Initial Defibrillator Pad Position and Outcomes for Shockable Out-of-Hospital Cardiac Arrest.

Importance: Ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT) are the most treatable causes of out-of-hospital cardiac arrest (OHCA). Yet, it remains unknown if defibrillator pad position, placement in the anterior-posterior (AP) or anterior-lateral (AL) locations, impacts patient outcomes in VF or pVT OHCA. Objective: To determine the association between initial defibrillator pad placement position and OHCA outcomes for patients presenting with VF or pVT. Design, Setting, and Participants: This prospective cohort study included patients with OHCA and VF or pVT treated by a single North American emergency medical services (EMS) agency from July 1, 2019, through June 30, 2023. The study included patients with OHCA treated by a large suburban fire-based EMS agency that covers a population of 550 000. Consecutive patients with an initial EMS-assessed rhythm of VF or pVT receiving EMS defibrillation were included. Pediatric patients (younger than 18 years), interfacility transfers, arrests of obvious traumatic etiology, and patients with preexisting do-not-resuscitate status were excluded. Exposure: AP or AL pad placement. Main Outcomes and Measures: Return of spontaneous circulation (ROSC) at any time with secondary outcomes of pulses present at emergency department (ED) arrival, survival to hospital admission, survival to hospital discharge, and functional survival at hospital discharge (cerebral performance category score of 2 or less). Measures included adjusted odds ratios (aOR), multivariable logistic regressions, and Fine-Gray competing risks regression. Results: A total of 255 patients with OHCA were included (median [IQR] age, 66 [55-74] years; 63 females [24.7%]), with initial pad positioning documented as either AP (158 patients [62.0%]; median [IQR] age, 65 [54-74] years; 37 females [23.4%]) or AL (97 patients [38.0%]; median [IQR] age, 66 [57-74] years; 26 females [26.8%]). Patients with AP placement had higher adjusted odds ratio (aOR) of ROSC at any time (aOR, 2.64 [95% CI, 1.50-4.65]), but not significantly different odds of pulses present at ED arrival (1.34 [95% CI, 0.78-2.30]), survival to hospital admission (1.41 [0.82-2.43]), survival to hospital discharge (1.55 [95% CI, 0.83-2.90]), or functional survival at hospital discharge (1.86 [95% CI, 0.98-3.51]). Competing risk analysis found significantly greater cumulative incidence of ROSC among those at risk with initial AP placement compared with AL (subdistribution hazard ratio, 1.81 [95% CI, 1.23-2.67]; P = .003). Conclusions and Relevance: In this cohort study of patients with OHCA and VF or pVT, AP defibrillator pad placement was associated with higher ROSC compared with AL placement.

Gender Differences in Defibrillator Practices in Out-of-Hospital Cardiac Arrest.

OBJECTIVES: Disparities remain in survival after out-of-hospital cardiac arrest (OHCA) for women compared to men. Our objective was to evaluate differences in automated external defibrillator (AED) use before Emergency Medical Services (EMS) arrival and time from arrival to initial EMS defibrillation by EMS-assessed gender (women or men). METHODS: This was a secondary analysis of adult non-traumatic, EMS-treated OHCA cases in the Portland Cardiac Arrest Epidemiologic Registry from 2018 to 2021. Emergency Medical Services-witnessed cardiac arrests were excluded and the primary outcomes were pre-EMS AED application and the time from EMS arrival to first defibrillation among patients in a shockable rhythm at first rhythm assessment without pre-EMS AED application. We examined pre-EMS AED application rates overall and separately for law enforcement, in cases where they were on-scene before EMS without a lay bystander AED applied, and lay responders, in cases where law enforcement had not applied an AED. We used multivariable logistic and linear regressions to adjust for potential confounders, including age, arrest location, witness status, bystander CPR, year, and time from dispatch to EMS arrival. We accounted for clustering by county of arrest using a mixed-effects approach. RESULTS: Of the 3,135 adult, EMS-treated non-traumatic OHCAs that were not witnessed by EMS, 3,049 had all variables for analysis, of which 1,011 (33.2%) were women. The adjusted odds (adjusted odds ratio [95% CI]) for any pre-EMS placement of an AED was significantly higher for men compared to women (1.40 [1.05-1.86]). These odds favoring men remained when examining law enforcement AED application (1.89 [1.16-3.07]), but not lay bystander AED application (1.19 [0.83-1.71]). Among patients still in arrest on EMS arrival, with a shockable initial EMS rhythm, and without pre-EMS AED application, the time from EMS arrival on-scene to initial defibrillation was significantly longer for women compared to men (+0.81 min [0.22-1.41 min]). CONCLUSIONS: Women with OHCA received lower rates of pre-EMS AED application and delays in initial EMS defibrillation compared to men.

Mycb and Mych stimulate Müller glial cell reprogramming and proliferation in the uninjured and injured zebrafish retina.

In the injured zebrafish retina, Müller glial cells (MG) reprogram to adopt retinal stem cell properties and regenerate damaged neurons. The strongest zebrafish reprogramming factors might be good candidates for stimulating a similar regenerative response by mammalian MG. Myc proteins are potent reprogramming factors that can stimulate cellular plasticity in differentiated cells; however, their role in MG reprogramming and retina regeneration remains poorly explored. Here, we report that retinal injury stimulates mycb and mych expression and that, although both Mycb and Mych stimulate MG reprogramming and proliferation, only Mych enhances retinal neuron apoptosis. RNA-sequencing analysis of wild-type, mychmut and mycbmut fish revealed that Mycb and Mych regulate ∼40% and ∼16%, respectively, of the genes contributing to the regeneration-associated transcriptome of MG. Of these genes, those that are induced are biased towards regulation of ribosome biogenesis, protein synthesis, DNA synthesis, and cell division, which are the top cellular processes affected by retinal injury, suggesting that Mycb and Mych are potent MG reprogramming factors. Consistent with this, forced expression of either of these proteins is sufficient to stimulate MG proliferation in the uninjured retina.

The association of early naloxone use with outcomes in non-shockable out-of-hospital cardiac arrest.

STUDY OBJECTIVE: Evaluate the association between early naloxone use and outcomes after out-of-hospital cardiac arrest (OHCA) with initial non-shockable rhythms. METHODS: This study was a secondary analysis of data collected in the Portland Cardiac Arrest Epidemiologic Registry, a database containing details of emergency medical services (EMS)-treated OHCA cases in the Portland, Oregon metropolitan region. Eligible patients had non-traumatic OHCA with an initial non-shockable rhythm and received naloxone by EMS or law enforcement prior to IV/IO access (exposure group). The primary outcome was ROSC at emergency department (ED) arrival. Secondary outcomes included survival to admission, survival to hospital discharge, and cerebral performance category score ≤2 at discharge (good neurologic outcome). We performed multivariable logistic regressions adjusting for age, sex, arrest location, witness status, bystander interventions, dispatch to EMS arrival time, initial rhythm, and county of arrest. RESULTS: There were 1807 OHCA cases from 2018 to 2021 meeting eligibility criteria, with 57 receiving naloxone before vascular access. Patients receiving naloxone prior to vascular access attempts had higher adjusted odds (aOR [95% CI]) of ROSC at any time (2.14 [1.20-3.81]), ROSC at ED arrival (2.14 [1.18-3.88]), survival to admission (2.86 [1.60-5.09]), survival to discharge (4.41 [1.78-10.97]), and good neurologic outcome (4.61 [1.74-12.19]). CONCLUSIONS: Patients with initial non-shockable OHCA who received law enforcement or EMS naloxone prior to IV/IO access attempts had higher adjusted odds of ROSC at any time, ROSC at ED arrival, survival to admission, survival to discharge, and good neurologic outcome.

Müller Glial Cell-Dependent Regeneration of the Retina in Zebrafish and Mice.

Sight is one of our most precious senses. People fear losing their sight more than any other disability. Thus, restoring sight to the blind is an important goal of vision scientists. Proregenerative species, such as zebrafish, provide a system for studying endogenous mechanisms underlying retina regeneration. Nonregenerative species, such as mice, provide a system for testing strategies for stimulating retina regeneration. Key to retina regeneration in zebrafish and mice is the Müller glial cell, a malleable cell type that is amenable to a variety of regenerative strategies. Here, we review cellular and molecular mechanisms used by zebrafish to regenerate a retina, as well as the application of these mechanisms, and other strategies to stimulate retina regeneration in mice. Although our focus is on Müller glia (MG), niche components and their impact on MG reprogramming are also discussed.

Artificial Intelligence Model Predicts Sudden Cardiac Arrest Manifesting With Pulseless Electric Activity Versus Ventricular Fibrillation.

BACKGROUND: There is no specific treatment for sudden cardiac arrest (SCA) manifesting as pulseless electric activity (PEA) and survival rates are low; unlike ventricular fibrillation (VF), which is treatable by defibrillation. Development of novel treatments requires fundamental clinical studies, but access to the true initial rhythm has been a limiting factor. METHODS: Using demographics and detailed clinical variables, we trained and tested an AI model (extreme gradient boosting) to differentiate PEA-SCA versus VF-SCA in a novel setting that provided the true initial rhythm. A subgroup of SCAs are witnessed by emergency medical services personnel, and because the response time is zero, the true SCA initial rhythm is recorded. The internal cohort consisted of 421 emergency medical services-witnessed out-of-hospital SCAs with PEA or VF as the initial rhythm in the Portland, Oregon metropolitan area. External validation was performed in 220 emergency medical services-witnessed SCAs from Ventura, CA. RESULTS: In the internal cohort, the artificial intelligence model achieved an area under the receiver operating characteristic curve of 0.68 (95% CI, 0.61-0.76). Model performance was similar in the external cohort, achieving an area under the receiver operating characteristic curve of 0.72 (95% CI, 0.59-0.84). Anemia, older age, increased weight, and dyspnea as a warning symptom were the most important features of PEA-SCA; younger age, chest pain as a warning symptom and established coronary artery disease were important features associated with VF. CONCLUSIONS: The artificial intelligence model identified novel features of PEA-SCA, differentiated from VF-SCA and was successfully replicated in an external cohort. These findings enhance the mechanistic understanding of PEA-SCA with potential implications for developing novel management strategies.

Adverse Safety Events in Emergency Medical Services Care of Children With Out-of-Hospital Cardiac Arrest.

Importance: Survival for children with out-of-hospital cardiac arrest (OHCA) remains poor despite improvements in adult OHCA survival. Objective: To characterize the frequency of and factors associated with adverse safety events (ASEs) in pediatric OHCA. Design, Setting, and Participants: This population-based retrospective cohort study examined patient care reports from 51 emergency medical services (EMS) agencies in California, Georgia, Oregon, Pennsylvania, Texas, and Wisconsin for children younger than 18 years with an OHCA in which resuscitation was attempted by EMS personnel between 2013 and 2019. Medical record review was conducted from January 2019 to April 2022 and data analysis from October 2022 to February 2023. Main Outcomes and Measure: Severe ASEs during the patient encounter (eg, failure to give an indicated medication, 10-fold medication overdose). Results: A total of 1019 encounters of EMS-treated pediatric OHCA were evaluated; 465 patients (46%) were younger than 12 months. At least 1 severe ASE occurred in 610 patients (60%), and 310 patients (30%) had 2 or more. Neonates had the highest frequency of ASEs. The most common severe ASEs involved epinephrine administration (332 [30%]), vascular access (212 [19%]), and ventilation (160 [14%]). In multivariable logistic regression, the only factor associated with severe ASEs was young age. Neonates with birth-related and non-birth-related OHCA had greater odds of a severe ASE compared with adolescents (birth-related: odds ratio [OR], 7.0; 95% CI, 3.1-16.1; non-birth-related: OR, 3.4; 95% CI, 1.2-9.6). Conclusions and Relevance: In this large geographically diverse cohort of children with EMS-treated OHCA, 60% of all patients experienced at least 1 severe ASE. The odds of a severe ASE were higher for neonates than adolescents and even higher when the cardiac arrest was birth related. Given the national increase in out-of-hospital births and ongoing poor outcomes of OHCA in young children, these findings represent an urgent call to action to improve care delivery and training for this population.

Out-of-hospital cardiac arrest outcomes when law enforcement arrives before emergency medical services.

BACKGROUND: Law enforcement (LE) professionals are often dispatched to out-of-hospital cardiac arrests (OHCA) to provide early cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) application with mixed evidence of a survival benefit. Our objective was to comprehensively evaluate LE care in OHCA. METHODS: This is a secondary analysis of adults with non-traumatic OHCA not witnessed by EMS and without bystander AED use from 2018-2021. Our primary outcome was survival with Cerebral Perfusion Category score ≤ 2 (functional survival). Our exposures included: LE On-scene Only (without providing care); LE CPR Only (without applying an AED); LE Ideal Care (ensuring CPR and AED application). Our control group had no LE arrival before EMS. We performed multivariable logistic regression analyses adjusting for confounders and stratified our analyses by patients with and without bystander CPR. RESULTS: There were 2569 adult, non-traumatic OHCAs from 2018-2021 meeting inclusion criteria. There were no differences in the odds of functional survival for LE On-scene Only (adjusted odds ratio [95% CI]: 1.28 [0.47-3.45]), LE CPR Only (1.26 [0.80-1.99]), or LE Ideal Care (1.36 [0.79-2.33]). In patients without bystander CPR, LE Ideal Care had significantly higher odds of functional survival (2.01 [1.06-3.81]) compared to no LE on-scene, with no significant associations for LE On-scene Only or LE CPR Only. There were no significant differences by LE care in patients already receiving bystander CPR. CONCLUSIONS: LE arrival before EMS and ensuring both CPR and AED application is associated with significantly improved functional survival in OHCA patients not already receiving bystander CPR.

Dynamic electrocardiogram changes are a novel risk marker for sudden cardiac death.

BACKGROUND AND AIMS: Electrocardiogram (ECG) abnormalities have been evaluated as static risk markers for sudden cardiac death (SCD), but the potential importance of dynamic ECG remodelling has not been investigated. In this study, the nature and prevalence of dynamic ECG remodelling were studied among individuals who eventually suffered SCD. METHODS: The study population was drawn from two prospective community-based SCD studies in Oregon (2002, discovery cohort) and California, USA (2015, validation cohort). For this present sub-study, 231 discovery cases (2015-17) and 203 validation cases (2015-21) with ≥2 archived pre-SCD ECGs were ascertained and were matched to 234 discovery and 203 validation controls based on age, sex, and duration between the ECGs. Dynamic ECG remodelling was measured as progression of a previously validated cumulative six-variable ECG electrical risk score. RESULTS: Oregon SCD cases displayed greater electrical risk score increase over time vs. controls [+1.06 (95% confidence interval +0.89 to +1.24) vs. -0.05 (-0.21 to +0.11); P < .001]. These findings were successfully replicated in California [+0.87 (+0.7 to +1.04) vs. -0.11 (-0.27 to 0.05); P < .001]. In multivariable models, abnormal dynamic ECG remodelling improved SCD prediction over baseline ECG, demographics, and clinical SCD risk factors in both Oregon [area under the receiver operating characteristic curve 0.770 (95% confidence interval 0.727-0.812) increased to area under the receiver operating characteristic curve 0.869 (95% confidence interval 0.837-0.902)] and California cohorts. CONCLUSIONS: Dynamic ECG remodelling improved SCD risk prediction beyond clinical factors combined with the static ECG, with successful validation in a geographically distinct population. These findings introduce a novel concept of SCD dynamic risk and warrant further detailed investigation.

Utility of end-tidal carbon dioxide to guide resuscitation termination in prolonged out-of-hospital cardiac arrest.

STUDY OBJECTIVE: To evaluate if the change in end-tidal carbon dioxide (ETCO2) over time has improved discriminatory value for determining resuscitation futility compared to a single ETCO2 value in prolonged, refractory non-shockable out-of-hospital cardiac arrest (OHCA). METHODS: This is a retrospective analysis of adult refractory non-shockable, non-traumatic OHCA patients in the Portland Cardiac Arrest Epidemiologic Registry (PDX Epistry) from 2018 to 2021. We defined refractory non-shockable OHCA cases as patients with lack of a shockable rhythm at any time or return of spontaneous circulation at any time prior to 30-min of on-scene resuscitation. We abstracted ETCO2 values first recorded after advanced airway placement and nearest to the 30-min mark of on-scene resuscitation (30 min-ETCO2) from EMS charts. The primary outcome was survival to hospital discharge. We compared 30 min-ETCO2 cutoffs of 10 mmHg and 20 mmHg to the trend (increasing or not) from initial to 30 min-ETCO2 (delta-ETCO2) using sensitivity, specificity, and area under the receiver operating curves (AUROC). RESULTS: Of 3837 adult OHCA, 2850 were initially non-shockable, and there were 617 (16.1%) cases of refractory non-shockable OHCA at 30-min. We excluded 320 cases without at least two ETCO2 recordings in the EMS chart, leaving 297 cases that met inclusion criteria. Of these, 176 (59.3%) were transported and 2 (0.7%) survived to discharge. Using absolute 30 min-ETCO2 cutoffs, both survivors were in the >10 mmHg group (sensitivity 100.0%, specificity 12.5%), whereas only one survivor was identified in the >20 mmHg group (sensitivity 50.0%, specificity 32.5%). Using delta-ETCO2, both survivors were in the increasing ETCO2 group (sensitivity 100.0%, specificity 60.7%). In comparing the two tests that did not misclassify survivors, the AUROC [95% CI] was higher when using delta-ETCO2 (0.803 [0.775-0.831]) compared to an absolute cutoff of 10 mmHg (0.563 [0.544-0.582]). CONCLUSIONS: Nearly one-sixth of EMS-treated adult OHCA patients had refractory non-shockable arrests after at least 30 min of ongoing resuscitation. In this group, the ETCO2 trend following advanced airway placement may be more accurate in guiding termination of resuscitation than an absolute ETCO2 cutoff of 10 or 20 mmHg.

Remission of severe forms of long COVID following monoclonal antibody (MCA) infusions: A report of signal index cases and call for targeted research.

OBJECTIVE: Long COVID has afflicted tens of millions globally leaving many previously-healthy persons severely and indefinitely debilitated. The objective here was to report cases of complete, rapid remission of severe forms of long COVID following certain monoclonal antibody (MCA) infusions and review the corresponding pathophysiological implications. DESIGN: Case histories of the first three index events (among others) are presented. Unaware of others with similar remissions, each subject independently completed personal narratives and standardized surveys regarding demographics/occupation, past history, and the presence and respective severity grading of 33 signs/symptoms associated with long COVID, comparing the presence/severity of those symptoms during the pre-COVID, long-COVID, post-vaccination, and post-MCA phases. SETTING: Patient interviews, e-mails and telephone conversations. SUBJECTS: Three previously healthy, middle-aged, highly-functioning persons, two women and one man (ages 60, 43, and 63 years respectively) who, post-acute COVID-19 infection, developed chronic, unrelenting fatigue and cognitive impairment along with other severe, disabling symptoms. Each then independently reported incidental and unanticipated complete remissions within days of MCA treatment. INTERVENTIONS: The casirivimab/imdevimab cocktail. MEASUREMENTS AND MAIN RESULTS: Irrespective of sex, age, medical history, vaccination status, or illness duration (18, 8 and 5 months, respectively), each subject experienced the same complete remission of their persistent disabling disease within a week of MCA infusion. Each rapidly returned to normal health and previous lifestyles/occupations with normalized exercise tolerance, still sustained to date over two years later. CONCLUSIONS: These index cases provide compelling clinical signals that MCA infusions may be capable of treating long COVID in certain cases, including those with severe debilitation. While the complete and sustained remissions observed here may only apply to long COVID resulting from pre-Delta variants and the specific MCA infused, the striking rapid and complete remissions observed in these cases also provide mechanistic implications for treating/managing other post-viral chronic conditions and long COVID from other variants.

Outcomes with Tibial and Humeral Intraosseous Access Compared to Peripheral Intravenous Access in Out-of-Hospital Cardiac Arrest.

BACKGROUND: The optimal initial vascular access strategy for out-of-hospital cardiac arrest (OHCA) remains unknown. Our objective was to evaluate the association between peripheral intravenous (PIV), tibial intraosseous (TIO), or humeral intraosseous (HIO) as first vascular attempt strategies and outcomes for patients suffering OHCA. METHOD: This was a secondary analysis of the Portland Cardiac Arrest Epidemiologic Registry, which included adult patients (≥18 years-old) with EMS-treated, non-traumatic OHCA from 2018-2021. The primary independent variable in our analysis was the initial vascular access strategy, defined as PIV, TIO, or HIO based on the first access attempt. The primary outcome for this study was the return of spontaneous circulation (ROSC) at emergency department (ED) arrival (a palpable pulse on arrival to the hospital). Secondary outcomes included survival to: admission, discharge, and discharge with a favorable outcome (Cerebral Perfusion Category score of ≤2). We conducted multivariable logistic regressions, adjusting for confounding variables and for clustering using a mixed-effects approach, with prespecified subgroup analyses by initial rhythm. RESULTS: We included 2,993 patients with initial vascular access strategies of PIV (822 [27.5%]), TIO (1,171 [39.1%]), and HIO (1,000 [33.4%]). Multivariable analysis showed lower odds of ROSC at ED arrival (adjusted odds ratio [95% CI]) with TIO (0.79 [0.64-0.98]) or HIO (0.75 [0.60-0.93]) compared to a PIV-first strategy. These associations remained in stratified analyses for those with shockable initial rhythms (0.60 [0.41-0.88] and 0.53 [0.36-0.79]) but not in patients with asystole or pulseless electrical activity for TIO and HIO compared to PIV, respectively. There were no statistically significant differences in adjusted odds for survival to admission, discharge, or discharge with a favorable outcome for TIO or HIO compared to the PIV-first group in the overall analysis. Patients with shockable initial rhythms had lower adjusted odds of survival to discharge (0.63 [0.41-0.96] and 0.64 [0.41-0.99]) and to discharge with a favorable outcome (0.60 [0.39-0.93] and 0.64 [0.40-1.00]) for TIO and HIO compared to PIV, respectively. CONCLUSIONS: TIO or HIO as first access strategies in OHCA were associated with lower odds of ROSC at ED arrival compared to PIV.

Warning symptoms associated with imminent sudden cardiac arrest: a population-based case-control study with external validation.

BACKGROUND: Sudden cardiac arrest is a global public health problem with a mortality rate of more than 90%. Prearrest warning symptoms could be harnessed using digital technology to potentially improve survival outcomes. We aimed to estimate the strength of association between symptoms and imminent sudden cardiac arrest. METHODS: We conducted a case-control study of individuals with sudden cardiac arrest and participants without sudden cardiac arrest who had similar symptoms identified from two US community-based studies of patients with sudden cardiac arrest in California state, USA (discovery population; the Ventura Prediction of Sudden Death in Multi-Ethnic Communities [PRESTO] study), and Oregon state, USA (replication population; the Oregon Sudden Unexpected Death Study [SUDS]). Participant data were obtained from emergency medical services reports for people aged 18-85 years with witnessed sudden cardiac arrest (between Feb 1, 2015, and Jan 31, 2021) and an inclusion symptom. Data were also obtained from corresponding control populations without sudden cardiac arrest who were attended by emergency medical services for similar symptoms (between Jan 1 and Dec 31, 2019). We evaluated the association of symptoms with sudden cardiac arrest in the discovery population and validated our results in the replication population by use of logistic regression models. FINDINGS: We identified 1672 individuals with sudden cardiac arrest from the PRESTO study, of whom 411 patients (mean age 65·7 [SD 12·4] years; 125 women and 286 men) were included in the analysis for the discovery population. From a total of 76 734 calls to emergency medical services, 1171 patients (mean age 61·8 [SD 17·3] years; 643 women, 514 men, and 14 participants without data for sex) were included in the control group. Patients with sudden cardiac arrest were more likely to have dyspnoea (168 [41%] of 411 vs 262 [22%] of 1171; p<0·0001), chest pain (136 [33%] vs 296 [25%]; p=0·0022), diaphoresis (50 [12%] vs 90 [8%]; p=0·0059), and seizure-like activity (43 [11%] vs 77 [7%], p=0·011). Symptom frequencies and patterns differed significantly by sex. Among men, chest pain (odds ratio [OR] 2·2, 95% CI 1·6-3·0), dyspnoea (2·2, 1·6-3·0), and diaphoresis (1·7, 1·1-2·7) were significantly associated with sudden cardiac arrest, whereas among women, only dyspnoea was significantly associated with sudden cardiac arrest (2·9, 1·9-4·3). 427 patients with sudden cardiac arrest (mean age 62·2 [SD 13·5]; 122 women and 305 men) were included in the analysis for the replication population and 1238 patients (mean age 59·3 [16·5] years; 689 women, 548 men, and one participant missing data for sex) were included in the control group. Findings were mostly consistent in the replication population; however, notable differences included that, among men, diaphoresis was not associated with sudden cardiac arrest and chest pain was associated with sudden cardiac arrest only in the sex-stratified multivariable analysis. INTERPRETATION: The prevalence of warning symptoms was sex-specific and differed significantly between patients with sudden cardiac arrest and controls. Warning symptoms hold promise for prediction of imminent sudden cardiac arrest but might need to be augmented with additional features to maximise predictive power. FUNDING: US National Heart Lung and Blood Institute.

Temporal Trends in Incidence and Survival From Sudden Cardiac Arrest Manifesting With Shockable and Nonshockable Rhythms: A 16-Year Prospective Study in a Large US Community.

STUDY OBJECTIVE: The proportion of nonshockable sudden cardiac arrests (pulseless electrical activity and asystole) continues to rise. Survival is lower than shockable (ventricular fibrillation [VF]) sudden cardiac arrests, but there is little community-based information on temporal trends in the incidence and survival from sudden cardiac arrests based on presenting rhythms. We investigated community-based temporal trends in sudden cardiac arrest incidence and survival by presenting rhythm. METHODS: We prospectively evaluated the incidence of each presenting sudden cardiac arrest rhythm and survival outcomes for out-of-hospital events in the Portland, Oregon metro area (population of approximately 1 million, 2002 to 2017). We limited inclusion to cases of likely cardiac cause with resuscitation attempted by emergency medical services. RESULTS: Out of 3,723 overall sudden cardiac arrest cases, 908 (24%) presented with pulseless electrical activity, 1,513 (41%) with VF, and 1,302 (35%) with asystole. The incidence of pulseless electrical activity-sudden cardiac arrest remained stable over 4-year periods (9.6/100,000 in 2002 to 2005, 7.4/100,000 in 2006 to 2009, 5.7/100,000 in 2010 to 2013, and 8.3/100,000 in 2014 to 2017; unadjusted beta [ß] -0.56; 95% confidence interval [CI], -3.98 to 2.85). The incidence of VF-sudden cardiac arrests decreased over time (14.6/100,000 in 2002 to 2005, 13.4/100,000 in 2006 to 2009, 12.0/100,000 in 2010 to 2013, and 11.6/100,000 in 2014 to 2017; unadjusted ß -1.05; 95% CI, -1.68 to -0.42) and asystole-sudden cardiac arrests (8.6/100,000 in 2002 to 2005, 9.0/100,000 in 2006 to 2009, 10.3/100,000 in 2010 to 2013, and 15.7/100,000 in 2014 to 2017; unadjusted ß 2.25; 95% CI -1.24 to 5.73) did not change significantly over time. Survival increased over time for pulseless electrical activity-sudden cardiac arrests (5.7%, 4.3%, 9.6%, 13.6%; unadjusted ß 2.8%; 95% CI 1.3 to 4.4) and VF-sudden cardiac arrests (27.5%, 29.8%, 37.9%, 36.6%; unadjusted ß 3.5%; 95% CI 1.4 to 5.6), but not for asystole-sudden cardiac arrests (1.7%, 1.6%, 4.0%, 2.4%; unadjusted ß 0.3%; 95% CI, -0.4 to 1.1). Enhancements in the emergency medical services system's pulseless electrical activity-sudden cardiac arrest management were temporally associated with the increasing pulseless electrical activity survival rates. CONCLUSIONS: Over a 16-year period, the incidence of VF/ventricular tachycardia decreased over time, but pulseless electrical activity incidence remained stable. Survival from both VF-sudden cardiac arrests and pulseless electrical activity-sudden cardiac arrests increased over time with a more than 2-fold increase for pulseless electrical activity-sudden cardiac arrests.

Survival by time-to-administration of amiodarone, lidocaine, or placebo in shock-refractory out-of-hospital cardiac arrest.

BACKGROUND: Amiodarone and lidocaine have not been shown to have a clear survival benefit compared to placebo for out-of-hospital cardiac arrest (OHCA). However, randomized trials may have been impacted by delayed administration of the study drugs. We sought to evaluate how timing from emergency medical services (EMS) arrival on scene to drug administration affects the efficacy of amiodarone and lidocaine compared to placebo. METHOD: This is a secondary analysis of the 10-site, 55-EMS-agency double-blind randomized controlled amiodarone, lidocaine, or placebo in OHCA study. We included patients with initial shockable rhythms who received the study drugs of amiodarone, lidocaine, or placebo before achieving return of spontaneous circulation. We performed logistic regression analyses evaluating survival to hospital discharge and secondary outcomes of survival to admission and functional survival (modified Rankin scale score ≤ 3). We evaluated the samples stratified by early (<8 min) and late administration groups (≥8 min). We compared outcomes for amiodarone and lidocaine compared to placebo and adjust for potential confounders. RESULTS: There were 2802 patients meeting inclusion criteria, with 879 (31.4%) in the early (<8 min) and 1923 (68.6%) in the late (≥8 min) groups. In the early group, patients receiving amiodarone, compared to placebo, had significantly higher survival to admission (62.0% vs. 48.5%, p = 0.001; adjusted OR [95% CI] 1.76 [1.24-2.50]), survival to discharge (37.1% vs. 28.0%, p = 0.021; 1.56 [1.07-2.29]), and functional survival (31.6% vs. 23.3%, p = 0.029; 1.55 [1.04-2.32]). There were no significant differences with early lidocaine compared to early placebo (p > 0.05). Patients in the late group who received amiodarone or lidocaine had no significant differences in outcomes at discharge compared to placebo (p > 0.05). CONCLUSIONS: The early administration of amiodarone, particularly within 8 min, is associated with greater survival to admission, survival to discharge, and functional survival compared to placebo in patients with an initial shockable rhythm.

Sudden cardiac arrest during the COVID-19 pandemic: A two-year prospective evaluation in a North American community.

BACKGROUND: Early during the coronavirus disease 2019 (COVID-19) pandemic, higher sudden cardiac arrest (SCA) incidence and lower survival rates were reported. However, ongoing effects on SCA during the evolving pandemic have not been evaluated. OBJECTIVE: The purpose of this study was to assess the impact of COVID-19 on SCA during 2 years of the pandemic. METHODS: In a prospective study of Ventura County, California (2020 population 843,843; 44.1% Hispanic), we compared SCA incidence and outcomes during the first 2 years of the COVID-19 pandemic to the prior 4 years. RESULTS: Of 2222 out-of-hospital SCA cases identified, 907 occurred during the pandemic (March 2020 to February 2022) and 1315 occurred prepandemic (March 2016 to February 2020). Overall age-standardized annual SCA incidence increased from 39 per 100,000 (95% confidence [CI] 37-41) prepandemic to 54 per 100,000 (95% CI 50-57; P <.001) during the pandemic. Among Hispanics, incidence increased by 77%, from 38 per 100,000 (95% CI 34-43) to 68 per 100,000 (95% CI 60-76; P <.001). Among non-Hispanics, incidence increased by 26%, from 39 per 100,000 (95% CI 37-42; P <.001) to 50 per 100,000 (95% CI 46-54). SCA incidence rates closely tracked COVID-19 infection rates. During the pandemic, SCA survival was significantly reduced (15% to 10%; P <.001), and Hispanics were less likely than non-Hispanics to receive bystander cardiopulmonary resuscitation (45% vs 55%; P = .005) and to present with shockable rhythm (15% vs 24%; P = .003). CONCLUSION: Overall SCA rates remained consistently higher and survival outcomes consistently lower, with exaggerated effects during COVID infection peaks. This longer evaluation uncovered higher increases in SCA incidence among Hispanics, with worse resuscitation profiles. Potential ethnicity-specific barriers to acute SCA care warrant urgent evaluation and intervention.

Sudden Cardiac Arrest During Sports Activity in Older Adults.

BACKGROUND: Sports activity among older adults is rising, but there is a lack of community-based data on sports-related sudden cardiac arrest (SrSCA) in the elderly. OBJECTIVES: In this study, the authors investigated the prevalence and characteristics of SrSCA among subjects ≥65 years of age in a large U.S. METHODS: All out-of-hospital sudden cardiac arrests (SCAs) were prospectively ascertained in the Portland, Oregon, USA, metro area (2002-2017), and Ventura County, California, USA (2015-2021) (catchment population ∼1.85 million). Detailed information was obtained for SCA warning symptoms, circumstances, and lifetime clinical history. Subjects with SCA during or within 1 hour of cessation of sports activity were categorized as SrSCA. RESULTS: Of 4,078 SCAs among subjects ≥65 years of age, 77 were SrSCA (1.9%; 91% men). The crude annual SrSCA incidence among age ≥65 years was 3.29/100,000 in Portland and 2.10/100,000 in Ventura. The most common associated activities were cycling, gym activity, and running. SrSCA cases had lower burden of cardiovascular risk factors (P = 0.03) as well as comorbidities (P < 0.005) compared with non-SrSCA. Based on conservative estimates of community residents ≥65 years of age who participate in sports activity, the SrSCA incidence was 28.9/100,000 sport participation years and 18.4/100,000 sport participation years in Portland and Ventura, respectively. Crude survival to hospital discharge rate was higher in SrSCA, but the difference was nonsignificant after adjustment for confounding factors. CONCLUSIONS: Among free-living community residents age ≥65 years, SrSCA is uncommon, predominantly occurs in men, and is associated with lower disease burden than non-SrSCA. These results suggest that the risk of SrSCA is low, and probably outweighed by the high benefit of exercise.

Utilization and Effect of Direct Medical Oversight during Out-of-Hospital Cardiac Arrest.

STUDY OBJECTIVE: Direct medical oversight (DMO), where emergency medical services (EMS) clinicians contact a physician for real-time medical direction, is used by many EMS systems across the United States. Our objective was to characterize the recommendations made by DMO during out-of-hospital cardiac arrests (OHCA) and to determine their effect on EMS transport decisions and patient outcomes. METHODS: This is a secondary analysis of DMO call recordings from OHCA cases in the Portland, Oregon metropolitan area from January 1, 2018 to February 28, 2021. Data extracted from the audio recordings were linked to OHCA cases in the Portland Cardiac Arrest Epidemiologic Registry (PDX Epistry). The primary outcomes are recommendations made by DMO: transport, continued field resuscitation, or termination of resuscitation (TOR). Secondary outcomes include EMS transport decisions, survival to hospital admission, and survival to hospital discharge. We used descriptive statistics, unpaired t-tests, and chi-square tests as appropriate for data analysis. RESULTS: There were 239 OHCA cases for which DMO was contacted by EMS. The median time from EMS arrival to DMO contact was 25.6 min, and EMS requested TOR for 72.0% of patients. Compared to patients where EMS requested further treatment advice, patients for whom EMS requested TOR had poor prognostic signs including older age, asystole as an initial rhythm, and lower rates of transient return of spontaneous circulation prior to DMO call compared with cases where EMS did not request TOR. DMO recommended transport, continued field resuscitation, or TOR in 21.8%, 18.0%, and 60.2% of patients, respectively. Of the 239 patients, 59 (24.7%) were ultimately transported by EMS to the hospital, 14 (5.9%) survived to admission, and only 1 patient (0.4%) survived to hospital discharge and had an acceptable neurologic outcome (Cerebral Performance Category score of 2). CONCLUSIONS: Patients for whom EMS contacts DMO for further treatment advice or requesting field TOR after prolonged OHCA resuscitation have poor outcomes, even when DMO recommends transport or further resuscitation, and may represent opportunities to reduce unnecessary DMO contact or patient transports. More research is needed to determine which OHCA patients benefit from DMO contact.

A panel of blood biomarkers unique to sudden cardiac arrest.

BACKGROUND: The identification of circulating biomarkers specific for sudden cardiac arrest (SCA) could enhance risk prediction. Of particular interest are biomarkers specific to SCA, independent of coronary artery disease (CAD). OBJECTIVE: The purpose of this study was to identify biomarkers of SCA obtained close to the SCA event. METHODS: Twenty cases (survivors of SCA) and 40 age- and sex-matched controls were compared, with a replication analysis of 29 cases matched to 57 controls. A secondary analysis compared 20 SCA cases to 20 controls with CAD. Blood samples were obtained from SCA survivors at a median of 11 months after the SCA event. Proteins were analyzed on a mass spectrometer using data-independent acquisition; a subset of cytokines were analyzed using immunoassays; and 1153 lipids (13 classes) were analyzed. A false discovery rate P value of <.05 identified associated proteins. RESULTS: Patients had a mean age of 58 years (range 25-87 years), and 70% were male. A total of 26 protein biomarkers associated with SCA when cases were compared with controls, of which 20 differentiated SCA from CAD. The replication analysis identified 8 of 26 biomarkers, of which 6 were not overlapping with CAD. The top identified biological processes involved the extracellular matrix, coagulation cascades, and platelet activation. Lipids in the lysophosphatidylcholine class were implicated in SCA through the CAD pathway. CONCLUSION: We identified a panel of novel blood biomarkers specifically associated with SCA, including several that may be involved outside the CAD pathway. These biomarkers could have mechanistic significance and the potential to enhance clinical prediction of SCA.