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Background The aspects of extracorporeal cardiopulmonary resuscitation critical for reestablishing an organized rhythm and subsequent functional survival are unclear. This study characterizes the impact of reperfusion with extracorporeal membrane oxygenation (ECMO) and percutaneous coronary interventions (PCI) on achieving an organized rhythm in patients with refractory shockable out‐of‐hospital cardiac arrest (OHCA). Methods and Results Two hundred eighty‐nine consecutive patients in refractory shockable OHCA were placed on ECMO followed by coronary angiogram (n=289) and PCI (n=165). Patients were grouped based on the extracorporeal cardiopulmonary resuscitation stage where a sustained organized rhythm was achieved. Survival outcomes were evaluated by using the Cerebral Performance Category. Logistic regression analysis was performed to determine the relationship between Cerebral Performance Category and timing of organized rhythm. Standard advanced cardiac life support before hospital arrival resulted in 148 of 289 (51%) patients attaining an organized rhythm while 87 of 289 (30%) achieved an organized rhythm post ECMO cannulation but before PCI, and 37 of 289 (13%) achieved an organized rhythm following PCI. Obstructive coronary artery disease was observed in 192 of 289 (66%) patients. A total of 144 of 192 (75%) patients with obstructive coronary artery disease converted to an organized rhythm before PCI and 37 of 192 (19%) following PCI. Cerebral Performance Category score 1 or 2 was significantly more likely in patients with cardiac arrest and obstructive coronary artery disease who achieved an organized rhythm before PCI (odds ratio [OR], 3.9 [95% CI, 1.2–12.0], P=0.024). Conclusions Most patients undergoing extracorporeal cardiopulmonary resuscitation for refractory OHCA due to shockable rhythms achieved an organized rhythm before PCI independent of coronary artery disease burden. Also, neurologically favorable survival was more prevalent in those attaining an organized rhythm before PCI.

Background: The role of hypothermia in post-arrest neuroprotection is controversial. Animal studies suggest potential benefits with lower temperatures, but high-fidelity ECPR models evaluating temperatures below 30 °C are lacking. Objectives: To determine whether rapid cooling to 24 °C initiated upon reperfusion reduces brain injury compared to 34 °C in a swine model of ECPR. Methods: Twenty-four female pigs had electrically induced VF and mechanical CPR for 30 min. Animals were cannulated for VA-ECMO and cooled to either 34 °C for 4 h (n = 8), 24 °C for 1 h with rewarming to 34 °C over 3 h (n = 7), or 24 °C for 4 h without rewarming (n = 9). Cooling was initiated upon VA-ECMO reperfusion by circulating ice water through the oxygenator. Brain temperature and cerebral and systemic hemodynamics were continuously monitored. After four hours on VA-ECMO, brain tissue was obtained for examination. Results: Target brain temperature was achieved within 30 min of reperfusion (p = 0.74). Carotid blood flow was higher in the 24 °C without rewarming group throughout the VA-ECMO period compared to 34 °C and 24 °C with rewarming (p

Introduction: Epinephrine has been the main drug recommended for decades during cardiopulmonary resuscitation (CPR). But epinephrine’s ß-adrenergic effects might increase myocardial oxygen consumption and may cause arrythmias after ROSC. Norepinephrine has a weaker ß-adrenergic effect and could be useful during CPR. Studies on norepinephrine’s effect on hemodynamic parameters and cerebral perfusion are scarce. This study aimed to assess norepinephrine's hemodynamic impact in an experimental model of cardiac arrest. Methods: After an initial dose study to determine the optimal dose, we conducted a prospective randomized study with 19 pigs. After 3 minutes of untreated ventricular fibrillation, animals received boluses of 0.5 mg Epinephrine (EPI) or 1 mg Norepinephrine (NE) every 5 minutes during CPR. Coronary perfusion pressure (CPP), carotid blood flow (CBF) and cerebral perfusion pressure (CePP) were evaluated. Results: At baseline, hemodynamic parameters did not differ between the two groups. During CPR, CPP and CBF were similar: 17.3 (12.8; 31.8) in the EPI group vs 16.0 (11.1; 37.7) in the NE group, p = 0.9 and 28.4 (22.0; 54.8) vs 30.8 (12.2; 56.3) respectively, p = 0.9. CePP was not significantly lower during resuscitation in the NE group compared to the EPI group: 12.2 (−8.2; 42.2) vs 7.8 (−2.0; 32.0) p = 0.4. Survival rate was low with only one animal in the EPI group and 2 in the NE group. Conclusion: Cerebral perfusion pressure, coronary perfusion pressure and carotid blood flow during CPR did not significantly differ between the norepinephrine group and the epinephrine group. Further investigations should evaluate different options such as a continuous NE infusion.

Background Extracorporeal cardiopulmonary resuscitation improves outcomes after out‐of‐hospital cardiac arrest. However, bleeding and thrombosis are common complications. We aimed to describe the incidence and predictors of bleeding and thrombosis and their association with in‐hospital mortality. Methods and Results Consecutive patients presenting with refractory ventricular tachycardia/ventricular fibrillation out‐of‐hospital cardiac arrest between December 2015 and March 2022 who met the criteria for extracorporeal cardiopulmonary resuscitation initiation at our center were included. Major bleeding was defined by the Extracorporeal Life Support Organization's criteria. Adjusted analyses were done to seek out risk factors for bleeding and thrombosis and evaluate their association with mortality. Major bleeding occurred in 135 of 200 patients (67.5%), with traumatic bleeding from cardiopulmonary resuscitation in 73 (36.5%). Baseline demographics and arrest characteristics were similar between groups. In multivariable analysis, decreasing levels of fibrinogen were independently associated with bleeding (adjusted hazard ratio [aHR], 0.98 per every 10 mg/dL rise [95% CI, 0.96–0.99]). Patients who died had a higher rate of bleeds per day (0.21 versus 0.03, P

Introduction: Failure to restore spontaneous circulation remains a major cause of death for cardiac arrest (CA) patients. Mechanical circulatory support, specifically extracorporeal cardiopulmonary resuscitation (ECPR), has emerged as a feasible and efficacious rescue strategy for selected refractory CA patients. Methods: Mechanical Circulatory Support was one of six focus topics for the Wolf Creek XVII Conference held on June 14–17, 2023 in Ann Arbor, Michigan, USA. Conference invitees included international thought leaders and scientists in the field of CA resuscitation from academia and industry. Participants submitted via online survey knowledge gaps, barriers to translation and research priorities for each focus topic. Expert panels used the survey results and their own perspectives and insights to create and present a preliminary unranked list for each category that was debated, revised and ranked by all attendees to identify the top 5 for each category. Results: Top 5 knowledge gaps included optimal patient selection, pre-ECPR treatments, logistical and programmatic characteristics of ECPR programs, generalizability and effectiveness of ECPR, and prevention of reperfusion injury. Top 5 barriers to translation included cost/resource limitations, technical challenges, collaboration across multiple disciplines, limited patient population, and early identification of eligible patients. Top 5 research priorities focused on comparing the outcomes of prehospital/rapid transport strategies vs in-hospital ECPR initiation, implementation of high-performing ECPR system vs standard care, rapid patient identification tools vs standard clinical judgment, post-cardiac arrest bundled care vs no bundled care, and standardized ECPR clinical protocol vs routine care. Conclusion: This overview can serve as an innovative guide to transform the care and outcome of patients with refractory CA.

BackgroundPulmonary capillary wedge pressure (PCWP) is often used as a surrogate for left-ventricular end-diastolic pressure in patients (LVEDP) who are on veno-arterial extracorporeal membrane oxygenation (V-A ECMO) support for cardiogenic shock and cardiac arrest. However, the correlation between PCWP and LVEDP is not clear in the setting of V-A ECMO usage. We sought to evaluate this correlation in this case series.MethodsPatients were referred to our cardiac catheterization laboratory for invasive hemodynamic studies to assess their readiness for VA-ECMO decannulation. All patients underwent simultaneous left and right heart catheterization. Using standard techniques, we measured PCWP and LVEDP simultaneously. Continuous variables were reported as medians with interquartile ranges. The correlation between PCWP and LVEDP was evaluated using simple linear regression and reported as R2.ResultsFour patients underwent invasive hemodynamic studies 4 (2.5, 7) days after VA-ECMO cannulation. All four patients had suffered in-hospital cardiac arrest and had been put on VA-ECMO. At the baseline level of VA-ECMO flow of 4.1 (3.8, 4.4) L/min, the median LVEDP and PCWP were 6 (4, 7.5) mmHg and 12 (6.5, 16) mmHg, respectively. At the lowest level of VA-ECMO flow of 1.9 (1.6, 2.0) L/min, the median LVEDP and PCWP was 13.5 (8.5, 16) mmHg and 15 (13, 18) mmHg, respectively. There was a poor correlation between the simultaneously measured PCWP and LVEDP (R2 = 0.03, p = 0.66).ConclusionsThe PCWP may not correlate well with LVEDP in patients treated with VA-ECMO, particularly at high levels of VA-ECMO support.

There are 350,000 out-of-hospital cardiac arrest (OHCA) cases annually in the United States of America. Using automated external defibrillators (AEDs) has increased survival in cardiac arrests (CA) with an initial shockable rhythm. Thus, guidelines recommend complete geographical coverage with AEDs. To fill in the gaps in Minnesota, the Center for Resuscitation Medicine at the University of Minnesota raised an $18.8 million grant from the Helmsley Charitable Trust to supply law enforcement first responders with AEDs and, thus, increase survival rates after OHCA by reducing the time to first shock. This report elaborates on the decision-making, fundraising, and logistic strategy required to reach statewide AED coverage. Methods: The baseline need for AEDs was analyzed using a questionnaire sent out to state law enforcement agencies, state patrols, city and county agencies, and tribal agencies in 2021. Furthermore, OHCA cases of 2021 were reviewed. The combination of this information led to an action plan to equip and train all agencies throughout the state's eight regions with AEDs. Results: The electronic survey was initially sent out to 358 agencies. The initial response rate was 77% (n = 276). This resulted in a total need of 8300 AEDs to be deployed over three years (2022–2025). As of 2023, over 4769 AEDs have been distributed, covering 237 sites. Conclusion: By equipping first responders with AED systems, the Center for Resuscitation Medicine aims to shorten the gap in statewide AED coverage, thus increasing the chances of survival after OHCA.

Background: Chest compressions (CC) are the cornerstone of cardiopulmonary resuscitation (CPR). But CC are also known to cause injuries, specifically rib fractures. The effects of such fractures have not been examined yet. This study aimed to investigate hemodynamic effects of rib fractures during mechanical CPR in a porcine model of cardiac arrest (CA). Methods: We conducted a retrospective hemodynamic study in 31 pigs that underwent mechanical CC. Animals were divided into three groups based on the location of rib fractures: No Broken Ribs group (n = 11), Left Broken Ribs group (n = 13), and Right Broken Ribs group (n = 7). Hemodynamic measurements were taken at 10 seconds before and 10, 30, and 60 seconds after rib fractures. Results: Baseline hemodynamic parameters did not differ between the three groups. Systolic aortic pressure was overall higher in the Left Broken Ribs group than in the No Broken Ribs group at 10, 30, and 60 seconds after rib fracture (p = 0.02, 0.01, and 0.006, respectively). The Left Broken Ribs group had a significantly higher right atrial pressure compared to the No Broken Rib group after rib fracture (p = 0.02, 0.01, and 0.03, respectively). There was no significant difference for any parameter for the Right Broken Ribs group, when compared to the No Broken Ribs group. Conclusion: An increase in main hemodynamic parameters was observed after left rib fractures while right broken ribs were not associated with any change in hemodynamic parameters. Reporting fractures and their location seems worthwhile for future experimental studies.

Summary: Background: Refractory out-of-hospital cardiac arrest (OHCA) treated with standard advanced cardiac life support (ACLS) has poor outcomes. Transport to hospital followed by in-hospital extracorporeal cardiopulmonary resuscitation (ECPR) initiation may improve outcomes. We performed a pooled individual patient data analysis of two randomised controlled trials evaluating ECPR based approach in OHCA. Methods: The individual patient data from two published randomised controlled trials (RCTs) were pooled: ARREST (enrolled Aug 2019–June 2020; NCT03880565) and PRAGUE-OHCA (enrolled March 1, 2013–Oct 25, 2020; NCT01511666). Both trials enrolled patients with refractory OHCA and compared: intra-arrest transport with in-hospital ECPR initiation (invasive approach) versus continued standard ACLS. The primary outcome was 180-day survival with favourable neurological outcome (defined as Cerebral Performance Category 1–2). Secondary outcomes included: cumulative survival at 180 days, 30-day favourable neurological survival, and 30-day cardiac recovery. Risk of bias in each trial was assessed by two independent reviewers using the Cochrane risk-of-bias tool. Heterogeneity was assessed via Forest plots. Findings: The two RCTs included 286 patients. Of those randomised to the invasive (n = 147) and standard (n = 139) groups, respectively: the median age was 57 (IQR 47–65) and 58 years (IQR 48–66), and the median duration of resuscitation was 58 (IQR 43–69) and 49 (IQR 33–71) minutes (p = 0.17). In a modified intention to treat analysis, 45 (32.4%) in the invasive and 29 (19.7%) patients in the standard arm survived to 180 days with a favourable neurological outcome [absolute difference (AD), 95% CI: 12.7%, 2.6–22.7%, p = 0.015]. Forty-seven (33.8%) and 33 (22.4%) patients survived to 180 days [HR 0.59 (0.43–0.81); log rank test p = 0.0009]. At 30 days, 44 (31.7%) and 24 (16.3%) patients had favourable neurological outcome (AD 15.4%, 5.6–25.1%, p = 0.003), 60 (43.2%), and 46 (31.3%) patients had cardiac recovery (AD: 11.9%, 0.7–23%, p = 0.05), in the invasive and standard arms, respectively. The effect was larger in patients presenting with shockable rhythms (AD 18.8%, 7.6–29.4; p = 0.01; HR 2.26 [1.23–4.15]; p = 0.009) and prolonged CPR (>45 min; HR 3.99 (1.54–10.35); p = 0.005). Interpretation: In patients with refractory OHCA, the invasive approach significantly improved 30- and 180-day neurologically favourable survival. Funding: None.

Arrhythmogenic cardiovascular disorders are associated with considerable morbidity and mortality. Whether cardiac conduction disease is caused by genetic defects, procedural perturbations, valvular disease, ischemia, aging, or heart failure, new therapies are warranted. In this issue of the JCI, Goodyer et al. used state-of-the-art technologies to image the cardiac conduction system (CCS) in real time and to deliver targeted therapies to the CCS and its subcomponents. These findings advance the ability to image and treat specific lineages within the adult heart with the potential for broader applications in the treatment of cardiovascular diseases.

Background: Paravalvular leak (PVL) is a frequent TAVR complication. Prospective identification of patients who are likely to develop PVL after TAVR would likely lead to improved outcomes. Prior studies have used geometric characteristics to predict the likelihood of PVL development, but prediction and quantification has not been done. One of the reasons is that it is difficult to predict the mechanical deformation of the native diseased aortic valve prior to implantation of the prosthetic valve, as existing calcifications likely contribute to the seal between the prosthetic valve and the aortic annulus. However, the relatively amount the native valve plays in preventing PVL is unknown.Methods: A retrospective chart review was conducted identifying patients with mild or greater PVL. One patient who had substantial PVL was identified and a 3D printed (pre-TAVR) aortic root was created. Balloon-expandable TAVR stent frames were implanted within the 3D printed root and a new model was created. Using this geometry, computational fluid dynamics (CFD) simulations were done to quantify PVL. The PVL flow path was iteratively decreased to simulate the space occupied by a crushed native aortic valve and PVL was quantified.Results: PVL was found to decrease as the space occupying the PVL area increased, demonstrating that the native aortic valve contributes to reducing regurgitation. CFD simulations demonstrated that within the patient analyzed, the native valve occupies between 3–40% of the PVL pathway.Conclusion:A priori techniques that predict the development of post TAVR PVL should account for the native diseased valve as our simulations demonstrate that it plays a role in reducing PVL.

Objectives: To investigate the baseline risk of patients treated with Extracorporeal Cardiopulmonary Membrane Oxygenation (ECMO) in relation to cannulation strategy and indication for ECMO as well as the relation of cannulation strategy with survival and secondary hospitalization outcomes. Methods: Severity of illness and predicted mortality risk were assessed in 317 patients. Central cannulation was used in 52 patients unable to wean off cardiopulmonary bypass after cardiac surgery. Peripheral cannulation was used in 179 patients for extracorporeal cardiopulmonary resuscitation (eCPR) and in 86 patients who received ECMO for refractory cardiogenic shock (RCS). Results: Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were significantly worse (P

Acute myocardial infarction (AMI) leads to localized cardiac ischemia and can be fatal if untreated. Despite being treatable, the threat of ischemia-reperfusion (IR) injury remains high. Mitochondria are central to both propagation and mitigation of IR injury, and cardiac mitochondria are categorized into two major subtypes—subsarcolemmal and interfibrillar mitochondria (SSM and IFM, respectively). We hypothesized that, in our pre-clinical porcine model of AMI, SSM and IFM are differentially affected by reperfusion. AMI was induced in female pigs by balloon occlusion of the left anterior descending artery for 45 min, followed by 4 h of reperfusion. At the end of reperfusion, animals were euthanized. Cardiac SSM and IFM from the affected ischemic area and a nearby non-ischemic area were isolated to compare mitochondrial function using substrates targeting mitochondrial electron transport chain complexes I and II. Despite detecting overall significant differences in mitochondrial function including yield, mitochondrial S3 and S4 respirations, and calcium retention, consistent individual functional differences in the two mitochondrial subpopulations were not observed, both between the two mitochondrial subtypes, as well as between the ischemic and non-ischemic tissue. Nonetheless, this study describes the mitochondrial subtype response within the initial few hours of reperfusion in a clinically relevant model of AMI, which provides valuable information needed to develop novel mitochondrially targeted therapies for AMI.

Immune-mediated coronary spasm, called Kounis syndrome (KS), is not rare but is underdiagnosed. In this report, we present a case of KS induced by iodinated contrast resulting in cardiac arrest, requiring temporary mechanical circulatory support. We show angiographic evidence of KS and outline commonly associated clinical features that may predict KS. (Level of Difficulty: Beginner.)

Summary: Sodium nitroprusside–enhanced cardiopulmonary resuscitation has shown superior resuscitation rates and neurologic outcomes in large animal models supporting the need for a randomized human clinical trial. This study is the first to show nonselective pulmonary vasodilation as a potential mechanism for the hemodynamic benefits. The pulmonary shunting that is created requires increased oxygen treatment, but the overall improvement in blood flow increases minute oxygen delivery to tissues. In this context, hypoxemia is an important safety endpoint and a 100% oxygen ventilation strategy may be necessary for the first human clinical trial. Key Words: cardiopulmonary resuscitation, coronary perfusion pressure, lactic acid, pulmonary vasodilation, sodium nitroprusside

Abstract Objectives To evaluate invasive hemodynamics in assessing MC therapy success as well as evaluate its effectiveness as a predictor of functional outcomes. Background Mitral regurgitation grade is a poor predictor of functional outcomes after a MitraClip. There is a paucity of data on invasive hemodynamics as a predictor of outcomes. Methods Sixty‐nine patients underwent MC between 2015 and 2018 at the University of Minnesota Medical Center and were retrospectively analyzed. Invasive hemodynamics were performed before and after device deployment with transesophageal echocardiographic guidance. Statistical analysis was performed using STATA version 16. Student's t test was used for continuous variables and Pearson's chi‐squared test for categorical variables. Mann‐Whitney test was performed for continuous variables where data were not normally distributed. Logistic and linear regression were used to investigate relationships between variables and outcomes. Results A total of 69 patients were included in the study. The mean age was 83 (75‐87) years and 38 (55%) were male. Eighty‐one percentage had >/= NYHA III symptoms. Eighty‐seven percentage had severe MR. Pulmonary capillary wedge pressure was 20 (15‐24). Overall, there was significant improvement in left atrial pressure including mean left atrial pressure index, MR, and NYHA class after MC (

Objectives:. To construct a highly detailed yet practical, attainable roadmap for enhancing the likelihood of neurologically intact survival following sudden cardiac arrest. Design, Setting, and Patients:. Population-based outcomes following out-of-hospital cardiac arrest were collated for 10 U.S. counties in Alaska, California, Florida, Ohio, Minnesota, Utah, and Washington. The 10 identified emergency medical services systems were those that had recently reported significant improvements in neurologically intact survival after introducing a more comprehensive approach involving citizens, hospitals, and evolving strategies for incorporating technology-based, highly choreographed care and training. Detailed inventories of in-common elements were collated from the ten 9-1-1 agencies and assimilated. For reference, combined averaged outcomes for out-of-hospital cardiac arrest occurring January 1, 2017, to February 28, 2018, were compared with concurrent U.S. outcomes reported by the well-established Cardiac Arrest Registry to Enhance Survival. Interventions:. Most commonly, interventions and components from the ten 9-1-1 systems consistently included extensive public cardiopulmonary resuscitation training, 9-1-1 system-connected smart phone applications, expedited dispatcher procedures, cardiopulmonary resuscitation quality monitoring, mechanical cardiopulmonary resuscitation, devices for enhancing negative intrathoracic pressure regulation, extracorporeal membrane oxygenation protocols, body temperature management procedures, rapid cardiac angiography, and intensive involvement of medical directors, operational and quality assurance officers, and training staff. Measurements and Main Results:. Compared with Cardiac Arrest Registry to Enhance Survival (n = 78,704), the cohorts from the 10 emergency medical services agencies examined (n = 2,911) demonstrated significantly increased likelihoods of return of spontaneous circulation (mean 37.4% vs 31.5%; p < 0.001) and neurologically favorable hospital discharge, particularly after witnessed collapses involving bystander cardiopulmonary resuscitation and shockable cardiac rhythms (mean 10.7% vs 8.4%; p < 0.001; and 41.6% vs 29.2%; p < 0.001, respectively). Conclusions:. The likelihood of neurologically favorable survival following out-of-hospital cardiac arrest can improve substantially in communities that conscientiously and meticulously introduce a well-sequenced, highly choreographed, system-wide portfolio of both traditional and nonconventional approaches to training, technologies, and physiologic management. The commonalities found in the analyzed systems create a compelling case that other communities can also improve out-of-hospital cardiac arrest outcomes significantly by conscientiously exploring and adopting similar bundles of system organization and care.

Cardiogenic shock accounts for ~100,000 annual hospital admissions in the United States. Despite improvements in medical management strategies, in-hospital mortality remains unacceptably high. Multiple mechanical circulatory support devices have been developed with the aim to provide hemodynamic support and to improve outcomes in this population. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is the most advanced temporary life support system that is unique in that it provides immediate and complete hemodynamic support as well as concomitant gas exchange. In this review, we discuss the fundamental concepts and hemodynamic aspects of VA-ECMO support in patients with cardiogenic shock of various etiologies. In addition, we review the common indications, contraindications and complications associated with VA-ECMO use.

Abstract Etv2, an Ets-transcription factor, governs the specification of the earliest hemato-endothelial progenitors during embryogenesis. While the transcriptional networks during hemato-endothelial development have been well described, the mechanistic details are incompletely defined. In the present study, we described a new role for Etv2 as a regulator of cellular proliferation via Yes1 in mesodermal lineages. Analysis of an Etv2-ChIPseq dataset revealed significant enrichment of Etv2 peaks in the upstream regions of cell cycle regulatory genes relative to non-cell cycle genes. Our bulk-RNAseq analysis using the doxycycline-inducible Etv2 ES/EB system showed increased levels of cell cycle genes including E2f4 and Ccne1 as early as 6 h following Etv2 induction. Further, EdU-incorporation studies demonstrated that the induction of Etv2 resulted in a ~2.5-fold increase in cellular proliferation, supporting a proliferative role for Etv2 during differentiation. Next, we identified Yes1 as the top-ranked candidate that was expressed in Etv2-EYFP + cells at E7.75 and E8.25 using single cell RNA-seq analysis. Doxycycline-mediated induction of Etv2 led to an increase in Yes1 transcripts in a dose-dependent fashion. In contrast, the level of Yes1 was reduced in Etv2 null embryoid bodies. Using bioinformatics algorithms, biochemical, and molecular biology techniques, we show that Etv2 binds to the promoter region of Yes1 and functions as a direct upstream transcriptional regulator of Yes1 during embryogenesis. These studies enhance our understanding of the mechanisms whereby Etv2 governs mesodermal fate decisions early during embryogenesis.

In the most severe cases, novel coronavirus (SARS-CoV-2) infection leads to Acute Respiratory Distress Syndrome which may be refractory to standard medical interventions including mechanical ventilation. There are growing reports of the use of venovenous (VV) extracorporeal membrane oxygenation (ECMO) in these cases. A subset of critically ill COVID-19 patients develops cardiomyopathy as well, manifested by cardiogenic shock with reduced ejection fraction, dysrhythmias, and subsequent increase in mortality. One strategy for managing ARDS with an element of cardiogenic shock is venoarteriovenous (VAV) ECMO. Less than 1% of the cases in the worldwide ELSO COVID-19 database employed any form of hybrid cannulation. To date, there has only been one reported case of patient salvage with arterial or partial arterial support. We present a case that demonstrates the potential role of VAV ECMO in the case of concomitant severe ARDS with cardiomyopathy in the setting of COVID-19 infection.

Abstract Reperfusion injury is a complex pathological event involving processes that can lead to further disruption of the cell membrane and function following an ischemic event. Return of blood flow allows for the needed reperfusion; however, for a period of time before remaining viable cells stabilize, reperfusion results in additional cellular injury. In cardiomyocytes, loss of membrane integrity allows abnormal influx of extracellular calcium, leading to hyper‐contracture and cell death. Methods to improve the membrane integrity of cardiomyocytes overwhelmed by pathological disruptions, such as reperfusion injury, are needed to prevent cell death, because of the myocardium's limited ability to regenerate. Research has shown administration of the copolymer P(oloxamer) 188 before ischemia/reperfusion can protect cardiomyocytes through membrane stabilization. This study sought to determine whether the administration of P188 at the beginning of the clinically more relevant time of reperfusion after ischemia will attenuate any additional damage to cardiomyocytes by stabilizing membrane integrity to allow the cells to maintain function. Using an in‐vitro cardiomyocyte model subjected to hypoxia/reoxygenation to simulate ischemia/reperfusion injury, we show that reoxygenation significantly potentiates the injury caused by hypoxia itself. P188, with its unique combination of hydrophobic and hydrophilic chemical properties, and only delivered at the beginning of reoxygenation, dose‐dependently protected cardiomyocytes from injury due to reoxygenation by repairing cell membranes, decreasing calcium influx, and maintaining cellular morphology. Our study also shows the hydrophobic portion of P188 is necessary for the stabilization of cell membrane integrity in providing protection to cardiomyocytes against reoxygenation injury.

Objectives: We evaluated the feasibility of optimising coronary perfusion pressure (CPP) during cardiopulmonary resuscitation (CPR) with a closed-loop, machine-controlled CPR system (MC-CPR) that sends real-time haemodynamic feedback to a set of machine learning and control algorithms which determine compression/decompression characteristics over time. Background: American Heart Association CPR guidelines (AHA-CPR) and standard mechanical devices employ a “one-size-fits-all” approach to CPR that fails to adjust compressions over time or individualise therapy, thus leading to deterioration of CPR effectiveness as duration exceeds 15–20 ​min. Methods: CPR was administered for 30 ​min in a validated porcine model of cardiac arrest. Intubated anaesthetised pigs were randomly assigned to receive MC-CPR (6), mechanical CPR conducted according to AHA-CPR (6), or human-controlled CPR (HC-CPR) (10). MC-CPR directly controlled the CPR piston’s amplitude of compression and decompression to maximise CPP over time. In HC-CPR a physician controlled the piston amplitudes to maximise CPP without any algorithmic feedback, while AHA-CPR had one compression depth without adaptation. Results: MC-CPR significantly improved CPP throughout the 30-min resuscitation period compared to both AHA-CPR and HC-CPR. CPP and carotid blood flow (CBF) remained stable or improved with MC-CPR but deteriorated with AHA-CPR. HC-CPR showed initial but transient improvement that dissipated over time. Conclusion: Machine learning implemented in a closed-loop system successfully controlled CPR for 30 ​min in our preclinical model. MC-CPR significantly improved CPP and CBF compared to AHA-CPR and ameliorated the temporal haemodynamic deterioration that occurs with standard approaches.

Background The incidence and mortality of out‐of‐hospital cardiac arrest (OHCA) remains high, but predicting outcomes is challenging. Being able to better assess prognosis of hospitalized patients after return of spontaneous circulation would enable improved management of survival expectations. In this study, we assessed the predictive value of ECG indexes in hospitalized patients with OHCA. Methods and Results PR interval and QT interval corrected by the Bazett formula (QTc) for all leads were calculated from standard 12‐lead ECGs 24 hours after return of spontaneous circulation in 93 patients who were hospitalized following OHCA. PR interval and QT and QTc duration did not differentiate OHCA survivors and nonsurvivors. However, QT and QTc dispersion was significantly increased in patients who died during hospitalization compared with survivors discharged from the hospital (P

Summary: Extracorporeal membrane oxygenation (ECMO) is used in cardiopulmonary resuscitation (CPR) of refractory cardiac arrest. The authors used a 2 à 2 study design to compare ECMO versus CPR and epinephrine versus placebo in a porcine model of ischemic refractory ventricular fibrillation (VF). Pigs underwent 5 min of untreated VF and 10 min of CPR, and were randomized to receive epinephrine versus placebo for another 35 min. Animals were further randomized to left anterior descending artery (LAD) reperfusion at minute 45 with ongoing CPR versus venoarterial ECMO cannulation at minute 45 of CPR and subsequent LAD reperfusion. Four-hour survival was improved with ECMO whereas epinephrine showed no effect. Key Words: advanced cardiopulmonary life support, cardiac arrest, cardiopulmonary resuscitation, ECMO, extracorporeal membrane oxygenation, ischemic refractory ventricular fibrillation, ST-segment elevation myocardial infarction, ventricular fibrillation

Poloxamer 188 (P188) is a nonionic triblock copolymer believed to prevent cellular injury after ischemia and reperfusion. This study compared intracoronary (IC) infusion of P188 immediately after reperfusion with delayed infusion through a peripheral intravenous catheter in a porcine model of ST-segment elevation myocardial infarction (STEMI). STEMI was induced in 55 pigs using 45 min of endovascular coronary artery occlusion. Pigs were then randomized to 4 groups: control, immediate IC P188, delayed peripheral P188, and polyethylene glycol infusion. Heart tissue was collected after 4 h of reperfusion. Assessment of mitochondrial function or infarct size was performed. Mitochondrial yield improved significantly with IC P188 treatment compared with control animals (0.25% vs. 0.13%), suggesting improved mitochondrial morphology and survival. Mitochondrial respiration and calcium retention were also significantly improved with immediate IC P188 compared with control animals (complex I respiratory control index: 7.4 vs. 3.7; calcium retention: 1,152 nmol vs. 386 nmol). This benefit was only observed with activation of complex I of the mitochondrial respiratory chain, suggesting a specific effect from ischemia and reperfusion on this complex. Infarct size and serum troponin I were significantly reduced by immediate IC P188 infusion (infarct size: 13.9% vs. 41.1%; troponin I: 19.2 μg/l vs. 77.4 μg/l). Delayed P188 and polyethylene glycol infusion did not provide a significant benefit. These results demonstrate that intracoronary infusion of P188 immediately upon reperfusion significantly reduces cellular and mitochondrial injury after ischemia and reperfusion in this clinically relevant porcine model of STEMI. The timing and route of delivery were critical to achieve the benefit.

BackgroundThe HeartRescue Project is a multistate public health initiative focused on establishing statewide out‐of‐hospital cardiac arrest (OHCA) systems of care to improve case capture and OHCA care in the community, by emergency medical services (EMS), and at hospital level. Methods and ResultsFrom 2011 to 2015 in the 5 original HeartRescue states, all adults with EMS–treated OHCA due to a presumed cardiac cause were included. In an adult population of 32.8 million, a total of 64 988 OHCAs—including 10 046 patients with a bystander‐witnessed OHCA with a shockable rhythm—were treated by 330 EMS agencies. From 2011 to 2015, the case‐capture rate for all‐rhythm OHCA increased from an estimated 39.0% (n=6762) to 89.2% (n=16 103; P

Objectives. To evaluate whether collaboration between existing and new transcatheter aortic valve replacement (TAVR) programs could help reduce the number of cases needed to achieve optimal efficiency. Background. There is a well-documented learning curve for achieving procedural efficiency and safety in TAVR procedures. Methods. A multidisciplinary collaboration was established between the Minneapolis VA Medical Center (new program) and the University of Minnesota (established program since 2012, n=219) 1 year prior to launching the new program. Results. 269 patients treated with TAVR (50 treated in the first year at the new program). Mean age was 76 (±18) years and STS score was 6.8 (±6). Access included transfemoral (n=35, 70%), transapical (n=8, 16%), transaortic (n=2, 4%), and subclavian (n=5, 10%) types. Procedural efficiency (procedural time 158±59 versus 148±62, p=0.27), device success (96% versus 87%, p=0.08), length of stay (5±3 versus 6±7 days, p=0.10), and safety (in hospital mortality 4% versus 6%, p=0.75) were similar between programs. We found no difference in outcome measures between the first and last 25 patients treated during the first year of the new program. Conclusions. Establishing a partnership with an established program can help mitigate the learning curve associated with these complex procedures.

The U.S. national out-of-hospital and in-hospital cardiac arrest survival rates, although improving recently, have remained suboptimal despite the collective efforts of individuals, communities, and professional societies. Only until very recently, and still with inconsistency, has focus been placed specifically on survival with pre-arrest neurologic function. The reality of current approaches to sudden cardiac arrest is that they are often lacking an integrative, multi-disciplinary approach, and without deserved funding and outcome analysis. In this manuscript, a multidisciplinary group of authors propose practice, process, technology, and policy initiatives to improve cardiac arrest survival with a focus on neurologic function. [West J Emerg Med. 2014;15(7):-0.]

BackgroundIn 2015, the Minnesota Resuscitation Consortium (MRC) implemented an advanced perfusion and reperfusion life support strategy designed to improve outcome for patients with out‐of‐hospital refractory ventricular fibrillation/ventricular tachycardia (VF/VT). We report the outcomes of the initial 3‐month period of operations. Methods and ResultsThree emergency medical services systems serving the Minneapolis–St. Paul metro area participated in the protocol. Inclusion criteria included age 18 to 75 years, body habitus accommodating automated Lund University Cardiac Arrest System (LUCAS) cardiopulmonary resuscitation (CPR), and estimated transfer time from the scene to the cardiac catheterization laboratory of ≤30 minutes. Exclusion criteria included known terminal illness, Do Not Resuscitate/Do Not Intubate status, traumatic arrest, and significant bleeding. Refractory VF/VT arrest was defined as failure to achieve sustained return of spontaneous circulation after treatment with 3 direct current shocks and administration of 300 mg of intravenous/intraosseous amiodarone. Patients were transported to the University of Minnesota, where emergent advanced perfusion strategies (extracorporeal membrane oxygenation; ECMO), followed by coronary angiography and primary coronary intervention (PCI), were performed, when appropriate. Over the first 3 months of the protocol, 27 patients were transported with ongoing mechanical CPR. Of these, 18 patients met the inclusion and exclusion criteria. ECMO was placed in 83%. Seventy‐eight percent of patients had significant coronary artery disease with a high degree of complexity and 67% received PCI. Seventy‐eight percent of patients survived to hospital admission and 55% (10 of 18) survived to hospital discharge, with 50% (9 of 18) achieving good neurological function (cerebral performance categories 1 and 2). No significant ECMO‐related complications were encountered. ConclusionsThe MRC refractory VF/VT protocol is feasible and led to a high functionally favorable survival rate with few complications.

BackgroundIn 2013 the Minnesota Resuscitation Consortium developed an organized approach for the management of patients resuscitated from shockable rhythms to gain early access to the cardiac catheterization laboratory (CCL) in the metro area of Minneapolis‐St. Paul. Methods and ResultsEleven hospitals with 24/7 percutaneous coronary intervention capabilities agreed to provide early (within 6 hours of arrival at the Emergency Department) access to the CCL with the intention to perform coronary revascularization for outpatients who were successfully resuscitated from ventricular fibrillation/ventricular tachycardia arrest. Other inclusion criteria were age >18 and