Vedant Gupta

Objectives: There is emerging data supporting rapid triage of low-risk chest pain patients to help facilitate Emergency Department (ED) throughput. We assessed an algorithm for accelerated rule-out of acute coronary syndrome in low-risk patients with an undetectable initial high sensitivity cardiac troponin (hs-cTn assays; Roche Diagnostics) in a real-world clinical setting. Methods: All adults presenting with chief complaint of non-traumatic chest pain to our tertiary care ED with HEART score ≤3 with at least one hs-cTn and EKG obtained were included in our study. Data and outcomes were compared three months before and after implementation of our updated Acute Chest Pain Optimal Care Pathway that allowed discharge of patients with an initial troponin below detectable range (<6ng/L). The primary outcome was acute coronary syndrome at presentation or major adverse cardiovascular events within 30 days. Secondary outcomes included ED length of stay, cardiology consultations, and hospital admissions. Results: Of the 229 patients fitting our criteria with a low-risk heart score (≤3) and undetectable initial troponin, zero patients were diagnosed with ACS and one major adverse cardiac event occurred post-implementation (0.8%). There were no significant differences in median ED length of stay pre- (4.5 hours, IQR 3.8–6.6) versus post-implementation (4.6 hours, IQR 3.5–5.7; p=0.448), number of cardiology consults (p=0.305) and hospital admissions (p=0.261). However, protocol adherence was poor (50%). In a subgroup analysis post-implementation, patients whose care aligned with the algorithm (n=64, 50.0%) had significantly shorter ED stays (median 4.1 hours, IQR 3.3-4.9 vs 5.2 hours, IQR 4.4-6.9, p<0.001), fewer admissions (p=0.001) but not fewer cardiology consults (p=0.440). Conclusions: Our study supports current data regarding the safety of accelerated rule out strategy with hs-cTn. However, our conclusions are limited due to its small sample size and retrospective design.

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. 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. The stepwise cardioversion protocol has a high success rate of >99% and can be safely performed in outpatient or inpatient settings.

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.

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.

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.

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.

Purpose: Syncope is a complex symptom requiring thoughtful evaluation. The ACC/AHA/HRS published syncope management guidelines in 2017. Effective guideline implementation hinges on overcoming multilevel barriers, including providers’ perceptions that patients prefer aggressive diagnostic testing when presenting to the emergency department (ED) with syncope, which conflicts with the 2017 Guideline on Syncope. To better understand this perceived barrier, we explored patient and family caregiver expectations and preferences when presenting to the ED with syncope. Patients and Methods: We conducted semi-structured focus groups (N=12) and in-depth interviews (N=19) with patients presenting to the ED with syncope as well as with their family caregivers. Interviews were recorded, transcribed verbatim, and analyzed by a team of researchers following a directed content analysis. Results were reviewed and shared iteratively with all team members to confirm mutual understanding and agreement. Results: Syncope patients and caregivers discussed three main desires when presenting to the ED with syncope: 1) clarity regarding their diagnosis,; 2) context surrounding their care plan and diagnostic approach; and 3) to feel seen, heard and cared about by their health care team. Conclusion: Clinicians have cited patient preferences for aggressive diagnostic testing as a barrier to adhering to the 2017 Guideline on Syncope, which recommends against routine administration of imaging testing (eg, echocardiograms). Our results suggest that while participants preferred diagnostic testing as a means to achieve clarity and even a feeling of being cared for, other strategies, such as a patient-engaged approach to communication and shared decision-making, may address the spectrum of patient expectations when presenting to the ED with syncope while adhering to guideline recommendations.