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Although systemic thrombolysis (ST) is the standard of care in the treatment of high-risk pulmonary embolism (PE), large variations in real-world usage exist, including its use to treat intermediate-risk PE. A paucity of data is available to define the outcomes and practice patterns of the ST dose, duration, and treatment of presumed and imaging-confirmed PE.We performed a multicenter retrospective study to evaluate the real-world practice patterns of ST use in the setting of acute PE (presumed vs imaging-confirmed intermediate- and high-risk PE). Patients who had received tissue plasminogen activator for PE between 2017 and 2019 were included. We compared the baseline clinical characteristics, tissue plasminogen activator practice patterns, and outcomes for patients with confirmed vs presumed PE.A total of 104 patients had received ST for PE: 52 with confirmed PE and 52 with presumed PE. Significantly more patients who had been treated for presumed PE had experienced cardiac arrest (n = 47; 90%) compared with those with confirmed PE (n = 23; 44%; P .01). Survival to hospital discharge was 65% for the patients with confirmed PE vs 6% for those with presumed PE (P .01). The use of ST was contraindicated for 56% of the patients with confirmed PE, with major bleeding in 26% but no intracranial hemorrhage.The in-hospital mortality of patients with confirmed acute PE has remained high (35%) in contemporary practice for those treated with ST. A large proportion of these patients had had contraindications to ST, and the rates of major bleeding were significant. Those with confirmed PE had had a higher survival rate compared with those with presumed PE, including those with cardiac arrest. This observation suggests a limited role for empiric thrombolysis in cardiac arrest situations.

The oral factor Xa inhibitors (OFXAi) apixaban and rivaroxaban are increasingly utilized for the treatment of venous thromboembolism (VTE) with recommended initial higher dose 7- and 21-day lead-in regimens, respectively. In patients receiving initial parenteral anticoagulation, it remains unknown if the full recommended higher dose OFXAi lead-in regimens are warranted, or if days can be subtracted. We aimed to describe when clinicians may deviate from recommended lead-in durations and evaluate clinical outcomes in these scenarios. This is a retrospective, observational study of patients 18 years or older who were treated with rivaroxaban or apixaban for acute pulmonary embolism (PE) or symptomatic proximal deep vein thrombosis (DVT) that received parenteral anticoagulation for at least 24 h before transitioning to the OFXAi. Among our cohort of 171 patients with acute VTE who received parenteral anticoagulation for a median of 48 h, 134 (78%) were prescribed a full OFXAi lead-in and 37 (22%) were prescribed a reduced lead-in. Patients in the reduced lead-in group were older with more cardiac comorbidities and antiplatelet use. There were four recurrent thromboembolic events within 3 months, two in the reduced lead-in group and two in the full lead-in group (5% vs. 2%, p = 0.206). Bleeding within 3 months occurred in 9 (5%) patients, with 6 events occurring in the reduced lead-in group and 3 events in the full lead-in group (16% vs. 2%, p = 0.004). Prescribing patterns of OFXAi lead-in therapy duration are variable in patients receiving initial parenteral anticoagulation. Larger cohorts are needed to better define the safety and efficacy of lead-in reduction.

Background Histologic analyses of deep vein thrombi (DVTs) have used autopsy samples and animal models. To the best of our knowledge, no previous study has reported on thrombus composition after percutaneous mechanical extraction. Because elements of chronicity and organization render thrombus resistant to anticoagulation and thrombolysis, a better understanding of clot evolution could inform therapy. Methods We performed a histologic evaluation of DVTs from consecutive patients who had undergone mechanical thrombectomy for extensive iliofemoral DVTs using the Clottriever/Flowtriever device (Inari Medical, Irvine, Calif). The DVTs were scored using a semiquantitative method according to the degree of fibrosis (collagen deposition on trichrome staining) and organization (endothelial growth with capillaries and fibroblastic penetration). Results Twenty-three specimens were available for analysis, with 20 presenting as acute DVT (≤14 days from symptom onset). Of the 23 patients, 11 (48%) had had >5% fibrosis (ie, collagen deposition) and 14 (61%) had had >5% organization (ie, endothelial growth, capillaries, fibroblasts). Four patients with acute DVT had had ≥25% organized thrombus and two had had ≥25% collagen deposition. Of the 20 patients with acute DVT, 40% had had >5% fibrosis and 55% had had >5% organization. The acuity of DVT did not correlate with the amount of fibrosis or organizing scores. Conclusions A large proportion of patients with acute DVT will have histologic elements of chronicity and fibrosis. A better understanding of the relationship between such elements and the response to anticoagulant agents and fibrinolytic drugs could inform our approach to therapy.

Lung ultrasound (LUS) has gained considerable acceptance in emergency and critical care medicine but is yet to be fully implemented in cardiology. Standard imaging protocols for LUS in acute care settings have allowed the rapid and accurate diagnosis of dyspnea, respiratory failure, and shock. LUS is greatly additive to echocardiography and is superior to auscultation and chest radiography, particularly when the diagnosis of acute decompensated heart failure is in question. In this review, the authors describe LUS techniques, interpretation, and clinical applications, with the goal of informing cardiologists on the imaging modality. Additionally, the authors review LUS findings associated with various disease states most relevant to cardiac care. Although there is extensive literature on LUS in the acute care setting, there is a dearth of reviews directly focused for practicing cardiologists. Current evidence demonstrates that this modality is an important adjunct to echocardiography, providing valuable clinical information at the bedside.

Objective Heightened inflammation, dysregulated immunity, and thrombotic events are characteristic of hospitalized COVID‐19 patients. Given that platelets are key regulators of thrombosis, inflammation, and immunity they represent prime candidates as mediators of COVID‐19‐associated pathogenesis. The objective of this study was to understand the contribution of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) to the platelet phenotype via phenotypic (activation, aggregation) and transcriptomic characterization. Approach and Results In a cohort of 3915 hospitalized COVID‐19 patients, we analyzed blood platelet indices collected at hospital admission. Following adjustment for demographics, clinical risk factors, medication, and biomarkers of inflammation and thrombosis, we find platelet count, size, and immaturity are associated with increased critical illness and all‐cause mortality. Bone marrow, lung tissue, and blood from COVID‐19 patients revealed the presence of SARS‐CoV‐2 virions in megakaryocytes and platelets. Characterization of COVID‐19 platelets found them to be hyperreactive (increased aggregation, and expression of P‐selectin and CD40) and to have a distinct transcriptomic profile characteristic of prothrombotic large and immature platelets. In vitro mechanistic studies highlight that the interaction of SARS‐CoV‐2 with megakaryocytes alters the platelet transcriptome, and its effects are distinct from the coronavirus responsible for the common cold (CoV‐OC43). Conclusions Platelet count, size, and maturity associate with increased critical illness and all‐cause mortality among hospitalized COVID‐19 patients. Profiling tissues and blood from COVID‐19 patients revealed that SARS‐CoV‐2 virions enter megakaryocytes and platelets and associate with alterations to the platelet transcriptome and activation profile.

Accumulating evidence from clinical trials suggests that a lower (restrictive) hemoglobin threshold (8% g/dL) for red blood cell (RBC) transfusion, compared with a higher (liberal) threshold (≥10 g/dL) is safe. However, in anemic patients with acute myocardial infarction (MI), maintaining a higher hemoglobin level may increase oxygen delivery to vulnerable myocardium resulting in improved clinical outcomes. Conversely, RBC transfusion may result in increased blood viscosity, vascular inflammation, and reduction in available nitric oxide resulting in worse clinical outcomes. We hypothesize that a liberal transfusion strategy would improve clinical outcomes as compared to a more restrictive strategy.We will enroll 3500 patients with acute MI (type 1, 2, 4b or 4c) as defined by the Third Universal Definition of MI and a hemoglobin10 g/dL at 144 centers in the United States, Canada, France, Brazil, New Zealand, and Australia. We randomly assign trial participants to a liberal or restrictive transfusion strategy. Participants assigned to the liberal strategy receive transfusion of RBCs sufficient to raise their hemoglobin to at least 10 g/dL. Participants assigned to the restrictive strategy are permitted to receive transfusion of RBCs if the hemoglobin falls below 8 g/dL or for persistent angina despite medical therapy. We will contact each participant at 30 days to assess clinical outcomes and at 180 days to ascertain vital status. The primary endpoint is a composite of all-cause death or recurrent MI through 30 days following randomization. Secondary endpoints include all-cause mortality at 30 days, recurrent adjudicated MI, and the composite outcome of all-cause mortality, nonfatal recurrent MI, ischemia driven unscheduled coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting), or readmission to the hospital for ischemic cardiac diagnosis within 30 days. The trial will assess multiple tertiary endpoints.The MINT trial will inform RBC transfusion practice in patients with acute MI.

Over a third of patients surviving acute pulmonary embolism (PE) will experience long-term cardiopulmonary limitations. Persistent thrombi, impaired gas exchange, and altered hemodynamics account for aspects of the postpulmonary embolism syndrome that spans mild functional limitations to debilitating chronic thromboembolic pulmonary hypertension (CTEPH), the most worrisome long-term consequence. Though pulmonary endarterectomy is potentially curative for the latter, less is understood surrounding chronic thromboembolic disease (CTED) and post-PE dyspnea. Advances in pulmonary vasodilator therapies and growing expertise in balloon pulmonary angioplasty provide options for a large group of patients ineligible for surgery, or those with persistent postoperative pulmonary hypertension. In this clinical review, we discuss epidemiology and pathophysiology as well as advances in diagnostics and therapeutics surrounding the spectrum of disease that may follow months after acute PE.

OBJECTIVES: To investigate the incidence, characteristics, and outcomes of in-hospital cardiac arrest in patients with coronavirus disease 2019 and to describe the characteristics and outcomes for patients with in-hospital cardiac arrest within the ICU, compared with non-ICU patients with in-hospital cardiac arrest. Finally, we evaluated outcomes stratified by age. DATA SOURCES: A systematic review of PubMed, EMBASE, and preprint websites was conducted between January 1, 2020, and December 10, 2020. Prospective Register of Systematic Reviews identification: CRD42020203369. STUDY SELECTION: Studies reporting on consecutive in-hospital cardiac arrest with a resuscitation attempt among patients with coronavirus disease 2019. DATA EXTRACTION: Two authors independently performed study selection and data extraction. Study quality was assessed with the Newcastle-Ottawa Scale. Data were synthesized according to the Preferred Reporting Items for Systematic Reviews guidelines. Discrepancies were resolved by consensus or through an independent third reviewer. DATA SYNTHESIS: Eight studies reporting on 847 in-hospital cardiac arrest were included. In-hospital cardiac arrest incidence varied between 1.5% and 5.8% among hospitalized patients and 8.0-11.4% among patients in ICU. In-hospital cardiac arrest occurred more commonly in older male patients. Most initial rhythms were nonshockable (83.9%, [asystole = 36.4% and pulseless electrical activity = 47.6%]). Return of spontaneous circulation occurred in 33.3%, with a 91.7% in-hospital mortality. In-hospital cardiac arrest events in ICU had higher incidence of return of spontaneous circulation (36.6% vs 18.7%; p < 0.001) and relatively lower mortality (88.7% vs 98.1%; p < 0.001) compared with in-hospital cardiac arrest in non-ICU locations. Patients greater than or equal to 60 years old had significantly higher in-hospital mortality than those less than 60 years (93.1% vs 87.9%; p = 0.019). CONCLUSIONS: Approximately, one in 20 patients hospitalized with coronavirus disease 2019 received resuscitation for an in-hospital cardiac arrest. Hospital survival after in-hospital cardiac arrest within the ICU was higher than non-ICU locations and seems comparable with prepandemic survival for nonshockable rhythms. Although the data provide guidance surrounding prognosis after in-hospital cardiac arrest, it should be interpreted cautiously given the paucity of information surrounding treatment limitations and resource constraints during the pandemic. Further research is into actual causative mechanisms is needed.

Background Coronavirus Disease 2019 (COVID-19) has caused over 1 200 000 deaths worldwide as of November 2020. However, little is known about the clinical outcomes among hospitalized patients with active COVID-19 after in-hospital cardiac arrest (IHCA). Aim We aimed to characterize outcomes from IHCA in patients with COVID-19 and to identify patient- and hospital-level variables associated with 30-day survival. Methods We conducted a multicentre retrospective cohort study across 11 academic medical centres in the U.S. Adult patients who received cardiopulmonary resuscitation and/or defibrillation for IHCA between March 1, 2020 and May 31, 2020 who had a documented positive test for Severe Acute Respiratory Syndrome Coronavirus 2 were included. The primary outcome was 30-day survival after IHCA. Results There were 260 IHCAs among COVID-19 patients during the study period. The median age was 69 years (interquartile range 60–77), 71.5% were male, 49.6% were White, 16.9% were Black, and 16.2% were Hispanic. The most common presenting rhythms were pulseless electrical activity (45.0%) and asystole (44.6%). ROSC occurred in 58 patients (22.3%), 31 (11.9%) survived to hospital discharge, and 32 (12.3%) survived to 30 days. Rates of ROSC and 30-day survival in the two hospitals with the highest volume of IHCA over the study period compared to the remaining hospitals were considerably lower (10.8% vs. 64.3% and 5.9% vs. 35.7% respectively, p Conclusions We found rates of ROSC and 30-day survival of 22.3% and 12.3% respectively. There were large variations in centre-level outcomes, which may explain the poor survival in prior studies.

The right ventricular outflow tract (RVOT) velocity time integral (VTI), an echocardiographic measure of stroke distance, correlates with cardiac index. We sought to determine the prognostic significance of low RVOT VTI on clinical outcomes among patients with acute pulmonary embolism (PE).We conducted a retrospective review of echocardiograms on Pulmonary Embolism Response Team (PERT) activations at our institution. The main outcome was a composite of death, cardiac arrest, or hemodynamic deterioration.Of 188 patients, 30 met the combined outcome (16%) and had significantly lower RVOT VTI measurements (9.0 cm v 13.4 cm, p 0.0001). The AUC for RVOT VTI at a cutoff of 10 cm was 0.78 (95% CI 0.67-0.90) with a sensitivity, specificity, negative predictive value, and positive predictive value of 0.72, 0.81, 0.94, and 0.42, respectively. Fifty-two patients of the cohort were classified as intermediate-high-risk PE and 21% of those met the combined outcome. RVOT VTI was lower among outcome positive patients (7.3 cm v 10.7 cm, p = 0.02).Low RVOT VTI is associated with poor clinical outcomes among patients with acute PE.

Male sex, elevated troponin levels, and elevated D-dimer levels are associated with more complicated COVID-19 illness and greater mortality; however, while there are known sex differences in the prognostic value of troponin and D-dimer in other disease states, it is unknown whether they exist in the setting of COVID-19.We assessed whether sex modified the relationship between troponin, D-dimer, and severe COVID-19 illness (defined as mechanical ventilation, ICU admission or transfer, discharge to hospice, or death).We conducted a retrospective cohort study of patients hospitalized with COVID-19 at a large, academic health system. We used multivariable regression to assess associations between sex, troponin, D-dimer, and severe COVID-19 illness, adjusting for demographic, clinical, and laboratory covariates. To test whether sex modified the relationship between severe COVID-19 illness and troponin or D-dimer, models with interaction terms were utilized.Among 4,574 patients hospitalized with COVID-19, male sex was associated with higher levels of troponin and greater odds of severe COVID-19 illness, but lower levels of initial D-dimer when compared with female sex. While sex did not modify the relationship between troponin level and severe COVID-19 illness, peak D-dimer level was more strongly associated with severe COVID-19 illness in male patients compared to female patients (males: OR=2.91, 95%CI=2.63-2.34, p0.001; females: OR=2.31, 95%CI=2.04-2.63, p0.001; p-interaction=0.005).Sex did not modify the association between troponin level and severe COVID-19 illness, but did modify the association between peak D-dimer and severe COVID-19 illness, suggesting greater prognostic value for D-dimer in males with COVID-19.

Coronavirus disease 2019 (COVID-19) is associated with increased rates of deep vein thrombosis (DVT) and pulmonary embolism (PE). Pulmonary Embolism Response Teams (PERT) have previously been associated with improved outcomes. We aimed to investigate whether PERT utilization, recommendations, and outcomes for patients diagnosed with acute PE changed during the COVID-19 pandemic. This is a retrospective cohort study of all adult patients with acute PE who received care at an academic hospital system in New York City between March 1st and April 30th, 2020. These patients were compared against historic controls between March 1st and April 30th, 2019. PE severity, PERT utilization, initial management, PERT recommendations, and outcomes were compared. There were more cases of PE during the pandemic (82 vs. 59), but less PERT activations (26.8% vs. 64.4%, p

Supplemental Digital Content is available in the text., Objective: To determine the prevalence of D-dimer elevation in coronavirus disease 2019 (COVID-19) hospitalization, trajectory of D-dimer levels during hospitalization, and its association with clinical outcomes. Approach and Results: Consecutive adults admitted to a large New York City hospital system with a positive polymerase chain reaction test for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) between March 1, 2020 and April 8, 2020 were identified. Elevated D-dimer was defined by the laboratory-specific upper limit of normal (>230 ng/mL). Outcomes included critical illness (intensive care, mechanical ventilation, discharge to hospice, or death), thrombotic events, acute kidney injury, and death during admission. Among 2377 adults hospitalized with COVID-19 and ≥1 D-dimer measurement, 1823 (76%) had elevated D-dimer at presentation. Patients with elevated presenting baseline D-dimer were more likely than those with normal D-dimer to have critical illness (43.9% versus 18.5%; adjusted odds ratio, 2.4 [95% CI, 1.9–3.1]; P2000 ng/mL had the highest risk of critical illness (66%), thrombotic event (37.8%), acute kidney injury (58.3%), and death (47%). Conclusions: Abnormal D-dimer was frequently observed at admission with COVID-19 and was associated with higher incidence of critical illness, thrombotic events, acute kidney injury, and death. The optimal management of patients with elevated D-dimer in COVID-19 requires further study.

Immunoglobulin G4–related disease is a systemic fibroinflammatory disease; pericardial involvement has occasionally been reported in publications. A 79-year-old man with biopsy-proven immunoglobulin G4–related disease with pleural involvement was admitted in acute heart failure, with imaging and hemodynamic studies consistent with constrictive pericarditis. He was treated with corticosteroids for 2 months with partial response manifest by decreases in pericardial thickening and immunoglobulin G4 levels. However, persistent constriction required pericardiectomy, leading to significant symptomatic improvement. (Level of Difficulty: Intermediate.), Graphical abstract, Immunoglobulin G4–related disease is a systemic fibroinflammatory disease; pericardial involvement has occasionally been reported in publications. A…

Objectives The rate of thromboembolic events among patients with coronavirus disease 2019 is high; however, there is no robust method to identify those at greatest risk. We reviewed thromboelastography studies in critically ill patients with coronavirus disease 2019 to characterize their coagulation states. Design Retrospective. Setting Tertiary ICU in New York City. Patients Sixty-four patients with coronavirus disease 2019 admitted to the ICU with thromboelastography performed. Interventions None. Measurements and main results Fifty percent of patients had a clotting index in the hypercoagulable range (clotting index > 3) (median 3.05). Reaction time and K values were below the lower limit of normal in 43.8% of the population consistent with a hypercoagulable profile. The median α angle and maximum amplitude (75.8° and 72.8 mm, respectively) were in the hypercoagulable range. The α angle was above reference range in 70.3% of patients indicative of rapid clot formation. Maximum amplitude, a factor of fibrinogen and platelet count and function, and a measure of clot strength was above reference range in 60.1% of patients. Thirty-one percent had thromboembolic events; thromboelastography parameters did not correlate with events in our cohort. Those with D-dimer values greater than 2,000 were more likely to have shorter reaction times compared with those with D-dimer levels less than or equal to 2,000 (4.8 vs 5.6 min; p = 0.001). Conclusions A large proportion of critically ill patients with coronavirus disease 2019 have hypercoagulable thromboelastography profiles with additional derangements related to fibrinogen and platelet function. As the majority of patients have an elevated thromboelastography maximum amplitude, a follow-up study evaluating platelet aggregation would be instructive.

The left ventricular outflow tract (LVOT) velocity time integral (VTI) is an easily measured echocardiographic stroke volume index analog. Low values predict adverse outcomes in left ventricular failure. We postulate the left ventricular VTI may be a signal of right ventricular dysfunction in acute pulmonary embolism, and therefore a predictor of poor outcomes. We retrospectively reviewed echocardiograms on all Pulmonary Embolism Response Team activations at our institution at the time of pulmonary embolism diagnosis. Low LVOT VTI was defined as ⩽ 15 cm. We examined two composite outcomes: (1) in-hospital death or cardiac arrest; and (2) shock or need for primary reperfusion therapies. Sixty-one of 188 patients (32%) had a LVOT VTI of ⩽ 15 cm. Low VTI was associated with in-hospital death or cardiac arrest (odds ratio (OR) 6, 95% CI 2, 17.9; p = 0.0014) and shock or need for reperfusion (OR 23.3, 95% CI 6.6, 82.1; p < 0.0001). In a multivariable model, LVOT VTI ⩽ 15 remained significant for death or cardiac arrest (OR 3.48, 95% CI 1.02, 11.9; p = 0.047) and for shock or need for reperfusion (OR 8.12, 95% CI 1.62, 40.66; p = 0.011). Among intermediate–high-risk patients, low VTI was the only variable associated with the composite outcome of death, cardiac arrest, shock, or need for reperfusion (OR 14, 95% CI 1.7, 118.4; p = 0.015). LVOT VTI is associated with adverse short-term outcomes in acute pulmonary embolism. The VTI may help risk stratify patients with intermediate–high-risk pulmonary embolism.

Introduction: In-hospital cardiac arrest (IHCA) affects over 200 000 patients in the US annually. Approximately 20% will survive to hospital discharge, although outcomes vary between hospitals. Debriefing has been shown to improve resuscitation quality and teamwork and has been associated with improved IHCA outcomes. All IHCA at NYU Langone Health are attended by the ALERT team, a dedicated team of critical care nurses who perform active patient surveillance and respond to acute in-hospital emergencies. IHCA debriefs at NYU Langone Health have historically been performed on paper forms but were limited by low rates of compliance. As part of an ongoing quality improvement (QI) initiative, we designed and implemented an electronic debriefing tool for use after IHCA (eDebrief). Methods: The eDebrief tool was developed by the NYU Interdisciplinary Resuscitation Committee. The tool captures cardiopulmonary resuscitation (CPR) quality metrics, teamwork and leadership, use of resuscitation equipment (mechanical CPR, advanced airway adjuncts, and ultrasound), and outcomes. ALERT team nurses received an educational session and ad hoc refresher sessions if required. Data were collected at the conclusion of the event using an electronic device (iPhone, Apple, Cupertino CA). The tool is accessible using a QR code located on every code cart. Rates of IHCA debrief post-implementation (2/13/20-06/10/21) were compared to prior years (01/01/19 - 12/31/19 and 01/01/18-12/31/19). Results: The eDebrief tool was implemented on 2/13/20. During the post-implementation phase, there were 254 IHCA at NYU Langone Health. The eDebrief form was used in 175 events (69%). The debrief rate from previous calendar years were 38% and 42% for 2019 and 2018 respectively. Use of the eDebrief form has identified three targets for ongoing quality improvement and research projects: room overcrowding (identified in 64/175 IHCAs, 37%); ultrasound use (39/175 IHCAs, 22%); and optimization of mechanical CPR. Conclusions: Use of electronic debriefing is feasible at a large academic medical center and has been associated with increased uptake of IHCA debrief. Regular debriefs at our center have identified several targets for further quality improvement and research initiatives.

Introduction: Current consensus holds that CPR must balance chest compressions and ventilation rate (VR), with a low VR being essential for venous return and cardiac output. AHA guidelines recommend a VR of 10 ventilations per minute (vpm) after advanced airway placement. We sought to examine VR adherence and its impact on end-tidal CO 2 (ETCO 2 ) and ROSC >20 minutes. Methods: This is a retrospective analysis of data from AWARE II, a multicenter prospective observational study of adult in-hospital cardiac arrest (IHCA) outcomes at 14 US and UK sites. Inclusion criteria were: 1) adult patient in CA, 2) advanced airway already in place or placed during the CA, and 3) at least one minute of VR and ETCO 2 data available after removal of the last minute of CPR in subjects achieving ROSC (due to the rise of ETCO 2 just prior to ROSC). Results: A total of 563 subjects were enrolled in the parent study. Of these, 225 had ETCO 2 and VR tracings available, and 201 had sufficient data for inclusion. Mean age was 69.3 (range 18-100), patients were 63.7% male, and 16.4% had a shockable initial rhythm. A total of 116 subjects (57.7%) achieved ROSC, which was sustained in 76 (37.8%), leading to survival to hospital discharge with favorable neurological outcomes in 9 (4.5%). Mean VR was 16.3 vpm, with 171 (85.1%) subjects being ventilated in excess of guidelines; only 16 (8.0%) subjects received 8-10 vpm. Higher VR had a weak but significant association with increased mean ETCO 2 (linear R 2 = 0.11, p < 1x10 -6 ) and sustained ROSC (OR 1.05; 95% CI: 1.01-1.11; p = 0.02). Patients with sustained ROSC had a significantly higher VR at 17.7 vpm than those without sustained ROSC at 15.6 vpm (p = 0.007). Patients receiving a VR close to AHA guidelines (6-12 vpm) had a significantly lower rate of sustained ROSC (26.1%, n = 46) than patients receiving >12 vpm (42.0%, n = 148) (OR 2.30; 95% CI: 1.08-4.89; p = 0.031 using a multivariate model including patient age, shockable initial rhythm, known cardiac disease, witnessed IHCA, and use of mechanical compressions). Conclusions: VR within AHA guidelines is rare during IHCA. However, ventilation in excess of current guidelines may increase rates of sustained ROSC, an essential predicate to survival. AHA guidelines on VR in CPR with an advanced airway may not yet be optimized.

We evaluated the incidence of thrombosis in patients hospitalized with non-COVID-19 acute viral respiratory illnesses nationwide from 2012 to 2014 and compared this to the incidence among patients hospitalized with COVID-19 at a large health system in New York. Non-COVID-19 viral respiratory illness was complicated by acute MI in 2.8% of hospitalizations, VTE in 1.6%, ischemic stroke in 0.7%, and other systemic embolism in 0.1%. The proportion of hospitalizations complicated by thrombosis was lower in patients with viral respiratory illness in 2002-2014 than in COVID-19 (5% vs 16%; P< .001). Background Thrombosis is a prominent feature of the novel Coronavirus disease 2019 (COVID-19). The incidence of thrombosis during hospitalization for non-COVID-19 viral respiratory infections is uncertain. We evaluated the incidence of thrombosis in patients hospitalized with non-COVID-19 acute viral respiratory illnesses compared to COVID-19. Methods Adults age >18 years hospitalized with a non-COVID-19 viral respiratory illness between 2002 and 2014 were identified. The primary study outcome was a composite of venous and arterial thrombotic events, including myocardial infarction (MI), acute ischemic stroke, and venous thromboembolism (VTE), as defined by ICD-9 codes. The incidence of thrombosis in non-COVID-19 viral respiratory illnesses was compared to the recently published incidence of thrombosis in COVID-19 from 3,334 patients hospitalized in New York in 2020. Results Among 954,521 hospitalizations with viral pneumonia from 2002 to 2014 (mean age 62.3 years, 57.1% female), the combined incidence of arterial and venous thrombosis was 5.0%. Acute MI occurred in 2.8% of hospitalizations, VTE in 1.6%, ischemic stroke in 0.7%, and other systemic embolism in 0.1%. Patients with thrombosis had higher in-hospital mortality (14.9% vs 3.3%, P< .001) than those without thrombosis. The proportion of hospitalizations complicated by thrombosis was lower in patients with viral respiratory illness in 2002-2014 than in COVID-19 (median age 64; 39.6% female) in 2020 (5% vs 16%; P< .001) Conclusion In a nationwide analysis of hospitalizations for viral pneumonias, thrombosis risk was lower than that observed in patients with COVID-19. Investigations into mechanisms of thrombosis and risk reduction strategies in COVID-19 and other viral respiratory infections are necessary., Graphical abstract Image, graphical abstract

Given the evidence for a hyperactive platelet phenotype in COVID-19, we investigated effector cell properties of COVID-19 platelets on endothelial cells (ECs). Integration of EC and platelet RNA sequencing revealed that platelet-released factors in COVID-19 promote an inflammatory hypercoagulable endotheliopathy. We identified S100A8 and S100A9 as transcripts enriched in COVID-19 platelets and were induced by megakaryocyte infection with SARS-CoV-2. Consistent with increased gene expression, the heterodimer protein product of S100A8/A9, myeloid-related protein (MRP) 8/14, was released to a greater extent by platelets from COVID-19 patients relative to controls. We demonstrate that platelet-derived MRP8/14 activates ECs, promotes an inflammatory hypercoagulable phenotype, and is a significant contributor to poor clinical outcomes in COVID-19 patients. Last, we present evidence that targeting platelet P2Y12 represents a promising candidate to reduce proinflammatory platelet-endothelial interactions. Together, these findings demonstrate a previously unappreciated role for platelets and their activation-induced endotheliopathy in COVID-19.

Objective In the present study, we sought to better characterize the patients with coronavirus disease 2019 (COVID-19) most at risk of severe, outpatient thrombosis by defining the patients hospitalized with COVID-19 with arterial or venous thrombosis diagnosed at admission. Methods We conducted a single-center, retrospective analysis of COVID-19 patients. We found a shift in the proportions of thrombosis subtypes from 2019 to 2020, with declines in ST-segment myocardial infarction (from 22.0% to 10.1% of thrombotic events) and stroke (from 48.6% to 37.2%) and an increase in venous thromboembolism (from 29.4% to 52.7%). The patients with COVID-19–associated thrombosis were younger (age, 58 years vs 64 years; P = .043) and were less frequently women (31.3% vs 43.9%; P = .16). However, no differences were found in the body mass index or major comorbidities between those with and without COVID-19. COVID-19–associated thrombosis correlated with greater mortality (15.2% vs 4.3%; P = .016). The biometric profile of patients admitted with COVID-19–associated thrombosis compared with regular thrombosis showed significant changes in the complete blood count, liver function test results, D-dimer levels, C-reactive protein, ferritin, and coagulation panels. Conclusions Outpatients with COVID-19 who developed thrombosis requiring hospitalization had increased mortality compared with outpatients without COVID-19 who developed thrombosis requiring hospitalization. Given the significantly higher inflammatory marker levels, it is possible this is related to different mechanisms of thrombotic disease in these patients. The inflammation could be a therapeutic target to reduce the risk, or aid in the treatment, of thrombosis. We call for more studies elucidating the role that immunothrombosis might be playing in patients with COVID-19.

Objectives Venous thromboembolism, including deep venous thrombosis and pulmonary embolism, is a major source of morbidity, mortality, and healthcare utilization. Given the prevalence of venous thromboembolism and its associated mortality, our study sought to identify factors associated with loss to follow-up in venous thromboembolism patients. Methods This is a single-center retrospective study of all consecutive admitted (inpatient) and emergency department patients diagnosed with acute venous thromboembolism via venous duplex examination and/or chest computed tomography from January 2018 to March 2019. Patients with chronic deep venous thrombosis and those diagnosed in the outpatient setting were excluded. Lost to venous thromboembolism-specific follow-up (LTFU) was defined as patients who did not follow up with vascular, cardiology, hematology, oncology, pulmonology, or primary care clinic for venous thromboembolism management at our institution within three months of initial discharge. Patients discharged to hospice or dead within 30 days of initial discharge were excluded from LTFU analysis. Statistical analysis was performed using STATA 16 (College Station, TX: StataCorp LLC) with a p-value of Results During the study period, 291 isolated deep venous thrombosis, 25 isolated pulmonary embolism, and 54 pulmonary embolism with associated deep venous thrombosis were identified in 370 patients. Of these patients, 129 (35%) were diagnosed in the emergency department and 241 (65%) in the inpatient setting. At discharge, 289 (78%) were on anticoagulation, 66 (18%) were not, and 15 (4%) were deceased. At the conclusion of the study, 120 patients (38%) had been LTFU, 85% of whom were discharged on anticoagulation. There was no statistically significant difference between those LTFU and those with follow-up with respect to age, gender, diagnosis time of day, venous thromboembolism anatomic location, discharge unit location, or anticoagulation choice at discharge. There was a non-significant trend toward longer inpatient length of stay among patients LTFU (16.2 days vs. 12.3 days, p = 0.07), and a significant increase in the proportion of LTFU patients discharged to a facility rather than home ( p = 0.02). On multivariate analysis, we found a 95% increase in the odds of being lost to venous thromboembolism-specific follow-up if discharged to a facility (OR 1.95, CI 1.1–3.6, p = 0.03) as opposed to home. Conclusions Our study demonstrates that over one-third of patients diagnosed with venous thromboembolism at our institution are lost to venous thromboembolism-specific follow-up, particularly those discharged to a facility. Our work suggests that significant improvement could be achieved by establishing a pathway for the targeted transition of care to a venous thromboembolism-specific follow-up clinic.

The incidence of thrombotic complications among critically ill patients with COVID-19 is high despite thromboprophylaxis. We describe a case of a young, otherwise healthy patient admitted to our intensive care unit with COVID-19-associatred acute respiratory distress syndrome (ARDS). Despite an initial uncomplicated course, he suffered cardiopulmonary arrest with a right ventricular clot in transit (CIT) identified on point-of-care ultrasound (POCUS) and redemonstrated on transesophageal echocardiography (TEE). We highlight the association between COVID-19 and thrombosis as well as the utility of TEE during cardiac arrest for both diagnostic and therapeutic purposes.

Background: Management of patients with acute deterioration from novel coronavirus disease of 2019 (COVID-19) has posed a particular challenge for rapid response systems (RRSs) due to increased hospital strain and direct risk of infection to RRS team members. Objective: We sought to characterize RRS structure and protocols adaptions during the COVID-19 pandemic. Design, setting, and participants: Internet-based cross-sectional survey of RRS leaders, physicians, and researchers across the United States. Results: Clinicians from 46 hospitals were surveyed, 40 completed a baseline survey (87%), and 19 also completed a follow-up qualitative survey. Most reported an increase in emergency team resources during the COVID-19 pandemic. The number of sites performing simulation training sessions decreased from 88% before COVID-19 to 53% during the pandemic. Conclusions: Most RRSs reported pandemic-related adjustments, most commonly through increasing resources and implementation of protocol changes. There was a reduction in the number of sites that performed simulation training.

Purpose The coronavirus disease‐2019 (COVID‐19) led to a large influx of critically ill patients and altered echocardiography laboratory workflow. We developed a point‐of‐care ultrasound (POCUS) first approach to patients requiring echocardiography and describe our workflow and findings. Methods We performed a single‐center retrospective analysis of all POCUS studies performed on critically ill patients with COVID‐19. Sonography was performed by intensivists, uploaded and archived, and rapidly reviewed by echocardiographers. We evaluated each study based on the number of views obtained. Additionally, we provide a description of the workflow during the COVID‐19 surge at a tertiary care hospital in New York City. Results Fifty patients had POCUS studies performed by intensivists and reviewed by echocardiographers obviating the need for sonographer‐performed studies. Of the 48 cardiac POCUS studies, 17% of patients had 4 of 4 standard views available while 53% had 3 of 4 standard views. The parasternal long‐axis view was obtained on 81%, subxiphoid view on 79%, apical 4‐chamber view on 71%, and parasternal short‐axis view on 63% of patients. Conclusions Our POCUS workflow allowed intensivists to perform cardiac sonography for rapid bedside diagnosis of pathology with immediate interpretation performed by echocardiographers. At least 3 views were obtained in the majority of cases.

Purpose The COVID-19 surge required the deployment of large numbers of non-intensive care providers to assist in the management of the critically ill. Institutions took a variety of approaches to “uptraining” such providers though studies describing methods and effectiveness are lacking. Materials and methods One hundred and seventy-five providers underwent a 3 h simulation-based session focused on management of shock, mechanical ventilation, acute respiratory distress syndrome, and critical care ultrasound. All participants were sent surveys to assess their comfort with various aspects of critical care following return to their usual work environments. Results One hundred and eight providers of 175 (62%) completed the survey. Overall, 104/108 responders (96%) felt training either significantly or somewhat improved their knowledge in the management of ICU patients. Responders felt most comfortable in the management of hypoxemia in intubated patients and the management of ventilated patients with acute respiratory distress syndrome (93% strongly agree or agree, and 86% strongly agree or agree, respectively). Fewer responders felt more comfortable using focused echocardiography (70% strongly agree or agree) and lung ultrasonography in following progression of COVID-19 (76% strongly agree or agree). Conclusions Simulation-based training improved provider comfort in the management of critically ill patients with COVID-19., Highlights • Non-intensivist providers underwent simulation-based training to work in the COVID-19 ICU. • Simulation-based training improved comfort in management of critically ill patients. • Comfort in management of intubated patients was greatly improved.

Introduction: The COVID-19 surge at our institution required deployment of large numbers of non-intensive care unit (ICU) physicians and advanced practice providers to assist in the management of the critically ill. A 3-hour “uptraining” simulation session was offered to these providers that focused on various aspects of ICU care. Hypothesis: We hypothesized that following a 3-hour simulation session, providers would feel more comfortable in managing critically-ill patients with COVID-19. Methods: One hundred and seventy-five providers underwent a 3-hour simulation-based session focused on management of shock, acute respiratory distress syndrome, and critical care ultrasound. All participants were sent surveys to assess their comfort with various aspects of ICU care following return to their usual work environments. Results: One hundred and eight providers of 175 (62%) completed the surveys. Cardiology fellows and faculty accounted for 36% of the responders, acute care nurse practitioners (NPs) accounted for 16%, while other NPs, residents, and fellows accounted for the remainder. Prior to simulation training, 31% regularly managed patients in the ICU and 28% occasionally managed ICU patients. Following training, 71% of participants were deployed to a COVID-19 ICU as part of their workflow. Overall, 104/108 responders (96%) felt training either significantly or somewhat improved their knowledge in the management of ICU patients. Ninety-four participants (91%) felt training impacted their care of critically ill patients with COVID-19. Table 1 is a display of specific ICU skillsets taught in the session and if the participants felt better equipped to utilize what was covered post deployment. Conclusions: Simulation-based training improved provider comfort in the management of critically ill patients with COVID-19. Table 1: Participants response to “if they felt better equipped to utilize ICU skills following simulation training”

Background: Thrombosis is a major concern in respiratory infections such as influenza and now COVID-19. We investigated the magnitude and duration of risk for arterial and venous thrombosis following discharge after respiratory infections. Methods: Patients with respiratory infections were identified using the United States Nationwide Readmission Database from 2012-2014. Patients admitted with asthma or cellulitis served as comparators. Readmissions for myocardial infarction (MI) and venous thromboembolism (VTE) were evaluated at 30 to 180 days. The likelihood of a thrombotic event after hospital discharge was compared with a 30-day period prior to hospitalization using conditional logistic regression. Results: Among 5,271,068 patients discharged after a respiratory infection, 0.56% and 0.78% were readmitted within 30-days with MI and VTE, respectively. Relative to asthma and cellulitis, respiratory infection was associated with a greater age and sex-adjusted hazard of 30-day readmission for MI (adjusted HR [aHR] 1.58 [95% CI 1.52-1.64] vs. asthma; aHR 1.43 [95% CI 1.38-1.48] vs. cellulitis) and VTE (aHR 1.65 [95% CI 1.60-1.69] vs. asthma; aHR 1.45, [95% CI 1.41-1.50] vs. cellulitis). Risks of MI and VTE after respiratory infection attenuated over time, yet remained higher than asthma and cellulitis over 90 and 180 days (Figure). In a crossover-cohort analysis, the odds of MI (OR 1.68 [95% CI 1.62-1.73]) and VTE (OR 3.30 [95% 3.19-3.41]) were higher in the 30 days following discharge after respiratory infection than during the baseline period. The odds of MI (OR 2.44 [95% CI 1.95-3.05]) and VTE (OR 4.49 [95% 3.50-5.76]) at 30-days appeared highest when a viral respiratory pathogen was identified. Conclusions: Hospitalization for respiratory infection, particularly when of viral etiology, was associated with an increased risk of myocardial infarction and venous thrombosis that was highest in the first 30-days after discharge and declined over time.

Introduction: In the United States, the chance of dying in the hospital widely varies by hospital, with bottom-decile hospitals having twice the rates of risk-adjusted mortality when compared to top-decile hospitals. This suggests a need for improvement in health systems nationwide. Here, we describe the implementation of, and associated outcomes for a multi-faceted, evidence-based approach to reducing in-hospital mortality. Methods: This is a retrospective interrupted time-series conducted at a large, urban, academic health system. Specifically, we describe the implementation of the following evidence-based methods: 1) escalation of communication guidelines, 2) proactive rounding with nurse response teams, and 3) rapid response teams with dedicated staff. We then quantify the associated observed-to-expected (O:E) in-hospital mortality over a 12-year period at our main hospital, and subsequently over a 3-year period at an affiliated hospital where the same interventions were later implemented. Results: Over 12 years, 445,308 patients were discharged from our main hospital, with 3,948 (0.9%) being discharged to an acute care facility, 4,558 (1.0%) discharged to hospice, and 4,648 (1.0%) expiring in the hospital. Patients had an average age of 53.1 years (std.dev 22.8 years), with the majority being female (59.0%), non-Hispanic white (66.1%), and admitted from the outpatient setting (93.3%). From the years 2010 to 2013, there was decline in O:E mortality by 59.0% (Figure 1A). This effect was sustained from 2014-2018. At the affiliate hospital, there was a similar decline in O:E mortality after implementation of the same interventions (60.5%, Figure 1B). Conclusion: Our multi-faceted, programmatic approach was associated with over 50% reductions in in-hospital mortality that were sustained for several years after implementation, and were reproduced at an affiliated hospital.

Aims: To define outcomes of patients with COVID-19 compared to patients without COVID-19 suffering in-hospital cardiac arrest (IHCA). Materials and methods: We performed a single-center retrospective study of IHCA cases. Patients with COVID-19 were compared to consecutive patients without COVID-19 from the prior year. Return of spontaneous circulation (ROSC), 30-day survival, and cerebral performance category (CPC) at 30-days were assessed. Results: Fifty-five patients with COVID-19 suffering IHCA were identified and compared to 55 consecutive IHCA patients in 2019. The COVID-19 cohort was more likely to require vasoactive agents (67.3% v 32.7%, p = 0.001), invasive mechanical ventilation (76.4% v 23.6%, p

The COVID-19 pandemic has placed an extraordinary strain on healthcare systems across North America. Defining the optimal approach for managing a critically ill COVID-19 patient is rapidly changing. Goal-directed transesophageal echocardiography (TEE) is frequently used by physicians caring for intubated critically-ill patients as a reliable imaging modality that is well-suited to answer questions at bedside. A multi-disciplinary group of experts in point-of-care echocardiography and TEE representing intensive care, critical care cardiology and emergency medicine from the United States and Canada, convened to review the available evidence, share experiences, and produce a consensus statement aimed to provide clinicians with a framework to maximize the safety of patients and healthcare providers when considering TEE in critically ill patients during the COVID-19 pandemic. While transthoracic echocardiography (TTE) can provide the information needed in most patients, there are specific scenarios in which TEE represents the modality of choice. Among other critical care applications, TEE can allow hemodynamic assessment of patients during prone ventilation, perform serial evaluations of the lungs during recruitment maneuvers, guide cardiac arrest resuscitation, and facilitate veno-venous extra corporeal membrane oxygenation (VV-ECMO) cannulation. To aid other clinicians in performing TEE during the COVID-19 pandemic, we describe a set of principles and practical aspects for performing examinations with a focus on the logistics, personnel, equipment required before, during, and after an examination. In the right clinical scenario, TEE is a tool that can provide the information needed to deliver the best and safest possible care for the critically ill patient., Highlights • Diagnostic procedures and tools that promote efficiency and accuracy in care should be appropriately utilized during the COVID-19 pandemic. • TEE offers those caring for intubated critically-ill patients a high-quality imaging modality capable of answering goal-directed questions that can impact decision making at the bedside. • TEE can be useful during the pandemic when adequate TTE windows cannot be obtained, when there is need to address hemodynamic instability during prone ventilation, to perform serial evaluations of the lungs, during cardiac arrest resuscitation and to guide veno-venous ECMO cannulation. • Despite plausibility as an aerosol generating procedure, based on the available evidence and experience in the frontlines our group of interdisciplinary experts from across North America support the use of TEE as an invaluable tool for managing the critically ill patient with COVID-19.

Highlights • The risk of thromboembolic events in COVID-19 is substantial • Pulmonary embolism should be considered in cases of clinical deterioration • Management of clot in transit is controversial