Intermediate-risk Acute Pulmonary Embolism Research Articles

Low left ventricular outflow tract velocity time integral predicts normotensive shock in patients with acute pulmonary embolism

Abstract Funding Acknowledgements None. Introduction In patients with intermediate-risk acute pulmonary embolism (PE) outcomes vary widely, with mortality rates ranging from 3-15% and rates of normotensive shock up to 30%.1-3 Current risk models don't fully capture those at higher risk and identify patients who may benefit from advanced therapies. The left ventricular outflow tract (LVOT) velocity time integral (VTI), a surrogate marker of cardiac output, has been associated with increased mortality in acute PE.4 Our objective was to determine the association between LVOT VTI and its predictive value in identifying normotensive shock in this patient population. Methods Patients who underwent percutaneous mechanical thrombectomy (MT) between August 2020 and March 2023 at a large academic public hospital were considered for the study. Inclusion criteria comprised of normotensive patients (SBP ≥ 90 mmHg) with invasive measures of cardiac index (CI). VTI was obtained by pulsed wave doppler at the LVOT in either the apical 3 or apical 5 chamber view. The primary outcome was the association between LVOT VTI and normotensive shock and a cut off of 15 cm was used to examine this association based on prior studies.4 Results A total of 49 patients with intermediate-risk PE underwent MT, 16 patients had incomplete data, resulting in a final cohort of 33 patients (mean age: 57 ± 13yrs; 38% female). Patients with LVOT VTI of <15 cm were younger (53 vs 62 years p=0.02), had lower systolic blood pressure at presentation (122 vs 134 mmHg, p=0.047), higher heart rate (112.6 vs 96.2 beats/min, p=0.008), a higher composite shock score (CPES) (5 vs 3, p=0.012), lower cardiac index (1.9 vs 3.1 L/min/m2, p<0.001), a higher PASP (61.4 vs 48.9 mmHg, p=0.018), and higher rates of elevated lactate (90% vs 42%, p=0.027). LVOT VTI threshold of <15cm effectively identified patients with normotensive shock (90% vs 8% p<0.001). There was no statistically significant difference in the rates of saddle emboli, left ventricular ejection fraction, sPESI and BOVA scores in patients with VTI above or below 15cm. In patients with normotensive shock, 19/20 (95%) had LVOT VTI ≤ 15cm with a median of 13 cm (IQR 12, 14) (Figure). In patients without normotensive shock, 11/13 (84%) had LVOT VTI >15 with a median of 18 (IQR 17, 21). The area under the curve for LVOT VTI ≤ 15 cm in predicting normotensive shock was 0.89. The sensitivity and specificity of LVOT VTI ≤ 15 cm in predicting normotensive shock was 91.6% and 90.4% respectively. Conclusion Our study suggests that LVOT VTI is a reliable surrogate for cardiac output in patients with acute PE and can effectively identify those in the intermediate-risk group who are at risk for normotensive shock. A LVOT VTI <15cm may identify intermediate-risk patients at higher risk for hemodynamic decompensation and further studies are needed to evaluate whether these patients would benefit from upfront catheter-based therapies.

McConnell's sign predicts normotensive shock in patients with acute pulmonary embolism

Abstract Funding Acknowledgements None. Background Patients with intermediate-risk acute pulmonary embolism (PE) have mortality rates ranging from 3-15%, with incidence of normotensive shock occurring in up to 30% of patients.1-3 Existing risk models often fall short in accurately identifying those at heightened risk of normotensive shock and those who might derive benefit from advanced therapeutic interventions including catheter based therapies. Diagnosis of normotensive shock typically necessitates invasive right heart catheterization, however, McConnell's sign has been associated with higher risk PEs.4 Consequently, our objective was to assess the relationship between McConnell's sign, a readily available bedside point-of-care tool, and its predictive value in identifying normotensive shock in patients diagnosed with acute intermediate-risk PE. Methods All patients with intermediate-risk PE who underwent percutaneous mechanical thrombectomy (MT) between August 2020 and April 2023 at a large academic public hospital were included in the study. Normotensive shock was defined as patients with systolic blood pressure (SBP) ≥ 90mmHg in the absence of vasopressor support with pre-procedural invasive measures of CI £ 2.2 L/min/m2 and clinical evidence of hypoperfusion (i.e. elevated lactate, oliguria). The primary outcome was the association between McConnell’s sign and normotensive shock. Results A total of 49 patients with intermediate-risk PE underwent MT, 9 patients had incomplete data, resulting in a final cohort of 40 patients (mean age: 57 ± 13 years; 45% female). A total of 29/40 (72.5%) patients had McConnell’s sign. Patients with McConnell’s sign had higher rates of obesity (59% vs 18% p=0.02), higher heart rate (114 vs 99 beats/min, p=0.008), higher rates of elevated lactate (86% vs 55%, p=0..038), lower cardiac index (1.9 vs 3.1 L/min/m2, p=0.003), and higher rates of normotensive shock (76% vs 27%, p=0.005). There was no statistically significant difference in age, sex, race, rates of saddle emboli, left ventricular ejection fraction, pulmonary artery systolic pressure, presenting blood pressure, sPESI and composite pulmonary embolism shock score scores in patients with or without McConnell’s sign. In patients with normotensive shock, 22/25 (88%) had McConnell’s sign and only 53.3% had McConnell’s sign without shock (Figure 1). Patients with McConnell’s sign had an increased odds (OR 8.38, CI: 1.73-40.53; p=0.008, AUC 0.70, 95% CI: 0.56-0.85) of normotensive shock. Conclusion This is the first study to suggest that McConnell’s sign can effectively identify those in the intermediate-risk group who are at risk for normotensive shock. Further studies are needed to validate this non-invasive technique that can be rapidly performed at bedside with high reproducibility and whether it can help risk-stratify patients who may benefit from advanced PE therapies.

Risk Stratification and Management of Intermediate-Risk Acute Pulmonary Embolism.

Pulmonary embolism (PE) is the third most common cause of cardiovascular death and necessitates prompt, accurate risk assessment at initial diagnosis to guide treatment and reduce associated mortality. Intermediate-risk PE, defined as the presence of right ventricular (RV) dysfunction in the absence of hemodynamic compromise, carries a significant risk for adverse clinical outcomes and represents a unique diagnostic challenge. While small clinical trials have evaluated advanced treatment strategies beyond standard anticoagulation, such as thrombolytic or endovascular therapy, there remains continued debate on the optimal care for this patient population. Here, we review the most recent risk stratification models, highlighting differences between prediction scores and their limitations, and discuss the utility of serologic biomarkers and imaging modalities to detect right ventricular dysfunction. Additionally, we examine current treatment recommendations including anticoagulation strategies, use of thrombolytics at full and reduced doses, and utilization of invasive treatment options. Current knowledge gaps and ongoing studies are highlighted.

Focus on Intermediate-Risk Acute Pulmonary Embolism. Is the Combination of Biomarkers the Solution?

Focus on Intermediate-Risk Acute Pulmonary Embolism. Is the Combination of Biomarkers the Solution?

Effect of Pharmacomechanical Catheter-Directed Thrombolysis on Segmental Artery Occlusions: Insights From the RESCUE Trial

BackgroundReduction in distal vascular volume in acute pulmonary embolism (PE) is a significant predictor of 30- and 90-day mortality. The likely cause of this is pulmonary arterial obstruction. The effect of pharmacomechanical catheter-directed thrombolysis (PM-CDT) on the occlusions of these pulmonary artery (PA) branches is not known. ObjectivesThe RESCUE study evaluated PM-CDT with the Bashir endovascular catheter in patients with acute intermediate-risk PE. This analysis assessed PA occlusions using core laboratory data before and after PM-CDT therapy. MethodsThe baseline and 48-hour post-treatment contrast-enhanced chest computed tomography angiography of PE patients with right ventricular dilatation enrolled in the RESCUE trial were used. The primary analysis was the change in the number of segmental and proximal PA branches with total or subtotal (>65%) occlusions after 48 hours compared to baseline using McNemar’s test. ResultsA total of 107 patients enrolled across 18 United States sites comprised this analysis. At 48 hours post-PM-CDT, the number of segmental PA branches with total or subtotal occlusions decreased from 40.5% to 11.7% (P < 0.0001). Proximal PA branch total or subtotal occlusions decreased from 28.7% to 11.0% (P < 0.0001). The reduction in segmental artery occlusions correlated significantly with the magnitude of reduction in right ventricular/left ventricular ratio (correlation coefficient of 0.287 [95% CI: 0.102-0.452]; P = 0.0026), whereas that in the proximal PA arteries did not (correlation coefficient of 0.132 [95% CI: 0.059-0.314] P = 0.173). ConclusionsPM-CDT with the Bashir catheter was associated with a significant reduction in total and subtotal occlusion of segmental and proximal PAs.

OC 01.2 Oxygen vs Ambient Air in Patients with Intermediate-Risk Acute Pulmonary Embolism: The Air Randomized Clinical Trial

OC 01.2 Oxygen vs Ambient Air in Patients with Intermediate-Risk Acute Pulmonary Embolism: The Air Randomized Clinical Trial

Systemic thrombolysis with newer thrombolytics vs anticoagulation in acute intermediate risk pulmonary embolism: a systematic review and meta-analysis

BackgroundRandomized controlled trials (RCTs) comparing systemic thrombolysis to anticoagulation in intermediate risk pulmonary embolism (PE) have yielded mixed results. A prior meta-analysis on this topic had included studies that used lower than standard dose of thrombolytics and included thrombolytic agents that are no longer available. Hence, interpreting the findings of that paper is not valid in contemporary practice.ObjectivesWe undertook a systematic review and meta-analysis of randomized controlled trials of systemic thrombolysis with newer thrombolytic agents vs anticoagulation in intermediate risk PE.MethodsThis systematic review and meta-analysis is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement.ResultsNine randomized controlled trials were included in the study. We did not find any difference in in-hospital mortality (RR: 0.79; 95% CI: 0.42–1.50; I2: 0) or risk of major bleeding (RR:2.08;95% CI: 0.98–4.42; I2: 23.9%) between systemic thrombolysis and anticoagulation. Systemic thrombolysis was associated with lower risks for vasopressor use (RR: 0.27; 95% CI: 0.11–0.64, I2: 0) and secondary/rescue thrombolysis (RR: 0.25; 95% CI: 0.14–0.45; I2: 0). But systemic thrombolysis was found to have an increased risk of intracranial hemorrhage (RR: 4.55; 95% CI: 1.30–15.91; I2:0). There was no difference in mechanical ventilation between the two groups (RR: 0.61; 95% CI: 0.31–1.19, I2:0).ConclusionIn our meta-analysis of randomized controlled trials of systemic thrombolysis vs anticoagulation in intermediate risk PE, we did not find any difference in in-hospital mortality or overall risk of major bleeding. With systemic thrombolysis, we found lower risks for vasopressor use and need for secondary/ rescue thrombolysis and an increased risk of intracranial hemorrhage.

Oxygen Therapy in Patients With Intermediate-Risk Acute Pulmonary Embolism: A Randomized Trial

The effect of supplemental oxygen therapy in patients with intermediate-risk pulmonary embolism (PE) who do not have hypoxemia at baseline is uncertain. Does supplemental oxygen improve echocardiographic parameters in nonhypoxemic patients with intermediate-risk PE? This pilot trial randomly assigned nonhypoxemic patients with stable PE and echocardiographic right ventricle (RV) enlargement to receive anticoagulation plus supplemental oxygen for the first 48h vsanticoagulation alone. The primary outcome was normal echocardiographic RV size 48h after randomization. Secondary efficacy outcomes were the numerical change in the RV to left ventricle (LV) diameter ratio measured 48h and 7days after randomization with respect to the baseline ratio measured at inclusion. The study was stopped prematurely because of the COVID-19 pandemic after recruiting 70 patients (mean ± SD age, 67.3 ± 16.1 years; 36 female [51.4%]) with primary outcome data. Forty-eight h after randomization, normalization of the RV size occurred in 14 of the 33 patients (42.4%) assigned to oxygen and in eight of the 37 patients (21.6%) assigned to ambient air (P= .08). In the oxygen group, the mean RV to LV ratio was reduced from 1.28 ± 0.28 at baseline to 1.01 ± 0.16 at 48h (P< .001); in the ambient air group, mean RV to LV ratios were 1.21 ± 0.18 at baseline and 1.08 ± 0.19 at 48h (P< .01). At 90days, one major bleeding event and one death (both in the ambient air group) had occurred. In analyses limited by a small number of enrollees, compared with ambient air, supplemental oxygen did not significantly increase the proportion of patients with nonhypoxemic intermediate-risk PE whose RV to LV ratio normalized after 48h of treatment. This pilot trial showed improvement in some ancillary efficacy outcomes and provides support for a definitive clinical outcomes trial. ClinicalTrials.gov; No.: NCT04003116; URL: www. gov.

CT imaging determinants of persistent hypoxemia in acute intermediate-risk pulmonary embolism.

The factors associated with persistent hypoxemia after pulmonary embolus (PE) are not well understood. Predicting the need for oxygen post discharge at the time of diagnosis using available CT imaging will enable better discharge planning. To examine the relationship between CT derived imaging markers (automated computation of arterial small vessel fraction, pulmonary artery diameter to aortic diameter ratio (PA:A), right to left ventricular diameter ratio (RV:LV) and new oxygen requirement at the time of discharge in patients diagnosed with acute intermediate-risk PE. CT measurements were obtained in a retrospective cohort of patients with acute-intermediate risk PE admitted to Brigham and Women's Hospital between 2009 and 2017. Twenty one patients without a history of lung disease requiring home oxygen and 682 patients without discharge oxygen requirements were identified. There was an increased median PA:A ratio (0.98 vs. 0.92, p = 0.02) and arterial small vessel fraction (0.32 vs. 0.39, p = 0.001) in the oxygen-requiring group], but no difference in the median RV:LV ratio (1.20 vs. 1.20, p = 0.74). Being in the upper quantile for the arterial small vessel fraction was associated with decreased odds of oxygen requirement (OR 0.30 [0.10-0.78], p = 0.02). Loss of arterial small vessel volume as measured by arterial small vessel fraction and an increase in the PA:A ratio at the time of diagnosis were associated with the presence of persistent hypoxemia on discharge in acute intermediate-risk PE.

Recovery of right ventricular function after intermediate-risk pulmonary embolism: results from the multicentre Pulmonary Embolism International Trial (PEITHO)-2

BackgroundRight ventricular (RV) function plays a critical role in the pathophysiology and acute prognosis of pulmonary embolism (PE). We analyzed the temporal changes of RV function in the cohort of a prospective multicentre study investigating if an early switch to oral anticoagulation in patients with intermediate-risk PE is effective and safe.MethodsEchocardiographic and laboratory examinations were performed at baseline (PE diagnosis), 6 days and 6 months. Echocardiographic parameters were classified into categories representing RV size, RV free wall/tricuspid annulus motion, RV pressure overload and right atrial (RA)/central venous pressure.ResultsRV dysfunction based on any abnormal echocardiographic parameter was present in 84% of patients at baseline. RV dilatation was the most frequently abnormal finding (40.6%), followed by increased RA/central venous pressure (34.6%), RV pressure overload (32.1%), and reduced RV free wall/tricuspid annulus motion (20.9%). As early as day 6, RV size remained normal or improved in 260 patients (64.7%), RV free wall/tricuspid annulus motion in 301 (74.9%), RV pressure overload in 297 (73.9%), and RA/central venous pressure in 254 (63.2%). At day 180, the frequencies slightly increased. The median NT-proBNP level decreased from 1448 pg/ml at baseline to 256.5 on day 6 and 127 on day 180.ConclusionIn the majority of patients with acute intermediate-risk PE switched early to a direct oral anticoagulant, echocardiographic parameters of RV function normalised within 6 days and remained normal throughout the first 6 months. Almost one in four patients, however, continued to have evidence of RV dysfunction over the long term.Graphical

The rationale, design, and methods of a trial to evaluate the efficacy and safety of oxygen therapy in patients with intermediate-risk acute pulmonary embolism

In patients with intermediate-risk pulmonary embolism (PE), reversal of hypoxic vasoconstriction could constitute a target for treatment that protects the right ventricular (RV) function until endogenous fibrinolysis occurs. The Air vs oxygen for Intermediate-Risk pulmonary embolism (AIR) trial aims to assess the effect of oxygen therapy in patients with intermediate-risk acute PE who do not have hypoxemia at baseline. AIR is a prospective, multicenter, randomized, open-label, parallel-group, proof-of-concept trial. A total of 90 patients hospitalized with intermediate-risk PE and an oxygen saturation of 90% or higher at baseline will be randomized in a 1:1 fashion to receive supplemental oxygen or ambient air. The primary outcome is a RV/LV diameter ratio equal or less than 1.0 on echocardiography measured 48 hours after the start of treatment. Secondary efficacy outcomes are the numerical change in the ratio of the RV to the LV diameter measured 48 hours and 7 days after the start of treatment, with respect to the baseline ratio measured at randomization. Clinical adverse events will be also collected. Enrollment started in July 2019 and is expected to proceed until 2022. Median age of the first 50 patients was 74 years (interquartile range, 61-81), and 50% were female. This multicenter trial will provide information about the value of supplemental oxygen in patients with intermediate-risk acute PE who do not have hypoxemia at baseline. The results will contribute to research that may assist patients with intermediate-risk PE in the future.

WHERE ARE YOU GOING: EMERGENCY MANAGEMENT OF A THROMBUS-IN-TRANSIT WITH PERCUTANEOUS MECHANICAL THROMBECTOMY AT A COMMUNITY HOSPITAL

WHERE ARE YOU GOING: EMERGENCY MANAGEMENT OF A THROMBUS-IN-TRANSIT WITH PERCUTANEOUS MECHANICAL THROMBECTOMY AT A COMMUNITY HOSPITAL

Pharmacomechanical Catheter-Directed Thrombolysis With the Bashir Endovascular Catheter for Acute Pulmonary Embolism: The RESCUE Study

BackgroundCatheter-directed thrombolysis (CDT) has been associated with rapid recovery of right ventricular (RV) function. The Bashir catheter was developed for enhanced thrombolysis in large vessels such as the pulmonary arteries (PAs) with lower doses of tissue plasminogen activator (tPA). ObjectivesThe aim of this study was to evaluate the efficacy and safety of tPA infused using a pharmacomechanical (PM) CDT device called the Bashir endovascular catheter in patients with intermediate-risk acute pulmonary embolism (PE). MethodsPatients with symptoms of acute PE with computed tomographic evidence of RV dilatation were enrolled. The Bashir catheter was used to deliver 7 mg tPA into each PA over 5 hours. The primary efficacy endpoint was the core laboratory–assessed change in computed tomographic angiography–derived RV/left ventricular (LV) diameter ratio at 48 hours, and the primary safety endpoint was serious adverse events (SAEs) including major bleeding at 72 hours. ResultsAt 18 U.S. sites, 109 patients were enrolled. The median device placement time was 15 minutes. At 48 hours after PM-CDT, the RV/LV diameter ratio decreased by 0.56 (33.3%; P < 0.0001). PA obstruction as measured by the refined modified Miller index was reduced by 35.9% (P < 0.0001). One patient (0.92%) had 2 SAEs: a retroperitoneal bleed (procedure related) and iliac vein thrombosis (device related). Two other procedure-related SAEs were epistaxis and non–access site hematoma with anemia. ConclusionsPM-CDT with the Bashir endovascular catheter is associated with a significant reduction in RV/LV diameter ratio and a very low rate of adverse events or major bleeding in patients with intermediate-risk acute PE. The notable finding was a significant reduction in PA obstruction with low-dose tPA. (Recombinant tPA by Endovascular Administration for the Treatment of Submassive PE Using CDT for the Reduction of Thrombus Burden [RESCUE]; NCT04248868)

Catheter-directed therapies for the treatment of high risk (massive) and intermediate risk (submassive) acute pulmonary embolism.

Catheter-directed therapies for the treatment of high risk (massive) and intermediate risk (submassive) acute pulmonary embolism.

Short-term prognostic value of clinical data in hospitalized patients with intermediate-risk acute pulmonary embolism

BackgroundIntermediate-risk acute pulmonary embolism (APE) patients are usually defined as hemodynamically stable, comprehending a great therapeutic dilemma. Although anticoagulation therapy is sufficient for most intermediate-risk APE patients, some patients can deteriorate and eventually require a systemic fibrinolytic agent or thrombectomy. Hence, this study aimed to evaluate the predictive value of differences in clinical data for the short-term prognosis of intermediate-risk APE patients.MethodsA retrospective cohort of 74 intermediate-risk APE patients confirmed by computed tomography pulmonary angiography was analyzed in the present study. Adverse clinical event outcomes included PE-related in-hospital deaths, critical systolic blood pressure consistently under 90 mmHg, refractory to volume loading and vasopressor infusion requirements, mechanical ventilation, and cardiopulmonary resuscitation. The APE patients were stratified into two groups: adverse outcome (n = 25) and control (n = 49) groups. Then, the clinical data of the two groups were compared. Receiver operating characteristic (ROC) curves were used to explore the predictive value of white blood cell (WBC) counts and the right to left ventricular short-axis (RV/LV) ratio. Model calibration was assessed using the Hosmer–Lemeshow goodness-of-fit statistic.ResultsThe brain natriuretic peptide, WBC count, and the RV/LV ratio were higher in patients with adverse outcomes compared to controls. The APE patients with adverse outcomes presented significantly higher rates of syncope, Negative T waves (NTW) in V1–V3, intermediate-high risk, thrombolytic therapy, and low arterial oxygen saturation (SaO2) compared to controls. In the multivariate logistic regression analysis, the SaO2 < 90%, [odds ratio (OR) 5.343, 95% confidence interval (CI) 1.241–23.008; p = 0.024], RV/LV ratio (OR 7.429, 95% CI 1.145–48.209; p = 0.036), Syncope (OR 12.309, 95% CI 1.702–89.032; p = 0.013), NTW in V1–V3 (OR 5.617, 95% CI 1.228–25.683; p = 0.026), and WBC count (OR 1.212, 95% CI 1.035–1.419; p = 0.017) were independent predictors of in-hospital adverse outcomes among APE patients. The ROC curve analysis indicated that the RV/LV ratio can be used to predict adverse outcomes (AUC = 0.748, p < 0.01) and calibration (Hosmer–Lemeshow goodness of fit test, p = 0.070). Moreover, an RV/LV ratio > 1.165 was predictive of adverse outcomes with sensitivity and specificity of 88.00 and 59.20%, respectively. The WBC counts were also able to predict adverse outcomes (AUC = 0.752, p < 0.01) and calibration (Hosmer–Lemeshow goodness of fit test, p = 0.251). A WBC count > 9.05 was predictive of adverse outcomes with sensitivity and specificity of 68.00 and 73.50%, respectively.ConclusionOverall, a SaO2 < 90%, RV/LV ratio, Syncope, NTW in V1–V3, and WBC counts could independently predict adverse outcomes in hospitalized intermediate-risk APE patients.

A-55 | Peripheral Pulmonary Blood Volume Decreases in Patients with Intermediate Risk Acute Pulmonary Embolism Treated with Anticoagulation

Ultrasound-facilitated, catheter-directed fibrinolysis has been shown to increase peripheral pulmonary arterial blood volume distribution at 48 hours post-treatment as a mechanism for right ventricular (RV) recovery in intermediate risk pulmonary embolism (PE). The change in peripheral pulmonary blood volume distribution in patients receiving anticoagulation monotherapy remains unclear.

Novel Pharmacomechanical Thrombolysis for Treating Intermediate-Risk Acute Pulmonary Embolism: The Bashir Endovascular Catheter.

Novel Pharmacomechanical Thrombolysis for Treating Intermediate-Risk Acute Pulmonary Embolism: The Bashir Endovascular Catheter.

Efficacy and safety of early switch to oral anticoagulation in acute intermediate-risk pulmonary embolism

Abstract Background Guidelines recommend risk-adjusted management of pulmonary embolism (PE). We investigated whether treatment of acute intermediate-risk PE with parenteral anticoagulation for a short period of 72 hours, followed by switch to a direct oral anticoagulant (dabigatran), is effective and safe. Methods We conducted a prospective multicentre single-arm management trial in patients with intermediate-risk PE (EudraCT Identifier 2015–001830–12). Patients received parenteral heparin, switched to dabigatran 72 hours after diagnosis following standardised clinical assessment. The study was terminated early following sample size adaptation after the predefined interim analysis. Findings From January 2016 through July 2019, 402 patients were enrolled in 9 European countries. Adherence to protocol was 92.0% (Table 1). The primary outcome, recurrent symptomatic venous thromboembolism or PE-related death within 6 months (Table 2), occurred in 7 patients (1.7%; upper bound of right-sided 95% CI 3.2%; p=0.ehab724.192322 for rejecting H0), with all events in the intermediate-high-risk group (2.5%; upper bound of right-sided 95% CI 4.6%). Median duration of hospitalisation for the index event was 6 days, despite the fact that &amp;gt;70% of the patients had intermediate-high-risk PE. The six-month incidence of major bleeding was 2.7%; the only fatal haemorrhage occurred before switch to dabigatran. Interpretation A strategy of early switch from heparin to dabigatran following standardised clinical assessment was effective and safe in intermediate-risk PE. Our results can help to fine-tune guideline recommendations for initial treatment of PE, optimising the use of resources and avoiding prolonged hospitalisation. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): German Federal Ministry of Education and Research; and Boehringer Ingelheim Table 1. Time between diagnosis of pulmonary embolism and switch to dabigatran (N = 402 patients)Table 2. Efficacy and safety outcomes

THIRD TIME'S A CHARM: TREATING PULMONARY EMBOLISM WITH MECHANICAL THROMBECTOMY AFTER TWO FAILED ATTEMPTS WITH THROMBOLYTIC THERAPY

TOPIC: Procedures TYPE: Medical Student/Resident Case Reports INTRODUCTION: Pulmonary embolism (PE) can be a life-threatening condition. Massive PE, characterized by hemodynamic instability with signs of shock, comprises 4.5%-10% of all PE cases and has over 50% mortality rate. When medical therapy fails, aspiration thrombectomy is a treatment option for acute massive or submassive PE in patients with hemodynamic compromise or right ventricular (RV) dysfunction (Dopazo et al, 2018). CASE PRESENTATION: A 61-year-old male presented after an episode of syncope, chest pain, and dyspnea. Due to profound hypoxia, he was intubated. ECG as seen in figure 1 was changed from prior. Troponin was 0.80. In the ED, he was placed on norepinephrine and epinephrine due to hypotension. Bedside echocardiogram (ECHO) showed enlarged RV with severely reduced RV systolic function, hypokinetic RV free wall, and apex. The patient subsequently developed pulseless electrical activity (PEA) arrest. Two cycles of CPR were performed to achieve the return of spontaneous circulation. Due to the possibility of PE, weight-based tPA was administered. He had PEA arrest a second time and CPR was done for 9 minutes. A second dose of weight-based tPA was given after which his hemodynamics transiently improved. Epinephrine drip was discontinued, but norepinephrine drip was continued. He was transferred to ICU for monitoring and was placed on a heparin drip. Over the next 12 hours, despite multiple tPA doses, he progressively decompensated with systolic blood pressure to 40mmHg while on norepinephrine. Vasopressin drip was initiated. Lactic acidosis increased from 3.8 to 6.6 mmol/L, creatinine worsened from 1.6 to 4.0 mg/dL, and Hb 12.2 to 8.5 g/dL. CTA for PE confirmed saddle pulmonary embolism with evidence of RV strain with RV/LV ratio 1.1. He was taken emergently for cardiac catheterization on multiple vasopressors. A bilateral pulmonary artery thrombectomy with a T24 Inari catheter was done successfully, with subsequent improvement in hemodynamics. ECHO after the procedure showed improved RV function and RV size reduction. Within 24 hours of the thrombectomy, vasopressors were titrated off and the patient remained hemodynamically stable. DISCUSSION: Though systemic thrombolytic therapy is typically indicated for hemodynamically unstable patients with suspected pulmonary emboli, it was not effective in our patient, despite multiple doses. Catheter-directed therapies for PE can remove obstructive emboli directly, allowing for rapid patient improvement as seen in our case. Furthermore, though it is an invasive strategy, catheter-directed thrombectomy has the potential to offer both short- and long-term benefits over systemic thrombolysis including early recovery, reduced risk of bleeding, pulmonary hypertension, and reversal of RV failure. CONCLUSIONS: Catheter-directed techniques should be considered on a case-by-case basis, especially in patients who do not improve with thrombolysis. REFERENCE #1: 1.Ciampi-Dopazo, Juan José et al. "Aspiration Thrombectomy for Treatment of Acute Massive and Submassive Pulmonary Embolism: Initial Single-Center Prospective Experience.” Journal of vascular and interventional radiology : JVIR vol. 29,1 (2018): 101-106. doi:10.1016/j.jvir.2017.08.010 REFERENCE #2: 2.Tu, Thomas et al. "A Prospective, Single-Arm, Multicenter Trial of Catheter-Directed Mechanical Thrombectomy for Intermediate-Risk Acute Pulmonary Embolism: The FLARE Study.” JACC. Cardiovascular interventions vol. 12,9 (2019): 859-869. doi:10.1016/j.jcin.2018.12.022 DISCLOSURES: No relevant relationships by Mukul Bhattarai, source=Web Response No relevant relationships by radhika deshpande, source=Web Response no disclosure on file for Abdul Hafiz; No relevant relationships by Cameron Koester, source=Web Response No relevant relationships by Abhishek Kalidas Kulkarni, source=Web Response no disclosure on file for Mohsin Salih; No relevant relationships by Omar Siddiqui, source=Web Response

Early switch to oral anticoagulation in patients with acute intermediate-risk pulmonary embolism (PEITHO-2): a multinational, multicentre, single-arm, phase 4 trial

Current guidelines recommend a risk-adjusted treatment strategy for the management of acute pulmonary embolism. This is a particular patient category for whom optimal treatment (anticoagulant treatment, reperfusion strategies, and duration of hospitalisation) is currently unknown. We investigated whether treatment of acute intermediate-risk pulmonary embolism with parenteral anticoagulation for a short period of 72 h, followed by a switch to a direct oral anticoagulant (dabigatran), is effective and safe. We did a multinational, multicentre, single-arm, phase 4 trial at 42 hospitals in Austria, Belgium, France, Germany, Italy, Netherlands, Romania, Slovenia, and Spain. Adult patients (aged ≥18 years) with symptomatic intermediate-risk pulmonary embolism, with or without deep-vein thrombosis, were enrolled. Patients received parenteral low-molecular-weight or unfractionated heparin for 72 h after diagnosis of pulmonary embolism before switching to oral dabigatran 150 mg twice per day following a standard clinical assessment. The primary outcome was recurrent symptomatic venous thromboembolism or pulmonary embolism-related death within 6 months. The primary and safety outcomes were assessed in the intention-to-treat population. The study was terminated early, as advised by the data safety and monitoring board, following sample size adaptation after the predefined interim analysis on Dec 18, 2018. This trial is registered with the EU Clinical Trials Register (EudraCT 2015-001830-12) and ClinicalTrials.gov (NCT02596555). Between Jan 1, 2016, and July 31, 2019, 1418 patients with pulmonary embolism were screened, of whom 402 were enrolled and were included in the intention-to-treat analysis (median age was 69·5 years [IQR 60·0-78·0); 192 [48%] were women and 210 [52%] were men). Median follow-up was 217 days (IQR 210-224) and 370 (92%) patients adhered to the protocol. The primary outcome occurred in seven (2% [upper bound of right-sided 95% CI 3]; p<0·0001 for rejecting the null hypothesis) patients, with all events occurring in those with intermediate-high-risk pulmonary embolism (seven [3%; upper bound of right-sided 95% CI 5] of 283). At 6 months, 11 (3% [95% CI 1-5]) of 402 patients had at least one major bleeding event and 16 (4% [2-6]) had at least one clinically relevant non-major bleeding event; the only fatal haemorrhage occurred in one (<1%) patient before the switch to dabigatran. A strategy of early switch from heparin to dabigatran following standard clinical assessment was effective and safe in patients with intermediate-risk pulmonary embolism. Our results can help to refine guideline recommendations for the initial treatment of acute intermediate-risk pulmonary embolism, optimising the use of resources and avoiding extended hospitalisation. German Federal Ministry of Education and Research, University Medical Center Mainz, and Boehringer Ingelheim.