase (100ml) over 2 hours was started immediately along with intravenous normal saline and norepinephrine for hypotension, although, it was not recommended by the European Society of Cardiology (ESC) guideline, resulting a successful resolution of the PA thrombus and clinical improvement. She was discharged with oral anticoagulant Rivaroxaban. Bangladesh Heart Journal 2023; 38(2): 148-154

Do Patients with Antiphospholipid Syndrome Have More Significant Venous Thromboembolic Clot Burden?: A Single-Center Retrospective Analysis

Background: Antiphospholipid syndrome (APS) is a prothrombotic condition defined by arterial or venous thrombotic events and/or obstetrical morbidity in the presence of persistently positive antiphospholipid antibodies (aPL). Venous thromboembolic disease (VTE), comprised mostly of deep vein thrombosis (DVT) and pulmonary embolism (PE), is the initial presenting clinical manifestation in approximately 35% of APS diagnoses. VTE is a heterogenous disease and can present with varying degrees of clot burden. Lower extremity DVT can present with thrombus in the iliofemoral, femoropopliteal, and/or distal calf veins; pulmonary embolism can present with thrombus in the main pulmonary arteries, lobar branches, segmental, and/or subsegmental branches. In both DVT and PE, more proximal clot burden portends higher morbidity and mortality. While VTE is a commonly encountered clinical presentation, the decision regarding whom to test for APS is often challenging. Current guidelines recommend that clinicians consider testing for APS in patients with unexplained venous or arterial thrombotic events, especially young patients, or when a patient has one or more specific adverse outcomes related to pregnancy. To date, no data exist to suggest that patients with APS are more likely to present with more extensive venous thromboembolic clot burden as compared to patients without APS. Purpose: To assess clot burden in patients with a co-diagnosis of VTE and APS in comparison to patients with VTE without APS to determine if clot burden should be considered when deciding whom to test for APS. Methods: This retrospective cohort study included adult patients with a history of VTE who had also been tested for APS within a multihospital academic healthcare system from December 1, 2019 through January 31, 2022. All patients in the study had a history of VTE and were considered to be positive for APS if they had persistently positive aPL and/or lupus anticoagulant in accordance with the revised Sapporo APS Classification Criteria. Patients were excluded if they had confounding provoking risk factors for thrombosis. Patients were stratified as APS and non-APS. Significant clot burden was defined as PE involving the main and/or lobar pulmonary arteries or DVT involving the iliofemoral veins. Assessment of clot burden was performed by review of radiology reports of the sentinel clotting event.Patients were further stratified based on age, BMI, insurance status, severity of APS (triple-positive APS versus non-triple-positive APS), and type of APS (primary versus secondary). Exploratory analysis of the patient groups was performed. Summary statistics are presented as percentages for categorical data and median with interquartile range for quantitative data. Chi square test was used to compare percentages and t-test was used to compare means. Univariate and multivariate regression models were used to analyze the predictors of significant clot burden. Results: We identified 748 patients with a history of VTE who had also been tested for APS. The study population was comprised of 53.1% females with a median age of 59 (IQR 46-69). A majority of the patients were Caucasian (85%). APS was detected in 75 (10%) patients. Significant clot burden was present in 29 (38.7%) APS patients and 269 (40.0%) non-APS patients (OR 0.95, 95% CI 0.58-1.56; P = 0.85). On univariate analysis, age (OR 1.01, 95% CI 1.00-1.02; P = 0.02) and being uninsured (OR 9.2, 95% CI 1.10-76.10; P = 0.04) were associated with more significant clot burden. No predictors for significant clot burden were found on multivariable analysis. Triple positive APS (OR 0.83, 95% CI 0.16-4.21; P = 0.82) and primary APS (OR 0.72, 95% CI 0.15-3.45; P = 0.68) were not associated with more significant clot burden. Conclusions: In this retrospective cohort of 748 patients with a history of VTE, the presence of antiphospholipid syndrome was not associated with more significant VTE clot burden as compared to non-APS patients. Based on these data, VTE clot burden may not be a reliable predictor for the presence of APS. Study limitations include selection bias, retrospective design, and lack of precise volumetric measurement of blood clots.

Pulmonary embolism in COVID-19 pneumonia patients admitted to temporary hospital - The follow-up study

PurposeCoronavirus disease 2019 (COVID-19) is linked with major coagulation disorders, especially higher risk of developing pulmonary embolism (PE). Our study summarizes COVID-19 patients’ management with concomitant PE during the first weeks of pandemic and underlines the importance of D-dimer concentration assessment at admission in terms of prognosis. Material and methodsStudy group consisted of 107 outpatients (mean age 68.91 ​± ​12.83 years) admitted to the Temporary COVID-19 Hospital in Bialystok, Poland with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and suspicion of PE based on elevated D-dimer concentration (>500 ​μg/l) and/or low saturation rate (<90%). The clinical follow-up lasted 6 months. Death or re-hospitalization were used as composite clinical endpoint (CEP). ResultsCumulative incidence of PE was 62.3% (73/107 patients). Most of the patients were in the intermediate PE risk group according to the pulmonary embolism severity index (PESI) score. The mean total computed tomography (CT) lung involvement of COVID-19 findings was 48.42 ​± ​27.71%. Neither D-dimers nor NT-proBNP concentrations correlated significantly with the percentage of lung abnormalities in CT. Patients with baseline D-dimer concentration higher than 1429 ​μg/l had worse prognosis in 6-months observation, log-rank test, p ​= ​0.009. ConclusionsOngoing SARS-CoV-2 infection along with massive involvement of lung tissue and concomitant thrombi in pulmonary arteries are challenging for physicians. It seems that simple D-dimer concentration assessment at admission may be a helpful tool not only to predict PE but also to estimate the long-term prognosis.

腹臥位から仰臥位へ体位交換時に肺血栓塞栓症を発症した重症COVID–19肺炎の2例(Two cases of pulmonary embolism after position change from prone position during mechanical ventilation due to severe COVID–19 pneumonia)

COVID–19肺炎では腹臥位呼吸療法の有効性が注目されている。今回，腹臥位から仰臥位への体位交換時に発症した肺血栓塞栓症を2例経験したので報告する。1例目は59歳の男性，発症11日目に人工呼吸を開始し，15日目から腹臥位呼吸療法を開始した。17日目に仰臥位へ体位交換した30分後より，SpO2が94%から85%へと低下し，心拍数も90bpmから120bpmへ上昇した。D–ダイマーが9.2μg/mLから22.5μg/mLへ上昇していたため，肺血栓塞栓症を疑い，造影CTで左肺動脈血栓が判明した。2例目は46歳の男性，発症13日目で人工呼吸を開始し，同日腹臥位呼吸療法を開始した。14日目に仰臥位へ体位交換した10分後より血圧低下，12分後からSpO2が97%から84%へと低下した。D–ダイマーが5.6μg/mLから48.1μg/mLへ上昇していたことと，心臓超音波検査で右心負荷所見がみられたことから肺血栓塞栓症を疑い，造影CTで左内頸静脈血栓と右肺動脈血栓が判明した。今回の2症例は，いずれも腹臥位から仰臥位に体位交換した際に肺血栓塞栓症を発症しており，いずれも中心静脈カテーテル挿入側の内頸静脈に血栓を認めた。長時間の腹臥位から仰臥位への体位交換は，内頸静脈血栓から肺血栓塞栓症を発症させる可能性が示唆され，バイタルサインに留意して行うことが望ましい。 The prone position during mechanical ventilation has been reported to be effective in respiratory failure caused by COVID–19 pneumonia. We report two cases of pulmonary thromboembolism that may have occurred during return to the supine position. A 59–year–old man, with COVID–19 pneumonia, was put on mechanical ventilation in supine position from day 11 to day 15, and prone position from day 15 to day 17. Thirty minutes after returning to the supine position on day 17, he developed hypoxemia and tachycardia. Pulmonary thromboembolism was suspected based upon elevated D–dimer levels. Echo venogram of the right internal jugular vein showed thrombi, and contrast–enhanced computed tomography (CECT) showed thrombi in the left pulmonary artery. A 46–year–old man, with COVID–19 pneumonia, was put on mechanical ventilation in prone position from day 13 to day 14. On day 14, when he was returned to the supine position, he developed hypotension after 10 minutes, and hypoxemia after 12 minutes. CECT showed thrombi in the left internal jugular vein and right pulmonary artery. During mechanical ventilation, a change to the supine position after prolonged prone position may cause pulmonary thromboembolism from thrombi in the internal jugular vein, and should be performed with attention to vital signs. 腹臥位呼吸療法は，acute respiratory distress syndrome（ARDS）の死亡率を低下させる可能性があり 1，COVID–19肺炎にもしばしば実施される。当院でも，集中治療管理を要するCOVID–19肺炎患者に対し，16時から翌日10時の18時間を腹臥位，残りの6時間を仰臥位とする腹臥位呼吸療法を施行した。腹臥位呼吸療法での合併症として，気管チューブ閉塞，事故抜管，静脈路の事故抜去，褥瘡，視力障害，腕神経叢損傷などが報告されている 2。今回，腹臥位から仰臥位への体位交換を契機に発症した肺血栓塞栓症（pulmonary embolism: PE）を2例経験したので報告する。 なお，本症例の報告は倫理委員会の承諾は不要であり，個人情報保護法に基づいて匿名化がなされ，患者・家族の同意を得ている。 患 者：59歳の男性 既往歴：痛風，脂質異常症 現病歴：発熱・頭痛で発症し，同日SARS–CoV–2 PCR陽性と判明した。発症5日目に酸素化不良のため，当院に入院となった。11日目に呼吸状態悪化のため気管挿管し，人工呼吸管理となった。 入院後経過：気管挿管後より，深部静脈血栓症（deep vein venous thrombosis: DVT）予防を目的として，ヘパリンカルシウム5,000単位の皮下注射を1日2回開始した。発症13日目に撮像した体幹部造影CTでは，PE，DVTともに指摘されなかったが，14日目にD–ダイマーが9.8µg/mLと上昇した。超音波検査で，中心静脈カテーテル挿入側である右内頸静脈に血栓を認め（Fig. 1a），リバーロキサバン15mg内服を開始した。また，13日目に撮像したCTでは背側の無気肺が著明であり，人工呼吸器関連肺炎も併発したため，背面開放と体位ドレナージを目的とし，15日目より腹臥位呼吸療法を開始した。17日目に，腹臥位から仰臥位に体位交換した30分後より，SpO2が94%から85%へと低下し，心拍数も90bpmから120bpmへ上昇した（Fig. 2）。 Case 1: Jugular vein echo (a). major and minor axis image showing right internal jugular vein (white arrow). Chest computed tomography (b). Axial view showing left main pulmonary artery thrombus (white triangle). Case 1: Course at onset of pulmonary embolism. ベッドサイドで可能な検査や理学所見では，気胸や痰による閉塞性無気肺を認めなかった。超音波検査では右心拡大を認めなかったが，依然として右内頸静脈に血栓が存在していた。両側大腿静脈，膝窩静脈には，血栓はみられなかった。右内頸静脈血栓があること，D–ダイマーが22.5µg/mLと上昇（前日9.2µg/mL）していること，また長時間の腹臥位から体位交換をした際に起きた酸素化低下と頻脈であることから，PEを強く疑った。既にリバーロキサバン内服が行われていたが，治療量でなかったため30mgに増量し，翌日待機的に造影CTを施行した。造影CTでは，左主肺動脈に血栓塞栓症がみられた（Fig. 1b）。以上の所見より，腹臥位から仰臥位への体位交換を契機に発症したPEと診断した。 その後，COVID–19肺炎後器質化肺炎に対して，プレドニゾロン60mg/day（1mg/kg）を開始した。発症25日目に38度台の発熱があり，膿性痰が出現したため，人工呼吸器関連肺炎としてピペラシリン・タゾバクタム13.5ｇ/日を投与開始した。その後のCTで，左肺に多発空洞影を認め，肺化膿症と診断した。抗菌薬治療を60日間継続した後，発症93日目に，リハビリテーション目的に転院となった。 患 者：49歳の男性 既往歴：慢性中耳炎 現病歴：咽頭痛・発熱で発症し，翌日SARS–CoV–2 PCR陽性と判明した。呼吸困難感が出現したため，発症11日目に前医入院となった。呼吸状態悪化のため翌日当院に転院となり，13日目に気管挿管を施行し，人工呼吸管理を開始した。 入院後経過：気管挿管後より，DVT予防を目的として，ヘパリンカルシウム5,000単位の皮下注射を1日2回開始した。気管挿管後も酸素化が改善しなかったため，同日夕方より腹臥位呼吸療法を開始した。翌日，腹臥位から仰臥位に体位交換した10分後から，徐々に血圧が低下し，SpO2も低下した（Fig. 3）。 Case 2: Course at onset of pulmonary embolism. ベッドサイドで可能な検査や理学所見では，気胸や痰による閉塞性無気肺を認めなかった。超音波検査では，両側大腿静脈，膝窩静脈には血栓を認めなかったが，左内頸静脈の中心静脈カテーテル周囲に血栓を認め，右心拡大も認めた。左内頸静脈血栓があること，D–ダイマーが48.1µg/mLと上昇（前日5.6µg/mL）していること，右心負荷所見があり，長時間の腹臥位から体位交換をした際に起きた血圧低下，酸素化低下であることから，PEを強く疑った。APTTの目標を50secとしてヘパリンナトリウム14,000U/dayの持続静脈注射を開始し，同日に造影CTを施行した。造影CTでは左内頸静脈（下顎角から胸鎖関節付近の鎖骨下静脈合流部），および右肺動脈に血栓を認めた（Fig. 4a, b）。 Case 2: Chest computed tomography. Axial view showing right pulmonary artery thrombus in the middle lobe (a. white triangle). Axial view showing left internal jugular vein thrombus (b. white arrow). 以上の所見より，腹臥位から仰臥位へ体位交換した際に発症したPEと診断した。発症第15日目に人工呼吸器関連肺炎を発症したため，セフェピム3g/日を投与開始した。16日目に，P/F ratioが191から289へ改善し，18日目に気管チューブを抜去した。また，19日目にヘパリンからリバーロキサバン30mg/dayへ変更し，22日目に前医に再転院となった。 PEの塞栓源は，約90%が下肢あるいは骨盤内の静脈とされている。しかし，2例とも内頸静脈に血栓があり，超音波検査と造影CTで，両下肢静脈内に明らかな血栓はみられなかった。このことから，内頸静脈血栓からの塞栓子が原因で，PEを発症したと考えられる。集中治療を行う場合，内頸静脈への中心静脈カテーテル留置を行う機会が多いが，中心静脈カテーテルの挿入は内頸静脈血栓形成のリスクとして知られている 3。また，2例ともヘパリンの予防投与を行っていたが，中心静脈カテーテル挿入側の内頸静脈に血栓を認めた。COVID–19では，血管内皮細胞にもSARS–CoV–2感染が成立する。ウイルス感染により障害された血管内皮細胞からの凝固第VIII因子とvon Willebrand factorの放出や，サイトカインストームが血栓傾向の誘引となり，深部静脈血栓症の発症率が上昇するとされている 4。 なお，今回の2症例目では，中心静脈カテーテルを挿入した同日16時ごろから翌日10時ごろまで腹臥位呼吸療法を行い，仰臥位に体位交換をした際にPEを生じている。中心静脈カテーテル挿入時の超音波検査では血栓を認めておらず，腹臥位呼吸療法を行っている18時間の間に，血栓が形成された可能性が高い。鎖骨による鎖骨下静脈合流部への圧迫で内頸静脈の血流うっ滞が生じ，内頸静脈血栓の形成に腹臥位が寄与していた可能性が考えられる。1例目においても，長時間の腹臥位が，既存の内頸静脈血栓の伸展を助長した可能性がある。このような血栓形成のリスクが重なり，ヘパリン予防投与を行っていたにもかかわらず血栓が形成されたと考えられる。 DVTは，通常発生部位から中枢へ成長する過程で，血栓中枢端や伸展血栓が遊離，もしくは血栓の静脈壁接着面が剥離して塞栓子となる。関節周囲や下腿筋ポンプ内のような特殊な状況では，起立，歩行などの際に下肢の筋肉が収縮し，伸展血栓が容易に塞栓化しやすいとされている 5。腹臥位呼吸療法において，腹臥位から仰臥位へ体位交換したことを契機としてPEを発症したという報告は，我々の渉猟する限りみられなかったが，脊椎手術では数例報告されている 6, 7。腹臥位中は，鎖骨による圧迫や胸腔内圧上昇に伴い，内頸静脈や下大静脈のうっ滞が起こることが示唆されている。腹臥位から仰臥位への体位交換で，これらが解除されることにより，血行動態が一時的に変化しうる。それにより，体位交換という受動的な運動であっても，長時間の腹臥位の間に伸展，形成された内頸静脈血栓が遊離した可能性が考えられる。 腹臥位から仰臥位に体位交換した際の酸素化低下はしばしば経験され，原病が重篤，あるいは背側無気肺が著明である場合は，対症療法を行うのみで見過ごされてしまう可能性もある。しかし，今回1例目は頻脈，2例目では血圧低下と，SpO2の低下以外にもバイタルサインの変化を認めていた。COVID–19の血栓症発症リスクが高いことも踏まえ 8, 9，PEを鑑別にあげて対応し，治療介入することができた。さらに2例目は，1例目の経験から，仰臥位への体位交換が内頸静脈血栓を塞栓子としたPE発症の契機となる可能性があることを認識していた。そのため，ベッドサイドでの超音波検査で，両側大腿静脈に加え内頸静脈も観察を行い，内頸静脈血栓を認知することができ，PEを鑑別疾患の上位に挙げることができた。なお，両症例ともPE発症日の採血でD–ダイマーの上昇がみられていた。腹臥位呼吸療法施行中のD–ダイマー上昇は，血栓形成もしくは伸展を示唆している可能性があり，仰臥位に復帰した際にバイタルサイン変動がみられた場合には，PEの発症を疑う必要があると考える。なお，ARDS患者の腹臥位では健常人と異なり，換気血流比不均等の改善による右心負荷の軽減や，左心前負荷増大により，心拍出量が増加する 10。仰臥位への体位交換時には，これらの血行動態の変化は速やかに元に戻り，心拍出量は低下する。これは，PEを発症した際の重症度を高める可能性がある。 当院では，腹臥位からの体位交換時はSpO2，心電図，end–tidal CO2などの観血的動脈圧以外の一部モニターを外していた。同様にモニターを外しており初期症状であるバイタルサインの変化を察知できずに 11，心停止まで至った脊椎手術症例の報告もある 6。今回2例とも，モニターは仰臥位復帰後早急に再装着され，バイタルサインの変化に早期に気づくことができた。モニター未装着となる時間を短縮することが，早期にPEの兆候を察知するために重要である。なお，PE発症時にSpO2低下はよくみられるが，より劇的な症例では急激にend–tidal CO2が低下することが知られており，脊椎手術中end–tidal CO2低下がPE発症覚知の一助となった報告もある 12。当院では腹臥位から仰臥位への体位交換時，end–tidal CO2モニターを外していることがほとんどであった。end–tidal CO2モニターは，頭側で回路混線せずに装着したまま安全に体位交換できるため，今後の腹臥位療法では，装着を継続して体位交換することも，検討の余地がある。 腹臥位呼吸療法時は，内頸静脈還流のうっ滞などにより形成・伸展した内頸静脈血栓が，仰臥位への体位交換で遊離しPEを発症する恐れがあるため，注意して体位交換を行う必要がある。また，腹臥位からの体位復帰時に生じる循環虚脱や肺酸素化能の低下にはPEが関与している可能性があり，これらのバイタルサインの変化を早期に察知するために，装着可能なモニターはできる限り装着を継続し，困難な場合にもモニター未装着時間を可能な限り短縮して迅速な体位交換を行うことが望ましい。 著者全員に本論文に関する利益相反はない。

Choledochoscope-guided treatment of pulmonary embolism caused by ventricular myxoma

A 33-year male patient presented with a 6-month history of cough and shortness of breath upon physical activity. Echocardiography demonstrated right ventricular space-occupying lesions. Contrast-enhanced computed tomography of the chest showed multiple emboli in the pulmonary artery and its branches. Right ventricle tumor (myxoma) resection, tricuspid valve replacement, and clearance of the pulmonary artery thrombus were performed under cardiopulmonary bypass. Minimally invasive forceps and balloon urinary catheters were used to clear the thrombus. Clearance was confirmed by direct visualization using a choledochoscope. The patient recovered well and was discharged. The patient was prescribed oral warfarin 3 mg/day, and the international normalized ratio for prothrombin time was maintained between 2.0 and 3.0. Pre-discharge echocardiogram showed no lesion in the right ventricle or pulmonary arteries. The 6-month follow-up echocardiography indicated that the tricuspid valve was functioning well and showed no thrombus in the pulmonary artery.

Distribution of thrombus predicts severe reperfusion pulmonary edema after pulmonary endarterectomy

ObjectivesPatients underwent pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH). This study aimed to investigate the effect of thrombus distribution on the occurrence of severe reperfusion pulmonary edema (RPE) and identify specific parameters for predicting severe RPE. MethodsPatients with CTEPH who underwent PEA surgery were retrospectively analyzed. The thrombus in pulmonary arteries were evaluated through computed tomography pulmonary angiography. Based on presence of prolonged artificial ventilation, extracorporeal membrane oxygenation required, or perioperative death due to RPE, the patients were divided into the severe RPE and without severe RPE groups. Main resultsAmong the 77 patients (29 women), 16 (20.8%) patients developed severe RPE. The right major pulmonary artery (RPA) (0.64[0.58, 0.73] vs 0.58[0.49, 0.64]; p = 0.008) and pulmonary artery trunk (PAT) thrombus ratios (0.48[0.44, 0.61] vs 0.42[0.39, 0.50]; p = 0.009) (the PAT ratio is expressed as the sum of the right middle lobe clot burden and right lower lobe clot burden divided by the total clot burden multiplied by 100) of the severe RPE group was significantly higher than that of the without severe RPE group. Receiver operator characteristics curve identified a PAT ratio of 43.4% as the threshold with areas under the curve = 0.71(95%CI 0.582; 0.841) for the development of severe RPE (sensitivity 0.875, specificity 0.541). The logistic regression analysis demonstrated that age, period from symptom onset to PEA, NT-pro BNP, preoperative mPAP, preoperative PVR, RPA ratio, and PAT ratio were associated with the development of severe RPE. Multivariable logistic regression analysis revealed PAT ratio (odds ratio = 10.2; 95% confidence interval 1.87, 55.53, P = 0.007) and period from symptom onset to PEA (OR = 1.01; 95% CI = 1.00–1.02, P = 0.015) as independent risk factors for the development of severe RPE. ConclusionsThe thrombus distribution could be a key factor in the severity of RPE. PAT ratio and medical history could predict the development of severe RPE.

Venous Thrombosis Due to Duplication of the Inferior Vena Cava with Decreased Protein C Activity: A Case Report

Introduction: Duplication of the inferior vena cava (IVC) is a congenital venous malformation that occurs in 0.2%-3% of the population as a result of persistent left and right supracardinal veins. The IVC duplication is prone to deep vein thrombosis due to endothelial dysfunction and associated venous stasis. This is a rare case of recurrent venous thrombosis due to IVC duplication and decreased protein C activity. Case: A 57-year-old male presented with swelling of the left lower limb that gradually developed over a one-week period preceding his visit. He reported a history of superior mesenteric vein thrombosis, approximately three years ago, for which he received anticoagulation therapy for three months. Thoracoabdominal contrast-enhanced computed tomography (CT) revealed thrombi in the locations of the bilateral main pulmonary arteries, IVC duplication, left common iliac vein, left IVC, and left renal vein. Blood work confirmed protein C activity of 21% (baseline 64%-146%), that could have contributed to the recurrent IVC thrombosis and formation of pulmonary artery thrombus. Subsequently, the patient was hospitalized and started on anticoagulation therapy. The swelling in the left lower extremity gradually improved, and the patient was instructed to continue anticoagulation therapy permanently. Conclusion: When investigating venous thrombosis of unknown or recurrent origin, it is necessary to include venous malformations and abnormal activity of blood coagulation factors in differential diagnosis.

Assessment of Utility of Computed Tomography Pulmonary Angiography in Pulmonary Embolism

Background: Among all the available diagnostic tools, computed tomography (CT) is the preferred diagnostic tool for clinically suspected pulmonary embolism (PE) cases. Further, with the development of multi–detector row CT (MDCT) technology, previous limitations of CT have been overcome effectively. For patients with clinical suspicion of PE, MDCT pulmonary angiography has become the first line of modality for the diagnosis. Aims and Objectives: To evaluate various common observations of CT pulmonary angiography (CTPA) in suspected cases of PE that could accurately determine the choice of management. Materials and Methods: Fifty patients with clinically suspected PE referred to the department of Radiodiagnosis for CTPA from various departments were studied in the cross-sectional study. CT images were obtained with a SIEMENS 64-slice multi-detector CT scanner (somatom definition AS). Images were reconstructed into 3D, axial, coronal, sagittal maximum intensity projection sections, and volume rendering techniques. The axial as well as reformatted coronal and sagittal images were evaluated. Results: The incidence of PE was 52%. The incidence of PE was highest in patients older than 60 years (30.8%) and males (30.3%; p=0.662). The most common symptoms evoking a suspicion of pulmonary embolism were dyspnea (69.2%), followed by chest pain (15.4%), cough (11.5%), and hemoptysis (3.8%). Out of 26 patients who had PE, 61.5% had right ventricular enlargement. DVT (23.1%) was the most common past history. The majority of the patients had thrombus in the right main pulmonary artery (21.1 %), followed by the left main pulmonary artery (19.3 %). Conclusion: In clinically suspected cases of PE, MDCT pulmonary angiography was a useful diagnostic tool. CTPA is the modality of choice for its rapid, minimally invasive, and well-tolerated nature.

Retrospective Analysis of the Safety and Efficacy of AngioJet Rheolytic Thrombectomy for Acute Pulmonary Embolism: A Single-Center Study

To investigate the efficacy, safety and feasibility of AngioJet Rheolytic Thrombectomy (ART) in the treatment of acute pulmonary embolism (APE). Twelve patients with intermediate- or high-risk APE received ART and were followed up for 6 to 32 months. The technical success rate, clinical success rate, mortality, complication, and ancillary and laboratory tests before and after operation were analyzed retrospectively. The technical and clinical success rate of ART were both 91.67% (11/12). Except for the patient who died of heart failure during the operation, the rest of patients had no serious complications. After operation, PaO2 increased while HGB and Tn decreased (P<0.05). All patients were free of recurrence of APE after 6 to 32 months of follow-up. Pulmonary artery thrombosis significantly reduced or disappeared. ART is an effective treatment for intermediate- and high-risk APE. It quickly clears the main pulmonary artery thrombus, relieves pulmonary hypertension and improve the long-term prognosis of patients.

Pulmonary embolism caused by hepatocellular carcinoma with tumor thrombus extending from hepatic veins into inferior vena cava and right atrium.

A 63-year-old man presented to emergency department with a 2-hour history of chest tightness and suffocation. The oxygen saturation was 50% while he was breathing ambient air. Laboratory evaluation revealed D2 polymer level, 0.69 mg/L (reference range, 0 to 0.50), activated partial thromboplastin time, 75.0 s (reference range, 28.0 to 43.5). Computed tomography angiography of the chest showed thrombus in the right pulmonary artery, inferior vena cava and right atrium. Coronal view also demonstrated a hepatic mass with a massive neovascularization, extending from hepatic veins into the inferior vena cava.

Comparative study on Various Tube Voltages and Contrast Media Doses in CT Pulmonary Angiography to detect Pulmonary Thromboembolism

Background: Lowering the amount of iodinated contrast material and tube voltage may increase pulmonary artery opacification and thrombus identification without compromising picture quality. Objectives: To explore the efficiency of using lower tube voltage and a lower contrast medium dose for conducting computed tomography for pulmonary angiography (CTPA) aiming to increase its accuracy in detecting pulmonary thromboembolism (PTE). Subjects and Methods:100 patients scheduled for CTPA with a preoperative diagnosis of PTE were grouped into two: group A, (50 patients) got 1 mL/kg at 120 kV and group B, (50 patients) received 0.5 mL/kg at 80 kV.The technique of bolus tracking was implemented.Values of midpoint of multiple pulmonary artery divisions were used to assess attenuation.Significant values are those that exceed 300 Hounsfield units (HU). The dosage of radiation received by the patient, defined as the effective dose, was compared between groups. Results: Total mean attenuationdata for the pulmonary arteries have shown to be substantially greater in group-B compared to group-A (39110.4HU vs. 335.97.9HU, P=0.001). Moreover, total dose length product (DLP) values were substantially lower in group-B (934.9 mGy.cm vs. 384.443 mGy.cm, P=0.001). While effective dose values have shown to be significantly lower in group-B (2.90.3 mSv vs. 13.21.8 mSv, P 0.001). Conclusion: Low-kilovoltage technique and low quantity of iodinated contrast are useful in conducting (CTPA) with high accuracy in detection of pulmonary thromboembolism.