Guideline Compliance and Indications for Inferior Vena Cava Filter Placement at a Quaternary Care Medical Center.

PURPOSE: This study investigated physician compliance with indications for inferior vena cava (IVC) filter placement according to the 2012 American College of Chest Physicians (ACCP) and the 2011 Society of Interventional Radiology (SIR) guidelines. MATERIALS AND METHODS: A retrospective medical record review of 231 retrievable IVC filters placed between August 15, 2016, and December 28, 2017, at a large urban academic medical center. Guideline compliance to the 2012 ACCP and the 2011 SIR guidelines, and indications for IVC filter placements were assessed through an adjudication protocol. Filter retrieval and complication rates were also examined. RESULTS: Compliance to guidelines was low (60.2% for ACCP; 74.0% for SIR), especially for non-intensive care unit (ICU) patients (ICU 74.6% vs non-ICU 54.8%, p=0.007 for ACCP; ICU 82.5% vs non-ICU 70.8%, p=0.092 for SIR). After adjudication, 8.2% (19/231) of filters were considered non-indicated but reasonable, 17.7% (41/231) non-indicated and unreasonable, and 13.9% (32/231) SIR-indicated but not ACCP-indicated. The most common indication was venous thromboembolism with contraindication to anticoagulation. The most common reasons for non-compliance were distal deep venous thrombosis with contraindication to anticoagulation (19/60, 31.6%) and clot burden (19/60, 31.6%). One-year filter retrieval and 90-day complication rates were 32.0% (74/231) and 6.1% (14/231), respectively. CONCLUSION: Compliance to established guidelines was low. Reasons for non-compliance included limitations or discrepancies in guidelines, as well as non-evidence-based filter placements. CLINICAL IMPACT: Despite increasing utilization of inferior vena cava (IVC) filters, guideline compliance for IVC filter placement among providers is unclear. The results of this study indicate that physician compliance to established guidelines is poor, especially in non-intensive-care-unit patients. Noncompliance stems from non-evidence-based filter placement as well as differences and limitations in guidelines. Avoiding non-indicated IVC filter placement and consolidation of guidelines may significantly improve guideline compliance. The critical insights gained from this study can help promote judicious use of IVC filters and highlight the role of venous thromboembolism experts in navigating complex cases and nuances of guidelines.

Efficacy of Inhaled Treprostinil on Multiple Disease Progression Events in Patients with Pulmonary Hypertension due to Parenchymal Lung Disease in the INCREASE Trial.

Rationale: The INCREASE study of inhaled treprostinil met its primary endpoint of change in 6-minute-walk distance at Week 16. In addition, there were significantly fewer clinical worsening events in patients receiving inhaled treprostinil. However, the incidence of multiple events in the same patient is unknown. Objectives: This post hoc analysis evaluated the effect of continued treatment with inhaled treprostinil on the frequency and impact of multiple disease progression events. Methods: Patients enrolled in INCREASE were analyzed for disease progression events, defined as at least 15% decline in 6-minute-walk distance, exacerbation of underlying lung disease, cardiopulmonary hospitalization, lung transplantation, at least 10% decline in forced vital capacity, or death during the duration of the 16-week study. Measurements and Main Results: In total, 147 disease progression events occurred in the inhaled treprostinil group (89/163 patients, 55%) compared with 215 events (109/163 patients, 67%) in the placebo group (P = 0.018). There was a lower incidence of each disease progression component in the inhaled treprostinil group: 6-minute-walk distance decline (45 vs. 64 events), lung disease exacerbation (48 vs. 72 events), FVC decline (19 vs. 33), cardiopulmonary hospitalization (23 vs. 33 events), and death (10 vs. 12). Fewer patients receiving inhaled treprostinil had multiple progression events compared with those receiving the placebo (35 vs. 58, 22% vs. 36%; P = 0.005). Conclusions: Patients who received inhaled treprostinil were significantly less likely to experience further disease progression events after an initial event compared with patients receiving placebo. These results support the continuation of inhaled treprostinil despite the occurrence of disease progression in clinical practice.

COVID-19 and Its Implications for Thrombosis and Anticoagulation.

Venous thromboembolism, occlusion of dialysis catheters, circuit thrombosis in extracorporeal membrane oxygenation (ECMO) devices, acute limb ischemia, and isolated strokes, all in the face of prophylactic and even therapeutic anticoagulation, are features of novel coronavirus disease 2019 (COVID-19) coagulopathy. It seems well established at this time that a COVID-19 patient deemed sick enough to be hospitalized, should receive at least prophylactic dose anticoagulation. However, should some hospitalized patients have dosage escalation to intermediate dose? Should some be considered for full-dose anticoagulation without a measurable thromboembolic event and how should that anticoagulation be monitored? Should patients receive postdischarge anticoagulation and with what medication and for how long? What thrombotic issues are related to the various medications being used to treat this coagulopathy? Is antiphospholipid antibody part of this syndrome? What is the significance of isolated ischemic stroke and limb ischemia in this disorder and how does this interface with the rest of the clinical and laboratory features of this disorder? The aims of this article are to explore these questions and interpret the available data based on the current evidence.

Direct oral anticoagulants in chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) represents the later stage consequence of at least one or more unresolved episodes of acute pulmonary embolism; thus, indefinite anticoagulation is strongly recommended by current practice guidelines. Historically, vitamin K antagonists have been widely used in these patients. However, recent data indicate a shift toward direct oral anticoagulants (DOACs), despite lack of data on the safety and efficacy in this patient population. Herein, we briefly discuss the current rationale for oral anticoagulation use in CTEPH, addressing important issues and controversies involved with the use of DOACs, opening a strategy for further clinical research in the field of oral anticoagulation.

Combination Therapy with Oral Treprostinil for Pulmonary Arterial Hypertension. A Double-Blind Placebo-controlled Clinical Trial.

Rationale: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown.Objectives: To evaluate the effect of oral treprostinil compared with placebo on time to first adjudicated clinical worsening event in participants with PAH who recently began approved oral monotherapy.Methods: In this event-driven, double-blind study, we randomly allocated 690 participants (1:1 ratio) with PAH to receive placebo or oral treprostinil extended-release tablets three times daily. Eligible participants were using approved oral monotherapy for over 30 days before randomization and had a 6-minute-walk distance 150 m or greater. The primary endpoint was the time to first adjudicated clinical worsening event: death; hospitalization due to worsening PAH; initiation of inhaled or parenteral prostacyclin therapy; disease progression; or unsatisfactory long-term clinical response.Measurements and Main Results: Clinical worsening occurred in 26% of the oral treprostinil group compared with 36% of placebo participants (hazard ratio, 0.74; 95% confidence interval, 0.56-0.97; P = 0.028). Key measures of disease status, including functional class, Borg dyspnea score, and N-terminal pro-brain natriuretic peptide, all favored oral treprostinil treatment at Week 24 and beyond. A noninvasive risk stratification analysis demonstrated that oral treprostinil-assigned participants had a substantially higher mortality risk at baseline but achieved a lower risk profile from Study Weeks 12-60. The most common adverse events in the oral treprostinil group were headache, diarrhea, flushing, nausea, and vomiting.Conclusions: In participants with PAH, addition of oral treprostinil to approved oral monotherapy reduced the risk of clinical worsening.Clinical trial registered with www.clinicaltrials.gov (NCT01560624).

Chronic Thromboembolic Pulmonary Hypertension: the Bedside.

PURPOSE OF REVIEW: Chronic thromboembolic pulmonary hypertension (CTEPH), included in group 4 PH, is an uncommon complication of acute pulmonary embolism (PE), in which emboli in the pulmonary vasculature do not resolve but rather form into an organized scar-like obstruction which can result in right ventricular (RV) failure. Here we provide an overview of current diagnosis and management of CTEPH. RECENT FINDINGS: CTEPH management is complex with treatments that range from surgery, percutaneous interventions, to medical therapies. Current CTEPH medical therapies have largely been repurposed from pulmonary arterial hypertension (PAH). The diagnosis of CTEPH can be challenging, requiring a multimodality approach to differentiate from disease mimics. While these treatments improve symptoms, they may not reverse the underlying pathology of CTEPH.

Chronic Thromboembolic Pulmonary Hypertension: the Bench.

PURPOSE OF REVIEW: Chronic thromboembolic pulmonary hypertension (CTEPH) is an uncommon complication of acute pulmonary embolism (PE), in which the red, platelet-rich thrombus does not resolve but forms into an organized yellow, fibrotic scar-like obstruction in the pulmonary vasculature. Here we review the pathobiology of CTEPH. RECENT FINDINGS: Our current knowledge has predominantly been informed by studies of human samples and animal models that are inherently limited in their ability to recapitulate all aspects of the disease. These studies have identified alterations in platelet biology and inflammation in the formation of a scar-like thrombus that comprised endothelial cells, myofibroblasts, and immune cells, along with a small vessel pulmonary arterial hypertension-like vasculopathy. The development of CTEPH-specific therapies is currently hindered by a limited knowledge of its pathobiology. The development of new CTEPH medical therapies will require new insights into its pathobiology that bridge the gap from bench to bedside.

Association of N-Terminal Pro Brain Natriuretic Peptide and Long-Term Outcome in Patients With Pulmonary Arterial Hypertension.

BACKGROUND: NT-proBNP (N-terminal pro brain natriuretic peptide) levels are included in the multiparametric risk assessment approach for pulmonary arterial hypertension (PAH) outlined in PAH guidelines. However, data supporting the use of NT-proBNP risk thresholds in assessing prognosis in PAH are limited. The GRIPHON trial (Prostacyclin [PGI2] Receptor Agonist In Pulmonary Arterial Hypertension) provides an opportunity to assess the prognostic value of NT-proBNP thresholds in a controlled clinical trial and to evaluate the response to selexipag according to these thresholds. METHODS: The event-driven GRIPHON trial randomly assigned patients to selexipag or placebo. NT-proBNP was measured at regular intervals in GRIPHON. Here, patients were categorized post hoc into low, medium, and high NT-proBNP subgroups according to 2 independent sets of thresholds: (1) baseline tertiles: <271 ng/L; 271 to 1165 ng/L; >1165 ng/L; and (2) 2015 European Society of Cardiology/European Respiratory Society guidelines cutoffs: <300 ng/L; 300 to 1400 ng/L; >1400 ng/L. Hazard ratios (selexipag versus placebo) with 95% CIs were calculated for the primary end point (composite morbidity/mortality events) by NT-proBNP category at baseline using Cox proportional-hazards models, and at any time during the exposure period using a time-dependent Cox model. RESULTS: With both thresholds, baseline and follow-up NT-proBNP categories were highly prognostic for future morbidity/mortality events during the study ( P<0.0001). In the time-dependent analysis, the risk of experiencing a morbidity/mortality event was 92% and 83% lower in selexipag-treated patients with a low and medium NT-proBNP level, and 90% and 56% lower in placebo-treated patients with a low and medium NT-proBNP level, in comparison with patients with a high NT-proBNP level. Selexipag reduced the risk of morbidity/mortality events across all 3 NT-proBNP categories in both the baseline and time-dependent analyses, with a more pronounced treatment benefit of selexipag seen in the medium and low NT-proBNP subgroups (interaction P values 0.20 and 0.007 in the baseline and time-dependent analyses). CONCLUSIONS: These analyses further establish the prognostic relevance of NT-proBNP levels in PAH and provide first evidence for the association of NT-proBNP level and treatment response. Using 2 similar sets of thresholds, these analyses support the relevance of the low, medium, and high NT-proBNP categories as part of the multiparametric risk assessment approach outlined in the European Society of Cardiology/European Respiratory Society guidelines for the management of PAH patients. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01106014.

Portable Ventilation/Perfusion Scanning is Useful for Evaluating Clinically Significant Pulmonary Embolism in the ICU Despite Abnormal Chest Radiography.

OBJECTIVE: Computed tomography angiography is limited in the intensive care unit (ICU) due to renal insufficiency, hemodynamic instability, and difficulty transporting unstable patients. A portable ventilation/perfusion (V/Q) scan can be used. However, it is commonly believed that an abnormal chest radiograph can result in a nondiagnostic scan. In this retrospective study, we demonstrate that portable V/Q scans can be helpful in ruling in or out clinically significant pulmonary embolism (PE) despite an abnormal chest x-ray in the ICU. DESIGN: Two physicians conducted chart reviews and original V/Q reports. A staff radiologist, with 40 years of experience, rated chest x-ray abnormalities using predetermined criteria. SETTING: The study was conducted in the ICU. PATIENTS: The first 100 consecutive patients with suspected PE who underwent a portable V/Q scan. INTERVENTIONS: Those with a portable V/Q scan. RESULTS: A normal baseline chest radiograph was found in only 6% of patients. Fifty-three percent had moderate, 24% had severe, and 10% had very-severe radiographic abnormalities. Despite the abnormal x-rays, 88% of the V/Q scans were low probability for a PE despite an average abnormal radiograph rating of moderate. A high-probability V/Q for PE was diagnosed in 3% of the population despite chest x-ray ratings of moderate to severe. Six patients had their empiric anticoagulation discontinued after obtaining the results of the V/Q scan, and no anticoagulation was started for PE after a low-probability V/Q scan. CONCLUSION: Despite the large percentage of moderate-to-severe x-ray abnormalities, PE can still be diagnosed (high-probability scan) in the ICU with a portable V/Q scan. Although low-probability scans do not rule out acute PE, it appeared less likely that any patient with a low-probability V/Q scan had severe hypoxemia or hemodynamic instability due to a significant PE, which was useful to clinicians and allowed them to either stop or not start anticoagulation.

Use of the Bedside-Placed Angel Catheter IVC Filter for Venous Thromboembolic Disease in Critically Ill Medical Patients.

Venous thromboembolic disease is a major problem among critically ill patients, with significant associated morbidity and mortality. Many critically ill patients have contraindications to systemic anticoagulation, and inferior vena cava (IVC) filters are an important alternative in preventing pulmonary emboli (PE) in this population. The Angel Catheter (Mermaid, Stenlose, Denmark) is a novel percutaneous and removable IVC filter attached to the end of a triple lumen central venous catheter which has been demonstrated to reduce PE in surgical and trauma patients. This case series describes 18 critically ill medical patients who had an Angel catheter placed either for diagnosed PE or due to high risk for PE; over half had at least submassive PE at the time of Angel catheter placement. None of the patients had a recurrence of PE during Angel catheter use, 29.4% had clot found in the filter via cavogram upon removal, and only one had a minor complication which had no clinical consequence. In 2 patients, the placement of the Angel Catheter resulted in the prevention of PE during catheter-directed thrombolysis of extensive deep vein thrombosis. This case series demonstrates that in a population of critically ill, elderly, and obese medical patients the bedside placement of the Angel IVC filter is feasible, safe, and may be effective for preventing PE.

Development and External Validation of a Machine Learning Tool to Rule Out COVID-19 Among Adults in the Emergency Department Using Routine Blood Tests: A Large, Multicenter, Real-World Study.

BACKGROUND: Conventional diagnosis of COVID-19 with reverse transcription polymerase chain reaction (RT-PCR) testing (hereafter, PCR) is associated with prolonged time to diagnosis and significant costs to run the test. The SARS-CoV-2 virus might lead to characteristic patterns in the results of widely available, routine blood tests that could be identified with machine learning methodologies. Machine learning modalities integrating findings from these common laboratory test results might accelerate ruling out COVID-19 in emergency department patients. OBJECTIVE: We sought to develop (ie, train and internally validate with cross-validation techniques) and externally validate a machine learning model to rule out COVID 19 using only routine blood tests among adults in emergency departments. METHODS: Using clinical data from emergency departments (EDs) from 66 US hospitals before the pandemic (before the end of December 2019) or during the pandemic (March-July 2020), we included patients aged ≥20 years in the study time frame. We excluded those with missing laboratory results. Model training used 2183 PCR-confirmed cases from 43 hospitals during the pandemic; negative controls were 10,000 prepandemic patients from the same hospitals. External validation used 23 hospitals with 1020 PCR-confirmed cases and 171,734 prepandemic negative controls. The main outcome was COVID 19 status predicted using same-day routine laboratory results. Model performance was assessed with area under the receiver operating characteristic (AUROC) curve as well as sensitivity, specificity, and negative predictive value (NPV). RESULTS: Of 192,779 patients included in the training, external validation, and sensitivity data sets (median age decile 50 [IQR 30-60] years, 40.5% male [78,249/192,779]), AUROC for training and external validation was 0.91 (95% CI 0.90-0.92). Using a risk score cutoff of 1.0 (out of 100) in the external validation data set, the model achieved sensitivity of 95.9% and specificity of 41.7%; with a cutoff of 2.0, sensitivity was 92.6% and specificity was 59.9%. At the cutoff of 2.0, the NPVs at a prevalence of 1%, 10%, and 20% were 99.9%, 98.6%, and 97%, respectively. CONCLUSIONS: A machine learning model developed with multicenter clinical data integrating commonly collected ED laboratory data demonstrated high rule-out accuracy for COVID-19 status, and might inform selective use of PCR-based testing.

Percutaneous Thrombectomy in Emergency Department Patients with Pulmonary Embolism: The FLARE ED Sub-study.

BACKGROUND: The FlowTriever Pulmonary Embolectomy Clinical Study (FLARE) was a multicenter, single-arm trial that demonstrated effectiveness of the FlowTriever percutaneous pulmonary embolectomy system in reducing right ventricular/left ventricular (RV/LV) diameter ratio in patients with acute intermediate-risk pulmonary embolism (PE). Patients diagnosed in emergency departments (EDs) with acute PE may have a different presentation from those diagnosed in an in-hospital setting. OBJECTIVES: The goal of this sub-study was to evaluate the safety and effectiveness of mechanical embolectomy in ED patients with acute intermediate-risk PE. METHODS: ED patients with acute PE and RV/LV ratio ≥ 0.9 enrolled in the FLARE study were core laboratory analyzed. The primary efficacy endpoint was the change in RV/LV ratio from baseline to 48 h post procedure. The change in RV/LV ratio of patients with nonelevated cardiac troponin (cTn) and zero simplified PE Severity Index (sPESI) score (normal cTn-sPESI: intermediate-low risk) was also examined. Major adverse events (MAEs) included major bleeding, device-related death or clinical deterioration, and vascular or cardiac injury. RESULTS: Seventy-six ED patients were included. Thirty-nine had a sPESI score of ≥ 1 and 32 had elevated cTn. The median preprocedure RV/LV ratio for all ED patients was 1.50 (0.88-2.52), with a change by -0.37 postprocedure (p < 0.001.) Three patients experienced MAEs. Seventeen patients (22.4%) presented with normal cTn-sPESI and had an RV/LV ratio reduced by 0.27 (p < 0.001) after embolectomy. CONCLUSION: ED patients with intermediate-risk PE had significant improvement in their RV/LV ratio and low complication rates when treated with mechanical embolectomy, irrespective of their baseline cTn-sPESI risk score.

Chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of pulmonary embolism and a major cause of chronic PH leading to right heart failure and death. Lung ventilation/perfusion scintigraphy is the screening test of choice; a normal scan rules out CTEPH. In the case of an abnormal perfusion scan, a high-quality pulmonary angiogram is necessary to confirm and define the pulmonary vascular involvement and prior to making a treatment decision. PH is confirmed with right heart catheterisation, which is also necessary for treatment determination. In addition to chronic anticoagulation therapy, each patient with CTEPH should receive treatment assessment starting with evaluation for pulmonary endarterectomy, which is the guideline recommended treatment. For technically inoperable cases, PH-targeted medical therapy is recommended (currently riociguat based on the CHEST studies), and balloon pulmonary angioplasty should be considered at a centre experienced with this challenging but potentially effective and complementary intervention.

Enhancing Insights into Pulmonary Vascular Disease through a Precision Medicine Approach. A Joint NHLBI-Cardiovascular Medical Research and Education Fund Workshop Report.

The Division of Lung Diseases of the NHLBI and the Cardiovascular Medical Education and Research Fund held a workshop to discuss how to leverage the anticipated scientific output from the recently launched "Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics" (PVDOMICS) program to develop newer approaches to pulmonary vascular disease. PVDOMICS is a collaborative, protocol-driven network to analyze all patient populations with pulmonary hypertension to define novel pulmonary vascular disease (PVD) phenotypes. Stakeholders, including basic, translational, and clinical investigators; clinicians; patient advocacy organizations; regulatory agencies; and pharmaceutical industry experts, joined to discuss the application of precision medicine to PVD clinical trials. Recommendations were generated for discussion of research priorities in line with NHLBI Strategic Vision Goals that include: (1) A national effort, involving all the stakeholders, should seek to coordinate biosamples and biodata from all funded programs to a web-based repository so that information can be shared and correlated with other research projects. Example programs sponsored by NHLBI include PVDOMICS, Pulmonary Hypertension Breakthrough Initiative, the National Biological Sample and Data Repository for PAH, and the National Precision Medicine Initiative. (2) A task force to develop a master clinical trials protocol for PVD to apply precision medicine principles to future clinical trials. Specific features include: (a) adoption of smaller clinical trials that incorporate biomarker-guided enrichment strategies, using adaptive and innovative statistical designs; and (b) development of newer endpoints that reflect well-defined and clinically meaningful changes. (3) Development of updated and systematic variables in imaging, hemodynamic, cellular, genomic, and metabolic tests that will help precisely identify individual and shared features of PVD and serve as the basis of novel phenotypes for therapeutic interventions.

Selexipag for the treatment of connective tissue disease-associated pulmonary arterial hypertension.

Patients with connective tissue disease-associated pulmonary arterial hypertension (PAH-CTD) have a poor prognosis compared with other aetiologies. The underlying CTD can influence treatment response and outcomes. We characterised the GRIPHON study PAH-CTD subgroup and evaluated response to selexipag.Of 334 patients with PAH-CTD, PAH was associated with systemic sclerosis (PAH-SSc) in 170, systemic lupus erythematosus (PAH-SLE) in 82 and mixed CTD/CTD-other in 82. For the primary composite endpoint of morbidity/mortality, hazard ratios (HR) and 95% CI were calculated using Cox proportional hazard models.Compared with the overall GRIPHON population, the CTD subgroup was slightly older with a greater proportion of females and shorter time since diagnosis. Patients with PAH-SSc appeared to be more impaired at baseline, with a more progressive disease course. The converse was observed for PAH-SLE. Selexipag reduced the risk of composite morbidity/mortality events in patients with PAH-CTD by 41% (HR 0.59; 95% CI 0.41-0.85). Treatment effect was consistent irrespective of baseline PAH therapy or CTD subtype (interaction p=0.87 and 0.89, respectively). Adverse events were predominately prostacyclin-related and known for selexipag treatment.GRIPHON has allowed the comprehensive characterisation of patients with PAH-CTD. Selexipag delayed progression of PAH and was well-tolerated among PAH-CTD patients, including those with PAH-SSc and PAH-SLE.

Evaluation of a Device Combining an Inferior Vena Cava Filter and a Central Venous Catheter for Preventing Pulmonary Embolism Among Critically Ill Trauma Patients.

PURPOSE: To evaluate efficacy and safety of a novel device that combines an inferior vena cava (IVC) filter and central venous catheter (CVC) for prevention of pulmonary embolism (PE) in critically ill patients. MATERIALS AND METHODS: In a multicenter, prospective, single-arm clinical trial, the device was inserted at the bedside without fluoroscopy and subsequently retrieved before transfer from the intensive care unit (ICU). The primary efficacy endpoint was freedom from clinically significant PE or fatal PE 72 hours after device removal or discharge, whichever occurred first. Secondary endpoints were incidence of acute proximal deep venous thrombosis (DVT), catheter-related thrombosis, catheter-related bloodstream infections, major bleeding events, and clinically significant thrombus (occupying > 25% of volume of filter) detected by cavography before retrieval. RESULTS: The device was placed in 163 critically ill patients with contraindications to anticoagulation; 151 (93%) were critically ill trauma patients, 129 (85%) had head or spine trauma, and 102 (79%) had intracranial bleeding. The primary efficacy endpoint was achieved for all 163 (100%) patients (95% confidence interval [CI], 97.8%-100%, P < .01). Diagnosis of new or worsening acute proximal DVT was time dependent with 11 (7%) occurring during the first 7 days. There were no (0%) catheter-related bloodstream infections. There were 5 (3.1%) major bleeding events. Significant thrombus in the IVC filter occurred in 14 (8.6%) patients. Prophylactic anticoagulation was not initiated for a mean of 5.5 days ± 4.3 after ICU admission. CONCLUSIONS: This novel device prevented clinically significant and fatal PE among critically ill trauma patients with low risk of complications.

Massive Pulmonary Embolism: Extracorporeal Membrane Oxygenation and Surgical Pulmonary Embolectomy.

Massive pulmonary embolism (PE) refers to large emboli that cause hemodynamic instability, right ventricular failure, and circulatory collapse. According to the 2016 ACCP Antithrombotic Guidelines, therapy for massive PE should include systemic thrombolytic therapy in conjunction with anticoagulation and supportive care. However, in patients with a contraindication to systemic thrombolytics or in those who fail the above interventions, extracorporeal membrane oxygenation (ECMO) and/or surgical embolectomy may be used to improve oxygenation, achieve hemodynamic stability, and successfully treat massive PE. Randomized controlled human trials evaluating ECMO in this context have not been done, and its role has not been well-defined. The European Society of Cardiology 2014 acute PE guidelines briefly mention that ECMO can be used for massive PE as a method for hemodynamic support and as an adjunct to surgical embolectomy. The 2016 CHEST Antithrombotic Therapy for venous thromboembolism Disease guidelines do not mention ECMO in the management of massive PE. However, multiple case reports and small series cited benefit with ECMO for massive PE. Further, ECMO may facilitate stabilization for surgical embolectomy. Unfortunately, ECMO requires full anticoagulation to maintain the functionality of the system; hence, significant bleeding complicates its use in 35% of patients. Contraindications to ECMO include high bleeding risk, recent surgery or hemorrhagic stroke, poor baseline functional status, advanced age, neurologic dysfunction, morbid obesity, unrecoverable condition, renal failure, and prolonged cardiopulmonary resuscitation without adequate perfusion of end organs. In this review, we discuss management of massive PE, with an emphasis on the potential role for ECMO and/or surgical embolectomy.

Catheter-Based Approaches for the Treatment of Acute Pulmonary Embolism.

Except when contraindicated, anticoagulation should be initiated when pulmonary embolism (PE) is strongly suspected and the bleeding risk is perceived to be low, even if the evaluation has not been completed. Low-risk patients with acute PE are simply continued on anticoagulation. Severely ill patients with high-risk (massive) PE require aggressive therapy, and if the bleeding risk is acceptable, systemic thrombolysis should be considered. However, despite clear evidence that parenteral thrombolytic therapy leads to more rapid clot resolution than anticoagulation alone, the risk of major bleeding including intracranial bleeding is significantly higher with thrombolytic therapy. It has been demonstrated that right ventricular dysfunction as well as abnormal biomarkers (troponin and brain natriuretic peptide) are associated with increased mortality in acute PE. In spite of this, intermediate-risk (submassive) PE comprises a fairly broad clinical spectrum so that there is not a solid evidence base permitting a consistent algorithm for clinicians to follow. Thus, for several decades, thromboembolism basic scientists, clinical trialists, and clinicians have worked toward a lower risk solution for treatment of patients with more than simply low-risk PE. Catheter-based therapy, consisting of various devices and techniques, with or without low-dose thrombolytic therapy, offers one potential solution and continues to evolve.

Safety and Tolerability of High-dose Inhaled Treprostinil in Pulmonary Hypertension.

Pulmonary arterial hypertension (PAH) has emerging therapeutic options including prostacyclin analogs. Inhaled therapy offers advantages compared with alternative routes of administration. We aimed to determine the safety and tolerability of inhaled treprostinil (iTRE) titrated to target maintenance dose higher than the labeled dose for PAH. Our study included 80 consecutive patients (69% female, 70% White) followed at the Duke University Medical Center prescribed iTRE at dose >9 breaths (54 µg). Etiology of pulmonary hypertension was most frequently PAH (51%) or secondary to lung disease (35%). Median follow-up was 20.3 months (interquartile range 14.2-33.2). Most patients (91%) had titrated iTRE dose to 12 breaths (72 µg) four times daily. Common side effects reported with drug initiation were cough (41%), headache (28%), and throat irritation (8%); most of the side effects improved at follow-up. Overall, 25% patients discontinued iTRE: 9 transitioned to parenteral therapy, 4 had untolerable side effects, 3 died, and 4 had other reasons. Overall, iTRE taken at a higher dose than approved for use in PAH was safe and well-tolerated in our cohort of pulmonary hypertension patients.