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Background Use of oral contraceptives (OCs) may modulate the clinical course of women with congenital long QT syndrome (LQTS). The safety of OC use by sex hormone content has not been assessed in women with LQTS. Objective We aimed to evaluate the association of OCs with the risk of cardiac events (CEs) in women with LQTS. Methods Beginning in 2010, information on menarche onset, OC use, pregnancy, and menopause were obtained from women enrolled in the Rochester LQTS Registry. Type of OC was categorized as progestin-only, estrogen-only, or combined (estrogen/progestin). Andersen-Gill multivariate modeling was used to evaluate the association of time-dependent OC use with the burden of CE (total number of syncope, aborted cardiac arrest, and LQTS-related sudden cardiac death) from menarche onset through 40 years. Findings were adjusted for genotype, corrected QT duration, and time-dependent β-blocker therapy. Results A total of 1659 women with LQTS followed through March 2021, of whom 370 (22%) were treated with an OC. During a cumulative follow-up of 35,797 years, there were a total of 2027 CE. Multivariate analysis showed that progestin-only OC was associated with a pronounced 2.8-fold (P = .01) increased risk of CEs in women who did not receive β-blocker therapy, while β-blockers were highly protective during progestin-only OC treatment (hazard ratio 0.22; P = .01; P = .006 for β-blocker-by-OC interaction). The risk associated with OC use without concomitant β-blocker treatment was pronounced in women with LQTS type 2. Conclusion Our findings suggest that progestin-only OC should not be administered in women with LQTS without concomitant β-blocker therapy. OCs should be used with caution in women with LQTS type 2.

Importance Emergency research is challenging to do well as it involves time sensitive interventions in unstable patients. There is limited time to obtain informed consent from the patient or their legally authorized representative (LAR). Such research is permitted under exception from informed consent (EFIC) if specific criteria are met, including notification after enrollment. Some question whether the risks of EFIC outweighs its benefits. To date, there is limited empiric information about time to notification (TTN) and rates of withdrawal in such trials. Objective To describe variation in TTN and rates of withdrawal among that patients enrolled in EFIC trials over a twelve-year period. Design We performed post hoc descriptive analyses of data from five trials conducted under EFIC. Setting Emergency medical services and receiving hospitals participating in the Resuscitation Outcomes Consortium in the United States and Canada. Participants Patients with out-of-hospital cardiac arrest or life-threatening traumatic injury. Exposures Notification strategies were specified at each site before initiation of enrollment by a local institutional review board. We monitored TTN within each site centrally throughout each study’s enrollment period. Outcomes TTN was defined as time from randomization to first-reported notification of patient or LAR of enrollment. Withdrawal was defined as patient or LAR opt out of ongoing participation at the time of notification. Results Of 35,442 patients enrolled in five trials, 33,805 had cardiac arrest; and 1636 had traumatic injury. TTN varied overall and by patient outcome. Among those with cardiac arrest, TTN ranged from median (5%ile, 95%ile) of 6 (1,27) days to 28 (2, 53) days across sites. 0.3% of notified patients with cardiac arrest withdrew. Among those with traumatic injury, TTN ranged from 0 (0, 5) days to 36 (5, 68) days across sites. 7.7% of notified patients with traumatic injury withdrew. Conclusions and Relevance There is large variation in TTN in trials conducted under EFIC for emergency research. This may be due to several factors. It may or may not be modifiable. Overall rates of withdrawal are low, which suggests current practices related to EFIC are acceptable to those who have participated in emergency research.

BACKGROUND: A large, randomized trial showed no significant difference in survival to discharge between cardiopulmonary resuscitation (CPR) strategies of 30 compressions with pause for 2 ventilations per cycle (30:2) and continuous chest compression with asynchronous ventilations (CCC). Data from the same trial suggested that adherence to the intended CPR strategy was associated with significantly greater survival. We sought to determine the adherence rate with intended strategy and then explore the association of adherence with survival to discharge in the Resuscitation Outcomes Consortium (ROC). METHODS: This secondary analysis of data from the ROC included three interventional trials and a prospective registry. We modified an automated software algorithm that classified care as 30:2 or CCC before intubation based on compression segment length (defined as the elapsed time from start of compressions to subsequent pause of ≥2 seconds), number of pauses per minute ≥2 seconds in length and chest compression fraction. Intended CPR strategy for individual agencies was based on study randomization (during trial phase) or local standard of care (during registry phase). We defined CPR delivered as adherent when its classification matched the intended strategy. We characterized adherence with intended strategy across trial and registry periods. We examined its association with survival to hospital discharge using multivariate logistic regression after adjustment for Utstein and other potential confounders. Effect modification with intended strategy was assessed through a multiplicative interaction term. RESULTS: Included were 26,810 adults with out of hospital cardiac arrest, of which 10,942 had an intended strategy of 30:2 and 15,868 an intended strategy of CCC. The automated algorithm classified 12,276 cases as CCC, 7,037 as 30:2 and left 7,497 as unclassified. Adherence to intended strategy was 54.4%; this differed by intended strategy (58.6% for CCC vs 48.3% for 30:2). Overall adherence was less during the registry phase as compared to during the trial phase(s). The association between adherence and survival was modified by treatment arm (CCC OR: 0.72, 95% CI: 0.64–0.81 vs 30:2 OR: 1.05, 95% CI: 0.90–1.22; interaction p-value

Objectives Patients resuscitated from an out-of-hospital circulatory arrest (OHCA) commonly present without an obvious etiology. We assessed the diagnostic capability and safety of early head-to-pelvis computed tomography (CT) imaging in such patients. Methods From November 2015 to February 2018, we enrolled 104 patients resuscitated from OHCA without obvious cause (idiopathic OHCA) to an early sudden-death CT (SDCT) scan protocol within 6 h of hospital arrival. The SDCT protocol included a noncontrast CT head, an electrocardiogram-gated cardiac and thoracic CT angiogram, and a nongated venous-phase abdominopelvic CT angiogram. Patients needing urgent cardiac catheterization or hemodynamically unable to tolerate SDCT were excluded. Cardiac CT analyses were blinded, but other SDCT findings were clinically available. Primary endpoints were the number of OHCA causes identified by SDCT compared to the adjudicated cause and critical diagnoses identified by SDCT, including resuscitation complications. Safety endpoints were acute kidney injury (AKI) and inappropriate treatments based on SDCT findings. Acute coronary syndrome was the presumed etiology if any major coronary artery had a >50% stenosis without another OHCA cause. Results SDCT scans occurred within 1.9 ± 1.0 h of hospital arrival and identified 39% (41/104) of all OHCA causes and 95% (39/41) of causes potentially identifiable by SDCT. Critical findings were identified by SDCT in 98% (43/44) of patients that included potentially life-threatening resuscitation complications of liver or spleen laceration (n = 6); pneumothorax or thoracic organ laceration (n = 8); and mediastinal, pericardial, or vascular hemorrhage (n = 3). SDCT exclusively identified 13 (13%) OHCA causes that would otherwise not be identified without SDCT imaging. No inappropriate treatments resulted from SDCT findings. AKI was common (28%) but only one (1%) patient required new dialysis. Conclusions This observational cohort study suggests that early SDCT scanning is safe, can expedite the diagnosis of potential causes, and can meaningfully change clinical management after idiopathic OHCA.

We investigated the risk of coronavirus disease (COVID-19)­ patients transmitting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to emergency medical service (EMS) providers, stratified by aerosol-generating procedures (AGP), in King County, Washington, USA, during February 16–July 31, 2020. We conducted a retrospective cohort investigation using a statewide COVID-19 registry and identified 1,115 encounters, 182 with ≥1 AGP. Overall, COVID-19 incidence among EMS personnel was 0.57 infections/10,000 person-days. Incidence per 10,000 person-days did not differ whether or not infection was attributed to a COVID-19 patient encounter (0.28 vs. 0.59; p>0.05). The 1 case attributed to a COVID-19 patient encounter occurred within an at-risk period and involved an AGP. We observed a very low risk for COVID-19 infection attributable to patient encounters among EMS first responders, supporting clinical strategies that maintain established practices for treating patients in emergency conditions.

Background Emergency Medical Services (EMS) are often involved in end-of-life circumstances, yet little is known about how EMS interfaces with advance directives to forego unwanted resuscitation (Do Not Attempt Resuscitation (DNAR)). We evaluated the frequency of these directives involved in out-of-hospital cardiac arrest (OHCA) and how they impact care. Methods We conducted a cohort investigation of adult, EMS-attended OHCA from January 1 to December 31, 2018 in King County, WA. DNAR status was ascertained from dispatch, EMS, and hospital records. Resuscitation was classified according to DNAR status: not initiated, initiated but ceased due to the DNAR, or full efforts. Results Of 3152 EMS-attended OHCA, 314 (9.9%) had a DNAR directive. DNAR was present more often among those for whom EMS did not attempt resuscitation compared to when EMS provided some resuscitation (13.2% [212/1611] vs 6.6% [101/1541], (p Of those receiving resuscitation with a DNAR directive (n = 101), the DNAR was presented on average 6 min following EMS arrival. A total of 82% (n = 83) had EMS efforts ceased as a consequence of the DNAR while 18% (n = 18) received full efforts. Full-efforts compared to ceased-efforts were more likely to have a witnessed arrest (67% vs 36%), present with shockable rhythm (22% vs 6%), achieve spontaneous circulation by time of DNAR presentation (50% vs 4%), and have family contradict the DNAR (33% vs 0%) (p Conclusions Approximately 10% of EMS-attended OHCA involved DNAR. EMS typically fulfilled this end-of-life preference, though wishes were challenged by delayed directive presentation or contradictory family wishes.

Background The Utstein population is defined by non-traumatic, bystander-witnessed out-of-hospital cardiac arrest (OHCA) presenting with ventricular fibrillation (VF). It is used to compare resuscitation performance across emergency medical services (EMS) systems. We hypothesized a system-specific survival correlation between the current Utstein population and other VF populations defined by unwitnessed VF OHCA and VF OHCA after EMS arrival (EMS-witnessed). Expanding performance metrics to this more comprehensive population would make the Utstein definition more representative of the actual community burden and response to VF OHCA. Methods We performed a cohort investigation of all non-traumatic, VF OHCA in the Cardiac Arrest Registry to Enhance Survival from 1/1/2013-12/31/2018 among EMS agencies that treated > = 100 VF OHCA. We evaluated sample size and survival with the addition of the new VF populations. We used Pearson coefficient to assess whether there was a correlation of agency-specific survival outcomes between the current Utstein population and unwitnessed and EMS-witnessed VF OHCA. Results A total of 107 EMS agencies treated 38,836 VF arrests: 22,918 current Utstein, 11,297 unwitnessed VF, and 4621 EMS-witnessed VF OHCA. Overall, survival was 29.8% (11,567/38,836): 33.9% (7774/22,918) among current Utstein, 17.2% (1942/11,297) among unwitnessed VF, and 40.1% (1851/4621) among EMS-witnessed VF. For agency-specific survival outcome, the Pearson correlation was 0.52 between the current Utstein population versus combined unwitnessed and EMS-witnessed groups. For survival with Cerebral Performance Category 1–2, the Pearson correlation was 0.61. Conclusion Expanding the Utstein population to include unwitnessed and EMS-witnessed VF OHCA achieves a simpler, more inclusive case definition that minimizes variability in case determination and increases the number of survivors and eligible population by ∼50%, while still achieving a distinguishing metric of system-specific performance.

To test the diagnostic accuracy of ECG-gated coronary computed tomography angiography (CCTA) to detect coronary artery disease (CAD) among survivors of out-of-hospital circulatory arrest (OHCA).We prospectively studied head-to-pelvis computed tomography (CT) scanning (6 h from hospital arrival) in OHCA survivors. This sub-study tested the primary outcome of CCTA diagnostic accuracy to identify obstructive CAD (≥50% stenosis) compared to clinically-ordered invasive coronary angiography. Patients were not optimized with beta receptor blockade or nitroglycerin. Secondary analyses included CCTA accuracy for CAD in major coronary arteries, obstructive disease at ≥70% stenosis threshold, and where non-evaluable CCTA segments were considered either obstructive or non-obstructive.Of the 104 enrolled OHCA survivors, 28 (27%) received both CT and invasive angiography in this sub study. All CCTA studies were evaluable although 49/346 (14%) individual coronary segments were unevaluable, primarily due to being too small to evaluate (65%). Patient-level diagnostic accuracy for the ≥50% stenosis threshold was high at 0.93 (95% CI 0.77-0.98) with a specificity of 1.0 (95% CI 0.8-1.0), sensitivity of 0.85 (95%CI 0.58-0.96), negative predictive value of 0.88 (95% CI 0.66-0.97) and positive predictive value of 1.0 (0.74-1.0). When non-evaluable segments were considered obstructive, the sensitivity rose to 0.92 (95% CI 0.67-0.99) with lower specificity of 0.27 (95% CI 0.11-0.52).Early CCTA of OHCA survivors has high diagnostic accuracy to detect obstructive coronary artery disease. However, the number of non-diagnostic coronary segments is high suggesting further CCTA refinement is needed, such as the pre-CCTA use of nitroglycerin.NCT03111043 https://clinicaltrials.gov/ct2/show/record/NCT03111043.

Objective: Interruptions in chest compressions during treatment of out-of-hospital cardiac arrest are associated with lower likelihood of successful resuscitation. Real-time automated detection of chest compressions may improve CPR administration during resuscitation, and could facilitate application of next-generation ECG algorithms that employ different parameters depending on compression state. In contrast to accelerometer sensors, transthoracic impedance (TTI) is commonly acquired by defibrillators. We sought to develop and evaluate the performance of a TTI-based algorithm to automatically detect chest compressions. Methods: Five-second TTI segments were collected from patients with out-of-hospital cardiac arrest treated by one of four defibrillator models. Segments with and without chest compressions were collected prior to each of the first four defibrillation shocks (when available) from each case. Patients were divided randomly into 40% training and 60% validation groups. From the training segments, we identified spectral and time-domain features of the TTI associated with compressions. We used logistic regression to predict compression state from these features. Performance was measured by sensitivity and specificity in the validation set. The relationship between performance and TTI segment length was also evaluated. Results: The algorithm was trained using 1859 segments from 460 training patients. Validation sensitivity and specificity were >98% using 2727 segments from 691 validation patients. Validation performance was significantly reduced using segments shorter than 3.2 s. Conclusions: A novel method can reliably detect the presence of chest compressions using TTI. These results suggest potential to provide real-time feedback in order to improve CPR performance or facilitate next-generation ECG rhythm algorithms during resuscitation.

Resuscitation requires CPR interruptions every 2 min to assess rhythm and pulse status. We developed a method to predict real-time pulse status in organized rhythm ECG segments with and without CPR artifact.The study cohort included patients who received attempted resuscitation following ventricular fibrillation arrest. Using audio-supplemented defibrillator recordings, we annotated CPR, rhythm, and pulse status at each two-minute rhythm/pulse check. Paired ECG segments with and without CPR were extracted at each rhythm/pulse check. Using one-third of cases for training and two-thirds for validation, we developed three wavelet-based ECG features and combined them with a logistic model to predict pulse status. Predictive performances of each individual ECG feature and the combined logistic model were measured by the area under the receiver operator characteristic curve (AUC) in the validation cases with and without CPR.There were 238 cases and 911 ECG segment pairs. Among 319 organized rhythm segments in the validation set, AUC for pulse prediction during CPR ranged from 0.67 to 0.79 for the individual ECG features. The logistic model was more predictive than any individual feature (AUC 0.84, 95% CI 0.80-0.89, p 0.05 for each comparison) and performed similarly regardless of CPR (p = 0.2 for difference).ECG features extracted by wavelet analysis predicted pulse status with moderate accuracy among organized rhythm segments with and without CPR. Further study is required to understand how real-time pulse prediction during CPR could help direct care while limiting CPR interruption.

Background: Antiarrhythmic drugs have not proven to significantly improve overall survival after out-of-hospital cardiac arrest from shock-refractory ventricular fibrillation/pulseless ventricular tachycardia. How this might be influenced by the route of drug administration is not known. Methods: In this prespecified analysis of a randomized, placebo-controlled clinical trial, we compared the differences in survival to hospital discharge in adults with shock-refractory ventricular fibrillation/pulseless ventricular tachycardia out-of-hospital cardiac arrest who were randomly assigned by emergency medical services personnel to an antiarrhythmic drug versus placebo in the ALPS trial (Resuscitation Outcomes Consortium Amiodarone, Lidocaine or Placebo Study), when stratified by the intravenous versus intraosseous route of administration. Results: Of 3019 randomly assigned patients with a known vascular access site, 2358 received ALPS drugs intravenously and 661 patients by the intraosseous route. Intraosseous and intravenous groups differed in sex, time-to-emergency medical services arrival, and some cardiopulmonary resuscitation characteristics, but were similar in others, including time-to-intravenous/intrasosseous drug receipt. Overall hospital discharge survival was 23%. In comparison with placebo, discharge survival was significantly higher in recipients of intravenous amiodarone (adjusted risk ratio, 1.26 [95% CI, 1.06–1.50]; adjusted absolute survival difference, 5.5% [95% CI, 1.5–9.5]) and intravenous lidocaine (adjusted risk ratio, 1.21 [95% CI, 1.02–1.45]; adjusted absolute survival difference, 4.7% [95% CI, 0.7–8.8]); but not in recipients of intraosseous amiodarone (adjusted risk ratio, 0.94 [95% CI, 0.66–1.32]) or intraosseous lidocaine (adjusted risk ratio, 1.03 [95% CI, 0.74–1.44]). Survival to hospital admission also increased significantly when drugs were given intravenously but not intraosseously, and favored improved neurological outcome at discharge. There were no outcome differences between intravenous and intraosseous placebo, indicating that the access route itself did not demarcate patients with poor prognosis. The study was underpowered to assess intravenous/intraosseous drug interactions, which were not statistically significant. Conclusions: We found no significant effect modification by drug administration route for amiodarone or lidocaine in comparison with placebo during out-of-hospital cardiac arrest. However, point estimates for the effects of both drugs in comparison with placebo were significantly greater for the intravenous than for the intraosseous route across virtually all outcomes and beneficial only for the intravenous route. Given that the study was underpowered to statistically assess interactions, these findings signal the potential importance of the drug administration route during resuscitation that merits further investigation.

Background Air travel affords an opportunity to evaluate resuscitation performance and outcome in a setting where automated external defibrillators (AEDs) are readily available. Methods and Results The study cohort included people aged ≥18 years with out of hospital cardiac arrest (OHCA) traveling through Seattle‐Tacoma International Airport between January 1, 2004 and December 31, 2019 treated by emergency medical services (EMS). The primary outcomes were pre‐EMS therapies (cardiopulmonary resuscitation, application of AED), return of spontaneous circulation, and survival to hospital discharge. Over the 16‐year study period, there were 143 OHCA occurring before EMS arrival, 34 (24%) on‐plane and 109 (76%) off‐plane. Cardiac etiology (81%) was the most common mechanism of arrest. The majority of arrests were bystander‐witnessed and presented with a shockable rhythm; these characteristics were more common in off‐plane OHCA compared with on‐plane (witnessed: 89% versus 74% and shockable: 72% versus 50%). Pre‐EMS therapies including cardiopulmonary resuscitation and AED application were common regardless of arrest location. Compared with on‐plane OHCA, off‐plane OHCA was associated with greater rates of return of spontaneous circulation (68% versus 44%) and 3‐fold higher rate of survival to hospital discharge (44% versus 15%). All survivors of on‐plane OHCA had AED application with defibrillation before EMS arrival. Conclusions When applied to air travel volumes, we estimate 350 air travel‐associated OHCA occur in the United States and 2000 OHCA worldwide each year, nearly a quarter of which happen on‐plane. These events are survivable when early arrest interventions including rapid arrest recognition, AED application, and CPR are deployed.

Background We aimed to provide personalized risk estimates for cardiac events (CEs) and life‐threatening events in women with either type 1 or type 2 long QT. Methods and Results The prognostic model was derived from the Rochester Long QT Syndrome Registry, comprising 767 women with type 1 long QT (n=404) and type 2 long QT (n=363) from age 15 through 60 years. The risk prediction model included the following variables: genotype/mutation location, QTc‐specific thresholds, history of syncope, and β‐blocker therapy. A model was developed with the end point of CEs (syncope, aborted cardiac arrest, or long QT syndrome–related sudden cardiac death), and was applied with the end point of life‐threatening events (aborted cardiac arrest, sudden cardiac death, or appropriate defibrillator shocks). External validation was performed with data from the Mayo Clinic Genetic Heart Rhythm Clinic (N=467; type 1 long QT [n=286] and type 2 long QT [n=181]). The cumulative follow‐up duration among the 767 enrolled women was 22 243 patient‐years, during which 323 patients (42%) experienced ≥1 CE. Based on genotype‐phenotype data, we identified 3 risk groups with 10‐year projected rates of CEs ranging from 15%, 29%, to 51%. The corresponding 10‐year projected rates of life‐threatening events were 2%, 5%, and 14%. C statistics for the prediction model for the 2 respective end points were 0.68 (95% CI 0.65–0.71) and 0.71 (95% CI 0.66–0.76). Corresponding C statistics for the model in the external validation Mayo Clinic cohort were 0.65 (95% CI 0.60–0.70) and 0.77 (95% CI 0.70–0.84). Conclusions This is the first risk prediction model that provides absolute risk estimates for CEs and life‐threatening events in women with type 1 or type 2 long QT based on personalized genotype‐phenotype data. The projected risk estimates can be used to guide female‐specific management in long QT syndrome.

Background: Anoxic brain injury is a common mode of death following out-of-hospital cardiac arrest (OHCA). We assessed the course of regional cerebral oxygen saturation (rSO2) at the outset and during first responder resuscitation to understand its relationship with return of spontaneous circulation (ROSC) and functional survival. Methods: We undertook a prospective observational investigation of adult OHCA patients treated by a first-responder EMS agency in King County, WA. Cerebral oximetry was performed using the SenSmart® Model X-100 Universal Oximetry System (Nonin Medical, Inc). We determined cerebral oximetry rSO2 overall and stratified according to ROSC and favorable survival status defined by Cerebral Performance Category (CPC) of 1-2. Results: Among the 59 OHCA cases enrolled, 47% (n = 28) achieved ROSC and 14% (n = 8) survived with CPC 1-2. On average, initial rSO2 cerebral oximetry was 41% and was not different at the outset according to return of spontaneous circulation (ROSC) or survival status. Within 5 minutes of first responder resuscitation, those who would subsequently achieve ROSC had a higher rSO2 than those who would not achieve ROSC (51% vs. 43%, p = 0.03). Among patients who achieved ROSC, those who would survive with CPC 1-2 had a higher rSO2 cerebral oximetry following ROSC than nonsurvivors (74% vs. 60%, p = 0.04 at 5 minutes post ROSC), a difference that was not evident in the minutes prior to ROSC (55% vs. 51% at 3 minutes prior to ROSC, p = 0.5). Conclusion: In this observational study, where first responders applied cerebral oximetry, higher rSO2 during the course of care predicted ROSC among all patients and predicted favorable survival among those who achieved ROSC. Future investigation should evaluate whether and how treatments might modify rSO2 and in turn may influence prognosis.

Advances in resuscitation following out-of-hospital cardiac arrest (OHCA) provide an opportunity to improve public health. This review reflects on past developments, present status, and future possibilities using the science-education-implementation framework of the Utstein Formula and the clinical framework of the links in the chain of survival. With the discovery of CPR and defibrillation in the mid 20th century, resuscitation developed a scientific construct for progress. Systems of emergency community response provided operational efficiency to treat OHCA. Contemporary resuscitation involves integrated interventions in the chain of survival: early recognition, early CPR, early defibrillation, expert and timely advanced life support and hospital care, and multidimensional rehabilitation. Implementation of scientific advances is especially challenging given the unexpected nature of OHCA, the need for time-sensitive interventions, and the substantial collective of stakeholders involved in the chain of survival. Systematic measurement provides the foundation to evaluate performance and guide implementation initiatives. For many systems, telecommunicator CPR and high-performance CPR by emergency professionals are accessible, near-term programs to improve OHCA outcome. Smart technologies that activate, coordinate, and/or coach community "volunteers" to accelerate early CPR and defibrillation have conceptual promise, though robust implementation has been achieved by only a handful of systems. Longer-term strategies may leverage technology to develop a high-fidelity "life-detector" or engineer and disseminate a specialized consumer defibrillator designed to bridge care until arrival of professional response.

Thyroid hormones have long been known to have a range of effects on the cardiovascular system. However, significant knowledge gaps exist concerning the precise molecular and biochemical mechanisms governing these effects and the optimal strategies for management of abnormalities in thyroid function in patients with and without preexisting cardiovascular disease. In September 2017, the National Heart, Lung, and Blood Institute convened a Working Group with the goal of developing priorities for future scientific research relating thyroid dysfunction to the progression of cardiovascular disease. The Working Group reviewed and discussed the roles of normal thyroid physiology, the consequences of thyroid dysfunction, and the effects of therapy in 3 cardiovascular areas: cardiac electrophysiology and arrhythmias, the vasculature and atherosclerosis, and the myocardium and heart failure. This report describes the current state of the field, outlines barriers and challenges to progress, and proposes research opportunities to advance the field, including strategies for leveraging novel approaches using omics and big data. The Working Group recommended research in 3 broad areas: (1) investigation into the fundamental biology relating thyroid dysfunction to the development of cardiovascular disease and into the identification of novel biomarkers of thyroid hormone action in cardiovascular tissues; (2) studies that define subgroups of patients with thyroid dysfunction amenable to specific preventive strategies and interventional therapies related to cardiovascular disease; and (3) clinical trials focused on improvement in cardiovascular performance and cardiovascular outcomes through treatment with thyroid hormone or thyromimetic drugs.

Background\ud \ud Dispatcher-assisted cardiopulmonary resuscitation (DA-CPR) has been reported in individual studies to significantly increase the rate of bystander CPR and survival from cardiac arrest.\ud \ud Methods \ud \ud We undertook a systematic review and meta-analysis to evaluate the impact of DA-CPR programs on key clinical outcomes following out-of-hospital cardiac arrest. We searched the PubMED, EMBASE, CINAHL, ERIC and Cochrane Central Register of Controlled Trials databases from inception until July 2018. Eligible studies compared systems with and without dispatcher-assisted CPR programs. Included studies were divided into three groups: comparison of outcomes in systems providing DA-CPR; comparison of cases where DA-CPR was provided to cases where bystander CPR was ongoing, and DA-CPR was not provided; and comparison of cases where DA-CPR was provided to cases where no bystander CPR was provided (patient level comparisons). The GRADE system was used to assess certainty of evidence at an outcome level. We used random-effects models to produce summary effect sizes across all outcomes.\ud \ud Results \ud \ud Of 5,531 citations screened, 33 studies were eligible for inclusion. All included studies were observational. Evidence certainty across all outcomes was assessed as low or very low. In system-level and patient-level comparisons, the provision of DA-CPR compared with no DA-CPR was consistently associated with improved outcome across all analyses. Comparison of DA-CPR to bystander CPR produced conflicting results. Findings were consistent across sensitivity analyses and the pediatric sub-group.\ud \ud Conclusion \ud \ud These results support the recommendation that dispatchers provide CPR instructions to callers for adults and children with suspected OHCA.\ud

An increasing proportion of patients with OHCA present with non-shockable rhythms, among whom the benefit from AED application is not known.We performed a retrospective analysis of adults with non-traumatic, public, bystander-witnessed, non-shockable OHCA occurring between 2005-2015 at 9 locations participating in the Resuscitation Outcomes Consortium. Non-shockable arrest was defined as when no shock was administered by a bystander applied AED and confirmed by the initial rhythm on EMS arrival. Outcomes were compared between patients with non-shockable OHCA in whom a bystander AED was or was not applied.Among 2809 patients with non-shockable public, witnessed OHCA, 8.4% had an AED applied. CPR was more often performed in the AED-applied group (99% vs. 51% of patients, p 0.001). Among patients in whom an AED was not applied, 39.8% had any pre-hospital ROSC, 29.6% had a pulse at ED arrival and 11.1% survived to hospital discharge compared to 44.1%, 29.6% and 9.7%, respectively with AED application. After adjustment for the Utstein variables excluding bystander CPR, the OR for survival to hospital discharge for AED application was 0.90 (95% CI:0.57-1.42); when adjusted for the higher frequency of CPR in the AED group the OR was 0.92 (95% CI:0.57-1.47).The application of an AED in non-shockable public witnessed OHCA was associated with a higher frequency of bystander CPR. The probabilities of pre-hospital ROSC, pulse at ED arrival, and survival to hospital discharge were not altered by the application of an AED.

Aim To review data for non-invasive imaging in the diagnosis of non-traumatic out-of-hospital cardiac arrest (OHCA). Data sources We searched MEDLINE, EMBASE, Cochrane library, and clinicaltrials.gov databases from inception to January 2017 for studies utilizing non-invasive imaging to identify potential causes of OHCA [computed tomography (CT), ultrasound including echocardiography, and magnetic resonance (MRI)]. Study selection Inclusion criteria were the following: (1) randomized control trials, cohort studies or observational studies; (2) contained a population ≥18 years old with non-traumatic OHCA who underwent diagnostic imaging with CT, MRI, echocardiography, or abdominal ultrasound; (3) imaging was obtained for diagnostic purposes; (4) patients were alive or were undergoing cardiopulmonary resuscitation at the time of imaging; (5) contained potential causes of OHCA. Endpoints studied were the number of potential OHCA causes identified, diagnostic accuracy measures (sensitivity, specificity, positive and negative predictive values), and diagnostic utility (number of imaging findings with reported changes in clinical management). Results Of the total 5722 studies identified, 17 (0.3%) met inclusion criteria. The majority of studies assessed the utility of CT in OHCA (n = 10), and potential causes of OHCA were found in 8–54% of patients following head, abdominal and/or chest CT. Only 1/17 (6%) studies reported diagnostic accuracy measures, and 9/17 (53%) studies included a time to imaging criteria within 24 h. Conclusion Although non-invasive imaging is commonly performed in patients after OHCA, its diagnostic utility remains poorly characterized. Prospective studies are needed for appropriate imaging selection and their potential impact on treatment and outcome.

Out-of-hospital cardiac arrest (OHCA) causes brain injury. Functional status of survivors at hospital discharge is a core resuscitation measure, frequently using the Cerebral Performance Category (CPC) or modified Rankin Scale (mRS). Which scale better predicts long-term survival following OHCA is not known.We evaluated long-term survival after hospital discharge in a retrospective cohort of persons resuscitated from OHCA in King County, WA from 2007 to 2015. Patients were independently assessed at discharge using both scales, leveraging the regional quality improvement registry, which records the 5-level CPC, and concurrent research studies involving the Resuscitation Outcomes Consortium, which used the 7-level mRS, taken from information in the hospital record. The risk of mortality associated with CPC and mRS categories was estimated using Kaplan-Meier survival analysis and Cox proportional hazards regression.Among 878 eligible patients discharged alive, there were 358 deaths during 9118.5 person-years of follow-up. Overall 1, 5 and 10-year survival was 84.4%, 68.5%, and 53.7% and varied according to CPC and mRS (p0.01 per Kaplan-Meier). Compared to CPC-1, hazard ratio (HR) increased incrementally for CPC-2 = 1.33 (1.03-1.73), CPC-3 = 1.90 (1.37-2.65), and CPC-4 = 8.25 (5.63-12.10). Compared to mRS = 0, HR for mRS-1 = 1.02 (0.66-1.58), mRS-2 = 1.52 (1.00-2.32), mRS-3 = 1.41 (0.92-2.14), mRS-4 = 2.00 (1.37-2.97), and mRS-5 = 4.90 (3.23-7.44).In OHCA survivors, CPC and mRS scales both predicted long-term survival. However mRS 0-1 and 2-3 groups did not have distinct prognoses, suggesting that a consolidated mRS score may simplify capture of relevant prognostic information for survival predictions.

Importance Therapeutic delivery of sodium nitrite during resuscitation improved survival in animal models of cardiac arrest, but efficacy has not been evaluated in clinical trials in humans. Objective To determine whether parenteral administration of sodium nitrite given by paramedics during resuscitation for out-of-hospital cardiac arrest improved survival to hospital admission. Design, setting, and participants Double-blind, placebo-controlled, phase 2 randomized clinical trial including 1502 adults in King County, Washington, with out-of-hospital cardiac arrest from ventricular fibrillation or nonventricular fibrillation. Patients underwent resuscitation by paramedics and were enrolled between February 8, 2018, and August 19, 2019; follow-up and data abstraction were completed by December 31, 2019. Interventions Eligible patients with out-of-hospital cardiac arrest were randomized (1:1:1) to receive 45 mg of sodium nitrite (n = 500), 60 mg of sodium nitrite (n = 498), or placebo (n = 499), which was given via bolus injection by the paramedics as soon as possible during active resuscitation. Main outcomes and measures The primary outcome was survival to hospital admission and was evaluated with 1-sided hypothesis testing. The secondary outcomes included out-of-hospital variables (rate of return of spontaneous circulation, rate of rearrest, and use of norepinephrine to support blood pressure) and in-hospital variables (survival to hospital discharge; neurological outcomes at hospital discharge; cumulative survival to 24 hours, 48 hours, and 72 hours; and number of days in the intensive care unit). Results Among 1502 patients with out-of-hospital cardiac arrest who were randomized (mean age, 64 years [SD, 17 years]; 34% were women), 99% completed the trial. Overall, 205 patients (41%) in the 45 mg of sodium nitrite group and 212 patients (43%) in the 60 mg of sodium nitrite group compared with 218 patients (44%) in the placebo group survived to hospital admission; the mean difference for the 45-mg dose vs placebo was -2.9% (1-sided 95% CI, -8.0% to ∞; P = .82) and the mean difference for the 60-mg dose vs placebo was -1.3% (1-sided 95% CI, -6.5% to ∞; P = .66). None of the 7 prespecified secondary outcomes were significantly different, including survival to hospital discharge for 66 patients (13.2%) in the 45 mg of sodium nitrite group and 72 patients (14.5%) in the 60 mg of sodium nitrite group compared with 74 patients (14.9%) in the placebo group; the mean difference for the 45-mg dose vs placebo was -1.7% (2-sided 95% CI, -6.0% to 2.6%; P = .44) and the mean difference for the 60-mg dose vs placebo was -0.4% (2-sided 95% CI, -4.9% to 4.0%; P = .85). Conclusions and relevance Among patients with out-of-hospital cardiac arrest, administration of sodium nitrite, compared with placebo, did not significantly improve survival to hospital admission. These findings do not support the use of sodium nitrite during resuscitation from out-of-hospital cardiac arrest. Trial registration ClinicalTrials.gov Identifier: NCT03452917.

Key Points Question Can a machine learning model help medical dispatchers improve recognition of out-of-hospital cardiac arrest? Findings In this randomized clinical trial of 5242 emergency calls, a machine learning model listening to calls could alert the medical dispatchers in cases of suspected cardiac arrest. There was no significant improvement in recognition of out-of-hospital cardiac arrest during calls on which the model alerted dispatchers vs those on which it did not; however, the machine learning model had higher sensitivity that dispatchers alone. Meaning These findings suggest that while a machine learning model recognized a significantly greater number of out-of-hospital cardiac arrests than dispatchers alone, this did not translate into improved cardiac arrest recognition by dispatchers., This randomized clinical trial examines how a machine learning model trained to identify out-of-hospital cardiac arrest and alert dispatchers during emergency calls affected the recognition of and response to out-of-hospital cardiac arrests., Importance Emergency medical dispatchers fail to identify approximately 25% of cases of out-of-hospital cardiac arrest (OHCA), resulting in lost opportunities to save lives by initiating cardiopulmonary resuscitation. Objective To examine how a machine learning model trained to identify OHCA and alert dispatchers during emergency calls affected OHCA recognition and response. Design, Setting, and Participants This double-masked, 2-group, randomized clinical trial analyzed all calls to emergency number 112 (equivalent to 911) in Denmark. Calls were processed by a machine learning model using speech recognition software. The machine learning model assessed ongoing calls, and calls in which the model identified OHCA were randomized. The trial was performed at Copenhagen Emergency Medical Services, Denmark, between September 1, 2018, and December 31, 2019. Intervention Dispatchers in the intervention group were alerted when the machine learning model identified out-of-hospital cardiac arrest, and those in the control group followed normal protocols without alert. Main Outcomes and Measures The primary end point was the rate of dispatcher recognition of subsequently confirmed OHCA. Results A total of 169 049 emergency calls were examined, of which the machine learning model identified 5242 as suspected OHCA. Calls were randomized to control (2661 [50.8%]) or intervention (2581 [49.2%]) groups. Of these, 336 (12.6%) and 318 (12.3%), respectively, had confirmed OHCA. The mean (SD) age among of these 654 patients was 70 (16.1) years, and 419 of 627 patients (67.8%) with known gender were men. Dispatchers in the intervention group recognized 296 confirmed OHCA cases (93.1%) with machine learning assistance compared with 304 confirmed OHCA cases (90.5%) using standard protocols without machine learning assistance (P = .15). Machine learning alerts alone had a significantly higher sensitivity than dispatchers without alerts for confirmed OHCA (85.0% vs 77.5%; P

Introduction: Cardiac arrest resuscitation requires CPR interruption for ECG rhythm analysis, but pausing CPR is adversely associated with survival. Ideally, automated rhythm analysis would occur agnostic of CPR state throughout resuscitation and discriminate non-shockable from shockable rhythms. Transfer learning of pre-trained deep convolutional neural networks (CNNs) may enable accurate ECG analysis when applied to time-frequency representations of the ECG. We designed and evaluated a transfer learning algorithm to identify ventricular fibrillation (VF), asystole (AS), and organized (OR) rhythms agnostic of CPR. Methods: In this observational study of out-of-hospital cardiac arrest, rhythms were manually diagnosed in continuous defibrillator ECG recordings. Non-overlapping adjacent 2-s ECG segments were extracted from the first 30 min of each case regardless of CPR during VF, AS, and OR. Each segment was represented by an intrafrequency-normalized Morlet wavelet transform from 4-40 Hz. Using a 2/3 subset of patients for training, a series of two ResNet-101 CNNs were retrained to perform a shock decision (VF vs. non-shockable) followed by a specific non-shockable prediction (AS, OR, or Indeterminate). Performance was evaluated in a 1/3 validation subset of patients using a range of probability decision thresholds to predict the class of each segment. Results: In total, 275100 segments were collected from 461 patients. Of 90962 segments from 152 validation patients, using a 0.7 probability threshold for class prediction, 21% (18930/90962) were indeterminate, shock vs. no-shock sensitivity and specificity were 90% (19702/21930) and 97% (48421/50102), and specificities among non-shockable rhythms for AS vs. OR were 84% (5032/5998) and 86% (37760/44104), respectively (Fig 1). Conclusion: Transfer learning may enable shock/no-shock and rhythm-specific ECG classification continuously throughout resuscitation regardless of CPR.

Background: Current resuscitation protocols require pausing cardiopulmonary resuscitation (CPR) to check for a pulse. However, pausing CPR during a pulseless rhythm worsens patient outcome. We designed an ECG-based algorithm that predicts pulse status during uninterrupted CPR, and evaluated its performance both with and without CPR. Methods: We evaluated 383 patients who were treated for out-of-hospital cardiac arrest using defibrillators with real-time ECG, CPR, and audio recordings. We collected paired adjacent ECG segments with and without CPR during organized rhythms. Segments were collected during the 10-s CPR period just prior to pulse check, and 5-s segments without CPR during the pulse check. ECG segments with or without a pulse were identified by the audio annotation and recorded blood pressures. Patients were randomly divided into 60% (230/383) training and 40% (153/383) test groups. From training data, we developed an algorithm to predict clinical pulse status based on the wavelet transform of the bandpass-filtered ECG, applying principle component analysis (PCA). We then trained a linear discriminant model using 3 principle component modes as input features. Model performance was evaluated on test group segments with and without CPR using receiver operating curves overall and according to initial arrest rhythm. Results: There were 230 patients (540 pulse checks) in the training set and 153 patients (372 pulse checks) in the test set. In both of these sets, about 16% (37/230 and 25/153) of the patients presented with initial non-shockable rhythm . Overall 38% (351/912) of checks had a spontaneous pulse. The areas under the receiver operating characteristic curve (AUCs) for predicting pulse status with and without CPR on test data were 0.84 and 0.89, respectively. Conclusion: A novel ECG-based algorithm demonstrates potential to improve resuscitation by predicting presence of a spontaneous pulse without pausing CPR.

Background: The Utstein population is defined by non-traumatic, bystander-witnessed out-of-hospital cardiac arrest (OHCA) presenting with ventricular fibrillation (VF). It is used to compare resuscitation performance across emergency medical services (EMS) systems. We hypothesized there being a system-specific survival correlation between the current Utstein and other VF populations inclusive of unwitnessed and EMS-witnessed VF OHCA that supports expanding performance metrics to this more comprehensive population that is more representative of the actual community burden of VF OHCA. Methods: We performed a cohort investigation of all non-traumatic, VF OHCA in the Cardiac Arrest Registry to Enhance Survival from 1/1/2013-12/31/2018 among EMS agencies that treated >=100 VF OHCA. We evaluated sample size and survival with the addition of the new VF populations. We used the Pearson coefficient to assess the correlation of agency-specific survival between the current Utstein population and unwitnessed and EMS-witnessed VF OHCA. Results: A total of 107 EMS agencies treated 38,836 VF arrests: 22,918 current Utstein, 11,297 unwitnessed VF, and 4621 EMS-witnessed VF OHCA. Overall, survival was 29.8% (11,567/38,836): 33.9% (7,774/22,918) among current Utstein, 17.2% (1942/11,297) among unwitnessed VF, and 40.1% (1851/4621) among EMS-witnessed VF. For agency-specific survival outcome, the Pearson correlation was 0.52 between current the Utstein population versus combined unwitnessed and EMS-witnessed groups. For survival with Cerebral Performance Category 1-2, the Pearson correlation was 0.61. Conclusion: Expanding the Utstein population to include unwitnessed and EMS-witnessed VF OHCA achieves a simpler, more inclusive case definition that minimizes variability in case determination and increases the number of survivors and eligible population by ~50%, while still achieving a distinguishing metric of system-specific performance.

Background Sex differences in outcome have been reported in patients with congenital long QT syndrome. We aimed to report on the incidence of time‐dependent life‐threatening events in male and female patients with long QT syndrome with an implantable cardioverter defibrillator (ICD). Methods and Results A total of 60 patients with long QT syndrome received an ICD for primary or secondary prevention indications. Life‐threatening events were evaluated from the date of ICD implant and included ICD shocks for ventricular tachycardia, ventricular fibrillation, or death. ICDs were implanted in 219 women (mean age 38±13 years), 46 girls (12±5 years), 55 men (43±17 years), and 40 boys (11±4 years). Mean follow‐up post‐ICD implantation was 14±6 years for females and 12±6 years for males. At 15 years of follow‐up, the cumulative probability of life‐threatening events was 27% in females and 34% in males (log‐rank P =0.26 for the overall difference). In the multivariable Cox model, sex was not associated with significant differences in risk first appropriate ICD shock (hazard ratio, 0.83 female versus male; 95% CI, 0.52–1.34; P =0.47). Results were similar when stratified by age and by genotype: long QT syndrome type 1 (LQT1), long QT syndrome type 2 (LQT2), and long QT syndrome type 3 (LQT3). Incidence of inappropriate ICD shocks was higher in males versus females (4.2 versus 2.7 episodes per 100 patient‐years; P =0.018), predominantly attributed to atrial fibrillation. The first shock did not terminate ventricular tachycardia/ventricular fibrillation in 48% of females and 62% of males ( P =0.25). Conclusions In patients with long QT syndrome with an ICD, the risk and rate of life‐threatening events did not significantly differ between males and females regardless of ICD indications or genotype. In a substantial proportion of patients with long QT syndrome, first shock did not terminate ventricular tachycardia/ventricular fibrillation.

Background Recent advances in treatment for stroke give new possibilities for optimizing outcomes. To deliver these prehospital care needs to become more efficient. Aim To develop a framework to support improved delivery of prehospital care. The recommendations are aimed at clinicians involved in prehospital and emergency health systems who will often not be stroke specialists but need clear guidance as to how to develop and deliver safe and effective care for acute stroke patients. Methods Building on the successful implementation program from the Global Resuscitation Alliance and the Resuscitation Academy, the Utstein methodology was used to define a generic chain of survival for Emergency Stroke Care by assembling international expertise in Stroke and Emergency Medical Services (EMS). Ten programs were identified for Acute Stroke Care to improve survival and outcomes, with recommendations for implementation of best practice. Conclusions Efficient prehospital systems for acute stroke will be improved through public awareness, optimized prehospital triage and timely diagnostics, and quick and equitable access to acute treatments. Documentation, use of metrics and transparency will help to build a culture of excellence and accountability.

Tailoring hypothermia duration to ischemia duration may improve outcome from out-of-hospital cardiac arrest. We investigated the association between the hypothermia/ischemia ratio and functional outcome in a secondary analysis of data from the Resuscitation Outcomes Consortium Amiodarone, Lidocaine, or Placebo Study trial.Cohort study of out-of-hospital cardiac arrest patients screened for Resuscitation Outcomes Consortium-Amiodarone, Lidocaine, or Placebo Study.Multicenter study across North America.Adult, nontraumatic, out-of-hospital cardiac arrest patients screened for Resuscitation Outcomes Consortium-Amiodarone, Lidocaine, or Placebo Study who survived to hospital admission and received targeted temperature management between May 2012 and October 2015.Targeted temperature management in comatose survivors of out-of-hospital cardiac arrest. We defined hypothermia/ischemia ratio as total targeted temperature management time (initiation through rewarming) divided by calculated total ischemia time (approximate time of arrest [9-1-1 call or emergency medical services-witnessed] to return of spontaneous circulation).The primary outcome was hospital survival with good functional status (modified Rankin Score, 0-3) at hospital discharge. We fitted logistic regression models to estimate the association between hypothermia/ischemia ratio and the primary outcome, adjusting for demographics, arrest characteristics, and Resuscitation Outcomes Consortium enrolling site. A total of 3,429 patients were eligible for inclusion, of whom 36.2% were discharged with good functional outcome. Patients had a mean age of 62.0 years (SD, 15.8), with 69.7% male, and 58.0% receiving lay-rescuer cardiopulmonary resuscitation. Median time to return of spontaneous circulation was 21.1 minutes (interquartile range, 16.1-26.9), and median duration of targeted temperature management was 32.9 hours (interquartile range, 23.7-37.8). A total of 2,579 had complete data and were included in adjusted regression analyses. After adjustment for patient characteristics and Resuscitation Outcomes Consortium site, a greater hypothermia/ischemia ratio was associated with increased survival with good functional outcome (odds ratio, 2.01; 95% CI, 1.82-2.23). This relationship, however, appears to be primarily driven by time to return of spontaneous circulation in this patient cohort.Although a larger hypothermia/ischemia ratio was associated with good functional outcome after out-of-hospital cardiac arrest in this cohort, this association is primarily driven by duration of time to return of spontaneous circulation. Tailoring duration of targeted temperature management based on duration of time to return of spontaneous circulation or patient characteristics requires prospective study.

The fundamentals of cardiac resuscitation include the immediate provision of high-quality cardiopulmonary resuscitation combined with rapid defibrillation (as appropriate). These mainstays of therapy set the groundwork for other possible interventions such as medications, advanced airways, extracorporeal cardiopulmonary resuscitation, and post–cardiac arrest care, including targeted temperature management, cardiorespiratory support, and percutaneous coronary intervention. Since 2015, an increased number of studies have been published evaluating some of these interventions, requiring a reassessment of their use and impact on survival from cardiac arrest. This 2019 focused update to the American Heart Association advanced cardiovascular life support guidelines summarizes the most recent published evidence for and recommendations on the use of advanced airways, vasopressors, and extracorporeal cardiopulmonary resuscitation during cardiac arrest. It includes revised recommendations for all 3 areas, including the choice of advanced airway devices and strategies during cardiac arrest (eg, bag-mask ventilation, supraglottic airway, or endotracheal intubation), the training and retraining required, the administration of standard-dose epinephrine, and the decisions involved in the application of extracorporeal cardiopulmonary resuscitation and its potential impact on cardiac arrest survival.

Survival after out-of-hospital cardiac arrest requires an integrated system of care (chain of survival) between the community elements responding to an event and the healthcare professionals who continue to care for and transport the patient for appropriate interventions. As a result of the dynamic nature of the prehospital setting, coordination and communication can be challenging, and identification of methods to optimize care is essential. This 2019 focused update to the American Heart Association systems of care guidelines summarizes the most recent published evidence for and recommendations on the use of dispatcher-assisted cardiopulmonary resuscitation and cardiac arrest centers. This article includes the revised recommendations that emergency dispatch centers should offer and instruct bystanders in cardiopulmonary resuscitation during out-of-hospital cardiac arrest and that a regionalized approach to post–cardiac arrest care may be reasonable when comprehensive postarrest care is not available at local facilities.

It is hypothesized that intravenous (IV) sodium nitrite given during resuscitation of out-of-hospital cardiac arrest (OHCA) will improve survival. We performed a phase 1 open-label study of IV sodium nitrite given during resuscitation of 120 patents with OHCA from ventricular fibrillation or nonventricular fibrillation initial rhythms by Seattle Fire Department paramedics. A total of 59 patients received 25 mg (low) and 61 patients received 60 mg (high) of sodium nitrite during resuscitation from OHCA. Treatment effects were compared between high- and low-dose nitrite groups, and all patients in a concurrent local Emergency Medical Services registry of OHCA. Whole blood nitrite levels were measured in 97 patients. The rate of return of spontaneous circulation (48% vs 49%), rearrest in the field (15% vs 25%), use of norepinephrine (12% vs 12%), first systolic blood pressure (124 ± 32 vs 125 ± 38 mm Hg), survival to discharge (23.7% vs 16.4%), and neurologically favorable survival (18.6% vs 11.5%) were not significantly different in the low and high nitrite groups. There were no significant differences in these outcomes among patients who received IV nitrite compared with concurrent registry controls. We estimate that 60 mg achieves whole blood nitrite levels of 22 to 38 μM 10 minutes after administration, whereas 25 mg achieves a level of 9 to 16 μM 10 minutes after delivery. In conclusion, administration of IV nitrite is feasible and appears to be safe in patients with OHCA, permitting subsequent evaluation of the effectiveness of IV nitrite for the treatment of OHCA.

Context: Research in an emergency setting is challenging because the window of opportunity to treat may be short, and preclude time to obtain informed consent from the patient or their representative. Such research can be conducted under exception from informed consent (EFIC) if specific criteria are met. In the United States, this includes notification of an enrolled subject or their representative as soon as feasible after enrollment so that they have autonomy to opt out from ongoing study participation. To date, there is limited empiric information about time to notification (TTN). Objective: To describe variation in TTN among sites participating in randomized trials conducted under exception from informed consent for emergency research. Methods: Notification strategies were determined at each site prior to initiation of subject enrollment, and approved by a local institutional review board or equivalent. TTN was summarized overall, as well as stratified by site and clinical outcome among patients enrolled in multiple trials conducted by the Resuscitation Outcomes Consortium (ROC). Results: Included were 34,868 patients enrolled in four trials. Of these, 33,805 had with out-of-hospital cardiac arrest; and 1,063 had life-threatening traumatic injury. TTN varied (Table). Conclusions: There is large variation in TTN in trials conducted under EFIC for emergency research. Early notification is difficult; delayed notification may reduce the autonomy of patients or their representative.

Objective: Currently, cardiac arrest resuscitation requires interruptions in CPR every 2 minutes to assess cardiac rhythm and pulse. A method which analyzed the ECG during CPR to predict whether or not an organized rhythm generated a pulse could help to direct care and limit CPR interruptions. We evaluated a real-time method to predict pulse status from organized rhythm ECG segments with and without CPR. Methods: The study cohort received attempted resuscitation by a metropolitan EMS system following out-of-hospital ventricular fibrillation arrest. Two-minute rhythm/pulse checks on the continuous defibrillator recordings were annotated for CPR, rhythm, and pulse status using the ECG, impedance, and accelerometer signals, the audio recording, and EMS record. Pulse was defined by the presence of a palpable pulse by EMS. Paired ECG segments with and without CPR were extracted at each rhythm/pulse check. Using organized rhythm segments from one-third of cases for training, we developed four ECG features using wavelet analysis (median power values in three frequency bands and QRS rate) and a logistic model to predict pulse status. Predictive performances of each ECG feature and the logistic model were measured by AUC in the remaining validation cases with and without CPR. Results: There were 238 cases and 911 paired segments with a median of 3 (IQR 2,5) paired segments per case. Among 319 organized rhythm segments in the validation set, AUC for pulse prediction ranged from 0.67 to 0.79 for the individual ECG features (Figure). The logistic model was more predictive than any individual feature (AUC 0.84, 95% CI 0.80-0.89, p < 0.05 for each comparison). The model predicted pulse similarly regardless of CPR activity (p = 0.2). Conclusion: ECG features extracted by wavelet analysis were predictive of pulse status among organized rhythm segments with and without ongoing CPR. Further study is required to understand how pulse prediction could guide rescuer actions in real-time.

Objective: Analysis of the ventricular fibrillation (VF) ECG to predict patient outcomes can potentially improve defibrillation timing and monitor prognosis during resuscitation. However, accurate ECG analysis requires pausing CPR. We evaluated strategies to predict patient outcomes during CPR using novel ECG features, adaptive filtering, and dichotomous variables. Methods: We collected a 5-s VF ECG segment during chest compressions prior to 2137 shocks in 942 out-of-hospital VF arrests. Using training segments from 376 patients (40%), we designed ten features of the VF ECG to characterize amplitude, time-frequency energy, and complexity. Features were calculated with and without adaptive filtering. We used support vector machine and logistic models to combine ECG features with dichotomous variables presumed available during treatment: age Results: Of individual ECG variables, filtering improved amplitude features, and the best performance was observed using high-frequency energy features above CPR artifact frequencies (Table 1). Of dichotomous variables, age Conclusion: Combining ECG characteristics, adaptive filtering, and dichotomous variables may improve prediction of defibrillation outcomes during uninterrupted CPR.

Introduction: Out-of-hospital circulatory arrest (OHCA) is commonly assumed to be from a cardiac cause although routine early invasive coronary angiography (ICA) remains controversial and has a relatively high proportion of studies without obstructive coronary artery disease (CAD). The ability of coronary CT angiography (CCTA) to detect significant CAD in OHCA survivors has not been evaluated. Methods: The prospective CT-FIRST trial enrolled 104 OHCA survivors who had an early (50% stenosis. Patient-level diagnostic accuracy calculations for CCTA to identify obstructive CAD used ICA as the standard. Results: Of the 104 enrolled patients, 28 (27%) had both CT and ICA. All CCTA studies were evaluable. Diagnostic accuracy data are shown in the Table. Overall, diagnostic accuracy measures were excellent between CCTA and ICA at the patient level. Conclusions: Early CCTA in OHCA survivors has high diagnostic accuracy for obstructive coronary artery disease and could be used as a gatekeeper to ICA.

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research.

Background Prior observational studies suggest no additional benefit from advanced life support (ALS) when compared with providing basic life support (BLS) for patients with out-of-hospital cardiac arrest (OHCA). We compared the association of ALS care with OHCA outcomes using prospective clinical data from the Resuscitation Outcomes Consortium (ROC). Methods Included were consecutive adults OHCA treated by participating emergency medical services (EMS) agencies between June 1, 2011, and June 30, 2015. We defined BLS as receipt of cardiopulmonary resuscitation (CPR) and/or automated defibrillation and ALS as receipt of an advanced airway, manual defibrillation, or intravenous drug therapy. We compared outcomes among patients receiving: 1) BLS-only; 2) BLS + late ALS; 3) BLS + early ALS; and 4) ALS-first care. Using multivariable logistic regression, we evaluated the associations between level of care and return of spontaneous circulation (ROSC), survival to hospital discharge, and survival with good functional status, adjusting for age, sex, witnessed arrest, bystander CPR, shockable initial rhythm, public location, EMS response time, CPR quality, and ROC site. Results Among 35,065 patients with OHCA, characteristics were median age 68 years (IQR 56–80), male 63.9%, witnessed arrest 43.8%, bystander CPR 50.6%, and shockable initial rhythm 24.2%. Care delivered was: 4.0% BLS-only, 31.5% BLS + late ALS, 17.2% BLS + early ALS, and 47.3% ALS-first. ALS care with or without initial BLS care was independently associated with increased adjusted ROSC and survival to hospital discharge unless delivered greater than 6 min after BLS arrival (BLS + late ALS). Regardless of when it was delivered, ALS care was not associated with significantly greater functional outcome. Conclusion ALS care was associated with survival to hospital discharge when provided initially or within six minutes of BLS arrival. ALS care, with or without initial BLS care, was associated with increased ROSC, however it was not associated with functional outcome.

Objective Treatment: protocols for cardiac arrest rely upon rhythm analyses performed at two-minute intervals, neglecting possible rhythm changes during the intervening period of CPR. Our objective was to describe rhythm profiles (patterns of rhythm transitions during two-minute CPR cycles) following attempted defibrillation and to assess their relationship to survival. Methods The study included out-of-hospital cardiac arrest cases presenting with ventricular fibrillation from 2011 to 2015. The rhythm sequence was annotated during two-minute CPR cycles after the first and second shocks of each case, and the rhythm profile of each sequence was classified. We calculated absolute survival differences among rhythm profiles with the same rhythm at the two-minute check. Results Of 569 rhythm sequences after the first shock, 46% included a rhythm transition. Overall survival was 47%, and survival proportion varied by rhythm at the two-minute check: ventricular fibrillation (46%), organized (58%) and asystole (20%). Survival was similar between profiles which ended with an organized rhythm at the two-minute check. Likewise, survival was similar between profiles with asystole at the two-minute check. However, in patients with ventricular fibrillation at the two-minute check, survival was twice as high in those with a transient organized rhythm (69%) compared to constant ventricular fibrillation (32%) or transient asystole (28%). Conclusion Rhythm transitions are common after attempted defibrillation. Among patients with ventricular fibrillation at the subsequent two-minute check, transient organized rhythm during the preceding two-minute CPR cycle was associated with favorable survival, suggesting distinct physiologies that could serve as the basis for different treatment strategies.

Aim Amplitude Spectrum Area (AMSA) and Median Slope (MS) are ventricular fibrillation (VF) waveform measures that predict defibrillation shock success. Cardiopulmonary resuscitation (CPR) obscures electrocardiograms and must be paused for analysis. Studies suggest waveform measures better predict subsequent shock success when combined with prior shock success. We determined whether this relationship applies during CPR. Methods AMSA and MS were calculated from 5-second pre-shock segments with and without CPR, and compared to logistic models combining each measure with prior return of organized rhythm (ROR). Results VF segments from 692 patients were analyzed during CPR before 1372 shocks and without CPR before 1283 shocks. Combining waveform measures with prior ROR increased areas under receiver operating characteristic curves for AMSA/MS with CPR (0.66/0.68 to 0.73/0.74, p Conclusions Prior ROR improves prediction of shock success during CPR, and may enable waveform measure calculation without chest compression pauses.

Background: Out-of-hospital cardiac arrest (OHCA) commonly presents with nonshockable rhythms (asystole and pulseless electric activity). It is unknown whether antiarrhythmic drugs are safe and effective when nonshockable rhythms evolve to shockable rhythms (ventricular fibrillation/pulseless ventricular tachycardia [VF/VT]) during resuscitation. Methods: Adults with nontraumatic OHCA, vascular access, and VF/VT anytime after ≥1 shock(s) were prospectively randomized, double-blind, to receive amiodarone, lidocaine, or placebo by paramedics. Patients presenting with initial shock-refractory VF/VT were previously reported. The current study was a prespecified analysis in a separate cohort that initially presented with nonshockable OHCA and was randomized on subsequently developing shock-refractory VF/VT. The primary outcome was survival to hospital discharge. Secondary outcomes included discharge functional status and adverse drug-related effects. Results: Of 37 889 patients with OHCA, 3026 with initial VF/VT and 1063 with initial nonshockable-turned-shockable rhythms were treatment-eligible, were randomized, and received their assigned drug. Baseline characteristics among patients with nonshockable-turned-shockable rhythms were balanced across treatment arms, except that recipients of a placebo included fewer men and were less likely to receive bystander cardiopulmonary resuscitation. Active-drug recipients in this cohort required fewer shocks, supplemental doses of their assigned drug, and ancillary antiarrhythmic drugs than recipients of a placebo ( P P =0.24). No significant interaction between treatment assignment and discharge survival occurred with the initiating OHCA rhythm (asystole, pulseless electric activity, or VF/VT). Survival in each of these categories was consistently higher with active drugs, although the trends were not statistically significant. Adjusted absolute differences (95% confidence interval) in survival from nonshockable-turned-shockable arrhythmias with amiodarone versus placebo were 2.3% (−0.3, 4.8), P =0.08, and for lidocaine versus placebo 1.2% (−1.1, 3.6), P =0.30. More than 50% of these survivors were functionally independent or required minimal assistance. Drug-related adverse effects were infrequent. Conclusions: Outcome from nonshockable-turned-shockable OHCA is poor but not invariably fatal. Although not statistically significant, point estimates for survival were greater after amiodarone or lidocaine than placebo, without increased risk of adverse effects or disability and consistent with previously observed favorable trends from treatment of initial shock-refractory VF/VT with these drugs. Together the findings may signal a clinical benefit that invites further investigation. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01401647.

Objective To determine if arterial oxygen and carbon dioxide abnormalities in the first 24 h after return of spontaneous circulation (ROSC) are associated with increased mortality in adult out-of-hospital cardiac arrest (OHCA). Methods We used data from the Resuscitation Outcomes Consortium (ROC), including adult OHCA with sustained ROSC ≥1 h after Emergency Department arrival and at least one arterial blood gas (ABG) measurement. Among ABGs measured during the first 24 h of hospitalization, we identified the presence of hyperoxemia (PaO2 ≥ 300 mmHg), hypoxemia (PaO2 50 mmHg) and hypocarbia (PaCO2 Results Among 9186 OHCA included in the analysis, hospital mortality was 67.3%. Hyperoxemia, hypoxemia, hypercarbia, and hypocarbia occurred in 26.5%, 19.0%, 51.0% and 30.6%, respectively. Initial hyperoxemia only was not associated with hospital mortality (adjusted OR 1.10; 95% CI: 0.97–1.26). However, final and any hyperoxemia (1.25; 1.11–1.41) were associated with increased hospital mortality. Initial (1.58; 1.30–1.92), final (3.06; 2.42–3.86) and any (1.76; 1.54–2.02) hypoxemia (PaO2 50 mmHg) were associated with increased hospital mortality. Initial (1.13; 0.90–1.41), final (1.19; 1.04–1.37) and any (1.01; 0.91–1.12) hypocarbia (PaCO2 Conclusions In the first 24 h after ROSC, abnormal post-arrest oxygen and carbon dioxide tensions are associated with increased out of-hospital cardiac arrest mortality.

Although the intraosseous (IO) route is increasingly used for vascular access in out-of-hospital cardiac arrest (OHCA), little is known about its comparative effectiveness relative to intravenous (IV) access. We evaluated clinical outcomes following OHCA comparing drug administration via IO versus IV routes.This retrospective cohort study evaluated Emergency Medical Services (EMS)-treated adults with atraumatic OHCA in a large metropolitan EMS system between 9/1/2012-12/31/2014. Access was classified as IO or IV based on the route of first EMS drug administration. Study endpoints were survival to hospital discharge, return of spontaneous circulation (ROSC) and survival to hospital admission.Among 2164 adults with OHCA, 1800 met eligibility criteria, 1525 of whom were treated via IV and 275 principally via tibial-IO routes. Compared to IV, IO-treated patients were younger, more often women, had unwitnessed OHCA, a non-cardiac aetiology, and presented with non-shockable rhythms. IO versus IV-treated patients were less likely to survive to hospital discharge (14.9% vs 22.8%, p=0.003), achieve ROSC (43.6% vs 55.5%, p0.001) or be hospitalized (38.5% vs 50.0% p0.001). In multivariable adjusted analyses, IO treatment was not associated with survival to discharge (odds ratio (OR) (95% confidence interval) 0.81 (0.55, 1.21), p=0.31), but was associated with a lower likelihood of ROSC (OR=0.67 (0.50, 0.88), p=0.004) and survival to hospitalization (OR=0.68 (0.51, 0.91), p=0.009).Though not independently associated with survival to discharge, principally tibial IO versus IV treatment was associated with a lower likelihood of ROSC and hospitalization. How routes of vascular access influence clinical outcomes after OHCA merits additional study.

Over the last 15 years, treatment of comatose post-cardiac arrest patients has evolved to include therapeutic strategies such as urgent coronary angiography with percutaneous coronary intervention (PCI), targeted temperature management (TTM)-requiring mechanical ventilation and sedation-and more sophisticated and cautious prognostication. In 2015, collaboration between the European Resuscitation Council (ERC) and the European Society for Intensive Care Medicine (ESICM) resulted in the first European guidelines on post-resuscitation care. This review addresses the major recent advances in the treatment of cardiac arrest, recent trials that have challenged current practice and the remaining areas of uncertainty.

The International Liaison Committee on Resuscitation has initiated a near-continuous review of cardiopulmonary resuscitation science that replaces the previous 5-year cyclic batch-and-queue approach process. This is the first of an annual series of International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations summary articles that will include the cardiopulmonary resuscitation science reviewed by the International Liaison Committee on Resuscitation in the previous year. The review this year includes 5 basic life support and 1 paediatric Consensuses on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Each of these includes a summary of the science and its quality based on Grading of Recommendations, Assessment, Development, and Evaluation criteria and treatment recommendations. Insights into the deliberations of the International Liaison Committee on Resuscitation task force members are provided in Values and Preferences sections. Finally, the task force members have pri-oritised and listed the top 3 knowledge gaps for each population, intervention, comparator, and outcome question. (C) 2017 European Resuscitation Council and American Heart Association, Inc. Published by Elsevier B.V. All rights reserved.