Mechanical thrombectomy versus catheter directed thrombolysis in patients with pulmonary embolism: A multicenter experience.

OBJECTIVES: Compare in-hospital outcomes of patients treated with either mechanical thrombectomy (MT) or catheter directed lysis (CDL) in treatment of acute pulmonary embolism (PE). METHODS: This is a multicenter, retrospective cohort study of patients undergoing MT or CDL for acute PE between 2014 and 2021. The primary outcome was the composite of in-hospital death, significant bleed, vascular complication, or need for mechanical support post-procedure. Secondary outcomes included the individual components of the composite outcome in addition to blood transfusions, invasive hemodynamics, echocardiographic data, and intensive care unit (ICU) utilization. RESULTS: 458 patients were treated for PE with 266 patients in the CDL arm and 192 patients in the MT arm. The primary composite endpoint was not significantly different between the two groups with CDL 12% versus MT 11% (p = 0.5). There was a significant difference in total length of ICU time required with more in the CDL group versus MT (3.8 ± 2.0 vs. 2.8 ± 3.0 days, p = 0.009). All other secondary end points showed no significant difference between the groups. CONCLUSIONS: In patients undergoing catheter directed treatment of PE, there was no difference between MT and CDL in terms of in-hospital mortality, bleeds, catheter-related complications, and hemodynamics.

Be aware of non-specific presentation of pulmonary embolism: a case report.

BACKGROUND: The early diagnosis of non-specific presentation of pulmonary embolism (PE) is difficult because the symptoms are non-specific and varied. CASE PRESENTATION: A 69-year-old female patient had syncope accompanied by gait disturbance, without obvious inducement. The patient was initially suspected to have cerebral infarction, but the symptoms did not improve and myocardial markers increased after two days of symptomatic treatment for myocardial infarction. Hence, PE was suspected and computed tomography pulmonary angiography (CTPA) examination confirmed the diagnosis. CTPA showed multiple emboli in pulmonary artery and its branches, so high-risk PE was diagnosed. Intravenous thrombolysis was administered, and pulmonary CTA showed a significant reduction of emboli in pulmonary artery and its left and right branches. CONCLUSION: This case report highlights the importance of improving the clinical awareness about non-specific presentation of PE and avoiding misdiagnosis or missed diagnosis.

A comparison of the efficacy and safety between anticoagulation alone and combined with catheter-directed thrombolysis for treatment of pulmonary embolism on outcome: A systematic review and meta-analysis.

BACKGROUND: Catheter-directed thrombolysis (CDT) is one of the newest treatment options for submassive pulmonary embolism (sPE). This study will compare the efficacy and safety of catheter-directed thrombolysis (CDT) combine with anticoagulation versus anticoagulation alone (AC) in patients with PE. METHODS: A database search was conducted using PubMed, EMBASE, Cochrane Library, and Clinicaltrials.gov for trials that compared CDT with AC in patients with pulmonary embolism. The primary outcomes was1-year mortality. The secondary outcomes were in-hospital, 30 days, 90 days mortality, in-hospital major and minor bleeding (Thrombolysis in Myocardial Infarction (TIMI) classification), length of hospital stay (LOS), reduction of pulmonary arterial systolic pressure (PASP) and RV/LV diameter ratio. RESULTS: A total of 16 articles (3 RCTs and 13 non-RCTs) and 10595 patients were included in this study. 2237 patients were in the CDT group and 8358 patients were in the AC group. CDT group was associated with significantly lower in-hospital mortality (2.1% vs 6.2%,OR:0.36, 95%CI:0.26-0.51, p < .00001,I2 = 0%), 30 days mortality (3.1% vs 8.6%,OR:0.39,95%CI:0.23-0.66, p = .0005, I2 = 0%), 90 days mortality (3.8% vs 7.7%,OR:0.49,95%CI:0.29-0.80,p = .005,I2 = 7%), 1-year mortality (6.1% vs 11%, OR:0.51, 95%CI:0.35-0.76, p = .0008,I2 = 36%) compared to AC group, especially in ultrasound-assisted thrombolysis (USAT) subgroup. There were no differences on major bleeding between two groups (1.8% vs 2.2%, OR:1.10, 95%CI:0.61-1.98, p = .75, I2 = 0%). Minor bleeding was significantly higher in CDT group than AC group (6.2% vs 3.8%, OR:1.93,95%CI:1.27-2.94.66, p = .002, I2 = 1%). CDT group significantly reduced PASP (WMD:11.90,95%CI:6.45-17.35, p < .0001, I2 = 72%) and RV/LV (WMD:0.17,95%CI:0.04-0.30, p = .009, I2 = 69%) rapidly than AC group after treatment. LOS was similar between two groups (WMD:0.02,95%CI: -0.68-0.73, p = .95, I2 = 51%). CONCLUSION: Results thus confirmed that CDT reduced in-hospital, 30 days, 90 days and 1-year all-cause mortality in patients with sPE compared to AC, particularly in USAT subgroup. Nonetheless, CDT group was associated with a higher risk of minor bleeding.

Inpatient Management of Pulmonary Embolism: Clinical Characteristics and Mortality in a High-Volume Tertiary Care Center.

The optimal management strategy for submassive or intermediate risk pulmonary embolism (IRPE)-anticoagulation alone versus anticoagulation plus advanced therapies-remains in equipoise leading many institutions to create multidisciplinary PE response teams (PERTs) to guide therapy. Cause-specific mortality of IRPE has not been thoroughly examined, which is a meaningful outcome when examining the effect of specific interventions for PE. In this retrospective study, we reviewed all adult inpatient admissions between 8/1/2018 and 8/1/2019 with an encounter diagnosis of PE to study all cause and PE cause specific mortality as the primary outcomes and bleeding complications from therapies as a secondary outcome. There were 429 total inpatient admissions, of which 59.7% were IRPE. The IRPE 30-day all-cause mortality was 8.7% and PE cause-specific mortality was 0.79%. Treatment consisted of anticoagulation alone in 93.4% of cases. Advanced therapies-systemic thrombolysis, catheter directed thrombolysis, or mechanical thrombectomy, were performed in only six IRPE cases (2.3%). Decompensation of IRPE cases requiring higher level of care and/or rescue advanced therapy occurred in only five cases (2%). In-hospital major bleeding and clinically relevant non-major bleeding were more common in those receiving systemic thrombolysis (61.5%) compared to anticoagulation combined with other advanced therapies (11.7%). Despite the high overall acuity of PE cases at our institution, in-hospital all-cause mortality was low and cause-specific mortality for IRPE was rare. These data suggest the need to target other clinically meaningful outcomes when examining advanced therapies for IRPE.

Intermediate-Risk Pulmonary Embolism: A Review of Contemporary Diagnosis, Risk Stratification and Management.

Pulmonary embolism (PE) can have a wide range of hemodynamic effects, from asymptomatic to a life-threatening medical emergency. Pulmonary embolism (PE) is associated with high mortality and requires careful risk stratification for individualized management. PE is divided into three risk categories: low risk, intermediate-risk, and high risk. In terms of initial therapeutic choice and long-term management, intermediate-risk (or submassive) PE remains the most challenging subtype. The definitions, classifications, risk stratification, and management options of intermediate-risk PE are discussed in this review.

Predictors of reduced cardiac index in patients with acute submassive pulmonary embolism.

OBJECTIVES: Determine the baseline clinical, laboratory, and echocardiographic values that predict reduced cardiac index (CI) among subjects with acute submassive pulmonary embolism (PE). BACKGROUND: Submassive PE represents a large portion of acute PE population and there is controversy regarding optimal treatment strategies for these patients. There is significant heterogeneity within the submassive PE population and further refinement of risk stratification may aid clinical decision-making. METHODS: We identified subjects with normotensive acute PE who underwent echocardiogram and right heart catheterization (RHC) prior to catheter-directed thrombolysis (CDT). We sought to determine the predictors of reduced CI, defined as CI < 2.2 L min-1 m-2 . RESULTS: Thirty-two subjects met the inclusion criteria and 41% had reduced CI. Baseline variables did not distinguish subjects with reduced versus normal CI. Brain natriuretic peptide (BNP) was significantly different between the reduced versus normal CI groups (BNP 440 vs. 160 pg/ml, p = .004, respectively). Univariate logistic regression identified BNP, right ventricular (RV):left ventricular (LV) diameter ratio, tricuspid annular plane systolic excursion (TAPSE), and right ventricular systolic pressure as predictors of reduced CI. In a multivariate logistic regression model, only TAPSE was an independent predictor of reduced CI. ROC curve analysis identified the following optimal cut points for prediction of reduced CI: BNP > 216 pg/ml, RV:LV ratio > 1.41, or TAPSE <1.6 cm. CONCLUSIONS: Almost half of subjects with acute submassive PE have reduced CI, despite normal systemic blood pressure. Optimal cut points for BNP, RV:LV ratio, and TAPSE were identified to predict reduced CI among patients with acute PE. These findings may aid in clinical decision-making and risk stratification of patients with acute submassive PE.

Invasive hemodynamic assessment of patients with submassive pulmonary embolism.

OBJECTIVES: To investigate the invasive hemodynamics in patients with intermediate-risk pulmonary embolism (PE) and the change that occurs with catheter-directed thrombolysis (CDT). BACKGROUND: Intermediate-risk PE is associated with right ventricular strain and worse outcomes yet the invasive hemodynamics have not been well described. METHODS: Ninety-two consecutive patients with intermediate-risk PE referred for CDT at two tertiary medical centers with Pulmonary Embolism Response Teams were included in this prospective cohort study. Hemodynamics at baseline and after CDT therapy was measured. Patients with cardiac index (CI) ≤1.8 L min-1 m-2 were compared to those without shock (CI > 1.8). Linear regression analysis was performed to study the relationship between clinical variables and low CI. RESULTS: Thirty-seven out of 92 (40%) had a CI less than 1.8 L min-1 m-2 . When comparing the low CI to the normal CI groups, most demographics, vital signs, biomarkers, and PE severity index (PESI) scores were similar. The low CI group had more females and slightly lower systolic blood pressures although still in the normal range (122 vs. 132 mmHg, p = .026). Treatment with CDT was associated with significant improvement in CI, heart rate, and pulmonary artery pressures in both groups. Linear regression analysis did not reveal a strong correlation between CI and noninvasive metrics such as heart rate, blood pressure, or PESI score. CONCLUSIONS: Forty percent of patients with submassive PE had a depressed CI and treatment with CDT lead to hemodynamic improvements. Invasive hemodynamics may help better identify higher risk patients and guide therapy.

Long-term mortality after massive, submassive, and low-risk pulmonary embolism.

Guidelines for management of normotensive patients with acute pulmonary embolism (PE) emphasize further risk stratification on the basis of right ventricular (RV) size and biomarkers of RV injury or strain; however, the prognostic importance of these factors on long-term mortality is not known. We performed a retrospective cohort study of subjects diagnosed with acute PE from 2010 to 2015 at a tertiary care academic medical center. The severity of initial PE presentation was categorized into three groups: massive, submassive, and low-risk PE. The primary endpoint of all-cause mortality was ascertained using the Centers for Disease Control National Death Index (CDC NDI). A total of 183 subjects were studied and their median follow-up was 4.1 years. The median age was 65 years. The 30-day mortality rate was 7.7% and the overall mortality rate through the end of follow-up was 40.4%. The overall mortality rates for massive, submassive, and low-risk PE were 71.4%, 44.5%, and 28.1%, respectively (p < 0.001). Landmark analysis using a 30-day cutpoint demonstrated that subjects presenting with submassive PE compared with low-risk PE had increased mortality during both the short- and the long-term periods. The most frequent causes of death were malignancy, cardiac disease, respiratory disease, and PE. Independent predictors of all-cause mortality were cancer at baseline, age, white blood cell count, diabetes mellitus, liver disease, female sex, and initial presentation with massive PE. In conclusion, the diagnosis of acute PE was associated with substantial long-term mortality. The severity of initial PE presentation was associated with both short- and long-term mortality.

Performance of the right ventricular outflow tract/aortic diameter as a novel predictor of risk in patients with acute pulmonary embolism.

Right ventricular (RV) enlargement, determined via the ratio of the right to left ventricular diameters (RV/LV) by CT imaging is used to classify the severity of acute pulmonary embolism (PE) and impacts treatment decisions. The RV/LV ratio may be an unreliable marker of RV dysfunction, due in part to the complex RV geometry. This study compared the RV/LV ratio to a novel metric, the ratio of the right ventricular to aortic outflow tract diameters (RVOT/Ao) in patients with acute PE treated with catheter-directed therapies (CDT). RVOT/Ao and RV/LV ratios were measured on CT images from 103 patients who received CDT for acute submassive or massive PE and were compared to RV dysfunction severity determined by transthoracic echocardiography. Ratios and biomarkers on admission were assessed for correlation with invasively-measured hemodynamics [right atrial (RA) pressure, mean pulmonary artery (PA) pressure, cardiac output (CO)]. RVOT/Ao but not RV/LV ratios were increased in patients with moderate or severe RV dysfunction compared to those without RV dysfunction (p < 0.05). Neither ratio showed significant correlation with RA (r = 0.09 vs 0.055, p > 0.05), mean PA pressure (r = 0.167 vs 0.146, p > 0.05), or CO (r = 0.021 vs - 0.183, p > 0.05). proBNP correlated with mean PA pressure (r = 0.377, p < 0.05). The RVOT/Ao ratio may be better at assessing RV dysfunction than the RV/LV ratio in patients presenting with acute PE. Although currently accepted protocols rely on the RV/LV ratio in determining when CDT are of benefit, the RVOT/Ao ratio may be a more useful tool in identifying high risk patients.

Protocolized use of catheter-directed thrombolysis and echocardiography is highly effective in reversing acute right heart dysfunction in severe submassive pulmonary embolism patients.

OBJECTIVE: The objective of this study was to evaluate the efficacy of protocolized use of catheter-directed thrombolysis and echocardiography in submassive pulmonary embolism patients. METHODS: A retrospective study at a single institution of 28 patients that presented with submassive pulmonary embolism from July 2016 to September 2019 was performed. All patients were diagnosed using chest computed tomography demonstrating a pulmonary embolism and abnormal right ventricular to left ventricular ratio. Patients with severe right heart dysfunction (right ventricular to left ventricular ratio ⩾1.4) were protocolized to receive catheter-directed thrombolysis via EkoSonic catheters (EKOS Corporation, Bothell, WA, United States). Transthoracic echocardiogram was performed after 24 hours to assess right ventricular function and determine the need to continue thrombolysis. Patients after discharge then received follow-up echocardiograms at 6 weeks to determine new post-treatment baseline. RESULTS: The mean patient age was 54.6 years, mean body mass index was 35.0, and mean right ventricular to left ventricular ratio on admission computed tomography imaging was 1.70. Interval mean right ventricular to left ventricular ratio on echocardiography during thrombolysis therapy was 1.01 (p < 0.00001). Patients were tachycardic on admission (mean heart rate 102.2 beats per minute) with improvement by completion of thrombolysis (mean heart rate 72.9 beats per minute) (p < 0.00001). There was a 0% incidence of periprocedural complications. Overall 30-day complication rate was 7.1% (n = 1 arrhythmia, n = 1 delayed intracranial hemorrhage). At 6-week follow-up, 91% of the patients who received echocardiography had normal right ventricular function. CONCLUSION: This retrospective study demonstrates the effectiveness of protocolized use of catheter-directed thrombolysis and echocardiography in reversing severe right heart dysfunction in submassive pulmonary embolism patients.

Low-dose systemic thrombolytic therapy for treatment of submassive pulmonary embolism: Clinical efficacy but attendant hemorrhagic risks.

OBJECTIVES: The purpose of the present study is to evaluate the safety and efficacy of "low-dose" systemic thrombolytic therapy (TT) for treatment of patients with intermediate-high risk submassive pulmonary embolism (PE). BACKGROUND: TT is increasingly utilized in acute submassive PE. Strategies for TT include catheter-directed administration as well as traditional IV systemic therapy. Regardless of the route, most studies document the attendant significant bleeding complication rates expected from induction of a systemic lytic state. To mitigate bleeding, "low-dose" systemic TT (Alteplase 50 mg) has been advocated, based on recent studies which demonstrated clinical efficacy with elimination of any significant bleeding complications. METHODS: Over a 24-month period, our institutional PE Response Team treated 45 acute submassive PE patients with "Low Dose" IV Alteplase 50 mg. Clinical outcomes and bleeding complications were assessed. RESULTS: Overall clinical outcome was excellent, with 97.8% of patients surviving to discharge and a 30-day, all-cause mortality of 4.4%. Despite no patients having a HAS-BLED score > 2 (average score = 0.8 +/-), ISTH major and GUSTO moderate bleeding was observed in 11% (n = 5) of cases. CONCLUSIONS: The present observations document that low-dose systemic TT is associated with excellent clinical outcome for intermediate-high risk submassive PE, but with attendant risk for bleeding. These findings are consistent with the concept that induction of a therapeutic lytic state carries inextricable bleeding risk.

Submassive Pulmonary Embolism.

Pulmonary embolism (PE) presents a spectrum of hemodynamic consequences, ranging from being asymptomatic to a life-threatening medical emergency. Management of submassive and massive PE often involves clinicians from multiple specialties, which can potentially delay the development of a unified treatment plan. In addition, patients with submassive PE can deteriorate after their presentation and require escalation of care. Underlying comorbidities such as chronic obstructive pulmonary disease, cancer, congestive heart failure, and interstitial lung disease can impact the patient's hemodynamic ability to tolerate submassive PE. In this review, we address the definitions, risk stratification (clinical, laboratory, and imaging), management approaches, and long-term outcomes of submassive PE. We also discuss the role of the PE response team in management of patients with PE.

Systematic Review: The Role of Thrombolysis in Intermediate-Risk Pulmonary Embolism.

BACKGROUND: This systemic review provides practicing emergency physicians updated information about the role of thrombolysis in the treatment of intermediate-risk pulmonary embolism. METHODS: A PubMed literature search from January 1, 2005 to December 31, 2018 was conducted and limited to human clinical trials written in English with relevant keywords. High-quality studies were identified and then underwent a structured review. Recommendations are made based on the literature review. RESULTS: Sixty-three articles met criteria for rigorous review, of which 13 were appropriate for citation in this review. Of these 13, there were 6 prospective studies and 7 retrospective studies. CONCLUSIONS: Thrombolysis, either catheter-directed or systemic, is a treatment option in the management of patients with intermediate-risk pulmonary embolism and a high likelihood of clinical deterioration. Each method of thrombolysis carries risks and benefits. Based on the available evidence, transfer to a facility for the purpose of catheter-directed thrombolysis is not recommended.

The impact of a multi-specialty team for high risk pulmonary embolism on resident and fellow education.

The impact of the Pulmonary Embolism Response Team (PERT) model on trainee physician education and autonomy over the management of high risk pulmonary embolism (PE) is unknown. A resident and fellow questionnaire was administered 1 year after PERT implementation. A total of 122 physicians were surveyed, and 73 responded. Even after 12 months of interacting with the PERT consultative service, and having formal instruction in high risk PE management, 51% and 49% of respondents underestimated the true 3-month mortality for sub-massive and massive PE, respectively, and 44% were unaware of a common physical exam finding in patients with PE. Comparing before and after PERT implementation, physicians perceived enhanced confidence in identifying ( p<0.001), and managing ( p=0.003) sub-massive/massive PE, enhanced confidence in treating patients appropriately with systemic thrombolysis ( p=0.04), and increased knowledge of indications for systemic thrombolysis and surgical embolectomy ( p=0.043 and p<0.001, respectively). Respondents self-reported an increased fund of knowledge of high risk PE pathophysiology (77%), and the perception that a multi-disciplinary team improves the care of patients with high risk PE (89%). Seventy-one percent of respondents favored broad implementation of a PERT similar to an acute myocardial infarction team. Overall, trainee physicians at a large institution perceived an enhanced educational experience while managing PE following PERT implementation, believing the team concept is better for patient care.

A pulmonary embolism response team's initial 20 month experience treating 87 patients with submassive and massive pulmonary embolism.

Pulmonary Embolism Response Teams (PERTs) have emerged to provide rapid multidisciplinary assessment and treatment of PE patients. However, descriptive institutional experience and preliminary outcomes data from such teams are sparse. PERT activations were identified through a retrospective review. Only confirmed submassive or massive PEs were included in the data analysis. In addition to baseline variables, the therapeutic intervention, length of stay (LOS), in-hospital mortality, and bleeding rate/severity were recorded. A total of 124 PERT activations occurred over 20 months: 43 in the first 10 months and 81 in the next 10. A total of 87 submassive (90.8%) and massive (9.2%) PE patients were included. The median age was 65 (51-75 IQR) years. Catheter-directed thrombolysis (CDT) was administered to 25 patients, systemic thrombolysis (ST) to six, and anticoagulation alone (AC) to 54. The median ICU stay and overall LOS were 6 (3-10 IQR) and 7 (4-14 IQR) days, respectively, with no association with any variables except a brain natriuretic peptide (BNP) >100 pg/mL ( p=0.008 ICU LOS; p=0.047 overall LOS). Twelve patients (13.7%) died in the hospital, nine of whom had metastatic or brain cancer, with a median overall LOS of 13 (11-17 IQR) days. There were five major bleeds: one in the CDT group, one in the ST group, and three in the AC group. Overall, (1) PERT activations increased after the first 10 months; (2) BNP >100 pg/mL was associated with a longer LOS; (3) rates of mortality and bleeding did not correlate with treatment; and (4) the majority of in-hospital deaths occurred in patients with advanced cancer.

Short- and Long-term Mortality Risk After Acute Pulmonary Embolism.

PURPOSE OF REVIEW: Acute pulmonary embolism is a major cause of morbidity and mortality in the USA and throughout the world. This review will summarize recent developments in short- and long-term mortality risk assessment after an acute pulmonary embolism. RECENT FINDINGS: Recent guidelines have emphasized risk stratification of acute PE patients on the basis of blood pressure, right ventricular size, and biomarker status. Ongoing work is testing various acute treatment strategies for improvement of symptom burden, length of stay, quality of life, and possibly mortality risk reduction. Long-term outcomes among subjects with acute PE are less well studied. Long-term mortality largely correlates with baseline co-morbidity burden, although there may be an association between acute PE severity and long-term outcomes. Acute PE risk stratification and treatment, as well as long-term follow-up of patients with acute PE, are rapidly developing areas and many promising innovations are underway.

Four key questions surrounding thrombolytic therapy for submassive pulmonary embolism.

Submassive pulmonary embolism (PE) remains a vexing entity, and the appropriate use of thrombolytic therapy for this subgroup continues to be actively debated. Catheter-directed thrombolysis has shown efficacy for submassive PE and is gaining momentum because of theoretically improved safety. This review poses and responds to four questions that explore the complex issues surrounding optimal therapy of submassive PE.

Current Controversies in Thrombolytic Use in Acute Pulmonary Embolism.

BACKGROUND: Acute pulmonary embolism (PE) has an annual incidence of 100,000 cases in the United States and is divided into three categories: nonmassive, submassive, and massive. Several studies have evaluated the use of thrombolytics in submassive and massive PE. OBJECTIVE: Our aim was to provide emergency physicians with an updated review of the controversy about the use of thrombolytics in submassive and massive PE. DISCUSSION: Nonmassive PE is defined as PE in the setting of no signs of right ventricular strain (echocardiogram or biomarker) and hemodynamic stability. Submassive PE is defined as evidence of right ventricular strain with lack of hemodynamic instability. Massive PE occurs with occlusive thromboembolism that causes hemodynamic instability. Thrombolysis is warranted in patients with massive PE. Thrombolytic use in submassive PE with signs of right ventricular strain or damage presents a quandary for physicians. Several recent studies have evaluated the use of thrombolytics in patients with submassive PE. These studies have inconsistent definitions of submassive PE, evaluate differing primary outcomes, and use different treatment protocols with thrombolytics and anticoagulation agents. Although significant study heterogeneity exists, thrombolytics can improve long-term outcomes, with decreased bleeding risk with half-dose thrombolytics and catheter-directed treatments. Major bleeding significantly increases in patients over age 65 years. The risks and benefits of thrombolytic treatment-primarily improved long-term outcomes-should be considered on a case-by-case basis. Shared decision-making with the patient discussing the risks and benefits of treatment is advised. CONCLUSIONS: Thrombolytic use in massive PE is warranted, but patients with submassive PE require case-by-case analysis with shared decision making. The risks, including major hemorrhage, and benefits, primarily improved long-term outcomes, should be considered. Half-dose thrombolytics and catheter-directed treatment demonstrate advantages with decreased risk of bleeding and improved long-term functional outcomes. Further studies that assess risk stratification, functional outcomes, and treatment protocols are needed.

Submassive hepatic necrosis distinguishes HBV-associated acute on chronic liver failure from cirrhotic patients with acute decompensation.

BACKGROUND & AIMS: Distinguishing between acute on chronic liver failure (ACLF) and decompensated liver cirrhosis is difficult due to a lack of pathological evidence. METHODS: A prospective single-center study investigated 174 patients undergoing liver transplantation due to acute decompensation of hepatitis B virus (HBV)-associated liver cirrhosis. Two groups were distinguished by the presence or absence of submassive hepatic necrosis (SMHN, defined as necrosis of 15-90% of the entire liver on explant). Core clinical features of ACLF were compared between these groups. Disease severity scoring systems were applied to describe liver function and organ failure. Serum cytokine profile assays, gene expression microarrays and immunohistochemical analyzes were used to study systemic and local inflammatory responses. RESULTS: SMHN was identified in 69 of 174 patients proven to have cirrhosis by histological means. Characteristic features of SMHN were extensive necrosis along terminal hepatic veins and spanning multiple adjacent cirrhotic nodules accompanied by various degrees of liver progenitor cell-derived regeneration, cholestasis, and ductular bilirubinostasis. Patients with SMHN presented with more severely impaired hepatic function, a higher prevalence of multiple organ failure (as indicated by higher CLIF-SOFA and SOFA scores) and a shorter interval between acute decompensation and liver transplantation than those without SMHN (p<0.01 for all parameters). Further analyzes based on serum cytokine profile assays, gene expression microarrays and immunohistochemical analyzes revealed higher levels of anti-inflammatory cytokines in patients with SMHN. CONCLUSIONS: SMHN is a critical histological feature of HBV-associated ACLF. Identification of a characteristic pathological feature strongly supports that ACLF is a separate entity in end-stage liver disease.

A retrospective analysis of catheter-based thrombolytic therapy for acute submassive and massive pulmonary embolism.

Catheter-based thrombolysis (CBT) is emerging as an option for acute pulmonary embolism (PE). Although prior studies have demonstrated improvement in right ventricular function, little data is available regarding clinical patient outcomes. Our institution adopted CBT as an option for patients with submassive and massive PE and we evaluated its effect on patient outcomes. Two hundred and twenty-one patients who presented to our institution with submassive and massive PE were analyzed over three years by time period; 102 prior to the use of CBT and 119 during the time CBT was performed. The primary outcome was in-hospital major adverse clinical events (a composite of death, recurrent embolism, major bleeding, or stroke). Secondary outcomes were overall and ICU length of stay and individual components of the composite outcome. Mean age was 56.3±16 years with high rates of central PE (57.9%), RV dysfunction (37%), and myocardial necrosis (26%). Mean RV/LV ratio was 1.2. Thirty-two patients were treated with CBT. The composite endpoint occurred more frequently in the CBT era vs the pre-CBT era (21.0% vs 14.7%, p=0.23). After multivariate adjustment, CBT treatment demonstrated no effect on major adverse clinical events (OR 0.84, CI 0.22-3.22, p=0.80). CBT era patients had an unadjusted 37% increase in ICU days and 54% increase in total length of stay (p<0.001). Within the CBT era, CBT treatment resulted in an adjusted 190% increase in overall length of stay (p<0.001). CBT did not demonstrate improvement in hospital outcomes, despite adjustments of PE severity, and was associated with a significant increase in overall and ICU length of stay.