Abstract:
:Acute respiratory distress syndrome in patients with Coronavirus disease 19 is associated with an unusually high incidence of pulmonary embolism and microthrombotic disease, with evidence for reduced fibrinolysis. We describe seven patients requiring invasive ventilation for COVID-19-associated acute respiratory distress syndrome with pulmonary thromboembolic disease, pulmonary hypertension ± severe right ventricular dysfunction on echocardiography, who were treated with alteplase as fibrinolytic therapy. All patients were non-smokers, six (86%) were male and median age was 56.7 (50-64) years. They had failed approaches including therapeutic anticoagulation, prone ventilation (n = 4), inhaled nitric oxide (n = 5) and nebulised epoprostenol (n = 2). The median duration of mechanical ventilation prior to thrombolysis was seven (5-11) days. Systemic alteplase was administered to six patients (50 mg or 90 mg bolus over 120 min) at 16 (10-22) days after symptom onset. All received therapeutic heparin pre- and post-thrombolysis, without intracranial haemorrhage or other major bleeding. Alteplase improved PaO2/FiO2 ratio (from 97.0 (86.3-118.6) to 135.6 (100.7-171.4), p = 0.03) and ventilatory ratio (from 2.76 (2.09-3.49) to 2.36 (1.82-3.05), p = 0.011) at 24 h. Echocardiographic parameters at two (1-3) days (n = 6) showed right ventricular systolic pressure (RVSP) was 63 (50.3-75) then 57 (49-66) mmHg post-thrombolysis (p = 0.26), tricuspid annular planar systolic excursion (TAPSE) was unchanged (from 18.3 (11.9-24.5) to 20.5 (15.4-24.2) mm, p = 0.56) and right ventricular fractional area change (from 15.4 (11.1-35.6) to 31.2 (16.4-33.1)%, p = 0.09). At seven (1-13) days after thrombolysis, using dual energy computed tomography imaging (n = 3), average relative peripheral lung enhancement increased from 12.6 to 21.6% (p = 0.06). In conclusion, thrombolysis improved PaO2/FiO2 ratio and ventilatory ratio at 24 h as rescue therapy in patients with right ventricular dysfunction due to COVID-19-associated ARDS despite maximum therapy, as part of a multimodal approach, and warrants further study.
journal_name
Pulm Circjournal_title
Pulmonary circulationauthors
Price LC,Garfield B,Bleakley C,Keeling AGM,Mcfadyen C,McCabe C,Ridge CA,Wort SJ,Price S,Arachchillage DJdoi
10.1177/2045894020973906subject
Has Abstractpub_date
2020-12-15 00:00:00pages
2045894020973906issue
4eissn
2045-8932issn
2045-8940pii
10.1177_2045894020973906journal_volume
10pub_type
杂志文章abstract::Despite the discovery more than 15 years ago that patients with hereditary pulmonary arterial hypertension (HPAH) inherit BMP type 2 receptor ( BMPR2) mutations, it is still unclear how these mutations cause disease. In part, this is attributable to the rarity of HPAH and difficulty obtaining tissue samples from patie...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894018765840
更新日期:2018-04-01 00:00:00
abstract::Atrial arrhythmias are common during episodes of acute respiratory failure in patients with chronic lung disease-associated pulmonary hypertension. Expert opinion suggests that management of atrial arrhythmias in patients with pulmonary hypertension should aim to restore sinus rhythm. This is clinically challenging in...
journal_title:Pulmonary circulation
pub_type: 杂志文章,评审
doi:10.1177/2045894020910685
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abstract::With the advancement of computed tomography pulmonary angiography, differentiating between acute and chronic thrombus in pulmonary embolism has become more feasible. However, whether pulmonary embolism with chronic thrombus contributes to a higher mortality than pulmonary embolism with acute thrombus remains undetermi...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894020905510
更新日期:2020-05-01 00:00:00
abstract::Late-onset pulmonary arterial hypertension (PAH) is a rare but fatal complication in patients with childhood surgical repair of dextro-transposition of great arteries (D-TGA), especially with the Mustard and Senning procedures. The pathogenic mechanisms of PAH in patients with repaired D-TGA are not well understood an...
journal_title:Pulmonary circulation
pub_type:
doi:10.1177/2045893217699228
更新日期:2017-04-01 00:00:00
abstract::Patients with chronic thromboembolic pulmonary hypertension (CTEPH) require lifelong anticoagulation therapy. However, the bleeding risk and recurrence of venous thromboembolism (VTE) in CTEPH patients who are administered warfarin have not been adequately evaluated. The purpose of this study was to evaluate the risk ...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045893217717258
更新日期:2017-07-01 00:00:00
abstract::A loss of K+ efflux in pulmonary arterial smooth muscle cells (PASMCs) contributes to abnormal vasoconstriction and PASMC proliferation during pulmonary hypertension (PH). Activation of high-conductance Ca2+-activated (BK) channels represents a therapeutic strategy to restore K+ efflux to the affected PASMCs. However,...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/688838
更新日期:2016-12-01 00:00:00
abstract::Pulmonary hypertension is recognized as a leading cause of morbidity and mortality in patients with sickle cell disease (SCD). We now report benchtop phenotyping from the explanted lungs of the first successful lung transplant in SCD. Pulmonary artery smooth muscle cells (PASMCs) cultured from the explanted lungs were...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/674754
更新日期:2013-12-01 00:00:00
abstract::Transforming growth factor-β (TGF-β) inhibition is an investigational therapy for pulmonary arterial hypertension with promising results in experimental studies. The present work compared this approach with endothelin-receptor blockade and evaluated the effects of combined administration. Pulmonary arterial hypertensi...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.4103/2045-8932.105034
更新日期:2012-10-01 00:00:00
abstract::Carboxyl terminus of Hsc70-interacting protein (CHIP) is a 35-kDa cytoplasmic protein expressed in human striated muscle, brain, aortic smooth muscle, endothelial cells, and other tissues. Studies have confirmed that CHIP regulates cell growth, apoptosis, cell phenotype, metabolism, neurodegeneration, etc. However, wh...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894019875343
更新日期:2019-09-09 00:00:00
abstract::Echocardiography, a non-invasive and cost-effective method for monitoring cardiac function, is commonly used for evaluation and pre-clinical diagnostics of pulmonary hypertension (PH). Previous echocardiographic studies in experimental models of PH are fragmentary in terms of the evaluation of right ventricle (RV) fun...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894019841987
更新日期:2019-04-01 00:00:00
abstract::Oral treprostinil (TRE) is a prostacylin that is approved for the treatment of patients with pulmonary arterial hypertension (PAH). Dosing is approved for two or three times daily (t.i.d.); however, adverse effects, including gastrointestinal-related symptoms, may limit the ability to reach optimal doses. We report ou...
journal_title:Pulmonary circulation
pub_type:
doi:10.1177/2045893217744512
更新日期:2018-01-01 00:00:00
abstract::Inhaled iloprost is an effective therapy for patients with pulmonary arterial hypertension (PAH); however, some patients experience extended inhalation times when using the V10 formulation (10.0 µg/mL) to deliver a 5 -µg dose (at mouthpiece) and are at risk of incomplete inhalations and reduced inhalation frequency. V...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894018798921
更新日期:2018-10-01 00:00:00
abstract::South America is a territory of 17,819,100 km(2), where ∼388 million people live in 13 countries. In the region, access to medical assistance (e.g., for treatment of cardiovascular disorders) is relatively easy in metropolitan areas but difficult in remote places such as the Andes and the Amazon. Altitudes up to ∼6,70...
journal_title:Pulmonary circulation
pub_type: 杂志文章,评审
doi:10.1086/676747
更新日期:2014-09-01 00:00:00
abstract::Pharmacokinetic studies with oral treprostinil demonstrate that three times daily (TID) dosing reduces peak-to-trough plasma trepostinil fluctuations compared with twice daily (BID) dosing. TID dosing may allow for faster titration, higher total daily doses, and potentially improve the tolerability of oral trepostinil...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894018770654
更新日期:2018-04-01 00:00:00
abstract::Many dyspneic patients who undergo computerized tomographic pulmonary angiography (CTPA) for presumed acute pulmonary embolism (PE) have no identified cause for their dyspnea yet have persistent symptoms, leading to more CTPA scanning. Right ventricular (RV) dysfunction or overload can signal treatable causes of dyspn...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/679723
更新日期:2015-03-01 00:00:00
abstract::In a subgroup of patients with systemic sclerosis (SSc), vasospasm affecting the pulmonary circulation may contribute to worsening respiratory symptoms, including dyspnea. Noninvasive assessment of pulmonary blood flow (PBF), utilizing inert-gas rebreathing (IGR) and dual-energy computed-tomography pulmonary angiograp...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/682221
更新日期:2015-09-01 00:00:00
abstract::Our aim is to assess the safety and potential efficacy of a novel treatment paradigm in pulmonary arterial hypertension (PAH), immunomodulation by blocking interleukin-6 (IL6) signaling with the IL6 receptor antagonist, tocilizumab. Inflammation and autoimmunity are established as important in PAH pathophysiology. One...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045893217735820
更新日期:2018-01-01 00:00:00
abstract::Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of unresolved organised pulmonary emboli/thrombi obstructing the major pulmonary arteries. The aim of this study was to estimate the incidence and risk factors of CTEPH in a cohort with first venous thromboembolism (VTE). This was a population-bas...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894018791358
更新日期:2018-07-01 00:00:00
abstract::Cardiac magnetic resonance-derived ventricular variables are predictive of mortality in pulmonary arterial hypertension. Rodent models which emphasize ventricular function, allowing serial monitoring, are needed to identify pathophysiological features and novel therapies for pulmonary arterial hypertension. We investi...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894019897513
更新日期:2020-02-10 00:00:00
abstract::Radiotherapy as a primary treatment for thoracic malignancies induces deleterious effects, such as acute or subacute radiation-induced lung injury (RILI). Although the molecular etiology of RILI is controversial and likely multifactorial, a potentially important cellular target is the lung endothelial cytoskeleton tha...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/686491
更新日期:2016-06-01 00:00:00
abstract::Schistosomiasis-associated pulmonary arterial hypertension (PAH) is one of the most common causes of pulmonary hypertension worldwide. A potential contributing mechanism to the pathogenesis of this disease is a localized immune reaction to retained and persistent parasite-derived antigens. We sought to identify Schist...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.4103/2045-8932.93544
更新日期:2011-10-01 00:00:00
abstract::Right-ventricular function is a good indicator of pulmonary arterial hypertension (PAH) prognosis; however, how the right ventricle (RV) adapts to the pressure overload is not well understood. Here, we aimed at characterizing the time course of RV early remodeling and discriminate the contribution of ventricular geome...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894018800439
更新日期:2018-10-01 00:00:00
abstract::This study aimed to identify receptors mediating sphingosine-1-phosphate (S1P)-induced vasoconstriction in the normotensive and chronic hypoxia-induced hypertensive rat pulmonary circulation. In isolated perfused lungs from normoxic rats, infusion of S1P caused a sustained vasoconstriction, which was not reduced by co...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.4103/2045-8932.87309
更新日期:2011-07-01 00:00:00
abstract::Inappropriate mechanical ventilation may induce hemodynamic alterations through cardiopulmonary interactions. The aim of this study was to explore the relationship between airway pressure and central venous pressure during the first 72 h of mechanical ventilation and its relevance to patient outcomes. We conducted a r...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894020970363
更新日期:2020-11-25 00:00:00
abstract::Endothelial dysfunction plays an important role in the pathogenesis of pulmonary arterial hypertension (PAH) in sickle cell disease (SCD). A variety of evidence suggests that circulating endothelial progenitor cells (EPCs) play an integral role in vascular repair. We hypothesized that SCD patients with PAH are deficie...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.4103/2045-8932.94834
更新日期:2012-01-01 00:00:00
abstract::Inhaled treprostinil (Tyvaso) has been shown to be a safe and effective addition to pulmonary arterial hypertension (PAH) oral therapies; however, the respiratory-related safety profile of inhaled treprostinil required further elucidation in the setting of routine clinical care. The objectives of this study were to ch...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/688059
更新日期:2016-09-01 00:00:00
abstract::Pulmonary hypertension currently has minimal guidelines for outpatient disease management. Congestive heart failure studies, however, have shown effectiveness of disease management plans in reducing all-cause mortality and all-cause and congestive heart failure-related hospital readmissions. Heart failure exacerbation...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894020968471
更新日期:2020-12-07 00:00:00
abstract::Despite recent advances, the prognosis of pulmonary hypertension (PH) remains poor. While the initial insult in PH implicates the pulmonary vasculature, the functional state, exercise capacity, and survival of such patients are closely linked to right ventricular (RV) function. In the current study, we sought to inves...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894019862435
更新日期:2019-07-01 00:00:00
abstract::In 301 treatment-naïve patients with pulmonary arterial hypertension stratified by the European Society of Cardiology/European Respiratory Society risk score, further stratification of intermediate-risk patients based on six-minute walk distance and the tricuspid annular plane systolic excursion/systolic pulmonary art...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894020961739
更新日期:2020-10-07 00:00:00
abstract::Scleroderma-associated pulmonary arterial hypertension (SSc-PAH) is associated with worse outcome than idiopathic pulmonary arterial hypertension (IPAH), potentially due to worse right ventricular adaptation to load as suggested by pressure-volume loop analysis. The value of non-invasive load-adaptability metrics has ...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894018788268
更新日期:2018-07-01 00:00:00