Simplified echocardiographic assessment of regional left ventricular wall motion pattern in patients with takotsubo and acute coronary syndrome: The randomized blinded Two-chamber Apical Kinesis Observation (TAKO) study.

BACKGROUND: Differentiating Takotsubo cardiomyopathy (TTC) from acute coronary syndrome involving the left anterior descending coronary artery (LAD-ACS) is difficult due to left ventricular apical wall motion abnormality pattern in both and typically requires an invasive coronary angiography (ICA) study for diagnostic confirmation. OBJECTIVES: To identify differences in the regional wall motion abnormality (RWMA) pattern using a comprehensive comparative analysis of the transthoracic echocardiographic (TTE) findings in patients with TTC versus LAD-ACS. METHODS: This was a retrospective, randomized, blinded comparison study including a derivation cohort of 105 patients with TTC (N=52) or LAD-ACS (N=53) with concomitant TTE and ICA identified from our institutional database. A comprehensive echocardiographic wall motion analysis was performed (unblinded) to search for subtle differences in RWMA patterns by marking the exact locations of the end-systolic hinge points (HP) - defined as the intersection between the normal and abnormal regional myocardial thickening - in all apical views. The HP location relative to mitral annulus in each apical view was compared for symmetry and the apical 2-chamber (A2C) view was identified as having the most consistent, quantitative difference between TTC and LAD-ACS. This A2C quantitative model was then prospectively studied in a randomized, blinded, validation cohort of 30 subjects with either TTC or LAD-ACS by eight echocardiographic readers with all levels of clinical experience. RESULTS: In the unblinded derivation cohort, the A2C view showed that the ratio (1.02) and the absolute distance between the anterior HP (3.57 cm) and the inferior HP (3.53 cm) in TTC was significantly different than the ratio (0.761) and the absolute differences between the AHP (4.5 cm) and the IHP (5.93 cm) in LAD-ACS. An AHP: IHP of 0.96 for men and 0.84 for women was able to correctly categorize 84.8% of male and 91.7% of female patients. When applied to the validation cohort, the model showed fairly accurate results with a 74% prediction rate in diagnosing TTC in female patients. CONCLUSION: We propose a relatively simple 2-D TTE diagnostic tool emphasizing subtle differences in the RWMA pattern in the A2C view alone as a semi-quantitative imaging parameter to help differentiate TTC from LAD-ACS.

Improvement of Emergency Department Chest Pain Evaluation Using Hs-cTnT and a Risk Stratification Pathway.

BACKGROUND: Chest pain is among the most common reasons for presentation to the emergency department (ED) worldwide. Additional studies on most cost-effective ways of differentiating serious vs. benign causes of chest pain are needed. OBJECTIVES: Our study aimed to evaluate the effectiveness of a novel risk stratification pathway utilizing 5th generation high-sensitivity cardiac troponin T assay (Hs-cTnT) and HEART score (History, Electrocardiogram, Age, Risk factors, Troponin) in assessing nontraumatic chest pain patients in reducing ED resource utilization. METHODS: A retrospective chart review was performed 6 months prior to and after the implementation of a novel risk stratification pathway that combined hs-cTnT with HEART score to guide evaluation of adult patients presenting with nontraumatic chest pain at a large academic quaternary care ED. Primary outcome was ED length of stay (LOS); secondary outcomes included cardiology consult rates, admission rates, number of ED boarders, and number of eloped patients. RESULTS: A total of 1707 patients and 1529 patients were included pre- and postimplementation, respectively. Median overall ED LOS decreased from 317 to 286 min, an absolute reduction of 31 min (95% confidence interval 22-41 min), after pathway implementation (p < 0.001). Furthermore, cardiology consult rate decreased from 26.9% to 16.0% (p < 0.0001), rate of admission decreased from 30.1% to 22.7% (p < 0.0001), and number of ED boarders as a proportion of all nontraumatic chest pain patients decreased from 25.13% preimplementation to 18.63% postimplementation (p < 0.0001). CONCLUSIONS: Implementation of our novel chest pain pathway improved numerous ED throughput metrics in the evaluation of nontraumatic chest pain patients.

Association of Fluid Overload with Escalation of Respiratory Support and Endotracheal Intubation in Acute Bronchiolitis Patients.

Fluid overload has been associated with increased oxygen requirement, prolonged duration of mechanical ventilation, and longer length of hospital stay in children hospitalized with pulmonary diseases. Critically ill infants with bronchiolitis admitted to the pediatric intensive care unit (PICU) also tend to develop fluid overload and there is limited information of its role on noninvasive respiratory support. Thus, our primary objective was to study the association of fluid overload in patients with bronchiolitis admitted to the PICU with respiratory support escalation (RSE) and need for endotracheal intubation (ETI). Infants ≤24 months of age with bronchiolitis and admitted to the PICU between 9/2009 and 6/2015 were retrospectively studied. Demographic variables, clinical characteristics including type of respiratory support and need for ETI were evaluated. Fluid overload as assessed by net fluid intake and output (net fluid balance), cumulative fluid balance (CFB) (mL/kg), and percentage fluid overload (FO%), was compared between patients requiring and not requiring RSE and among patients requiring ETI and not requiring ETI at 0 (PICU admission), 12, 24, 36, 48, 72, 96, and 120 hours. One-hundred sixty four of 283 patients with bronchiolitis admitted to the PICU qualified for our study. Thirty-four of 164 (21%) patients required escalation of respiratory support within 5 days of PICU admission and of these 34 patients, 11 patients required ETI. Univariate analysis by Kruskal-Wallis test of fluid overload as assessed by net fluid balance, CFB, and FO% between 34 patients requiring and 130 patients not requiring RSE and among 11 patients requiring ETI and 153 patients not requiring ETI, at 0, 12, 24, 36, 48, 72, 96 and 120 hours did not reveal any significant difference ( p >0.05) at any time interval. Multivariable logistic regression analysis revealed higher PRISM score (odds ratio [OR]: 4.95, 95% confidence interval [95% CI]: 1.79-13.66; p = 0.002), longer hours on high flow nasal cannula (OR: 4.86, 95% CI: 1.68-14.03; p = 0.003) and longer hours on noninvasive ventilation (OR: 11.16, 95% CI: 3.36-36.98; p < 0.001) were associated with RSE. Fluid overload as assessed by net fluid balance, CFB, and FO% was not associated with RSE or need for ETI in critically ill bronchiolitis patients admitted to the PICU. Further prospective studies involving larger number of patients with bronchiolitis are needed to corroborate our findings.

Bivalirudin versus unfractionated heparin in patients with myocardial infarction undergoing percutaneous coronary intervention: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Bivalirudin is an alternative accepted therapy to unfractionated heparin for patients with myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI). We aimed in this meta-analysis to compare bivalirudin versus unfractionated heparin in patients with MI undergoing PCI. METHODS: We have screened PubMed/MEDLINE, Cochrane Library, and ClinicalTrials.gov (inception through January 8th, 2023) for randomized controlled trials (RCTs) evaluating bivalirudin versus unfractionated heparin in patients with MI undergoing PCI. The DerSimonian and Laird method was used for estimation of tau2 to calculate the risk ratio (RR) and 95 % confidence interval (CI). RESULTS: Ten RCTs with a total of 40,069 participants were included in our analysis. Bivalirudin as compared with unfractionated heparin was associated with significant decrease in major bleeding (RR 0.64 [0.52 to 0.79]; p < 0.01; I2 = 69 %) and cardiovascular mortality (RR 0.79 [0.67 to 0.92]; p < 0.01; I2 = 0 %). There was no significant difference between bivalirudin and unfractionated heparin groups in terms of major adverse cardiovascular events (RR 1.02 [0.91 to 1.14]; p = 0.73; I2 = 52 %), all-cause mortality (RR 0.89 [0.77 to 1.04]; p = 0.15; I2 = 23 %), MI (RR 1.02 [0.87 to 1.19]; p = 0.80; I2 = 36 %), stent thrombosis (RR 1.12 [0.52 to 2.40]; p = 0.77; I2 = 82 %), or stroke (RR 0.97 [0.73 to 1.29]; p = 0.85; I2 = 0 %). CONCLUSION: Our meta-analysis suggests that bivalirudin compared with unfractionated heparin in patients with MI undergoing PCI was associated with lower rates of major bleeding and cardiovascular mortality without a significant difference in major adverse cardiovascular events, all-cause mortality, MI, stroke, or stent thrombosis.

Determination of Left Main Coronary Artery Stenosis Through Noninvasive Testing to Guide Revascularization in Ischemic Heart Disease.

Anatomically severe left main coronary artery (LMCA) stenosis (>50%) remains one of the few groups to benefit from early revascularization in stable ischemic heart disease (SIHD). Identification of these patients through widely available noninvasive testing would decrease the need for additional upfront anatomic testing, lowering the overall cost of healthcare. Patients with SIHD who underwent either percutaneous or surgical revascularization over a 7-year period at our institution were retrospectively analyzed and categorized as having LMCA stenosis versus non-LM stenosis. All preceding noninvasive testing, including resting electrocardiogram, echocardiogram, and functional testing was evaluated and compared between groups using chi-square and t test. In total, 806 patients were evaluated. Of those, 121 were identified as having significant LMCA stenosis with 685 patients in the non-LM cohort. Between LMCA versus non-LM cohorts, there were similar rates of electrocardiogram abnormalities (68.9% vs 70.8%, p >0.05), abnormal echocardiograms (72.7% vs 69.7%, p >0.05), abnormal functional testing (83.3% vs 77.4%, p >0.05), and high-risk imaging findings (5.6% vs 4.8%, p >0.05). More importantly, of those with a complete workup, there were similar rates of normal results between the LMCA (3 of 18, 16.7%) and non-LM stenosis (9 of 189, 4.8%) groups. A comprehensive noninvasive profile of patients with IHD failed to identify or exclude patients with anatomically severe LMCA stenosis, necessitating anatomic assessment.

Decreasing Goal Oxygen Saturations in Bronchiolitis Is Associated With Decreased Length of Stay.

OBJECTIVES: For patients hospitalized with bronchiolitis, many hospitals have implemented clinical practice guidelines to decrease variability in care. Our hospital updated its bronchiolitis clinical pathway by lowering goal oxygen saturation from 90% to 88%. We compared clinical outcomes before and after this change within the context of the pathway update. METHODS: This was a retrospective analysis of patients <24 months old admitted to a pediatric tertiary care center from 2019 to 2021 with bronchiolitis. Patients with congenital heart disease, asthma, home oxygen, or admitted to an ICU were excluded. The data were stratified for patients admitted before and after the clinical pathway update. Statistical methods consisted of 2 group comparisons using the χ-square test for categorical variables, the Wilcoxon rank-sum test for continuous variables, and multiple regression analysis. RESULTS: A total of 1386 patients were included, 779 preupdate and 607 postupdate. There was no statistically significant difference in the admission rate of patients presenting to the emergency department with bronchiolitis between the 2 groups (P value .60). The median time to room air was 40.0 hours preupdate versus 30.0 hours postupdate (P value < .001). The median length of stay was 48.0 hours preupdate versus 41.0 hours postupdate (P value < .001). Readmission rate was 2.7% within 7 days of discharge preupdate, and 2.1% postupdate (P value .51). CONCLUSIONS: Decreasing goal oxygen saturation to 88% was associated with a statistically significant decrease in time spent on oxygen and length of stay for patients admitted with bronchiolitis with no increase in readmissions.

Perspectives of Health Care Personnel on the Benefits of Bronchiolitis Interventions.

OBJECTIVES: Many interventions in bronchiolitis are low-value or poorly studied. Inpatient bronchiolitis management is multidisciplinary, with varying degrees of registered nurse (RN) and respiratory therapist (RT) autonomy. Understanding the perceived benefit of interventions for frontline health care personnel may facilitate deimplementation efforts. Our objective was to examine perceptions surrounding the benefit of common inpatient bronchiolitis interventions. METHODS: We conducted a cross-sectional survey of inpatient pediatric RNs, RTs, and physicians/licensed practitioners (P/LPs) (eg, advanced-practice practitioners) from May to December of 2021 at 9 university-affiliated and 2 community hospitals. A clinical vignette preceded a series of inpatient bronchiolitis management questions. RESULTS: A total of 331 surveys were analyzed with a completion rate of 71.9%: 76.5% for RNs, 57.4% for RTs, and 71.2% for P/LPs. Approximately 54% of RNs and 45% of RTs compared with 2% of P/LPs believe albuterol would be "extremely or somewhat likely" to improve work of breathing (P < .001). Similarly, 52% of RNs, 32% of RTs, and 23% of P/LPs thought initiating or escalating oxygen in the absence of hypoxemia was likely to improve work of breathing (P < .001). Similar differences in perceived benefit were observed for steroids, nebulized hypertonic saline, and deep suctioning, but not superficial nasal suctioning. Hospital type (community versus university-affiliated) did not impact the magnitude of these differences. CONCLUSIONS: Variation exists in the perceived benefit of several low-value or poorly studied bronchiolitis interventions among health care personnel, with RNs/RTs generally perceiving higher benefit. Deimplementation, educational, and quality improvement efforts should be designed with an interprofessional framework.

A stepwise external cardioversion protocol for atrial fibrillation to maximize acute success rate.

AIMS: Cardioversion is a very commonly performed procedure for persistent atrial fibrillation (AF). However, there is no well-defined protocol to address failed external electrical direct current cardioversion. The aim of the study is to test the efficacy of a pre-defined stepwise cardioversion protocol for patients with persistent AF of ≤12 months. Success was the achievement of sinus rhythm. METHODS AND RESULTS: The study population included patients with persistent AF of ≤12 months duration requiring rhythm management. Patients were offered cardioversion using a pre-defined stepwise protocol using different electrode placement locations, applying compression at end of expiration, and higher energy delivered simultaneously through two defibrillators. : A total of 414 patients were included in the study, of which 362 (87.4%) required a single successful cardioversion. The remaining 52 (12.5%) patients required additional cardioversion attempts using the stepwise cardioversion protocol with an overall success rate of 99.3%. Two simultaneous defibrillators were required in 14 patients (3.4%). Patients with multiple cardioversions (13.5%) experienced more local skin irritation and pain compared with patients with single cardioversion (13.5% vs. 3.5%, P = 0.004). The predictor for the need for multiple cardioversion attempts is high body mass index, while high transthoracic impedance is associated with failed cardioversion. No major complications were observed during the study. CONCLUSION: The stepwise cardioversion protocol has a high success rate of >99% and can be safely performed in outpatient or inpatient settings.

Prognostic Implication of Pre-Cannulation Cardiac Arrest in Patients Undergoing Extracorporeal Membrane Oxygenation for the Management of Cardiogenic Shock.

BACKGROUND: The application of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in contemporary management of cardiogenic shock (CS) has dramatically increased. Despite increased utilization, few predictive models exist to estimate patient survival based on pre-ECMO characteristics. Furthermore, the prognostic implications of pre-ECMO cardiac arrest are not well defined. METHODS: Utilizing an institutional VA-ECMO database, all consecutive patients undergoing VA-ECMO for the management of CS from January 1, 2014, to July 1, 2019, were identified. Survival to hospital discharge was analyzed based on cannulation indication in patients with and without pre-ECMO cardiac arrest. Patients who received extracorporeal cardiopulmonary resuscitation (eCPR) were analyzed separately. RESULTS: Of the 214 patients identified, 110 did not suffer a cardiac arrest prior to cannulation (cohort 1), 57 patients had a cardiac arrest with sustained ROSC (cohort 2), and 47 were cannulated as a component of eCPR (cohort 3). Despite sustained ROSC (cohort 2), the presence of pre-ECMO cardiac arrest was associated with a significant reduction in survival to hospital discharge (22.8% vs. 55.5% in cohort 1; p < 0.001). Comparatively, survival to discharge was similar in patients undergoing eCPR (22.8% vs. 17.0%; p = 0.464). Finally, patients with a cardiac arrest were significantly more likely to have a neurological etiology death with VA-ECMO than patients supported prior to hemodynamic collapse (18.3% vs. 2.7%; p < 0.001). This result is seen in those with sustained ROSC (21.1% vs. 2.7%; p < 0.001) and those with eCPR (14.9% vs. 2.7%; p = 0.004). CONCLUSION: In our cohort, pre-ECMO cardiac arrest carries a negative prognostic value across all indications and is associated with an increased prevalence of neurological-etiology death. This finding is true in patients with sustained ROSC as well as those resuscitated with eCPR. Cardiac arrest can inform survival probability with VA-ECMO as early implementation of VA-ECMO may mitigate adverse outcomes in patients at the highest risk of hemodynamic collapse.

Study on restless leg syndrome and its relationship with quality of sleep among the general population of Mangalore, India.

Background: Restless leg syndrome (RLS) is a common neurological morbidity. It is, however, a frequently underdiagnosed medical condition. This study was hence done to assess the occurrence and severity of RLS among participants and to study its determinants and its association with quality of sleep. This was a cross-sectional study conducted among the general population of Mangalore in July 2021. Data were collected using a Google Form. The International Restless Legs Syndrome Study Group Rating Scale was used to diagnose RLS and its severity. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. Results: The prevalence of RLS among the 202 participants was 24(11.9%). Among them, 5 were already diagnosed with RLS. Their mean age at onset was 40.4 ± 25.3 years. Among the rest 197 participants, 19(9.6%) were newly diagnosed with RLS. The severity of RLS was mild, moderate and severe among 7(36.8%), 9(47.4%) and 3(15.8%) participants, respectively. Five (26.3%) of the 19 newly diagnosed participants were identified as RLS sufferers. In multivariable analysis, the presence of diabetes mellitus and family history of RLS were  associated with the presence of RLS among the participants. The mean Global PSQI value was 5.0 ± 3.1. Sleep latency was prolonged (p = 0.001), and sleep disturbances (p = 0.01) were higher among participants newly diagnosed with RLS (n = 19) compared to those without RLS (n = 178). Subjective sleep quality was poor (p = 0.038), and sleep disturbances (p = 0.016) were more among participants with severe degree RLS. Conclusions: The prevalence of RLS in the present study was higher than that reported in previous Indian studies. Unpleasant sensations in RLS affected sleep initiation and maintenance among the affected. A multi-disciplinary approach is required to control its determinants and address other sleep-related problems among the RLS affected population.

Establishing a Cardiac ICU Recovery Clinic: Characterizing a Model for Continuity of Cardiac Critical Care.

BACKGROUND: Care in the cardiovascular intensive care unit (CICU) has become increasingly intricate due to a temporal rise in noncardiac diagnoses and overall clinical complexity with high risk for short-term rehospitalization and mortality. Survivors of critical illness are often faced with debility and limitations extending beyond the index hospitalization. Comprehensive ICU recovery programs have demonstrated some efficacy but have primarily targeted survivors of acute respiratory distress syndrome or sepsis. The efficacy of dedicated ICU recovery programs on the CICU population is not defined. METHODS: We aim to describe the design and initial experience of a novel CICU-recovery clinic (CICURC). The primary outcome was death or rehospitalization in the first 30 days following hospital discharge. Self-reported outcome measures were performed to assess symptom burden and independence in activities of daily living. RESULTS: Using standardized criteria, 41 patients were referred to CICURC of which 78.1% established care and were followed for a median of 88 (56-122) days. On intake, patients reported a high burden of heart failure symptoms (KCCQ overall summary score 29.8 [18.0-47.5]), and nearly half (46.4%) were dependent on caretakers for activities of daily living. Thirty days postdischarge, no deaths were observed and the rate of rehospitalization for any cause was 12.2%. CONCLUSIONS: CICU survivors are faced with significant residual symptom burden, dependence upon caretakers, and impairments in mental health. Dedicated CICURCs may help prioritize treatment of ICU related illness, reduce symptom burden, and improve outcomes. Interventions delivered in ICU recovery clinic for patients surviving the CICU warrant further investigation.

The burden of malnutrition & frailty in patients with coronary artery disease: An under-recognized problem.

Elderly patients with coronary artery disease have a high prevalence of frailty and malnutrition. Frailty syndrome is associated with poor outcomes in patients with myocardial infarction. There is a known overlap between frailty and malnutrition, yet these are two different entities. Fried Frailty Phenotype, Frail Scale, timed up and go test, and gait speed are rapid screening tests that may identify patients with frailty in everyday clinical setting. Short Form MNA is a sensitive tool to screen for malnutrition. Despite the availability of several tools for screening for both these conditions, the screening rates remain low. We aim to create awareness about the impacts of frailty and malnutrition, provide a brief overview of tools available and highlight the importance of screening in this high-risk population.

Trends and Outcomes of Oral Anticoagulation With Direct Current Cardioversion for Atrial Fibrillation/Flutter at an Academic Medical Center.

Background: Increasing reports suggest the safe use of direct oral anticoagulants (DOACs) in electrical cardioversion. The aim of this study was to assess the trends and 30-day outcomes associated with anticoagulation for cardioversion. Methods: Patients who underwent electrical cardioversion from January 2015 to October 2020 with a 30-day follow-up were included; and outcomes including stroke, transient ischemic attack, intracranial hemorrhage (ICH), and major gastrointestinal bleeding were recorded. Results: Of the 515 patients, 351 (68%) were men and 164 (32%) were women, with a mean CHA2DS2VASc score of 2.6 ± 1.6. Outpatient apixaban use increased from 10% in 2015 to 46% in 2020 (P < 0.001) with a decline in the use of warfarin from 24% in 2015 to 10% in 2020 (P = 0.023). Apixaban use peri-procedurally for cardioversion increased from 32% in 2015 to 35% in 2020 (P = 0.317), while warfarin use decreased from 23% in 2015 to 14% in 2020 (P = 0.164). At discharge, apixaban prescriptions increased from 21% in 2015 to 61% in 2020 (P < 0.001), while warfarin prescriptions declined from 30% in 2015 to 13% in 2020 (P = 0.009). No ICH was recorded in the 30 days after cardioversion. Ischemic stroke occurred in four (0.7%) patients with one (0.29%) of the 338 patients on a DOAC, one (0.8%) of the 124 patients on warfarin and two (5.5%) of the 36 patients not receiving anticoagulation post cardioversion. There were seven (1%) major gastrointestinal bleeding events in patients on oral anticoagulation, of which four (3%) were on warfarin and three (0.8%) were on DOACs. Conclusions: Our study shows the increasing and safe use of DOACs for the purpose of cardioversion. The rates of 30-day ischemic stroke post cardioversion were low and only occurred in patients admitted in the intensive care unit.

Predicting mortality in nonsurgical patients before cannulation for veno-arterial extracorporeal life support: Development and validation of the LACT-8 score.

OBJECTIVES: We sought to derive and validate a model to predict inpatient mortality after veno-arterial extracorporeal life support (VA-ECLS) based on readily available, precannulation clinical data. BACKGROUND: Refractory cardiogenic shock supported by VA-ECLS is associated with high morbidity and mortality. METHODS: VA-ECLS cases at our institution from January 2014 through July 2019 were retrospectively reviewed. Exclusion criteria were cannulation: (1) at another institution; (2) for primary surgical indication; or (3) for extracorporeal cardiopulmonary resuscitation. Multivariable logistic regression compared those with and without inpatient mortality. Multiple imputation was performed and optimism-adjusted area under the curve (oAUC) values were computed. RESULTS: VA-ECLS cases from August 2019 through November 2020 were identified as a validation cohort. In the derivation cohort (n = 135), the final model included Lactate (mmol/L), hemoglobin (g/dl; Anemia), Coma (Glasgow Coma Scale [GCS] < 8) and resusciTATEd cardiac arrest (LACTATE score; oAUC = 0.760). In the validation cohort (n = 30, LACTATE showed similar predictability [AUC = 0.710]). A simplified (LACT-8) score was derived by dichotomizing lactate (>8) and hemoglobin (<8) and summing together the number of components for each patient. LACT-8 performed similarly (derivation, oAUC = 0.724; validation, AUC = 0.725). In the derivation cohort, both scores outperformed SAVE (oAUC = 0.568) and SOFA (oAUC = 0.699) scores. A LACT-8 ≥ 3 had a specificity for mortality of 97.9% and 92.9%, in the derivation and validation cohorts, respectively. CONCLUSIONS: The LACT-8 score can predict inpatient mortality prior to before cannulation for VA-ECLS. LACT-8 can be implemented utilizing clinical data without the need for an online calculator.

Developing and Demonstrating the Viability and Availability of the Multilevel Implementation Strategy for Syncope Optimal Care Through Engagement (MISSION) Syncope App: Evidence-Based Clinical Decision Support Tool.

BACKGROUND: Syncope evaluation and management is associated with testing overuse and unnecessary hospitalizations. The 2017 American College of Cardiology/American Heart Association (ACC/AHA) Syncope Guideline aims to standardize clinical practice and reduce unnecessary services. The use of clinical decision support (CDS) tools offers the potential to successfully implement evidence-based clinical guidelines. However, CDS tools that provide an evidence-based differential diagnosis (DDx) of syncope at the point of care are currently lacking. OBJECTIVE: With input from diverse health systems, we developed and demonstrated the viability of a mobile app, the Multilevel Implementation Strategy for Syncope optImal care thrOugh eNgagement (MISSION) Syncope, as a CDS tool for syncope diagnosis and prognosis. METHODS: Development of the app had three main goals: (1) reliable generation of an accurate DDx, (2) incorporation of an evidence-based clinical risk tool for prognosis, and (3) user-based design and technical development. To generate a DDx that incorporated assessment recommendations, we reviewed guidelines and the literature to determine clinical assessment questions (variables) and likelihood ratios (LHRs) for each variable in predicting etiology. The creation and validation of the app diagnosis occurred through an iterative clinician review and application to actual clinical cases. The review of available risk score calculators focused on identifying an easily applied and valid evidence-based clinical risk stratification tool. The review and decision-making factors included characteristics of the original study, clinical variables, and validation studies. App design and development relied on user-centered design principles. We used observations of the emergency department workflow, storyboard demonstration, multiple mock review sessions, and beta-testing to optimize functionality and usability. RESULTS: The MISSION Syncope app is consistent with guideline recommendations on evidence-based practice (EBP), and its user interface (UI) reflects steps in a real-world patient evaluation: assessment, DDx, risk stratification, and recommendations. The app provides flexible clinical decision making, while emphasizing a care continuum; it generates recommendations for diagnosis and prognosis based on user input. The DDx in the app is deemed a pragmatic model that more closely aligns with real-world clinical practice and was validated using actual clinical cases. The beta-testing of the app demonstrated well-accepted functionality and usability of this syncope CDS tool. CONCLUSIONS: The MISSION Syncope app development integrated the current literature and clinical expertise to provide an evidence-based DDx, a prognosis using a validated scoring system, and recommendations based on clinical guidelines. This app demonstrates the importance of using research literature in the development of a CDS tool and applying clinical experience to fill the gaps in available research. It is essential for a successful app to be deliberate in pursuing a practical clinical model instead of striving for a perfect mathematical model, given available published evidence. This hybrid methodology can be applied to similar CDS tool development.

APOΕ4 lowers energy expenditure in females and impairs glucose oxidation by increasing flux through aerobic glycolysis.

BACKGROUND: Cerebral glucose hypometabolism is consistently observed in individuals with Alzheimer's disease (AD), as well as in young cognitively normal carriers of the Ε4 allele of Apolipoprotein E (APOE), the strongest genetic predictor of late-onset AD. While this clinical feature has been described for over two decades, the mechanism underlying these changes in cerebral glucose metabolism remains a critical knowledge gap in the field. METHODS: Here, we undertook a multi-omic approach by combining single-cell RNA sequencing (scRNAseq) and stable isotope resolved metabolomics (SIRM) to define a metabolic rewiring across astrocytes, brain tissue, mice, and human subjects expressing APOE4. RESULTS: Single-cell analysis of brain tissue from mice expressing human APOE revealed E4-associated decreases in genes related to oxidative phosphorylation, particularly in astrocytes. This shift was confirmed on a metabolic level with isotopic tracing of 13C-glucose in E4 mice and astrocytes, which showed decreased pyruvate entry into the TCA cycle and increased lactate synthesis. Metabolic phenotyping of E4 astrocytes showed elevated glycolytic activity, decreased oxygen consumption, blunted oxidative flexibility, and a lower rate of glucose oxidation in the presence of lactate. Together, these cellular findings suggest an E4-associated increase in aerobic glycolysis (i.e. the Warburg effect). To test whether this phenomenon translated to APOE4 humans, we analyzed the plasma metabolome of young and middle-aged human participants with and without the Ε4 allele, and used indirect calorimetry to measure whole body oxygen consumption and energy expenditure. In line with data from E4-expressing female mice, a subgroup analysis revealed that young female E4 carriers showed a striking decrease in energy expenditure compared to non-carriers. This decrease in energy expenditure was primarily driven by a lower rate of oxygen consumption, and was exaggerated following a dietary glucose challenge. Further, the stunted oxygen consumption was accompanied by markedly increased lactate in the plasma of E4 carriers, and a pathway analysis of the plasma metabolome suggested an increase in aerobic glycolysis. CONCLUSIONS: Together, these results suggest astrocyte, brain and system-level metabolic reprogramming in the presence of APOE4, a 'Warburg like' endophenotype that is observable in young females decades prior to clinically manifest AD.

Passive antipyretic therapy is not as effective as invasive hypothermia for maintaining normothermia after cardiac arrest.

AIM OF THE STUDY: Targeted temperature management is a class I indication in comatose patients after a cardiac arrest. While the literature has primarily focused on innovative methods to achieve target temperatures, pharmacologic therapy has received little attention. We sought to examine whether pharmacologic therapy using antipyretics is effective in maintaining normothermia in post cardiac arrest patients. MATERIALS AND METHODS: Patients ≥18 years who were resuscitated after an in-hospital or out-of-hospital cardiac arrest and admitted at our institution from January 2012 to September 2015 were retrospectively included. Patients were divided into groups based on the method of temperature control that was utilized. The primary outcome was temperature control <38 °C during the first 48 h after the cardiac arrest. RESULTS: 671 patients were identified in Group 1 (no hypothermia), 647 in Group 2 (antipyretics), 44 in Group 3 (invasive hypothermia), and 51 in Group 4 (invasive hypothermia and antipyretics). Mean patient age was 59 (SD ±15.7) years with 40.6% being female. Using Group 1 as the control arm, 57.7% of patients maintained target temperature with antipyretics alone (p < 0.001), compared to 69.3% in the control group and 82.1% in the combined hypothermia groups 3&4 (p = 0.01). Patients receiving both invasive hypothermia and antipyretics (Group 4), had the greatest mean temperature decrease of 5.2 °C. CONCLUSIONS: Among patients undergoing targeted temperature management, relying solely on as needed use of antipyretics is not sufficient to maintain temperatures <38 °C. However, antipyretics could be used as an initial strategy if given regularly and/or in conjunction with more aggressive cooling techniques.

Planning Implementation Success of Syncope Clinical Practice Guidelines in the Emergency Department Using CFIR Framework.

Background and Objectives: Overuse and inappropriate use of testing and hospital admission are common in syncope evaluation and management. Though guidelines are available to optimize syncope care, research indicates that current clinical guidelines have not significantly impacted resource utilization surrounding emergency department (ED) evaluation of syncope. Matching implementation strategies to barriers and facilitators and tailoring strategies to local context hold significant promise for a successful implementation of clinical practice guidelines (CPG). Our team applied implementation science principles to develop a stakeholder-based implementation strategy. Methods and Materials: We partnered with patients, family caregivers, frontline clinicians and staff, and health system administrators at four health systems to conduct quantitative surveys and qualitative interviews for context assessment. The identification of implementation strategies was done by applying the CFIR-ERIC Implementation Strategy Matching Tool and soliciting stakeholders' inputs. We then co-designed with patients and frontline teams, and developed and tested specific strategies. Results: A total of 114 clinicians completed surveys and 32 clinicians and stakeholders participated in interviews. Results from the surveys and interviews indicated low awareness of syncope guidelines, communication challenges with patients, lack of CPG protocol integration into ED workflows, and organizational process to change as major barriers to CPG implementation. Thirty-one patients and their family caregivers participated in interviews and expressed their expectations: clarity regarding their diagnosis, context surrounding care plan and diagnostic testing, and a desire to feel cared about. Identifying change methods to address the clinician barriers and patients and family caregivers expectations informed development of the multilevel, multicomponent implementation strategy, MISSION, which includes patient educational materials, mentored implementation, academic detailing, Syncope Optimal Care Pathway and a corresponding mobile app, and Lean quality improvement methods. The pilot of MISSION demonstrated feasibility, acceptability and initial success on appropriate testing. Conclusions: Effective multifaceted implementation strategies that target individuals, teams, and healthcare systems can be employed to plan successful implementation and promote adherence to syncope CPGs.