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Background: Studies examining gender-based differences in outcomes of patients experiencing out-of-hospital cardiac arrest have demonstrated that, despite a higher likelihood of return of spontaneous circulation, women do not have higher survival. Methods: Patients successfully resuscitated from out-of-hospital cardiac arrest enrolled in the CCC trial (Trial of Continuous or Interrupted Chest Compressions during CPR) were included. Hierarchical multivariable logistic regression models were constructed to evaluate the association between gender and survival after adjustment for age, gender, cardiac arrest rhythm, witnessed status, bystander cardiopulmonary resuscitation, episode location, epinephrine dose, emergency medical services response time, and duration of resuscitation. Do not resuscitate (DNR) and withdrawal of life-sustaining therapy (WLST) order status were used to assess whether differences in postresuscitation outcomes were modified by baseline prognosis. The analysis was replicated among ALPS trial (Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest) participants. Results: Among 4875 successfully resuscitated patients, 1825 (37.4%) were women and 3050 (62.6%) were men. Women were older (67.5 versus 65.3 years), received less bystander cardiopulmonary resuscitation (49.1% versus 54.9%), and had a lower proportion of cardiac arrests that were witnessed (55.1% versus 64.5%) or had shockable rhythm (24.3% versus 44.6%, P P =0.009) and had WLST (32.8% versus 29.8%, P =0.03). Discharge survival was significantly lower in women (22.5% versus 36.3%, P P =0.005). The association between gender and survival to discharge was modified by DNR and WLST order status such that women had significantly reduced survival to discharge among patients who were not designated DNR (31.3% versus 49.9%, P =0.005; adjusted odds ratio, 0.74 [95% CI, 0.60–0.91]) or did not have WLST (32.3% versus 50.7%, P =0.002; adjusted odds ratio, 0.73 [95% CI, 0.60–0.89]). In contrast, no gender difference in survival was noted among patients receiving a DNR order (6.7% versus 7.4%, P =0.90) or had WLST (2.8% versus 2.4%, P =0.93). Consistent patterns of association between gender and postresuscitation outcomes were observed in the secondary cohort. Conclusions: Among patients resuscitated after experiencing out-of-hospital cardiac arrest, discharge survival was significantly lower in women than in men, especially among patients considered to have a favorable prognosis.

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.

Introduction: Current patterns of use of coronary angiography (CAG) among out-of-hospital cardiac arrest (OHCA) patients based on ST segment elevation (STE) on post-resuscitation ECG are not well described. Methods: Using data from the Continuous Chest Compressions trial between 2011 and 2016, we identified OHCA patients who survived to hospitalization. We examined rates of CAG across different trial clusters in the overall cohort and among pre-specified subgroups with presumed cardiac etiology of arrest e.g. initial shockable rhythm and STE on presenting ECG. Results: Of 26,148 OHCA patients across 49 trial clusters, 5608 survived to hospital admission. The mean age of patients was 64 years, with 65% men and 43% with initial shockable rhythm. Among patients with initial shockable rhythm 44% had STE on initial ECG compared with 18% of patients with initial non-shockable rhythm. Use of CAG was significantly higher in patients presenting with STE compared with no STE on initial ECG irrespective of initial rhythm: 70% vs. 31%, pFigure ). This variation persisted among pre-specified subgroups with the proportion of patients within a trial cluster receiving CAG ranged from 11% - 75% for patients with initial shockable rhythm, 0% to 19% with initial non-shockable rhythm, 16% - 82% with STE, 2% - 28% without STE and 0% - 63% in patients with initial shockable rhythm and no STE on presenting ECG ( Figure ). Conclusion: There is a higher use of CAG in STE and shockable cardiac arrest, consistent with presumed cardiac etiology of arrest; however, there is large variation in the use of CAG across sites, even among patients with a presumed cardiac etiology of cardiac arrest suggesting challenges with interpretation of current guidelines.

Introduction: Since March, the CDC has reported weekly excess deaths of up to 40% in the US. Spikes in excess deaths were associated with spikes in COVID-19 cases. In Texas, 55% of excess deaths from March 1 to May 30, 2020 were unattributed to COVID-19. One possible source of this unaccounted excess death is out-of-hospital cardiac arrest, which corresponds to a notable decline in hospitalizations for acute cardiovascular events. Objective: To compare the number of out-of-hospital cardiac arrest (OOHCA) and dead-on-scene cases in Dallas, Texas in years prior to and during the COVID-19 pandemic. Methods: The Dallas-Fort Worth Center for Resuscitation Research Cardiac Arrest Registry provided data for this IRB-approved study. Eligible cases were non-traumatic OOHCAs who received cardiopulmonary resuscitation (CPR) from emergency medical services (EMS) providers. We compared monthly case numbers in 2017, 2018, and 2019 with case numbers in 2020 at the time of the COVID-19 pandemic in Dallas, TX. Additionally, we compared the numbers of non-traumatic deaths (declared dead on scene without receiving CPR from EMS providers) in the same timeframes. Results: While total counts of out-of-hospital cardiac arrest during the months of March to June decreased from 2017 to 2019 by 9.2% and 1.2% respectively, the number of cardiac arrest cases rose dramatically by 47.9% in 2020 (p < 0.05).(Table) The percentage of OOHCAs with an initial rhythm of asystole increased as well, from 50.1% in 2018 and 2019 to 60.4% in 2020. The total number of dead-on-scene cases was also higher in March to June 2020 than in 2017 to 2019 (NS). Conclusion: Increased out-of-hospital cardiac arrest is likely contributing to the unattributed excess deaths noted during the months of the COVID-19 pandemic in Dallas, TX. The rise in cases may be indirectly attributable to COVID-19 as cardiovascular events go untreated or treated too late.

Background: There is an urgent need to identify strategies which improve outcomes for out-of-hospital cardiac arrest (OHCA). Determining the optimal access route to deliver medications during resuscitation from OHCA may be one such strategy. Methods: Using data from the Continuous Chest compression trial between 2011 and 2016, we examined rates of sustained return of spontaneous circulation (ROSC) i.e. ROSC on ER arrival, survival to discharge and survival with favorable neurological function (modified Rankin scale ≤3) among patients with attempted IV and IO access. Results: Among 19,731 patients with available access information, IO or IV access was attempted in 3,068 (15.5%) and 16,663 (84.5%) patients, respectively and was successful in 2,975 (97%) and 15,485 (92%) of these patients. Overall, patients with attempted IO access were younger, more likely female, received less bystander CPR, had lower proportions of shockable and witnessed arrests, marginally faster times to access and to epinephrine administration, and less frequently received therapeutic hypothermia and coronary angiography as compared with patients with IV access ( Table ) . Unadjusted rates of sustained ROSC, discharge survival and survival with favorable neurological function were significantly lower in patients with attempted IO access ( Table) . After adjustment for age, sex, initial rhythm, bystander CPR, public location, witnessed status, EMS response time and trial cluster, attempted IO access was associated with lower sustained ROSC rates (OR 0.79, 95% CI 0.71-0.89, p Conclusions: Among patients with OHCA, intraosseous access was attempted in 1 in 7 OHCA patients and associated with worse ROSC rates but no difference in survival. Further studies are necessary to elucidate the optimal access route among OHCA patients.

Background: Previous studies examining sex-based differences among out-of-hospital cardiac arrest (OHCA) patients have been conflicting. Methods: Patients with OHCA enrolled in the Continuous Chest Compression trial between 2011 and 2016 were included in the present analysis. Hierarchical multivariable logistic regression models were constructed to evaluate the association between sex and sustained ROSC i.e. ROSC on ER arrival, discharge survival and survival with favorable neurological function after adjustment for age, witnessed status, presenting rhythm, public location, bystander CPR, resuscitation duration, and EMS response time. Results: Among 22,540 OHCA patients, 8,099 (35.9%) were women. Women were older (median 71 vs. 67 years), received less bystander CPR (45% vs. 47%), and had a lower proportion of cardiac arrests that were witnessed (39% vs. 45%) or had an initial shockable rhythm (15% vs. 28%, pTable ) but no difference in likelihood of discharge survival and survival with favorable neurological function. In the adjusted landmark analysis beginning after achieving ROSC, women had significantly lower likelihood of discharge survival and survival with favorable neurological function ( Table ) . Conclusions: Among resuscitated OHCA patients, women have a higher likelihood of achieving sustained ROSC despite a higher burden of poor prognostic factors. However, after successful ROSC, the likelihood of discharge survival is significantly lower in women (vs. men). Future studies are needed to understand how care provided post-ROSC may modify the sex-disparities in discharge survival outcomes.

Background: Chronic kidney disease (CKD) and acute kidney injury (AKI) have both been associated with adverse short-term outcomes after MI. However, the impact of AKI on long-term outcomes and the interaction of AKI with baseline renal function have not been well described. Methods: ACTION Registry®-GWTGTM records from 2008-2012 were linked to Medicare data yielding a population of 76,500 acute MI patients from 581 hospitals who survived to hospital discharge. We excluded patients with cardiogenic shock, cardiac arrest, and those undergoing CABG or currently on dialysis. CKD status was defined using the Kidney Disease Outcome Quality Initiative criteria based on admission GFR estimated using the MDRD equation. No, mild, moderate and severe AKI were defined as changes in creatinine (Cr) from baseline to peak of < 0.3, 0.3 to < 0.5, 0.5 to < 1.0 and ≥ 1.0 mg/dl respectively. Cox proportional hazard modeling was used to examine associations between AKI and 1-year mortality. Covariates for risk adjustment were adapted from the CRUSADE long-term mortality risk model. Results: The median age was 77 years, 30% had STEMI and 78% underwent diagnostic angiography.The incidence of mild, moderate and severe AKI was 7.5%, 6.0% and 3.0%. CKD stages 3, 4, and 5 were present in 41.2%, 6.7%, and 1.0% of patients. Both CKD and AKI were significantly associated with 1-year mortality (p< 0.0001 for each). A significant interaction was noted between CKD and AKI with respect to 1-year mortality (p-interaction Conclusion: One-year mortality increased in proportion to severity of AKI, with even a small increase in Cr associated with worse outcomes. The association of AKI with outcomes was modified by baseline Cr, with a greater impact of AKI observed among patients with higher baseline eGFR.

Introduction: Current guidelines recommend supervised exercise training (SET) as the initial treatment modality for patients with intermittent claudication (IC), in addition to optimal medical therapy. The role of endovascular revascularization (ER) as a primary treatment option has been controversial. We performed a meta-analysis to compare the efficacy of initial ER vs. initial SET in patients with IC using data from randomized controlled trials. Methods: The primary outcome was treadmill-measured maximum walking distance (MWD) at the end of follow-up. Secondary outcomes included resting ankle brachial index (ABI) and treadmill-measured ischemic claudication distance (ICD) on follow-up. Risk of adverse limb events (revascularization, amputations) was also compared between the two groups. Random effects models were used for all analyses. Results: We included 1,145 patients from nine trials with a mean follow up duration of 13.7 months (42% aortoiliac lesions; 35% stent use; mean baseline ABI 0.64 vs. 0.67 for ER vs. SET). Follow-up MWD was not significantly different between patients undergoing ER vs. SET [Weighted mean difference (WMD) (95% CI): 19.1 m (-79.6 to 117.8 m); publication bias p=0.86]. Metaregression did not identify significant differences based on stent use or presence of aortoiliac disease. ICD was also similar between the two groups [WMD (95% CI): 36.1 m (-99.4 to 171.5 m)]. In contrast, patients undergoing ER had higher resting ABI on follow-up [WMD (95% CI): 0.14 (0.11 to 0.17), p Conclusion: Compared with initial SET, initial ER significantly improves resting ABI values. Although longer walking distance and lower rates of adverse limb events also appeared favorable for ER, these differences were not statistically significant in these intermediate term studies. Longer-term studies and those incorporating contemporary revascularization techniques are necessary.