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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.

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.

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.

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 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.

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.

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.

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.

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.

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.

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.

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.

Introduction Quantitative waveform measures are a surrogate of the acute physiological status of the myocardium and predict survival following ventricular fibrillation out-of-hospital cardiac arrest (OHCA). We investigated whether the amplitude spectrum area (AMSA) waveform measure mediates the adverse relationship between increasing burden of chronic health conditions and lower likelihood of survival. Methods We performed a cohort investigation of persons > = 18 years who suffered ventricular fibrillation OHCA between 2008–2015 in a metropolitan emergency medical service (EMS) system. The count of chronic health conditions was determined using the Charlson Comorbidity Index (CCI). AMSA was calculated just prior to the initial shock. We used multivariable logistic regression to assess the relationship between CCI and survival-to-discharge in models first without and then with AMSA to determine the extent to which AMSA attenuated the CCI-survival association. Results Of the 716 eligible patients, 422/716 (59%) had at least one chronic health condition; 21.8% with one, 19.6% with two, 10.3% with 3, and 7.3% with ≥4. Survival-to-discharge was 45% (324/716). In the multivariable model adjusted for traditional Utstein characteristics, increasing CCI was associated with lower odds of survival (Odds ratio (OR) (95% confidence interval] = 0.82 [0.72, 0.93] for each additional chronic health condition). The addition of AMSA to the model only modestly attenuated the CCI-survival association (OR = 0.85 [0.74,0.98]). Conclusion The waveform measure AMSA – a surrogate for the physiological status of the myocardium – mediated only a modest portion of the association between increasing burden of chronic health conditions and lower likelihood of survival following ventricular fibrillation OHCA.

Coronary artery disease is prevalent in different causes of out-of-hospital cardiac arrest (OHCA), especially in individuals presenting with shockable rhythms of ventricular fibrillation/pulseless ventricular tachycardia (VF/pVT). The purpose of this report is to review the known prevalence and potential importance of coronary artery disease in patients with OHCA and to describe the emerging paradigm of treatment with advanced perfusion/reperfusion techniques and their potential benefits on the basis of available evidence. Although randomized clinical trials are planned or ongoing, current scientific evidence rests principally on observational case series with their potential confounding selection bias. Among patients resuscitated from VF/pVT OHCA with ST-segment elevation on their postresuscitation ECG, the prevalence of coronary artery disease has been shown to be 70% to 85%. More than 90% of these patients have had successful percutaneous coronary intervention. Conversely, among patients resuscitated from VF/pVT OHCA without ST-segment elevation on their postresuscitation ECG, the prevalence of coronary artery disease has been shown to be 25% to 50%. For these patients, early access to the cardiac catheterization laboratory is associated with a 10% to 15% absolute higher functionally favorable survival rate compared with more conservative approaches of late or no access to the cardiac catheterization laboratory. In patients with VF/pVT OHCA refractory to standard treatment, a new treatment paradigm is also emerging that uses venoarterial extracorporeal membrane oxygenation to facilitate return of normal perfusion and to support further resuscitation efforts, including coronary angiography and percutaneous coronary intervention. The burden of coronary artery disease is high in this patient population, presumably causative in most patients. The strategy of venoarterial extracorporeal membrane oxygenation, coronary angiography, and percutaneous coronary intervention has resulted in functionally favorable survival rates ranging from 9% to 45% in observational studies in this patient population. Patients with VF/pVT should be considered at the highest severity in the continuum of acute coronary syndromes. These patients have a significant burden of coronary artery disease and acute coronary thrombotic events. Evidence from randomized trials will further define optimal clinical practice.

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: Quantitative measures of the ventricular fibrillation (VF) ECG waveform can assess myocardial physiology and predict cardiac arrest outcomes, making these measures a candidate to help guide resuscitation. Chest compressions are typically paused for waveform measure calculation because compressions cause ECG artifact. However, such pauses contradict resuscitation guideline recommendations to minimize cardiopulmonary resuscitation interruptions. We evaluated a comprehensive group of VF measures with and without ongoing compressions to determine their performance under both conditions for predicting functionally-intact survival, the study’s primary outcome. Methods: Five-second VF ECG segments were collected with and without chest compressions before 2755 defibrillation shocks from 1151 out-of-hospital cardiac arrest patients. Twenty-four individual measures and 3 combination measures were implemented. Measures were optimized to predict functionally-intact survival (Cerebral Performance Category score ≤2) using 460 training cases, and their performance evaluated using 691 independent test cases. Results: Measures predicted functionally-intact survival on test data with an area under the receiver operating characteristic curve ranging from 0.56 to 0.75 (median, 0.73) without chest compressions and from 0.53 to 0.75 (median, 0.69) with compressions ( P P =0.75 for difference). Conclusions: VF waveform measures predict functionally-intact survival when calculated during chest compressions, but prognostic performance is generally reduced compared with compression-free analysis. However, support vector machine models exhibited similar performance with and without compressions while also achieving the highest area under the receiver operating characteristic curve. Such machine learning models may, therefore, offer means to guide resuscitation during uninterrupted cardiopulmonary resuscitation.

Antiarrhythmic medications are commonly administered during and immediately after a ventricular fibrillation/pulseless ventricular tachycardia cardiac arrest. However, it is unclear whether these medications improve patient outcomes. This 2018 American Heart Association focused update on advanced cardiovascular life support guidelines summarizes the most recent published evidence for and recommendations on the use of antiarrhythmic drugs during and immediately after shock-refractory ventricular fibrillation/pulseless ventricular tachycardia cardiac arrest. This article includes the revised recommendation that providers may consider either amiodarone or lidocaine to treat shock-refractory ventricular fibrillation/pulseless ventricular tachycardia cardiac arrest.

Background: Bystander cardiopulmonary resuscitation (BCPR) improves survival from out-of-hospital cardiac arrest (OHCA), yet BCPR rates remain low. It is unknown whether BCPR delivery disparities exist based on victim gender. We measured BCPR rates by gender in private and public environments, hypothesizing that females would be less likely than males to receive BCPR in public settings, with an associated difference in survival to hospital discharge. Methods and Results: We analyzed data from adult, nontraumatic OHCA events within the Resuscitation Outcomes Consortium registry (2011–2015). Using logistic regression, we modeled the likelihood of receiving BCPR by gender, including patient-level variables, stratified by location. A cohort of 19 331 OHCAs was assessed. Mean age was 64±17 years, and 63% (12 225/19 331) were male. Overall, 37% of OHCA victims received bystander CPR. In public locations, 39% (272/694) of females and 45% (1170/2600) of males received BCPR ( P P =NS). Among public OHCAs, males had significantly increased odds of receiving BCPR compared with females (odds ratio, 1.27; 95% CI, 1.05–1.53; P =0.01); this was not the case in the private setting (odds ratio, 0.93; 95% CI, 0.87–1.01; P =NS). Controlling for site, age, and race, BCPR was significantly associated with survival to hospital discharge (odds ratio, 1.69; 95% CI, 1.54–1.85; P P Conclusions: Males had an increased likelihood of receiving BCPR compared with females in public. BCPR improved survival to discharge, with greater survival among males compared with females.

Background— The impact of patient age on the risks of death or rehospitalization after primary prevention implantable cardioverter-defibrillator (ICD) placement is uncertain. Methods and Results— Data from 5 major ICD trials were merged: the Multicenter Automatic Defibrillator Implantation Trial I (MADIT-I), the Multicenter UnSustained Tachycardia Trial (MUSTT), the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II), the Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation Trial (DEFINITE), and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). Median age at enrollment was 62 (interquartile range 53–70) years. Compared with their younger counterparts, older patients had a greater burden of comorbid illness. In unadjusted exploratory analyses, ICD recipients were less likely to die than nonrecipients in all age groups: among patients aged Conclusions— In this analysis, the survival benefit of the ICD exists but is attenuated with increasing age. The latter finding may be because of the higher burden of comorbid illness, competing causes of death, or limited sample size of older patients. There was no evidence that age modifies the association between ICD treatment and rehospitalization.

Objectives The aim of this study was to determine if the benefit of implantable cardioverter-defibrillators (ICDs) is modulated by medical comorbidity. Background Primary prevention ICDs improve survival in patients at risk for sudden cardiac death. Their benefit in patients with significant comorbid illness has not been demonstrated. Methods Original, patient-level datasets from MADIT I (Multicenter Automatic Defibrillator Implantation Trial I), MADIT II, DEFINITE (Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation), and SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) were combined. Patients in the combined population (N = 3,348) were assessed with respect to the following comorbidities: smoking, pulmonary disease, diabetes, peripheral vascular disease, atrial fibrillation, ischemic heart disease, and chronic kidney disease. The primary outcome was overall mortality, using the hazard ratio (HR) of time to death for patients receiving an ICD versus no ICD by extent of medical comorbidity, and adjusted for age, sex, race, left ventricular ejection fraction, use of antiarrhythmic drugs, beta-blockers, and angiotensin-converting enzyme inhibitors. Results Overall, 25% of patients (n = 830) had Conclusions Patients with extensive comorbid medical illnesses may experience less benefit from primary prevention ICDs than those with less comorbidity; implantation should be carefully considered in sick patients. Further study of ICDs in medically complex patients is warranted.

Cardiac arrest results in devastating injuries, particularly to the heart and brain. These are the most common causes of hospital death following an initially successful resuscitation from out-of-hospital cardiac arrest (OHCA). Brain and/or heart-related complications kill, on average, 2 of every 3

Background No precise tools exist to predict appropriate shocks in patients with a primary prevention ICD. We sought to identify characteristics predictive of appropriate shocks in patients with a primary prevention implantable cardioverter defibrillator (ICD). Methods Using patient-level data from the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), we identified patients with any appropriate shock. Clinical and demographic variables were included in a logistic regression model to predict appropriate shocks. Results There were 1,463 patients randomized to an ICD, and 285 (19%) had ≥1 appropriate shock over a median follow-up of 2.59 years. Compared with patients without appropriate ICD shocks, patients who received any appropriate shock tended to have more severe heart failure. In a multiple logistic regression model, predictors of appropriate shocks included NYHA class (NYHA II vs I: OR 1.65, 95% CI 1.07-2.55; NYHA III vs I: OR 1.74, 95% CI 1.10-2.76), lower LVEF (per 1% change) (OR 1.04, 95% CI 1.02-1.06), absence of beta blocker therapy (OR 1.61, 95% CI 1.23-2.12), and single chamber ICD (OR 1.67, 95% CI 1.13-2.45). Conclusion In this meta-analysis of patient level data from MADIT-II and SCD-HeFT, higher NYHA class, lower LVEF, no beta blocker therapy, and single chamber ICD (versus dual chamber) were significant predictors of appropriate shocks. This article is protected by copyright. All rights reserved

Aim There is limited information on the outcomes after primary prevention implantable cardioverter-defibrillator (ICD) implantation in patients with heart failure (HF) and diabetes. This analysis evaluates the effectiveness of a strategy of ICD plus medical therapy vs. medical therapy alone among patients with HF and diabetes. Methods and results A patient-level combined-analysis was conducted from a combined dataset that included four primary prevention ICD trials of patients with HF or severely reduced ejection fractions: Multicenter Automatic Defibrillator Implantation Trial I (MADIT I), MADIT II, Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE), and Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). In total, 3359 patients were included in the analysis. The primary outcome of interest was all-cause death. Compared with patients without diabetes (n = 2363), patients with diabetes (n = 996) were older and had a higher burden of cardiovascular risk factors. During a median follow-up of 2.6 years, 437 patients without diabetes died (178 with ICD vs. 259 without) and 280 patients with diabetes died (128 with ICD vs. 152 without). ICDs were associated with a reduced risk of all-cause mortality among patients without diabetes [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.46-0.67] but not among patients with diabetes (HR 0.88, 95% CI 0.7-1.12; interaction P = 0.015). Conclusion Among patients with HF and diabetes, primary prevention ICD in combination with medical therapy vs. medical therapy alone was not significantly associated with a reduced risk of all-cause death. Further studies are needed to evaluate the effectiveness of ICDs among patients with diabetes.

Some patients with out-of-hospital cardiac arrest (OHCA) assessed by emergency medical services (EMS) do not receive attempts at resuscitation on the basis of perceived futility.1) To measure variability in the initiation of resuscitation attempts in EMS-assessed OHCA patients across EMS agencies, 2) to evaluate the association between selected EMS agency characteristics and the proportion of patients receiving resuscitation attempts, and 3) to evaluate the association between proportion receiving resuscitation attempts and survival.A retrospective cohort study using data from 129 EMS agencies participating in the Resuscitation Outcomes Consortium (ROC) epidemiologic registry (EPISTRY) - Cardiac Arrest from 12/01/2005 to 12/31/2010. We included non-traumatic OHCA patients assessed by EMS.We included 86,912 OHCA patients. Overall, 54.8% had resuscitation attempted by EMS providers, varying from 23.9% to 100% (p=0.001) across EMS agencies. The proportion of patients receiving a resuscitation attempt was 7.87% less (95% CI 3.73-12.0) among agencies with longer average response intervals (≥6min) compared with shorter average response intervals (6min) and 16.9% less (95% CI 11.9-21.9) among agencies with higher levels of advanced life support (ALS) availability (≥50% of available units) compared with lower levels of ALS availability (50% of available units). There was a moderate positive correlation between the proportion of patients with resuscitation attempts and survival to hospital discharge (r=0.54, p0.001).The proportion of patients with OHCA who receive resuscitation attempts is variable across EMS agencies and is associated with EMS response interval, ALS unit availability and geographic region. On average, survival was higher among EMS agencies more likely to initiate resuscitation.

Background Primary prevention implantable cardioverter defibrillator (ICD) reduce all-cause mortality by reducing sudden cardiac death. There are conflicting data regarding whether patients with more advanced heart failure derive ICD benefit owing to the competing risk of nonsudden death. Methods We performed a patient-level meta-analysis of New York Heart Association (NYHA) class II/III heart failure patients (left ventricular ejection fraction ≤35%) from 4 primary prevention ICD trials (MADIT-I, MADIT-II, DEFINITE, SCD-HeFT). Bayesian-Weibull survival regression models were used to assess the impact of NYHA class on the relationship between ICD use and mortality. Results Of the 2,763 patients who met study criteria, 68% (n = 1,867) were NYHA II and 52% (n = 1,435) were randomized to an ICD. In a multivariable model including all study patients, the ICD reduced mortality (hazard ratio [HR] 0.65, 95% posterior credibility interval [PCI]) 0.40-0.99). The interaction between NYHA class and the ICD on mortality was significant (posterior probability of no interaction = .036). In models including an interaction term for the NYHA class and ICD, the ICD reduced mortality among NYHA class II patients (HR 0.55, PCI 0.35-0.85), and the point estimate suggested reduced mortality in NYHA class III patients (HR 0.76, PCI 0.48-1.24), although this was not statistically significant. Conclusions Primary prevention ICDs reduce mortality in NYHA class II patients and trend toward reducing mortality in the heterogeneous group of NYHA class III patients. Improved risk stratification tools are required to guide patient selection and shared decision making among NYHA class III primary prevention ICD candidates.

Background Whether there is an optimal time to place an implantable cardioverter-defibrillator (ICD) more than 40 days after myocardial infarction (MI) in guideline-eligible patients is unknown. Objective To evaluate the effect of time from MI to randomization on mortality, rehospitalizations, and complications. Methods Individual data on patients enrolled in 9 primary prevention ICD trials were provided. Clinical trials were eligible for the current analysis if they enrolled patients with an MI more than 40 days prior to randomization to primary prevention ICD therapy vs usual care: Multicenter Automatic Defibrillator Implantation Trial I, Multicenter UnSustained Tachyardia Trial, Multicenter Automatic Defibrillator Implantation Trial II, and Sudden Cardiac Death in Heart Failure Trial. Results ICD recipients died less frequently than nonrecipients at 5 years across all subgroups of time from MI to randomization. In unadjusted Cox proportional hazards regression, a survival benefit was evident in most subgroups. Adjusted Bayesian Weibull survival modeling yielded hazard ratio (HR) 0.50, 95% posterior credible interval (PCI) 0.20–1.25 41–180 days after MI; HR 0.98, 95% PCI 0.37–2.37 181–365 days after MI; HR 0.22, 95% PCI 0.07–0.59>1–2 years after MI; HR 0.42, 95% PCI 0.17–0.90>2–5 years after MI; HR 0.55, 95% PCI 0.25–1.15>5–10 years after MI; and HR 0.48, 95% PCI 0.20–1.02>10 years after MI. There was no evidence of an interaction between time from MI and all-cause mortality, rehospitalizations, or complications. Conclusions In this meta-analysis, there was scant evidence that the efficacy of primary prevention ICD therapy depends on time to implantation more than 40 days after MI. Similarly, there was no evidence that the risks of rehospitalizations or complications depend on time more than 40 days after MI.

Background Early determination of the acute etiology of cardiac arrest could help guide resuscitation or post-resuscitation care. In experimental studies, quantitative measures of the ventricular fibrillation waveform distinguish ischemic from non-ischemic etiology. Methods We investigated whether waveform measures distinguished arrest etiology among adults treated by EMS for out-of-hospital ventricular fibrillation between January 1, 2006–December 31, 2014. Etiology was classified using hospital information into three exclusive groups: acute coronary syndrome (ACS) with ST elevation myocardial infarction (STEMI), ACS without ST elevation (non-STEMI), or non-ischemic arrest. Waveform measures included amplitude spectrum area (AMSA), centroid frequency (CF), mean frequency (MF), and median slope (MS) assessed during CPR-free epochs immediately prior to the initial and second shock. Waveform measures prior to the initial shock and the changes between first and second shock were compared by etiology group. We a priori chose a significance level of 0.01 due to multiple comparisons. Results Of the 430 patients, 35% (n=150) were classified as STEMI, 29% (n=123) as non-STEMI, and 37% (n=157) with non-ischemic arrest. We did not observe differences by etiology in any of the waveform measures prior to shock 1 (Kruskal–Wallis Test) (p=0.28 for AMSA, p=0.07 for CF, p=0.63 for MF, and p=0.39 for MS). We also did not observe differences for change in waveform between shock 1 and 2, or when the two acute ischemia groups (STEMI and non-STEMI) were combined and compared to the non-ischemic group. Conclusion This clinical investigation suggests that waveform measures may not be useful in distinguishing cardiac arrest etiology.

Aim Quantitative waveform measures of the ventricular fibrillation (VF) electrocardiogram (ECG) predict defibrillation outcome. Calculation requires an ECG epoch without chest compression artifact. However, pauses in CPR can adversely affect survival. Thus the potential use of waveform measures is limited by the need to pause CPR. We sought to characterize the relationship between the length of the CPR-free epoch and the ability to predict outcome. Methods We conducted a retrospective investigation using the CPR-free ECG prior to first shock among out-of-hospital VF cardiac arrest patients in a large metropolitan region (n = 442). Amplitude Spectrum Area (AMSA) and Median Slope (MS) were calculated using ECG epochs ranging from 5 s to 0.2 s. The relative ability of the measures to predict return of organized rhythm (ROR) and neurologically-intact survival was evaluated at different epoch lengths by calculating the area under the receiver operating characteristic curve (AUC) using the 5-s epoch as the referent group. Results Compared to the 5-s epoch, AMSA performance declined significantly only after reducing epoch length to 0.2 s for ROR (AUC 0.77–0.74, p = 0.03) and with epochs of ≤0.6 s for neurologically-intact survival (AUC 0.72–0.70, p = 0.04). MS performance declined significantly with epochs of ≤0.8 s for ROR (AUC 0.78–0.77, p = 0.04) and with epochs ≤1.6 s for neurologically-intact survival (AUC 0.72–0.71, p = 0.04). Conclusion Waveform measures predict defibrillation outcome using very brief ECG epochs, a quality that may enable their use in current resuscitation algorithms designed to limit CPR interruption.

Sudden cardiac death (SCD) accounts for >300 000 deaths in the United States annually.1 Although the majority of these deaths occur in low-risk populations2 in which aggressive interventions are not practical, some higher-risk populations have been established in whom intervention with an implantable cardioverter-defibrillator (ICD) has been shown in randomized trials to reduce mortality.3–7 Additionally, there is a population of patients who may benefit from automatic emergency cardioversion-defibrillation but are not deemed appropriate candidates for ICD implantation at the time of presentation. This group is defined by 2 populations. The first subgroup comprises those who are at perceived risk but for whom there may be optimism for clinical improvement (eg, patients soon after revascularization or those with a recent diagnosis of myocardial infarction [MI] or cardiomyopathy). Alternatively stated, the optimal management of these patients at risk (or perceived risk) during the waiting period before an ICD is indicated remains unknown. The second subgroup includes those who have a clear indication for ICD but also have a contraindication to immediate ICD placement (eg, active infection or unknown prognosis). The wearable cardioverter-defibrillator (WCD) is a device designed for patients at risk of SCD who are not immediate candidates for ICD therapy. By providing automatic therapy, the WCD does not depend on a second person to defibrillate, as required with a manual or automated external defibrillator (AED). Unlike the ICD (including both transvenous and subcutaneous devices), the WCD requires no surgical operation, can be provided for a short period of time, is temporary, and is easily removed. These characteristics of the WCD, along with safety and efficacy data presented to the US Food and Drug Administration (FDA), resulted in approval in the United States in 2002.8 Because of the increasing use of the WCD and uncertainty of indications …

Background— Out-of-hospital cardiac arrest (OHCA) claims millions of lives worldwide each year. OHCA survival from shockable arrhythmias (ventricular fibrillation/ tachycardia) improved in several communities after implementation of American Heart Association resuscitation guidelines that eliminated “stacked” shocks and emphasized chest compressions. “Nonshockable” rhythms are now the predominant presentation of OHCA; the benefit of such treatments on nonshockable rhythms is uncertain. Methods and Results— We studied 3960 patients with nontraumatic OHCA from nonshockable initial rhythms treated by prehospital providers in King County, Washington, over a 10-year period. Outcomes during a 5-year intervention period after adoption of new resuscitation guidelines were compared with the previous 5-year historical control period. The primary outcome was 1-year survival. Patient demographics and resuscitation characteristics were similar between the control (n=1774) and intervention (n=2186) groups, among whom 471 of 1774 patients (27%) versus 742 of 2186 patients (34%), respectively, achieved return of spontaneous circulation; 82 (4.6%) versus 149 (6.8%) were discharged from hospital, 60 (3.4%) versus 112 (5.1%) with favorable neurological outcome; 73 (4.1%) versus 135 (6.2%) survived 1 month; and 48 (2.7%) versus 106 patients (4.9%) survived 1 year (all P ≤0.005). After adjustment for potential confounders, the intervention period was associated with an improved odds of 1.50 (95% confidence interval, 1.29–1.74) for return of spontaneous circulation, 1.53 (95% confidence interval, 1.14–2.05) for hospital survival, 1.56 (95% confidence interval, 1.11–2.18) for favorable neurological status, 1.54 (95% confidence interval, 1.14–2.10) for 1-month survival, and 1.85 (95% confidence interval, 1.29–2.66) for 1-year survival. Conclusion— Outcomes from OHCA resulting from nonshockable rhythms, although poor by comparison with shockable rhythm presentations, improved significantly after implementation of resuscitation guideline changes, suggesting their potential to benefit all presentations of OHCA.

Background In a departure from the previous strategy of immediate defibrillation, the 2005 resuscitation guidelines from the American Heart Association–International Liaison Com mittee on Resuscitation suggested that emergency medical service (EMS) personnel could provide 2 minutes of cardiopulmonary resuscitation (CPR) before the first analysis of cardiac rhythm. We compared the strategy of a brief period of CPR with early analysis of rhythm with the strategy of a longer period of CPR with delayed analysis of rhythm. Methods We conducted a cluster-randomized trial involving adults with out-of-hospital cardiac arrest at 10 Resuscitation Outcomes Consortium sites in the United States and Canada. Patients in the early-analysis group were assigned to receive 30 to 60 seconds of EMS-administered CPR and those in the later-analysis group were assigned to receive 180 seconds of CPR, before the initial electrocardiographic analysis. The primary outcome was survival to hospital discharge with satisfactory functional status (a modified Rankin scale score of ≤3, on a scale of 0 to 6, with higher scores indicating greater disability). Results We included 9933 patients, of whom 5290 were assigned to early analysis of cardiac rhythm and 4643 to later analysis. A total of 273 patients (5.9%) in the later-analysis group and 310 patients (5.9%) in the early-analysis group met the criteria for the primary outcome, with a cluster-adjusted difference of −0.2 percentage points (95% confidence interval, −1.1 to 0.7; P = 0.59). Analyses of the data with adjustment for confounding factors, as well as subgroup analyses, also showed no survival benefit for either study group. Conclusions Among patients who had an out-of-hospital cardiac arrest, we found no difference in the outcomes with a brief period, as compared with a longer period, of EMS-administered CPR before the first analysis of cardiac rhythm. (Funded by the National Heart, Lung, and Blood Institute and others; ROC PRIMED ClinicalTrials.gov number, NCT00394706.)

The impedance threshold device (ITD) is designed to enhance venous return and cardiac output during cardiopulmonary resuscitation (CPR) by increasing the degree of negative intrathoracic pressure. Previous studies have suggested that the use of an ITD during CPR may improve survival rates after cardiac arrest.We compared the use of an active ITD with that of a sham ITD in patients with out-of-hospital cardiac arrest who underwent standard CPR at 10 sites in the United States and Canada. Patients, investigators, study coordinators, and all care providers were unaware of the treatment assignments. The primary outcome was survival to hospital discharge with satisfactory function (i.e., a score of ≤3 on the modified Rankin scale, which ranges from 0 to 6, with higher scores indicating greater disability).Of 8718 patients included in the analysis, 4345 were randomly assigned to treatment with a sham ITD and 4373 to treatment with an active device. A total of 260 patients (6.0%) in the sham-ITD group and 254 patients (5.8%) in the active-ITD group met the primary outcome (risk difference adjusted for sequential monitoring, -0.1 percentage points; 95% confidence interval, -1.1 to 0.8; P=0.71). There were also no significant differences in the secondary outcomes, including rates of return of spontaneous circulation on arrival at the emergency department, survival to hospital admission, and survival to hospital discharge.Use of the ITD did not significantly improve survival with satisfactory function among patients with out-of-hospital cardiac arrest receiving standard CPR. (Funded by the National Heart, Lung, and Blood Institute and others; ROC PRIMED ClinicalTrials.gov number, NCT00394706.).

The incidence of ventricular fibrillation or pulseless ventricular tachycardia as the first recorded rhythm after out-of-hospital cardiac arrest has unexpectedly declined. The success of bystander-deployed automated external defibrillators (AEDs) in public settings suggests that this may be the more common initial rhythm when out-of-hospital cardiac arrest occurs in public. We conducted a study to determine whether the location of the arrest, the type of arrhythmia, and the probability of survival are associated.Between 2005 and 2007, we conducted a prospective cohort study of out-of-hospital cardiac arrest in adults in 10 North American communities. We assessed the frequencies of ventricular fibrillation or pulseless ventricular tachycardia and of survival to hospital discharge for arrests at home as compared with arrests in public.Of 12,930 evaluated out-of-hospital cardiac arrests, 2042 occurred in public and 9564 at home. For cardiac arrests at home, the incidence of ventricular fibrillation or pulseless ventricular tachycardia was 25% when the arrest was witnessed by emergency-medical-services (EMS) personnel, 35% when it was witnessed by a bystander, and 36% when a bystander applied an AED. For cardiac arrests in public, the corresponding rates were 38%, 60%, and 79%. The adjusted odds ratio for initial ventricular fibrillation or pulseless ventricular tachycardia in public versus at home was 2.28 (95% confidence interval [CI], 1.96 to 2.66; P0.001) for bystander-witnessed arrests and 4.48 (95% CI, 2.23 to 8.97; P0.001) for arrests in which bystanders applied AEDs. The rate of survival to hospital discharge was 34% for arrests in public settings with AEDs applied by bystanders versus 12% for arrests at home (adjusted odds ratio, 2.49; 95% CI, 1.03 to 5.99; P = 0.04).Regardless of whether out-of-hospital cardiac arrests are witnessed by EMS personnel or bystanders and whether AEDs are applied by bystanders, the proportion of arrests with initial ventricular fibrillation or pulseless ventricular tachycardia is much greater in public settings than at home. The incremental value of resuscitation strategies, such as the ready availability of an AED, may be related to the place where the arrest occurs.

Objectives: Procainamide is an antiarrhythmic drug of unproven efficacy in cardiac arrest. The association between procainamide and survival from out-of-hospital cardiac arrest was investigated to better determine the drug’s potential role in resuscitation. Methods: The authors conducted a 10-year study of all witnessed, out-of-hospital, ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) cardiac arrests treated by emergency medical services (EMS) in King County, Washington. Patients were considered eligible for procainamide if they received more than three defibrillation shocks and intravenous (IV) bolus lidocaine. Four logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CI) describing the relationship between procainamide and survival. Results: Of the 665 eligible patients, 176 received procainamide, and 489 did not. On average, procainamide recipients received more shocks and pharmacologic interventions and had lengthier resuscitations. Adjusted for their clinical and resuscitation characteristics, procainamide recipients had a lower likelihood of survival to hospital discharge (OR = 0.52; 95% CI = 0.36 to 0.75). Further adjustment for receipt of other cardiac medications during resuscitation negated this apparent adverse association (OR = 1.02; 95% CI = 0.66 to 1.57). Conclusions: In this observational study of out-of-hospital VF and pulseless VT arrest, procainamide as second-line antiarrhythmic treatment was not associated with survival in models attempting to best account for confounding. The results suggest that procainamide, as administered in this investigation, does not have a large impact on outcome, but cannot eliminate the possibility of a smaller, clinically relevant effect on survival. ACADEMIC EMERGENCY MEDICINE 2010; 17:617–623 © 2010 by the Society for Academic Emergency Medicine

Lethal ventricular arrhythmias responsible for sudden cardiac arrest (SCA) have been attributed to multiple causes. Evidence points to the important role of the autonomic nervous system (ANS) in producing susceptibility to ventricular fibrillation in subsets of patients with heart disease. Findings demonstrate that patients at risk for cardiac arrest exhibit a reduction in parasympathetic nervous system activity. Protection against SCA may be achieved through mechanisms that increase parasympathetic tone,1 exercise being one of these therapies.2 Exercise interventions in cardiac arrest survivors who have an implantable cardioverter defibrillator (ICD) have not been well studied. Health care providers are often reluctant to prescribe exercise for this group because of the belief that it will provoke ventricular arrhythmias and cardiac arrest. Patients are often afraid to exercise because of concern for receiving an ICD shock. It has been unclear if the amount of exercise required to improve cardiopulmonary function and parasympathetic nervous system activity can be achieved in this group. However, exercise offers the potential benefit of stabilization of autonomic function and protection against future arrhythmic occurrences, in a population of cardiac patients who could potentially benefit the most.3 Exercise training is an inexpensive, non-pharmacological intervention that is essentially available to everyone. Therefore the purpose of this study was to determine the impact of 8 weeks of aerobic exercise on: 1) cardiopulmonary fitness and activity, 2) heart rate variability (HRV), 3) health outcomes, and 4) high sensitivity C-reactive protein (hsCRP) in persons who have an ICD for the secondary prevention of cardiac arrest. Follow-up at 6 months after completing the exercise program was done to determine if early effects of aerobic training were sustained.