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Venous thromboembolism (VTE) is a significant contributor to morbidity and mortality, with large disparities in incidence rates between Black and White Americans. Polygenic risk scores (PRSs) limited to variants discovered in genome-wide association studies in European-ancestry samples can identify European-ancestry individuals at high risk of VTE. However, there is limited evidence on whether high-dimensional PRS constructed using more sophisticated methods and more diverse training data can enhance the predictive ability and their utility across diverse populations. We developed PRSs for VTE using summary statistics from the International Network against Venous Thrombosis (INVENT) consortium genome-wide association studies meta-analyses of European- (71 771 cases and 1 059 740 controls) and African-ancestry samples (7482 cases and 129 975 controls). We used LDpred2 and PRS-CSx to construct ancestry-specific and multi-ancestry PRSs and evaluated their performance in an independent European- (6781 cases and 103 016 controls) and African-ancestry sample (1385 cases and 12 569 controls). Multi-ancestry PRSs with weights tuned in European-ancestry samples slightly outperformed ancestry-specific PRSs in European-ancestry test samples (e.g. the area under the receiver operating curve [AUC] was 0.609 for PRS-CSx_combinedEUR and 0.608 for PRS-CSxEUR [P = 0.00029]). Multi-ancestry PRSs with weights tuned in African-ancestry samples also outperformed ancestry-specific PRSs in African-ancestry test samples (PRS-CSxAFR: AUC = 0.58, PRS-CSx_combined AFR: AUC = 0.59), although this difference was not statistically significant (P = 0.34). The highest fifth percentile of the best-performing PRS was associated with 1.9-fold and 1.68-fold increased risk for VTE among European- and African-ancestry subjects, respectively, relative to those in the middle stratum. These findings suggest that the multi-ancestry PRS might be used to improve performance across diverse populations to identify individuals at highest risk for VTE.
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BACKGROUND AND AIMS: Home treatment is considered safe in acute pulmonary embolism (PE) patients selected by a validated triage tool (e.g. simplified PE severity index score or Hestia rule), but there is uncertainty regarding the applicability in underrepresented subgroups. The aim was to evaluate the safety of home treatment by performing an individual patient-level data meta-analysis. METHODS: Ten prospective cohort studies or randomized controlled trials were identified in a systematic search, totalling 2694 PE patients treated at home (discharged within 24â h) and identified by a predefined triage tool. The 14- and 30-day incidences of all-cause mortality and adverse events (combined endpoint of recurrent venous thromboembolism, major bleeding, and/or all-cause mortality) were evaluated. The relative risk (RR) for 14- and 30-day mortalities and adverse events is calculated in subgroups using a random effects model. RESULTS: The 14- and 30-day mortalities were 0.11% [95% confidence interval (CI) 0.0-0.24, I2 = 0) and 0.30% (95% CI 0.09-0.51, I2 = 0). The 14- and 30-day incidences of adverse events were 0.56% (95% CI 0.28-0.84, I2 = 0) and 1.2% (95% CI 0.79-1.6, I2 = 0). Cancer was associated with increased 30-day mortality [RR 4.9; 95% prediction interval (PI) 2.7-9.1; I2 = 0]. Pre-existing cardiopulmonary disease, abnormal troponin, and abnormal (N-terminal pro-)B-type natriuretic peptide [(NT-pro)BNP] at presentation were associated with an increased incidence of 14-day adverse events [RR 3.5 (95% PI 1.5-7.9, I2 = 0), 2.5 (95% PI 1.3-4.9, I2 = 0), and 3.9 (95% PI 1.6-9.8, I2 = 0), respectively], but not mortality. At 30 days, cancer, abnormal troponin, and abnormal (NT-pro)BNP were associated with an increased incidence of adverse events [RR 2.7 (95% PI 1.4-5.2, I2 = 0), 2.9 (95% PI 1.5-5.7, I2 = 0), and 3.3 (95% PI 1.6-7.1, I2 = 0), respectively]. CONCLUSIONS: The incidence of adverse events in home-treated PE patients, selected by a validated triage tool, was very low. Patients with cancer had a three- to five-fold higher incidence of adverse events and death. Patients with increased troponin or (NT-pro)BNP had a three-fold higher risk of adverse events, driven by recurrent venous thromboembolism and bleeding.
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BACKGROUND: High-risk pulmonary embolism (PE) is a complex, life-threatening condition, and emergency clinicians must be ready to resuscitate and rapidly pursue primary reperfusion therapy. The first-line reperfusion therapy for patients with high-risk PE is systemic thrombolytics (ST). Despite consensus guidelines, only a fraction of eligible patients receive ST for high-risk PE. OBJECTIVE: This review provides emergency clinicians with a comprehensive overview of the current evidence regarding the management of high-risk PE with an emphasis on ST and other reperfusion therapies to address the gap between practice and guideline recommendations. DISCUSSION: High-risk PE is defined as PE that causes hemodynamic instability. The high mortality rate and dynamic pathophysiology of high-risk PE make it challenging to manage. Initial stabilization of the decompensating patient includes vasopressor administration and supplemental oxygen or high-flow nasal cannula. Primary reperfusion therapy should be pursued for those with high-risk PE, and consensus guidelines recommend the use of ST for high-risk PE based on studies demonstrating benefit. Other options for reperfusion include surgical embolectomy and catheter directed interventions. CONCLUSIONS: Emergency clinicians must possess an understanding of high-risk PE including the clinical assessment, pathophysiology, management of hemodynamic instability and respiratory failure, and primary reperfusion therapies.
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Embolia Pulmonar , Terapia Trombolítica , Humanos , Embolia Pulmonar/etiología , Fibrinolíticos/uso terapéutico , Embolectomía/efectos adversos , Servicio de Urgencia en Hospital , Resultado del TratamientoRESUMEN
BACKGROUND: Transthoracic echocardiography (TTE) is an essential tool for risk-stratifying patients with pulmonary embolism (PE), but its availability is limited, often requiring hospitalization. Minimal research exists evaluating clinical and laboratory criteria to predict lack of abnormal TTE findings. OBJECTIVE: We aimed to identify predictors associated with abnormal TTE results in patients with PE to potentially identify those safe for early discharge. METHODS: In this retrospective study, we analyzed an existing database of patients with venous thromboembolism (VTE) at two academic emergency departments, including adult patients with confirmed PE who underwent TTE. The primary goal was to develop and validate a score predicting abnormal TTE, defined as presence of one of the following: right ventricle (RV) dilatation or hypokinesis, septal flattening, right heart thrombus in transit, or ejection fraction < 50%. Variables were demographic characteristics, symptoms, computed tomography (CT) RV strain, troponin T, and N-terminal prohormone of brain natriuretic peptide (NTproBNP). Stepwise logistic regression was used to identify variables independently associated with abnormal TTE. Model discrimination was evaluated using area under the curve (AUC) of the receiver operating characteristic curve. A clinical prediction rule was developed. RESULTS: 530 of 2235 patients were included; 56% (297 of 530) had an abnormal TTE. The following six variables were independently associated with abnormal TTE: dyspnea, dizziness, troponin T ≥ 0.1 ng/mL, NTproBNP > 900 pg/mL, CT RV strain, and nonsubsegmental PE. A clinical prediction rule using these six criteria yielded scores between 0 and 7, performing well with AUC of 0.80 (95% CI 0.79-0.80). A score of 1 was 99.7% sensitive in identifying no abnormality. A score ≥ 5 was 98% specific for an abnormality. CONCLUSIONS: The PEACE (Pulmonary Embolism and Abnormal Cardiac Echocardiogram) criteria, composed of six variables, is highly effective in predicting abnormal TTE in patients with PE, potentially identifying who is safe for early discharge from the hospital.
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Embolia Pulmonar , Disfunción Ventricular Derecha , Adulto , Humanos , Estudios Retrospectivos , Troponina T , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/complicaciones , Ecocardiografía/métodos , Tomografía Computarizada por Rayos X , Enfermedad AgudaRESUMEN
OBJECTIVES: In acute pulmonary embolism (PE), the right ventricle (RV) may dilate compromising left ventricular (LV) size, thereby increasing RV/LV ratio. End-diastolic RV/LV ratio is often used in PE risk stratification, though the cause of death is RV systolic failure. We aimed to confirm our pre-clinical observations of higher RV/LV ratio in systole compared to diastole in human patients with PE. METHODS: We blinded and independently analyzed echocardiograms from 606 patients with PE, evaluated by a Pulmonary Embolism Response Team. We measured RV/LV ratios in end-systole and end-diastole and fractional area change (FAC). Our primary outcome was a composite of 7-day clinical deterioration, treatment escalation or death. Secondary outcomes were 7-day and 30-day all-cause mortality. RESULTS: RV/LV ratio was higher in systole compared to diastole (median 1.010 [.812-1.256] vs. .975 [.843-1.149], p < .0001). RV/LV in systole and diastole were correlated (slope = 1.30 [95% CI 1.25-1.35], p < .0001 vs. slope = 1). RV/LV ratios in both systole and diastole were associated with the primary composite outcome but not with all-cause mortality. CONCLUSION: The RV/LV ratio is higher when measured in systole versus in diastole in patients with acute PE. The two approaches had similar associations with clinical outcomes, that is, it appears reasonable to measure RV/LV ratio in diastole.
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Insuficiencia Cardíaca , Embolia Pulmonar , Humanos , Ventrículos Cardíacos/diagnóstico por imagen , Diástole , Sístole , Embolia Pulmonar/diagnóstico por imagen , Ecocardiografía , Enfermedad AgudaRESUMEN
PURPOSE: Right ventricular strain (RVS) is used to risk stratify patients with acute pulmonary embolism (PE) and influence treatment decisions. Guidelines suggest that either computed tomography pulmonary angiography (CTPA) or transthoracic echocardiography (TTE) can be used to assess RVS. We sought to determine how often CTPA and TTE yield discordant results and to assess the test characteristics of CTPA compared to TTE. METHODS: We analyzed data from a single-center registry of PE cases severe enough to warrant activation of the hospital's Pulmonary Embolism Response Team (PERT). We defined RVS as a right ventricular to left ventricular ratio (RV/LV) ≥ 1 or radiologist's interpretation of RVS on CTPA or as the presence of either RV dilation, hypokinesis, or septal bowing on TTE. RESULTS: We included 554 patients in our analysis, of whom 333 (60%) had concordant RVS findings on CTPA and TTE. Using TTE as the reference standard, CTPA had a sensitivity of 95% (95% CI 92-97%) and a specificity of 4% (95% CI 2-8%) for identifying RVS. CONCLUSIONS: In a selected population of patients with acute PE for which PERT was activated, CTPA is highly sensitive but not specific for the detection of RVS when compared to TTE.
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Embolia Pulmonar , Humanos , Embolia Pulmonar/diagnóstico por imagen , Ecocardiografía , Ventrículos Cardíacos/diagnóstico por imagen , Enfermedad AgudaRESUMEN
Pulmonary embolism response teams (PERT) aim to improve treatment of acute pulmonary embolism (PE). PERT focus on intermediate- and high-risk PE patients, but recent multicenter studies show that low-risk PE patients compose one in five of all PERT cases. Conversely, not all intermediate- and high-risk PE patients elicit a PERT activation. The factors leading to PERT activations remain unknown. This study aims to describe the patient characteristics associated with PERT activation for low-risk PE patients and characteristics precluding PERT activation for intermediate/high-risk PE patients. We analysed data from all patients with confirmed PE diagnosed in the Massachusetts General Hospital Emergency Department from August 2013 to February 2017 and cross-referred these data with patients who received a PERT activation and patients who did not. Patients were stratified into low-risk or intermediate/high-risk PE. Univariate analyses were performed within each risk group comparing patients with a PERT activation and patients without. Fifteen percent (56/374) of low-risk PE patients triggered a PERT activation. Patient characteristics associated with PERT activation were: (1) vascular disease, (2) pulmonary diseases, (3) thrombophilia, (4) current use of anticoagulants, (5) central PE and (6) concurrent DVT. Thirty-five percent (110/283) of intermediate/high-risk PE patients did not elicit a PERT activation. Patient characteristics precluding a PERT activation were: (1) vascular disease, (2) malignancies and (3) asymptomatic presentation. Low-risk PE patients with PERT activations had more extensive clot burden, complex comorbidities, or had failed anticoagulation treatment. Intermediate/high-risk PE patients without PERT activations tended to have malignancies or vascular disease.
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Grupo de Atención al Paciente , Embolia Pulmonar , Anticoagulantes , Humanos , Massachusetts/epidemiología , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/terapia , Factores de RiesgoRESUMEN
BACKGROUND: COVID-19 has been associated with increased risk of thromboembolism in critically ill patients. OBJECTIVE: We sought to examine the association of SARS-CoV-2 test positivity and subsequent acute vascular thrombosis, including venous thromboembolism (VTE) or arterial thrombosis (AT), in a large nationwide registry of emergency department (ED) patients tested with a nucleic acid test for suspected SARS-CoV-2. METHODS: The RECOVER (Registry of Potential COVID-19 in Emergency Care) registry includes 155 EDs across the United States. We performed a retrospective cohort study to produce odds ratios (ORs) for COVID-19-positive vs. COVID-19-negative status as a predictor of 30-day VTE or AT, adjusting for age, sex, active cancer, intubation, hospital length of stay, and intensive care unit (ICU) care. RESULTS: Comparing 14,056 COVID-19-positive patients with 12,995 COVID-19-negative patients, the overall 30-day prevalence of VTE events was 1.4% vs. 1.3%, respectively (p = 0.44, χ2). Multivariable analysis identified that testing positive for SARS-CoV-2 status was negatively associated with both VTE (OR 0.76; 95% confidence interval [CI] 0.61-0.94) and AT (OR 0.51; 95% CI 0.32-0.80), whereas intubation, ICU care, and age 50 years or older were positively associated with both VTE and AT. CONCLUSIONS: In contrast to other reports, results from this large, hetereogenous national sample of ED patients tested for SARS-CoV-2, showed no association between vascular thrombosis and COVID-19 test positivity.
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COVID-19 , Trombosis , Tromboembolia Venosa , Atención Ambulatoria , COVID-19/diagnóstico , COVID-19/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , SARS-CoV-2/aislamiento & purificación , Evaluación de Síntomas , Trombosis/epidemiología , Tromboembolia Venosa/epidemiologíaRESUMEN
BACKGROUND: Studies have reported COVID-19 as an independent risk factor for arterial thromboemboli. METHODS: From a cross-sectional sample, we determined the incidence and location of arterial thromboemboli (myocardial infarction, ischemic stroke, peripheral artery), stratified by COVID-19 status, in the RECOVER database, which included data on patients at 45 United States medical centers in 22 states. Epidemiological factors, clinical characteristics and outcomes were collected through a combination of individual chart review and automatic electronic query and recorded in REDCap®. We investigated the association of baseline comorbidities on the development of arterial thromboemboli and analyzed results based on the presence or absence of concomitant COVID-19 infection, testing this association with Chi-squared. We also described use of anticoagulants and statins. RESULTS: Data were collected on 26,974 patients, of which 13,803 (51.17%) tested positive for COVID-19. Incidence of arterial thromboemboli during hospitalization was 0.13% in patients who tested positive for COVID-19 and 0.19% in patients who tested negative. Arterial thromboemboli tended to be more common in extremities than in core organs (heart, kidney, lung, liver) in patients with COVID-19, odds ratio 2.04 (95% CI 0.707 - 5.85). Patients with COVID-19 were less likely to develop an arterial thrombus when on baseline statin medication (p=0.014). Presence of metabolic syndrome predicted presence of core arterial thrombus (p=0.001) and extremity arterial thrombus (p=0.010) in those with COVID-19. Arterial thromboemboli were less common in patients with COVID-19 than in those who tested negative for COVID-19. CONCLUSIONS: Presence of a composite metabolic syndrome profile may be associated with arterial clot formation in patients with COVID-19 infection.
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BACKGROUND: Risk stratification of patients with pulmonary embolism (PE) is essential to guide advanced interventional management and proper disposition. OBJECTIVES: In this study, we sought to assess individual echocardiographic markers of right ventricular (RV) strain and left ventricular (LV) function in patients with high-risk PE and identify their association with the need for advanced intervention (such as thrombolysis) and 30-day mortality. METHODS: This was a retrospective study of ED patients with PE who were subject to a pulmonary embolism response team activation over a 5-year period. Cardiac point-of-care ultrasound studies were performed as part of patient care and later assessed for septal bowing, RV hypokinesis, McConnell sign, RV enlargement, tricuspid annular place systolic excursion, and LV systolic dysfunction. Outcome variables included need for advanced intervention and 30-day mortality. RESULTS: The pulmonary embolism response team was activated in 893 patients, of which 718 had a confirmed PE. Of these, 90 had adequate cardiac point-of-care ultrasound images available for review. Patients who needed an advanced intervention were more likely to have septal bowing (odds ratio [OR] 8.69, 95% confidence interval [CI] 2.37-31.86), RV enlargement (OR 4.02, 95% CI 1.43-11.34), and a McConnell sign (OR 2.79, 95% CI 1.09-7.13). LV dysfunction was the only statistically significant predictor of 30-day mortality (OR 9.63, 95% CI 1.74-53.32). CONCLUSION: In patients with PE in the ED, sonographic findings of RV strain that are more commonly associated with advanced intervention included septal bowing, McConnell sign, and RV enlargement. LV dysfunction was associated with a higher 30-day mortality. These findings can help inform decisions about ED management and disposition of patients with PE.
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Embolia Pulmonar , Disfunción Ventricular Izquierda , Disfunción Ventricular Derecha , Enfermedad Aguda , Ecocardiografía , Humanos , Embolia Pulmonar/complicaciones , Estudios Retrospectivos , Disfunción Ventricular Derecha/complicacionesRESUMEN
Although recent Genome-Wide Association Studies have identified novel associations for common variants, there has been no comprehensive exome-wide search for low-frequency variants that affect the risk of venous thromboembolism (VTE). We conducted a meta-analysis of 11 studies comprising 8,332 cases and 16,087 controls of European ancestry and 382 cases and 1,476 controls of African American ancestry genotyped with the Illumina HumanExome BeadChip. We used the seqMeta package in R to conduct single variant and gene-based rare variant tests. In the single variant analysis, we limited our analysis to the 64,794 variants with at least 40 minor alleles across studies (minor allele frequency [MAF] ~0.08%). We confirmed associations with previously identified VTE loci, including ABO, F5, F11, and FGA. After adjusting for multiple testing, we observed no novel significant findings in single variant or gene-based analysis. Given our sample size, we had greater than 80% power to detect minimum odds ratios greater than 1.5 and 1.8 for a single variant with MAF of 0.01 and 0.005, respectively. Larger studies and sequence data may be needed to identify novel low-frequency and rare variants associated with VTE risk.
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Exoma/genética , Estudio de Asociación del Genoma Completo/métodos , Secuenciación de Nucleótidos de Alto Rendimiento , Análisis por Micromatrices/métodos , Tromboembolia Venosa/genética , Negro o Afroamericano/genética , Alelos , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/estadística & datos numéricos , Humanos , Masculino , Análisis por Micromatrices/estadística & datos numéricos , Oportunidad Relativa , Polimorfismo de Nucleótido Simple , Tamaño de la Muestra , Tromboembolia Venosa/etnologíaRESUMEN
Pulmonary embolism (PE) represents the third leading cause of cardiovascular mortality. The technological landscape for management of acute intermediate- and high-risk PE is rapidly evolving. Two interventional devices using pharmacomechanical means to recanalize the pulmonary arteries have recently been cleared by the US Food and Drug Administration for marketing, and several others are in various stages of development. The purpose of this document is to clarify the current state of endovascular interventional therapy for acute PE and to provide considerations for evidence development for new devices that will define which patients with PE would derive the greatest net benefit from their use in various clinical settings. First, definitions and limitations of commonly used risk stratification tools for PE are reviewed. An adjudication of risks and benefits of available interventional therapies for PE follows. Next, considerations for optimal future evidence development in this field are presented in the context of the current US regulatory framework. Finally, the document concludes with a discussion of the pros and cons of the rapidly expanding PE response team model of care delivery.
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Embolectomía/normas , Procedimientos Endovasculares/normas , Embolia Pulmonar/terapia , Terapia Trombolítica/normas , American Heart Association , Toma de Decisiones Clínicas , Consenso , Técnicas de Apoyo para la Decisión , Embolectomía/efectos adversos , Embolectomía/instrumentación , Embolectomía/mortalidad , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/instrumentación , Procedimientos Endovasculares/mortalidad , Humanos , Selección de Paciente , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/mortalidad , Embolia Pulmonar/fisiopatología , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/instrumentación , Terapia Trombolítica/mortalidad , Resultado del Tratamiento , Estados UnidosRESUMEN
The novel coronavirus SARS-CoV-2 (COVID-19) pandemic has created diagnostic uncertainty with regards to distinguishing this infection from pulmonary embolism (PE). Although there appears to be an increased incidence of thromboembolic disease in patients with COVID-19 infection, recommendations regarding anticoagulation are lacking. We present the case of a 61-year-old woman with clinically significant venous and arterial thromboemboli in the setting of COVID-19 infection requiring tissue plasminogen activator (tPA).
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COVID-19/complicaciones , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Tromboembolia/diagnóstico , Dolor Abdominal/etiología , COVID-19/diagnóstico , Angiografía por Tomografía Computarizada , Femenino , Humanos , Persona de Mediana Edad , SARS-CoV-2 , Tromboembolia/etiologíaRESUMEN
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.
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Servicio de Urgencia en Hospital , Embolia Pulmonar/cirugía , Trombectomía/métodos , Enfermedad Aguda , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Medición de Riesgo , Estados Unidos , Función Ventricular Izquierda , Función Ventricular DerechaRESUMEN
INTRODUCTION: Venous thromboembolism (VTE) is highly heritable. Physical activity, physical inactivity and body mass index (BMI) are also risk factors, but evidence of interaction between genetic and environmental risk factors is limited. METHODS: Data on 2,134 VTE cases and 3,890 matched controls were obtained from the Nurses' Health Study (NHS), Nurses' Health Study II (NHS II), and Health Professionals Follow-up Study (HPFS). We calculated a weighted genetic risk score (wGRS) using 16 single nucleotide polymorphisms associated with VTE risk in published genome-wide association studies (GWAS). Data on three risk factors, physical activity (metabolic equivalent [MET] hours per week), physical inactivity (sitting hours per week) and BMI, were obtained from biennial questionnaires. VTE cases were incident since cohort inception; controls were matched to cases on age, cohort, and genotype array. Using conditional logistic regression, we assessed joint effects and interaction effects on both additive and multiplicative scales. We also ran models using continuous wGRS stratified by risk-factor categories. RESULTS: We observed a supra-additive interaction between wGRS and BMI. Having both high wGRS and high BMI was associated with a 3.4-fold greater risk of VTE (relative excess risk due to interaction = 0.69, p = 0.046). However, we did not find evidence for a multiplicative interaction with BMI. No interactions were observed for physical activity or inactivity. CONCLUSION: We found a synergetic effect between a genetic risk score and high BMI on the risk of VTE. Intervention efforts lowering BMI to decrease VTE risk may have particularly large beneficial effects among individuals with high genetic risk.
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Índice de Masa Corporal , Ejercicio Físico , Predisposición Genética a la Enfermedad , Tromboembolia Venosa/genética , Adulto , Femenino , Estudios de Seguimiento , Estudio de Asociación del Genoma Completo , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Modelos Genéticos , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
The original version of the article unfortunately contained an error in conflict of interest. This erratum is published with the correct conflict of interest.
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Multidisciplinary pulmonary embolism response teams (PERTs) are being implemented to improve care of patients with life-threatening PE. We sought to determine how the creation of PERT affects treatment and outcomes of patients with serious PE. A pre- and post-intervention study was performed using an interrupted time series design, to compare patients with PE before (2006-2012) and after (2012-2016) implementation of PERT at a university hospital. T-tests, Chi square tests and logistic regression were used to compare outcomes, and multivariable regression were used to adjust for differences in PE severity. Two-sided p-value < 0.05 was considered significant. For the interrupted time-series analysis, data was divided into mutually exclusive 6-month time periods (11 pre- and 7 post-PERT). To examine changes in treatment and outcomes associated with PERT, slopes and change points were compared pre- and post-PERT. Two-hundred and twelve pre-PERT and 228 post-PERT patients were analyzed. Patient demographics were generally similar, though pre-PERT, PE were more likely to be low-risk (37% vs. 19%) while post-PERT, PE were more likely to be submassive (32% vs. 49%). More patients underwent catheter directed therapy (1% vs. 14%, p = < 0.0001) or any advanced therapy (19 [9%] vs. 44 [19%], p = 0.002) post PERT. Interrupted time series analysis demonstrated that this increase was sudden and coincident with implementation of PERT, and most noticeable among patients with submassive PE. There were no differences in major bleeding or mortality pre- and post-PERT. While the use of advanced therapies, particularly catheter-directed therapies, increased after creation of PERT, especially among patients with submassive PE, there was no apparent increase in bleeding.
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Atención a la Salud/organización & administración , Grupo de Atención al Paciente/organización & administración , Embolia Pulmonar/terapia , Atención a la Salud/tendencias , Medicina de Emergencia/tendencias , Femenino , Hospitales Universitarios , Humanos , Estudios Longitudinales , Masculino , Grupo de Atención al Paciente/tendencias , Estudios Retrospectivos , Medición de Riesgo , Resultado del TratamientoRESUMEN
OBJECTIVES: There is growing evidence that venous thromboembolism (VTE) patients with distal clots (distal calf deep vein thrombosis [DVT] and sub-segmental pulmonary embolism [PE]) may not routinely benefit from anticoagulation. We compared the D-dimer levels in VTE patients with distal and proximal clots. METHODS: We conducted a multinational, prospective observational study of low-to-intermediate risk adult patients presenting to the emergency department (ED) with suspected VTE. Patients were classified as distal (calf DVT or sub-segmental PE) or proximal (proximal DVT or non-sub-segmental PE) clot groups and compared with univariate and multivariate analyses. RESULTS: Of 1752 patients with suspected DVT, 1561 (89.1%) had no DVT, 78 (4.4%) had a distal calf DVT, and 113 (6.4%) had a proximal DVT. DVT patients with proximal clots had higher D-dimer levels (3760 vs. 1670â¯mg/dL) than with distal clots. Sensitivity and negative predictive value (NPV) for proximal DVT at an optimal D-dimer cutoff of 5770â¯mg/dL were 40.7% and 52.1% respectively. Of 1834 patients with suspected PE, 1726 (94.1%) had no PE, 7 (0.4%) had isolated sub-segmental PE, and 101 (5.5%) had non-sub-segmental PE. PE patients with proximal clots had higher D-dimer levels (4170 vs. 2520â¯mg/dL) than those with distal clots. Sensitivity and NPV for proximal PE at an optimal D-dimer cutoff of 3499â¯mg/dL were 57.4% and 10.4% respectively. CONCLUSIONS: VTE patients with proximal clots had higher D-dimer levels than patients with distal clots. However, D-dimer levels cannot be used alone to discriminate between VTE patients with distal or proximal clots.
Asunto(s)
Anticoagulantes/uso terapéutico , Servicio de Urgencia en Hospital , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Embolia Pulmonar/metabolismo , Tromboembolia Venosa/metabolismo , Adulto , Anciano , Biomarcadores/metabolismo , Enfermedad Crítica , Procesamiento Automatizado de Datos , Femenino , Pruebas de Hemaglutinación , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Embolia Pulmonar/tratamiento farmacológico , Embolia Pulmonar/fisiopatología , Sensibilidad y Especificidad , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/fisiopatologíaRESUMEN
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been used to stabilize patients with massive pulmonary embolism though few reports describe this approach. We describe the presentation, management and outcomes of patients who received ECMO for massive pulmonary embolism (PE) in our pulmonary embolism response team (PERT) registry. METHODS: We enrolled a consecutive cohort of patients with confirmed PE for whom PERT was activated and selected patients treated with ECMO. We prospectively captured clinical, therapeutic and outcome data at the time of PERT activation and during the follow-up period for up to 365 days. RESULTS: Thirteen patients who had PERT activation with confirmed PE diagnosis have undergone ECMO since the initiation of our PERT program in 2012. The mean age was 49 ± 19 years. Six (46%) patients were female. All the patients had cardiac arrest, either as an initial presentation or in-hospital cardiac arrest after presentation. All the patients exhibited right ventricular (RV) dilation on echocardiogram with RV hypokinesis. Eight (62%) patients received systemic thrombolysis with intravenous tissue plasminogen activator (tPA) and three (23%) patients underwent catheter-directed thrombolysis therapy using the EKOS system (EKOS Corporation, Bothell, WA, USA). Four (31%) patients underwent surgical embolectomy. Mean ECMO duration was 5.5 days, ranging from 2-18 days. Thirty-day mortality was 31% and one-year mortality was 54%. CONCLUSIONS: Patients with massive pulmonary embolism who suffer a cardiac arrest have high morbidity and mortality. ECMO can be used in conjunction with systemic thrombolysis, catheter-directed therapy or as a bridge to surgical embolectomy.