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

BACKGROUND: Patients with intermediate-risk pulmonary embolism (PE) and normotensive shock may have worse outcomes. However, diagnosis of normotensive shock requires invasive hemodynamics. Our objective was to assess the predictive value of McConnell's sign in identifying normotensive shock in patients with intermediate-risk PE. METHODS: Patients with intermediate-risk PE who underwent percutaneous mechanical thrombectomy between August 2020 and April 2023 at a large academic public hospital were included in the study. Normotensive shock was defined as systolic blood pressure ≥ 90 mmHg without vasopressor support with pre-procedural invasive measures of cardiac index ≤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: Those with McConnell's sign (29/40, 72.5 %) had 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). McConnell's sign had a sensitivity of 88 % and specificity of 53 % for identifying intermediate-risk PE patients with normotensive shock. Patients with McConnell's sign had an increased odds (odds ratio 8.38, confidence interval: 1.73-40.53, p = 0.008; area under the curve 0.70, 95 % confidence interval: 0.56-0.85) of normotensive shock. CONCLUSION: This is the first study to suggest that McConnell's sign may identify those in the intermediate-risk group who are at risk for normotensive shock. Larger cohorts are needed to validate our findings.

Efficacy and safety of catheter-based thrombectomy versus catheter-directed thrombolysis in acute pulmonary embolism.

Data comparing catheter-based thrombectomy (CBT) and catheter-directed thrombolysis (CDT) in acute pulmonary embolism are lacking. To address this, we performed a meta-analysis of prospective and retrospective studies of CBT and compared it to performance goal rates of mortality and major bleeding from a recently published network meta-analysis. When compared with performance goal for CDT based on historical studies, CBT was noninferior for all-cause mortality (6.0% vs 6.87%; P-valueNI < .001), non-inferior and superior for major bleeding (4.9% vs 11%; P-valueNI < .001 and P < .001 for superiority).

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

In this study, we found that a low LVOT VTI (<15 cm), a simple bedside point-of-care measurement, predicts normotensive shock in patients with acute intermediate-risk PE.

Catheter-based therapy for high-risk or intermediate-risk pulmonary embolism: death and re-hospitalization.

BACKGROUND AND AIMS: Catheter-based therapies (CBTs) have been developed as a treatment option in patients with pulmonary embolism (PE). There remains a paucity of data to inform decision-making in patients with intermediate-risk or high-risk PE. The aim of this study was to characterize in-hospital and readmission outcomes in patients with intermediate-risk or high-risk PE treated with vs. without CBT in a large retrospective registry. METHODS: Patients hospitalized with intermediate-risk or high-risk PE were identified using the 2017-20 National Readmission Database. In-hospital outcomes included death and bleeding and 30- and 90-day readmission outcomes including all-cause, venous thromboembolism (VTE)-related and bleeding-related readmissions. Inverse probability of treatment weighting (IPTW) was utilized to compare outcomes between CBT and no CBT. RESULTS: A total of 14 903 [2076 (13.9%) with CBT] and 42 829 [8824 (20.6%) with CBT] patients with high-risk and intermediate-risk PE were included, respectively. Prior to IPTW, patients with CBT were younger and less likely to have cancer and cardiac arrest, receive systemic thrombolysis, or be on mechanical ventilation. In the IPTW logistic regression model, CBT was associated with lower odds of in-hospital death in high-risk [odds ratio (OR) 0.83, 95% confidence interval (CI) 0.80-0.87] and intermediate-risk PE (OR 0.76, 95% CI 0.70-0.83). Patients with high-risk PE treated with CBT were associated with lower risk of 90-day all-cause [hazard ratio (HR) 0.77, 95% CI 0.71-0.83] and VTE (HR 0.46, 95% CI 0.34-0.63) readmission. Patients with intermediate-risk PE treated with CBT were associated with lower risk of 90-day all-cause (HR 0.75, 95% CI 0.72-0.79) and VTE (HR 0.66, 95% CI 0.57-0.76) readmission. CONCLUSIONS: Among patients with high-risk or intermediate-risk PE, CBT was associated with lower in-hospital death and 90-day readmission. Prospective, randomized trials are needed to confirm these findings.

Percutaneous mechanical thrombectomy in acute pulmonary embolism: Outcomes from a safety-net hospital.

BACKGROUND: Our study aims to present clinical outcomes of mechanical thrombectomy (MT) in a safety-net hospital. METHODS: This is a retrospective study of intermediate or high-risk pulmonary embolism (PE) patients who underwent MT between October 2020 and May 2023. The primary outcome was 30-day mortality. RESULTS: Among 61 patients (mean age 57.6 years, 47% women, 57% Black) analyzed, 12 (19.7%) were classified as high-risk PE, and 49 (80.3%) were intermediate-risk PE. Of these patients, 62.3% had Medicaid or were uninsured, 50.8% lived in a high poverty zip code. The prevalence of normotensive shock in intermediate-risk PE patients was 62%. Immediate hemodynamic improvements included 7.4 mmHg mean drop in mean pulmonary artery pressure (-21.7%, p < 0.001) and 93% had normalization of their cardiac index postprocedure. Thirty-day mortality for the entire cohort was 5% (3 patients) and 0% when restricted to the intermediate-risk group. All 3 patients who died at 30 days presented with cardiac arrest. There were no differences in short-term mortality based on race, insurance type, citizenship status, or socioeconomic status. All-cause mortality at most recent follow up was 13.1% (mean follow up time of 13.4 ± 8.5 months). CONCLUSION: We extend the findings from prior studies that MT demonstrates a favorable safety profile with immediate improvement in hemodynamics and a low 30-day mortality in patients with acute PE, holding true even with relatively higher risk and more vulnerable population within a safety-net hospital.

Relationship between the mixed venous-to-arterial carbon dioxide gradient and the cardiac index in acute pulmonary embolism.

AIMS: Among patients with acute pulmonary embolism (PE) undergoing mechanical thrombectomy, the cardiac index (CI) is frequently reduced even among those without a clinically apparent shock. The purpose of this study is to describe the mixed venous-to-arterial carbon dioxide gradient (CO2 gap), a surrogate of perfusion adequacy, among patients with acute PE undergoing mechanical thrombectomy. METHODS AND RESULTS: This was a single-centre retrospective study of consecutive patients with PE undergoing mechanical thrombectomy and simultaneous pulmonary artery catheterization over a 3-year period. Of 107 patients, 97 had simultaneous mixed venous and arterial blood gas measurements available. The CO2 gap was elevated (>6 mmHg) in 51% of the cohort and in 49% of patients with intermediate-risk PE. A reduced CI (≤2.2 L/min/m2) was associated with an increased odds [odds ratio = 7.9; 95% confidence interval (CI) 3.49-18.1, P < 0.001] for an elevated CO2 gap. There was an inverse relationship between the CI and the CO2 gap. For every 1 L/min/m2 decrease in the CI, the CO2 gap increased by 1.3 mmHg (P = 0.001). Among patients with an elevated baseline CO2 gap >6 mmHg, thrombectomy improved the CO2 gap, CI, and mixed venous oxygen saturation. When the CO2 gap was dichotomized above and below 6, there was no difference in the in-hospital mortality rate (9 vs. 0%; P = 0.10; hazard ratio: 1.24; 95% CI 0.97-1.60; P = 0.085). CONCLUSION: Among patients with acute PE undergoing mechanical thrombectomy, the CO2 gap is abnormal in nearly 50% of patients and inversely related to the CI. Further studies should examine the relationship between markers of perfusion and outcomes in this population to refine risk stratification.

Successful Treatment of Confirmed Severe Bupropion Cardiotoxicity With Veno-Arterial Extracorporeal Membrane Oxygenation Initiation Prior to Cardiac Arrest.

Bupropion is a substituted cathinone (ß-keto amphetamine) norepinephrine/dopamine reuptake inhibitor andnoncompetitive nicotinic acetylcholine receptor antagonist that is frequently used to treat major depressive disorder. Bupropion overdose can cause neurotoxicity and cardiotoxicity, the latter of which is thought to be secondary to gap junction inhibition and ion channel blockade. We report a patient with a confirmed bupropion ingestion causing severe cardiotoxicity, for whom prophylactic veno-arterial extracorporeal membrane oxygenation (ECMO) was successfully implemented. The patient was placed on the ECMO circuit several hours before he experienced multiple episodes of hemodynamically unstable ventricular tachycardia, which were treated with multiple rounds of electrical defibrillation and terminated after administration of lidocaine. Despite a neurological examination notable for fixed and dilated pupils after ECMO cannulation, the patient completely recovered without neurological deficits. Multiple bupropion and hydroxybupropion concentrations were obtained and appear to correlate with electrocardiogram interval widening and toxicity.

Catheter-based therapy for intermediate or high-risk pulmonary embolism is associated with lower in-hospital mortality in patients with cancer: Insights from the National Inpatient Sample.

BACKGROUND: Pulmonary embolism (PE) is a common complication among patients with cancer and is a significant contributor to morbidity and mortality. Catheter-based therapies (CBT), including catheter-directed thrombolysis (CDT) and mechanical thrombectomy, have been developed and are used in patients with intermediate or high-risk PE. However, there is a paucity of data on outcomes in patients with cancer as most clinical studies exclude this group of patients. AIMS: To characterize outcomes of patients with cancer admitted with intermediate or high-risk PE treated with CBT compared with no CBT. METHODS: Patients with an admission diagnosis of intermediate or high-risk PE and a history of cancer from October 2015 to December 2018 were identified using the National Inpatient Sample. Outcomes of interest were in-hospital death or cardiac arrest (CA) and major bleeding. Inverse probability treatment weighting (IPTW) was utilized to compare outcomes between patients treated with and without CBT. Variables that remained unbalanced after IPTW were adjusted using multivariable logistic regression. RESULTS: A total of 2084 unweighted admissions (10,420 weighted) for intermediate or high-risk PE and cancer were included, of which 136 (6.5%) were treated with CBT. After IPTW, CBT was associated with lower death or CA (aOR 0.54, 95% CI 0.46-0.64) but higher major bleeding (aOR 1.41, 95% CI 1.21-1.65). After stratifying by PE risk type, patients treated with CBT had lower risk of death or CA in both intermediate (aOR 0.52, 95% CI 0.36-0.75) and high-risk PE (aOR 0.48, 95% CI 0.33-0.53). However, patients with CBT were associated with increased risk of major bleeding in intermediate-risk PE (aOR 2.12, 95% CI 1.67-2.69) but not in those with high-risk PE (aOR 0.84, 95% CI 0.66-1.07). CONCLUSIONS: Among patients with cancer hospitalized with intermediate or high-risk PE, treatment with CBT was associated with lower risk of in-hospital death or CA but higher risk of bleeding. Prospective studies and inclusion of patients with cancer in randomized trials are warranted to confirm our findings.

Quality and rapidity of anticoagulation in patients with acute pulmonary embolism undergoing mechanical thrombectomy.

The primary objective of our study was to determine the proportion of intermediate-risk PE patients undergoing mechanical thrombectomy (MT) who achieved therapeutic anticoagulation (AC) at the time of the procedure. The salient findings of our study showed that only a minority of patients (14.3%) were in the therapeutic range by ACT at the time of MT (primary outcome). Furthermore, in this higher-risk PE cohort selected for MT, 18.2% of patients were subtherapeutic after initially reaching therapeutic AC, 43% experienced supratherapeutic AC at some point before MT, and less than half (43%) attained therapeutic AC at 6 hours, highlighting the necessity for optimizing anticoagulation practices in acute PE.

Efficacy and Safety of Anticoagulation, Catheter-Directed Thrombolysis, or Systemic Thrombolysis in Acute Pulmonary Embolism.

BACKGROUND: The optimal treatment strategy of patients with pulmonary embolism (PE) (especially those with intermediate risk) continues to evolve and remains controversial. OBJECTIVES: This study sought to compare the efficacy and safety of anticoagulation (AC) alone, catheter-directed thrombolysis (CDT), and systemic thrombolysis (ST) in patients with acute PE. METHODS: PubMed and EMBASE were searched for randomized controlled trials or observational studies which compared outcomes of AC alone, CDT, and ST in acute PE. Efficacy outcome was all-cause mortality. Safety outcomes were major bleeding and intracranial hemorrhage (ICH). RESULTS: We identified 45 studies (17 randomized controlled trials, 2 prospective nonrandomized trials, and 26 retrospective observational trials), which included 81,705 patients. When compared with AC alone, CDT had lower mortality (OR: 0.55; 95% CI: 0.39-0.80) but higher major bleeding (OR: 1.84; 95% CI: 1.10-3.08) and numerically higher ICH (OR: 1.51; 95% CI: 0.75-3.04). ST was associated with no difference in mortality but higher major bleeding (OR: 2.16; 95% CI: 1.38-3.38) and ICH (OR: 2.26; 95% CI: 1.14-4.48) when compared with AC alone. The risk of mortality (OR: 2.05; 95% CI: 1.46-2.89) and ICH (OR: 1.50; 95% CI: 1.13-1.99) was higher with ST when compared with CDT. Findings were similar when analysis was restricted to trials of intermediate risk PE. CONCLUSIONS: In patients with acute PE, when compared with AC alone, CDT was associated with a lower mortality but higher risk of bleeding. Moreover, CDT had an enhanced safety profile when compared with ST.

Patient Outcomes and Lessons Learned From Treating Patients With Severe COVID-19 at a Long-term Acute Care Hospital: Single-Center Retrospective Study.

BACKGROUND: With the continuation of the COVID-19 pandemic, shifting active COVID-19 care from short-term acute care hospitals (STACHs) to long-term acute care hospitals (LTACHs) could decrease STACH census during critical stages of the pandemic and maximize limited resources. OBJECTIVE: This study aimed to describe the characteristics, clinical management, and patient outcomes during and after the acute COVID-19 phase in an LTACH in the Northeastern United States. METHODS: This was a single-center group comparative retrospective analysis of the electronic medical records of patients treated for COVID-19-related impairments from March 19, 2020, through August 14, 2020, and a reference population of medically complex patients discharged between December 1, 2019, and February 29, 2020. This study was conducted to evaluate patient outcomes in response to the holistic treatment approach of the facility. RESULTS: Of the 127 total COVID-19 admissions, 118 patients were discharged by the data cutoff. At admission, 29.9% (38/127) of patients tested positive for SARS-CoV-2 infection. The mean age of the COVID-19 cohort was lower than that of the reference cohort (63.3, 95% CI 61.1-65.4 vs 65.5, 95% CI 63.2-67.8 years; P=.04). There were similar proportions of males and females between cohorts (P=.38); however, the proportion of non-White/non-Caucasian patients was higher in the COVID-19 cohort than in the reference cohort (odds ratio 2.79, 95% CI 1.5-5.2; P=.001). The mean length of stay in the COVID-19 cohort was similar to that in the reference cohort (25.5, 95% CI 23.2-27.9 vs 29.9, 95% CI 24.7-35.2 days; P=.84). Interestingly, a positive correlation between patient age and length of stay was observed in the COVID-19 cohort (r2=0.05; P=.02), but not in the reference cohort. Ambulation assistance scores improved in both the reference and COVID-19 cohorts from admission to discharge (P<.001). However, the mean assistance score was greater in the COVID-19 cohort than in the reference cohort at discharge (4.9, 95% CI 4.6-5.3 vs 4.1, 95% CI 3.7-4.7; P=.001). Similarly, the mean change in gait distance was greater in the COVID-19 cohort than in the reference cohort (221.1, 95% CI 163.2-279.2 vs 146.4, 95% CI 85.6-207.3 feet; P<.001). Of the 16 patients mechanically ventilated at admission, 94% (15/16) were weaned before discharge (mean 11.3 days). Of the 75 patients admitted with a restricted diet, 75% (56/75) were discharged on a regular diet. CONCLUSIONS: The majority of patients treated at the LTACH for severe COVID-19 and related complications benefited from coordinated care and rehabilitation. In comparison to the reference cohort, patients treated for COVID-19 were discharged with greater improvements in ambulation distance and assistance needs during a similar length of stay. These findings indicate that other patients with COVID-19 would benefit from care in an LTACH.

Low-Dose Tocilizumab With High-Dose Corticosteroids in Patients Hospitalized for COVID-19 Hypoxic Respiratory Failure Improves Mortality Without Increased Infection Risk.

BACKGROUND: Severe hypoxic respiratory failure from COVID-19 pneumonia carries a high mortality risk. There is uncertainty surrounding which patients benefit from corticosteroids in combination with tocilizumab and the dosage and timing of these agents. The balance of controlling inflammation without increasing the risk of secondary infection is difficult. At present, dexamethasone 6 mg is the standard of care in COVID-19 hypoxia; whether this is the ideal choice of steroid or dosage remains to be proven. OBJECTIVES: The primary objective was to assess the impact on mortality of tocilizumab only, corticosteroids only, and combination therapy in patients with COVID-19 respiratory failure. METHODS: A multihospital, retrospective study of adult patients with severe respiratory failure from COVID-19 who received supportive therapy, corticosteroids, tocilizumab, or combination therapy were assessed for 28-day mortality, biomarker improvement, and relative risk of infection. Propensity-matched analysis was performed between corticosteroid alone and combination therapies to further assess mortality benefit. RESULTS: The steroid-only, tocilizumab-only, and combination groups showed hazard reduction in mortality at 28 days when compared with supportive therapy. In a propensity-matched analysis, the combination group (daily equivalent dexamethasone 10 mg and tocilizumab 400 mg) had an improved 28-day mortality compared with the steroid-only group (daily equivalent dexamethasone 10 mg; hazard ratio (95% CI) = 0.56 (0.38-0.84), P = 0.005] without increasing the risk of infection. CONCLUSION AND RELEVANCE: Combination of tocilizumab and corticosteroids was associated with improved 28-day survival when compared with corticosteroids alone. Modification of steroid dosing strategy as well as steroid type may further optimize therapeutic effect of the COVID-19 treatment.

Physician failure to stratify patients hospitalized with acute pulmonary embolism.

OBJECTIVES: In 2011, the AHA recommended risk stratification of patients with acute pulmonary embolism (PE). Failure to risk stratify may cause under recognition of intermediate-risk PE and its attendant short- and long-term consequences. We sought to determine if patients hospitalized with acute PE were appropriately risk stratified according to the 2011 AHA Scientific Statement within our hospital system and whether differences exist in adherence to risk stratification by hospital or treating hospital service. We also wished to know the frequency of in-hospital consultations for acute PE which might assist in the risk stratification process. METHODS: This is a retrospective chart audit of all patients hospitalized with a diagnosis of acute PE between January 2011 and December 2013 at our 937-bed metropolitan, three hospital system comprised of academic University, neuroscience Specialty, and teaching Community hospitals. We evaluated the presence of imaging, laboratory tests, and specialty consultation within 72 h of PE diagnosis by hospital. RESULTS: 701 patients with acute PE were admitted to our hospital system during the study period. 308 patients (43.9%) met criteria for intermediate-risk PE. 347 patients (49.5%) were considered 'Low-Risk - At Risk', patients defined in a low-risk category not having undergone all recommended risk stratification testing and so truly may have been in a higher risk category. No specialty consultations were utilized for 265 patients (37.8%). CONCLUSIONS: Our large metropolitan hospital system inadequately risk stratifies hospitalized patients with acute PE. Because nearly one-half of patients with acute PE did not have all recommended testing, clinicians may be under recognizing patients with intermediate-risk PE and their risk for long-term morbidity. Specialty consultations were underutilized and may help guide medical decision-making.

Differential effects of hypoxic and hyperoxic stress-induced hypertrophy in cultured chick fetal cardiac myocytes.

The adult heart responds to contraction demands by hypertrophy, or enlargement, of cardiac myocytes. Adaptive hypertrophy can occur in response to hyperoxic conditions such as exercise, while pathological factors that result in hypoxia ultimately result in heart failure. The difference in the outcomes produced by pathologically versus physiologically induced hypertrophy suggests that the cellular signaling pathways or conditions of myocytes may be different at the cellular level. The structural and functional changes in myocytes resulting from hyperoxia (simulated using hydrogen peroxide) and hypoxia (using oxygen deprivation) were tested on fetal chick cardiac myocytes grown in vitro. Structural changes were measured using immunostaining for α-sarcomeric actin or MyoD, while functional changes were assessed using immunostaining for calcium/calmodulin-dependent kinase (CaMKII) and by measuring intracellular calcium fluxes using live cell fluorescence imaging. Both hypoxic and hyperoxic stress resulted in an upregulation of actin and MyoD expression. Similarly, voltage-gated channels governing myocyte depolarization and the regulation of CaMK were unchanged by hyperoxic or hypoxic conditions. However, the dynamic features of calcium fluxes elicited by caffeine or epinephrine were different in cells subjected to hypoxia versus hyperoxia, suggesting that these different conditions differentially affect components of ligand-activated signaling pathways that regulate calcium. Our results suggest that changes in signaling pathways, rather than structural organization, may mediate the different outcomes associated with hyperoxia-induced versus hypoxia-induced hypertrophy, and these changes are likely initiated at the cellular level.