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Item Assessing quality of life after pulmonary embolism: Comparing results from the PEmb-QoL with semistructured interviews(Elsevier, 2022-06-19) Hernandez-Nino, Jackeline; Ott, Mary A.; Thomas, Mary; Alexander, Andreia B.; Kline, Jeffrey A.; Emergency Medicine, School of MedicineBackground: The Pulmonary Embolism Quality of Life questionnaire (PEmb-QoL) assesses quality of life (QoL) in patients with previous pulmonary embolism (PE). Objective: Our aim was to assess the agreement between the PEmb-QoL and interviews and to explore other QoL concerns in patients diagnosed with PE. Methods: This mixed-method study included interviews with 21 patients about QoL after PE, followed by the PEmb-QoL questionnaire. In interviews, patients were asked about their lived experiences and impact of PE. Our analysis identified the frequency and severity of decreased QoL in qualitative interviews and compared with the PEmb-QoL score. Excerpts that described the effect of PE on QoL in interview transcripts were transcoded to match the answers corresponding to the 1 to 6 numeric values for each question from the PEmb-QoL using a predetermined matrix (eg, "constant" and "daily" = all of the time = value 1) and directly compared with responses on the PEmb-QoL in the areas of emotional complaints and activities of daily living/social limitations. Results: Interviews showed more functional impairment than predicted by PEmb-QoL. For fear of recurrence, 86% of participants had disagreements between PEmb-QoL scores and transcoded interview scores. We found 42% disagreement between reported descriptions of the inability to do or enjoy hobbies in interviews and the PEmb-QoL score. Conclusion: Patient interviews showed discordances compared with a validated psychometric tool. To capture a more detailed and accurate picture of the effect of PE on QoL, providers and researchers should consider the addition of qualitative methods to assess outcomes.Item Assessment of Right Ventricular Function in the Research Setting: Knowledge Gaps and Pathways Forward. An Official American Thoracic Society Research Statement(American Thoracic Society, 2018-08-15) Lahm, Tim; Douglas, Ivor S.; Archer, Stephen L.; Bogaard, Harm J.; Chesler, Naomi C.; Haddad, Francois; Hemnes, Anna R.; Kawut, Steven M.; Kline, Jeffrey A.; Kolb, Todd M.; Mathai, Stephen C.; Mercier, Olaf; Michelakis, Evangelos D.; Naeije, Robert; Tuder, Rubin M.; Ventetuolo, Corey E.; Vieillard-Baron, Antoine; Voelkel, Norbert F.; Vonk-Noordegraaf, Anton; Medicine, School of MedicineBACKGROUND: Right ventricular (RV) adaptation to acute and chronic pulmonary hypertensive syndromes is a significant determinant of short- and long-term outcomes. Although remarkable progress has been made in the understanding of RV function and failure since the meeting of the NIH Working Group on Cellular and Molecular Mechanisms of Right Heart Failure in 2005, significant gaps remain at many levels in the understanding of cellular and molecular mechanisms of RV responses to pressure and volume overload, in the validation of diagnostic modalities, and in the development of evidence-based therapies. METHODS: A multidisciplinary working group of 20 international experts from the American Thoracic Society Assemblies on Pulmonary Circulation and Critical Care, as well as external content experts, reviewed the literature, identified important knowledge gaps, and provided recommendations. RESULTS: This document reviews the knowledge in the field of RV failure, identifies and prioritizes the most pertinent research gaps, and provides a prioritized pathway for addressing these preclinical and clinical questions. The group identified knowledge gaps and research opportunities in three major topic areas: 1) optimizing the methodology to assess RV function in acute and chronic conditions in preclinical models, human studies, and clinical trials; 2) analyzing advanced RV hemodynamic parameters at rest and in response to exercise; and 3) deciphering the underlying molecular and pathogenic mechanisms of RV function and failure in diverse pulmonary hypertension syndromes. CONCLUSIONS: This statement provides a roadmap to further advance the state of knowledge, with the ultimate goal of developing RV-targeted therapies for patients with RV failure of any etiology.Item At a crossroads: COVID-19 recovery and the risk of pulmonary vascular disease(Wolters Kluwer, 2021) Cascino, Thomas M.; Desai, Ankit A.; Kanthi, Yogendra; Medicine, School of MedicinePurpose of review: The coronavirus disease 2019 (COVID-19) pandemic has led to almost 3,000,000 deaths across 139 million people infected worldwide. Involvement of the pulmonary vasculature is considered a major driving force for morbidity and mortality. We set out to summarize current knowledge on the acute manifestations of pulmonary vascular disease (PVD) resulting from COVID-19 and prioritize long-term complications that may result in pulmonary hypertension (PH). Recent findings: Acute COVID-19 infection can result in widespread involvement of the pulmonary vasculature, myocardial injury, evidence of persistent lung disease, and venous thromboembolism. Post COVID-19 survivors frequently report ongoing symptoms and may be at risk for the spectrum of PH, including group 1 pulmonary arterial hypertension, group 2 PH due to left heart disease, group 3 PH due to lung disease and/or hypoxia, and group 4 chronic thromboembolic PH. Summary: The impact of COVID-19 on the pulmonary vasculature is central to determining disease severity. Although the long-term PVD manifestations of COVID-19 are currently uncertain, optimizing the care of risk factors for PH and monitoring for the development of PVD will be critical to reducing long-term morbidity and improving the health of survivors.Item Chronic Embolic Pulmonary Hypertension Caused by Pulmonary Embolism and Vascular Endothelial Growth Factor Inhibition(Elsevier, 2017-04) Neto-Neves, Evandro M.; Brown, Mary B.; Zaretskaia, Maria V.; Rezania, Samin; Goodwill, Adam G.; McCarthy, Brian P.; Persohn, Scott A.; Territo, Paul R.; Kline, Jeffrey A.; Emergency Medicine, School of MedicineOur understanding of the pathophysiological basis of chronic thromboembolic pulmonary hypertension (CTEPH) will be accelerated by an animal model that replicates the phenotype of human CTEPH. Sprague-Dawley rats were administered a combination of a single dose each of plastic microspheres and vascular endothelial growth factor receptor antagonist in polystyrene microspheres (PE) + tyrosine kinase inhibitor SU5416 (SU) group. Shams received volume-matched saline; PE and SU groups received only microspheres or SU5416, respectively. PE + SU rats exhibited sustained pulmonary hypertension (62 ± 13 and 53 ± 14 mmHg at 3 and 6 weeks, respectively) with reduction of the ventriculoarterial coupling in vivo coincident with a large decrement in peak rate of oxygen consumption during aerobic exercise, respectively. PE + SU produced right ventricular hypokinesis, dilation, and hypertrophy observed on echocardiography, and 40% reduction in right ventricular contractile function in isolated perfused hearts. High-resolution computed tomographic pulmonary angiography and Ki-67 immunohistochemistry revealed abundant lung neovascularization and cellular proliferation in PE that was distinctly absent in the PE + SU group. We present a novel rodent model to reproduce much of the known phenotype of CTEPH, including the pivotal pathophysiological role of impaired vascular endothelial growth factor-dependent vascular remodeling. This model may reveal a better pathophysiological understanding of how PE transitions to CTEPH in human treatments.Item A clinical decision framework to guide the outpatient treatment of emergency department patients diagnosed with acute pulmonary embolism or deep vein thrombosis: Results from a multidisciplinary consensus panel(Wiley, 2021-12-15) Kabrhel, Christopher; Vinson, David R.; Mitchell, Alice Marina; Rosovsky, Rachel P.; Chang, Anna Marie; Hernandez-Nino, Jackeline; Wolf, Stephen J.; Emergency Medicine, School of MedicineThe outpatient treatment of select emergency department patients with acute pulmonary embolism (PE) or deep vein thrombosis (DVT) has been shown to be safe, cost effective and associated with high patient satisfaction. Despite this, outpatient PE and DVT treatment remains uncommon. To address this, the American College of Emergency Physicians assembled a multidisciplinary team of content experts to provide evidence-based recommendations and practical advice to help clinicians safely treat patients with low-risk PE and DVT without hospitalization. The emergency clinician must stratify the patient's risk of clinical decompensation due to their PE or DVT as well as their risk of bleeding due to anticoagulation. The clinician must also select and start an anticoagulant and ensure that the patient has access to the medication in a timely manner. Reliable follow-up is critical, and the patient must also be educated about signs or symptoms that should prompt a return to the emergency department. To facilitate access to these recommendations, the consensus panel also created 2 web-based "point-of-care tools."Item Contribution of fibrinolysis to the physical component summary of the SF-36 after acute submassive pulmonary embolism(Springer US, 2015-08) Stewart, Lauren K.; Peitz, Geoffrey W.; Nordenholz, Kristen E.; Courtney, D. Mark; Kabrhel, Christopher; Jones, Alan E.; Rondina, Matthew T.; Diercks, Deborah B.; Klinger, James R.; Kline, Jeffrey A.; Department of Emergency Medicine, School of MedicineAcute pulmonary embolism (PE) can diminish patient quality of life (QoL). The objective was to test whether treatment with tenecteplase has an independent effect on a measurement that reflects QoL in patients with submassive PE. This was a secondary analysis of an 8-center, prospective randomized controlled trial, utilizing multivariate regression to control for predefined predictors of worsened QoL including: age, active malignancy, history of PE or deep venous thrombosis (DVT), recurrent PE or DVT, chronic obstructive pulmonary disease and heart failure. QoL was measured with the physical component summary (PCS) of the SF-36. Analysis included 76 patients (37 randomized to tenecteplase, 39 to placebo). Multivariate regression yielded an equation f(8, 67), P<0.001, with R2 = 0.303. Obesity had the largest effect on PCS (β = −8.6, P<0.001), with tenecteplase second (β = 4.73, P = 0.056). After controlling for all interactions, tenecteplase increased the PCS by +5.37 points (P = 0.027). In patients without any of the defined comorbidities, the coefficient on the tenecteplase variable was not significant (−0.835, P = 0.777). In patients with submassive PE, obesity had the greatest influence on QoL, followed by use of fibrinolysis. Fibrinolysis had a marginal independent effect on patient QoL after controlling for comorbidities, but was not significant in patients without comorbid conditions.Item Current Management of Acute Pulmonary Embolism(AME Publishing Company, 2020) Martinez Licha, Carlos R.; McCurdy, Chelsea M.; Maldonado, Sarina Masso; Lee, Lawrence S.; Medicine, School of MedicinePurpose: Acute pulmonary embolism (PE) remains a significant cause of morbidity and requires prompt diagnosis and management. While non-surgical approaches have supplanted surgery as primary treatment, surgical pulmonary embolectomy (SPE) remains a vital option for select patients. We review the current management of acute PE, with a focus on surgical therapy. Methods: A PubMed search was performed to identify literature regarding PE and treatment. Results were filtered to include the most comprehensive publications over the past decade. Results: PE is stratified based on presenting hemodynamic status or degree of mechanical pulmonary arterial occlusion. Although systemic or catheter-guided fibrinolysis is the preferred first-line treatment for the majority of cases, patients who are not candidates should be considered for SPE. Studies demonstrate no mortality benefit of thrombolysis over surgery. Systemic anticoagulation is a mainstay of treatment regardless of intervention approach. Following surgical embolectomy, direct oral anticoagulants (DOACs) have been shown to reduce recurrence of thromboembolism. Conclusions: Acute PE presents with varying degrees of clinical stability. Patients should be evaluated in the context of various available treatment options including medical, catheter-based, and surgical interventions. SPE is a safe and appropriate treatment option for appropriate patients.Item Derivation and Validation of a 4-Level Clinical Pretest Probability Score for Suspected Pulmonary Embolism to Safely Decrease Imaging Testing(JAMA, 2021-06-01) Roy, Pierre-Marie; Friou, Emilie; Germeau, Boris; Douillet, Delphine; Kline, Jeffrey A.; Righini, Marc; Le Gal, Grégoire; Moumneh, Thomas; Penaloza, Andrea; Emergency Medicine, School of MedicineImportance: In patients with suspected pulmonary embolism (PE), overuse of diagnostic imaging is an important point of concern. Objective: To derive and validate a 4-level pretest probability rule (4-Level Pulmonary Embolism Clinical Probability Score [4PEPS]) that makes it possible to rule out PE solely on clinical criteria and optimized D-dimer measurement to safely decrease imaging testing for suspected PE. Design, setting, and participants: This study included consecutive outpatients suspected of having PE from US and European emergency departments. Individual data from 3 merged management studies (n = 11 114; overall prevalence of PE, 11%) were used for the derivation cohort and internal validation cohort. The external validation cohorts were taken from 2 independent studies, the first with a high PE prevalence (n = 1548; prevalence, 21.5%) and the second with a moderate PE prevalence (n = 1669; prevalence, 11.7%). A prior definition of pretest probability target values to achieve a posttest probability less than 2% was used on the basis of the negative likelihood ratios of D-dimer. Data were collected from January 2003 to April 2016, and data were analyzed from June 2018 to August 2019. Main outcomes and measures: The rate of PE diagnosed during the initial workup or during follow-up and the rate of imaging testing. Results: Of the 5588 patients in the derivation cohort, 3441 (61.8%) were female, and the mean (SD) age was 52 (18.5) years. The 4PEPS comprises 13 clinical variables scored from -2 to 5. It results in the following strategy: (1) very low probability of PE if 4PEPS is less than 0: PE ruled out without testing; (2) low probability of PE if 4PEPS is 0 to 5: PE ruled out if D-dimer level is less than 1.0 μg/mL; (3) moderate probability of PE if 4PEPS is 6 to 12: PE ruled out if D-dimer level is less than the age-adjusted cutoff value; (4) high probability of PE if 4PEPS is greater than 12: PE ruled out by imaging without preceding D-dimer test. In the first and the second external validation cohorts, the area under the receiver operator characteristic curves were 0.79 (95% CI, 0.76 to 0.82) and 0.78 (95% CI, 0.74 to 0.81), respectively. The false-negative testing rates if the 4PEPS strategy had been applied were 0.71% (95% CI, 0.37 to 1.23) and 0.89% (95% CI, 0.53 to 1.49), respectively. The absolute reductions in imaging testing were -22% (95% CI, -26 to -19) and -19% (95% CI, -22 to -16) in the first and second external validation cohorts, respectively. The 4PEPS strategy compared favorably with all recent strategies in terms of imaging testing. Conclusions and relevance: The 4PEPS strategy may lead to a substantial and safe reduction in imaging testing for patients with suspected PE. It should now be tested in a formal outcome study.Item Effect of metabolic syndrome on mean pulmonary arterial pressures in patients with acute pulmonary embolism treated with catheter-directed thrombolysis(Elsevier, 2020-03-01) Stewart, Lauren K.; Beam, Daren M.; Casciani, Thomas; Cameron, Scott J.; Kline, Jeffrey A.; Emergency Medicine, School of MedicineBackground: Metabolic syndrome (MetS) has been associated with a procoagulant and hypofibrinolytic state. Current data exploring the role of MetS in venous thromboembolism (VTE) are limited. The objective was to measure the prevalence of MetS in patients with acute PE receiving catheter-directed thrombolysis (CDT) and to investigate its effect on mean pulmonary arterial pressure and overall treatment success. Methods: We used a 3-year prospective registry of ED patients with acute PE with severity qualifying for activation of a PE response team (PERT). All patients had CDT with catheter-measured mPAP and angiography. The presence or absence of MetS components were extracted from chart review based on the following criteria: 1. body mass index (BMI) >30 kg/m2; 2. diagnosed hypertension; 3. diabetes mellitus (including HbA1c >6.5%) and; 4. dyslipidemia (including triglycerides >150 mg/dL or high-density lipoprotein <40 mg/dL). Results: Of the 134 patients, 85% met the criteria for at least one of four MetS components, with obesity being most common, present in 71%. Results demonstrated a positive concordance between the number of criteria for MetS and MPAP, both pre- and post-fibrinolysis, as pressures tended to increase with each additional MetS criterion. Multivariate regression analysis determined age (-), BMI (+) and hypertension (+) to be significant independent predictor variables for mPAP. Conclusions: MetS was common in patients with more severe manifestations of PE and was associated with higher mPAP values both at diagnosis and following treatment with CDT.Item Fibrinolytics for the treatment of pulmonary embolism(Elsevier, 2020) Stewart, Lauren K.; Kline, Jeffrey A.; Emergency Medicine, School of MedicineThe use of fibrinolytic agents in acute pulmonary embolism (PE), first described over 50 years ago, hastens the resolution of RV stain, leading to earlier hemodynamic improvement. However, this benefit comes at the increased risk of bleeding. The strongest indication for fibrinolysis is in high-risk PE, or that characterized by sustained hypotension, while its use in patients with intermediate-risk PE remains controversial. Fibrinolysis is generally not recommended for routine use in intermediate-risk PE, although most guidelines advise that it may be considered in patients with signs of acute decompensation and an overall low bleeding risk. The efficacy of fibrinolysis often varies significantly between patients, which may be at least partially explained by several factors found to promote resistance to fibrinolysis. Ultimately, treatment decisions should carefully weigh the risks and benefits of the individual clinical scenario at hand, including the overall severity, the patient's bleeding risk, and the presence of factors known to promote resistance to fibrinolysis. This review aims to further explore the use of fibrinolytic agents in the treatment of PE including specific indications, outcomes, and special considerations.