Bleeding and Thrombosis in Patients With Out-of-Hospital Ventricular Tachycardia/Ventricular Fibrillation Arrest Treated With Extracorporeal Cardiopulmonary Resuscitation.

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<0.001) though bleeding was not significantly associated with in-hospital death (aHR, 0.81 [95% CI. 0.55-1.19]). A thrombotic event occurred in 23.5% (47/200) of patients. Venous thromboembolism occurred in 11% (22/200) and arterial thrombi in 15.5% (31/200). Clinical characteristics were comparable between groups. In adjusted analyses, no risk factors for thrombosis were identified. Thrombosis was not associated with in-hospital death (aHR, 0.65 [95% CI, 0.42-1.03]). CONCLUSIONS: Bleeding is a frequent complication of extracorporeal cardiopulmonary resuscitation that is associated with decreased fibrinogen levels on admission whereas thrombosis is less common. Neither bleeding nor thrombosis was significantly associated with in-hospital mortality.

The cerebral and cardiac effects of Norepinephrine in an experimental cardiac arrest model.

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.

Left ventricular hemodynamics with veno-arterial extracorporeal membrane oxygenation.

BACKGROUND: There is considerable debate about the hemodynamic effects of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). AIMS: To evaluate the changes in left ventricular (LV) function, volumes, and work in patients treated with VA-ECMO using invasive LV catheterization and three-dimensional echocardiographic volumes. METHODS: Patients on VA-ECMO underwent invasive hemodynamic evaluation due to concerns regarding candidacy for decannulation. Hemodynamic parameters were reported as means±standard deviations or medians (interquartile ranges) after evaluating for normality. Paired comparisons were done to evaluate hemodynamics at the baseline (highest) and lowest tolerated levels of VA-ECMO support. RESULTS: Twenty patients aged 52.3 ± 15.8 years were included. All patients received VA-ECMO for refractory cardiogenic shock (5/20 SCAI stage D, 15/20 SCAI stage E). At 3.0 (2.0, 4.0) days after VA-ECMO cannulation, the baseline LV ejection fraction was 20% (15%, 27%). The baseline and lowest VA-ECMO flows were 4.0 ± 0.6 and 1.5 ± 0.6 L/min, respectively. Compared to the lowest flow, full VA-ECMO support reduced LV end-diastolic volume [109 ± 81 versus 134 ± 93 mL, p = 0.001], LV end-diastolic pressure (14 ± 9 vs. 19 ± 9 mmHg, p < 0.001), LV stroke work (1858 ± 1413 vs. 2550 ± 1486 mL*mmHg, p = 0.002), and LV pressure-volume area (PVA) (4507 ± 1910 vs. 5193 ± 2388, p = 0.03) respectively. Mean arterial pressure was stable at the highest and lowest flows (80 ± 16 vs. 75 ± 14, respectively; p = 0.08) but arterial elastance was higher at the highest VA-ECMO flow (4.9 ± 2.2 vs lowest flow 2.7 ± 1.6; p < 0.001). CONCLUSIONS: High flow VA-ECMO support significantly reduced LV end-diastolic pressure, end-diastolic volume, stroke work, and PVA compared to minimal support. The Ea was higher and MAP was stable or minimally elevated on high flow.

Multi-omic and multispecies analysis of right ventricular dysfunction.

BACKGROUND: Right ventricular failure (RVF) is a leading cause of morbidity and mortality in multiple cardiovascular diseases, but there are no treatments for RVF as therapeutic targets are not clearly defined. Contemporary transcriptomic/proteomic evaluations of RVF are predominately conducted in small animal studies, and data from large animal models are sparse. Moreover, a comparison of the molecular mediators of RVF across species is lacking. METHODS: Transcriptomics and proteomics analyses defined the pathways associated with cardiac magnetic resonance imaging (MRI)-derived values of RV hypertrophy, dilation, and dysfunction in control and pulmonary artery banded (PAB) pigs. Publicly available data from rat monocrotaline-induced RVF and pulmonary arterial hypertension patients with preserved or impaired RV function were used to compare molecular responses across species. RESULTS: PAB pigs displayed significant right ventricle/ventricular (RV) hypertrophy, dilation, and dysfunction as quantified by cardiac magnetic resonance imaging. Transcriptomic and proteomic analyses identified pathways associated with RV dysfunction and remodeling in PAB pigs. Surprisingly, disruptions in fatty acid oxidation (FAO) and electron transport chain (ETC) proteins were different across the 3 species. FAO and ETC proteins and transcripts were mostly downregulated in rats but were predominately upregulated in PAB pigs, which more closely matched the human response. All species exhibited similar dysregulation of the dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy pathways. CONCLUSIONS: The porcine metabolic molecular signature was more similar to human RVF than rodents. These data suggest there may be divergent molecular responses of RVF across species, and pigs may more accurately recapitulate metabolic aspects of human RVF.

Incident Heart Failure Risk Reclassification With Race-Independent Estimated Glomerular Filtration Rate: A National Heart, Lung, and Blood Institute Pooled Cohorts Analysis.

BACKGROUND: This study compared the predictive value of the race-independent creatinine- and cystatin C-based estimated glomerular filtration rate (eGFRcr-cys) and the race-dependent creatinine-based eGFR (eGFRcr) for incident heart failure (HF). METHODS: This study combined the participant-level data from ARIC (Atherosclerosis Risk in Communities) (visit 4) and MESA (Multi-Ethnic Study of Atherosclerosis) (visit 1) to calculate eGFRcr-cys and eGFRcr. The primary outcome of the study was adjudicated incident HF over a follow-up period of 10 years. Multivariable Cox models were used to assess the risk of incident HF with the quartiles of eGFRcr-cys and eGFRcr. RESULTS: Among 15,615 individuals (median age: 62 [57-68] years; 55.0% females; 23.9% Black), the median eGFRcr-cys and eGFRcr were 91.4 (79.4, 102.0) mL/min/1.73m2 and 84.7 (72.0, 94.7) mL/min/1.73m2, respectively. Compared with the fourth quartile of eGFRcr-cys, the hazard ratio for incident HF was 1.02 (95% CI:0.80-1.30) in the third quartile, 1.02 (95% CI:0.80-1.30) in the second quartile, and 1.47 (95% CI:1.16-1.86) in the first quartile. Compared with the 4th quartile of the eGFRcr, the risk of incident HF was similar in the 3rd (HRadj:0.90 [95% CI:0.73-1.12]), 2nd (HRadj: 0.96 [95% CI:0.77-1.20]), and 1st (HRadj:1.15 [95% CI:0.93-1.44]) quartiles. C-statistics were similar for the multivariable-adjusted Cox models for incident HF using eGFRcr (0.80 [0.79-0.81]) and eGFRcr-cys (0.80 [0.79-0.82]). CONCLUSION: The eGFRcr and eGFRcr-cys had comparable predictive values for incident HF.

Wolf Creek XVII part 9: Wolf Creek Innovator in Cardiac Arrest and Resuscitation Science Award.

The Wolf Creek Conferences on Cardiac Arrest Resuscitation began in 1975, and have served as an important forum for thought leaders and scientists from industry and academia to come together with the common goal of advancing the field of cardiac arrest resuscitation. The Wolf Creek XVII Conference was hosted by the Max Harry Weil Institute of Critical Care Research and Innovation in Ann Arbor, Michigan on June 14-17, 2023. A new component of the conference was the Wolf Creek Innovator in Cardiac Arrest and Resuscitation Science Award competition. The competition was designed to recognize early career investigators from around the world who's science is challenging the current paradigms in the field. Finalists were selected by a panel of international experts and invited to present in-person at the conference. The winner was chosen by electronic vote of conference participants and awarded a $10,0000 cash prize. Finalists included Carolina Barbosa Maciel from the University of Florida, Adam Gottula from the University of Michigan, Rajat Kalra from the University of Minnesota, Ryan Morgan from the Children's Hospital of Philadelphia, Mitsuaki Nishikimi form Hiroshima University, and Jacob Sunshine from the University of Washington. Ryan Morgan from the Children's Hospital of Philadelphia was selected as the 2023 Wolf Creek Innovator Awardee. This manuscript provides a summary of the work presented by each of the finalists and provides a preview of the future of resuscitation science.

Cerebral hemodynamic effects of head-up CPR in a porcine model.

AIM: To assess the hemodynamic effects of head elevation on cerebral perfusion during cardiopulmonary resuscitation (CPR) in a porcine model of cardiac arrest. METHODS: VF was induced in eight 65 kg pigs that were treated with CPR after five minutes of no flow. Mean arterial pressure (MAP) was measured at the descending thoracic aorta. Internal carotid artery blood flow (CBF) was measured with an ultrasound probe. Cerebral perfusion pressure (CerPP) was calculated in two ways (CerPPICAP and CerPPreported) using the same intracranial pressure (ICP) measurement. CePPreported was calculated as MAP-ICP. CerPPICAP was calculated by using intracranial arterial pressure (ICAP) - ICP. The animals were switched between head up (HUP) and supine (SUP) CPR every five minutes for a total of twenty minutes of resuscitation. RESULTS: MAP and coronary perfusion pressure measurements were similar in both CPR positions (p = 0.36 and p = 0.1, respectively). ICP was significantly lower in the HUP CPR group (14.7 ± 1 mm Hg vs 26.9 ± 1 mm Hg, p < 0.001) as was ICAP (30.1 ± 2 mm Hg vs 42.6 ± 1 mmHg, p < 0.001). The proportional decrease in ICP and ICAP resulted in similar CerPPICAP comparing HUP and SUPCPR (p = 0.7). CBF was significantly lower during HUPCPR when compared to SUPCPR (58.5 ± 3 ml/min vs 78 ± 4 ml/min, p < 0.001). A higher CerPPreported was found during the HUP compared to SUP-CPR, when MAP was used (36.6 ± 2 mm Hg vs 23 ± 2 mm Hg, p < 0.001) without correcting for the hydrostatic pressure drop. CONCLUSION: HUP did not affect cerebral perfusion pressure and it significantly decreased internal carotid blood flow.

Case Report: Correlation between pulmonary capillary wedge pressure and left-ventricular diastolic pressure during treatment with veno-arterial extracorporeal membrane oxygenation.

Background: Pulmonary 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. Methods: Patients 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. Results: Four 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). Conclusions: The PCWP may not correlate well with LVEDP in patients treated with VA-ECMO, particularly at high levels of VA-ECMO support.

Independent prognostic value of high-risk ventricular premature complexes during exercise or recovery in asymptomatic patients: A meta-analysis of observational studies.

INTRODUCTION: Ventricular premature contractions (VPCs) are a common finding during cardiac stress tests. The independent prognostic value of these findings in patients in asymptomatic patients is unclear. METHODS: We conducted a systematic review and meta-analysis of observational studies exploring the independent prognostic value of VPCs to predict all-cause mortality. The secondary outcome was cardiovascular (CV) mortality. We excluded studies that did not report outcomes after adjusting for ≥1 confounder. Random effect meta-analyses were used to predict cumulative hazard ratios. We stratified results based on VPC during exercise or recovery. RESULTS: We found 7 studies with 24,518 patients that met our inclusion criteria. Two studies reported all-cause mortality only, 1 study reported CV mortality only, rest 4 reported both. There was significant heterogeneity in the baseline population, definition of high-risk VPCs, and variables used in adjusted models. Using multivariable summary estimates from individual studies, only VPCs during exercise were associated with a higher risk of all-cause mortality (HR 1.27, 95 % CI 1.07, 1.48). Both VPCs during exercise and recovery were associated with a higher risk CV mortality (HR 1.69, 95 % CI 1.19, 2.20, I2 = 17.6 % and 1.62, 95 % CI 1.25, 2.00, p < 0.001 for both). CONCLUSION: High-risk VPCs during exercise is associated with increased risk of all-cause and CV mortality, while those during recovery are associated with an increased risk of CV mortality only.

The Minnesota first-responder AED project: Aiming to increase survival in out-of-hospital cardiac arrest.

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.

Left rib fractures during cardiopulmonary resuscitation are associated with hemodynamic variations in a pig model of cardiac arrest.

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.

Trends of cardiovascular health in Asian American individuals: A national health and nutrition examination survey study.

Objective: Oversampling of Asian American individuals in the National Health and Nutrition Examination Survey (NHANES) provides a unique opportunity to assess the population-level cardiovascular health (CVH) in the fastest-growing racial group in the US. Methods: The Life's Essential 8 (LE8) score and its components were calculated in self-reported Asian American individuals ≥20 years of age and free of cardiovascular disease in the NHANES cycles from 2011-March 2020. Multivariable adjusted linear and logistic regression models were used for analysis. Results: Among 2,059 Asian American individuals, the weighted mean LE8 score was 69.1 (0.4) with US-born [69.0 (0.8)] and foreign-born individuals [69.1 (0.4)] having similar CVH. From 2011 to March 2020, CVH in the overall population [69.7 (0.8) to 68.1 (0.8); Ptrend: 0.009] and foreign-born individuals [69.7 (0.8) to 67.7 (0.8); Ptrend: 0.005] declined. Decreasing trends were noted in the body mass index score irrespective of stratification and in the blood pressure scores in the overall population and foreign-born Asian American individuals. Compared with US-born individuals, the odds of ideal levels of smoking [ORadj:<5 years: 2.23 (95%CI: 1.45-3.44); 5-15 years: 1.97 (95%CI: 1.27-3.05); 15-30 years: 1.61 (95%CI: 1.11-2.34); ≥30 years: 1.69(95%CI:1.20-2.36)] and diet [ORadj: <5 years: 1.87 (95%CI: 1.26-2.79); 5-15 years: 2.00 (95%CI: 1.38-2.89); 15-30 years: 1.74 (95%CI: 1.14-2.68)] were higher in foreign-born individuals. Foreign-born individuals had lower odds of ideal physical activity levels [ORadj: 5-15 years: 0.55 (95%CI: 0.39-0.79); 15-30 years: 0.68 (95%CI: 0.49-0.95)] and ideal cholesterol levels [ORadj: 5-15 years: 0.59 (95%CI: 0.42-0.82); 15-30 years: 0.54 (95%CI :0.38-0.76); ≥30 years: 0.52 (95%CI: 0.38-0.76)]. Conclusion: The CVH in Asian American individuals declined from 2011 to March 2020. The odds of ideal CVH decreased with increasing duration of stay in the US, with foreign-born individuals residing in the US for ≥30 years having ∼28% lower odds of ideal CVH compared with US-born individuals.

Sex-Associated Differences in the Clinical Outcomes of Left Ventricular Assist Device Recipients: Insights From Interagency Registry for Mechanically Assisted Circulatory Support.

BACKGROUND: Sex-associated differences in clinical outcomes among left ventricular assist device recipients in the United States have been recognized. However, an investigation of the social and clinical determinants of sex-associated differences is lacking. METHODS: Left ventricular assist device receiving patients enrolled in Interagency Registry for Mechanically Assisted Circulatory Support between 2005 and 2017 were included. The primary outcome was all-cause mortality. Secondary outcomes included heart transplantation and postimplantation adverse event rates. The cohort was stratified by the social subgroup of race and ethnicity (non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, and Hispanic), and clinical subgroups of device strategy (destination therapy, bridge to transplant, and bridge to candidacy), and implantation center volume (low [≤20 implants/y], medium [21-30 implants/y], and high [>30 implants/y]). A multivariable-adjusted Cox proportional hazard model was used to assess the risk of death and heart transplantation with prespecified interaction testing. Poisson regression was used to estimate adverse events by sex across the various subgroups. RESULTS: Among 18 525 patients, there were 3968 (21.4%) females. Compared with their male counterparts, Hispanic (adjusted hazard ratio [HRadj], 1.75 [1.23-2.47]) females had the highest risk of death followed by non-Hispanic White females (HRadj, 1.15 [1.07-1.25]; Pinteraction=0.02). Hispanic (HRadj, 0.60 [0.40-0.89]) females had the lowest cumulative incidence of heart transplantation followed by non-Hispanic Black females (HRadj, 0.76 [0.67-0.86]), and non-Hispanic White females (HRadj, 0.88 [0.80-0.96]) compared with their male counterparts (Pinteraction<0.001). Compared with their male counterparts, females on the bridge to candidacy strategy (HRadj, 1.32 [1.18-1.48]) had the highest risk of death (Pinteraction=0.01). The risk of death (Pinteraction=0.44) and cumulative incidence of heart transplantation (Pinteraction=0.40) did not vary by sex in the center volume subgroup. A higher incidence rate of adverse events after left ventricular assist device implantation was also seen in females compared with the males, overall, and across all subgroups. CONCLUSIONS: Among left ventricular assist device recipients, the risk of death, the cumulative incidence of heart transplantation, and adverse events differ by sex across the social and clinical subgroups.

The impact of BMI on arrest characteristics and survival of patients with out-of-hospital cardiac arrest treated with extracorporeal cardiopulmonary resuscitation.

AIM: To assess the impact of body mass index (BMI) on survival to hospital discharge of patients presenting with refractory ventricular fibrillation treated with extracorporeal cardiopulmonary resuscitation. We hypothesize that due to limitations in pre-hospital care delivery, people with high BMI have worse survival after prolonged resuscitation and ECPR. METHODS: This study is a retrospective single-centre study that included patients suffering refractory VT/VF OHCA from December 2015 to October 2021 and had a BMI calculated at hospital admission. We compared the baseline characteristics and survival between patients with obesity (>30 kg/m2) and those without (≤30 kg/m2). RESULTS: Two-hundred eighty-three patients were included in this study, and two-hundred twenty-four required mechanical support with veno-arterial extracorporeal cardiopulmonary membrane oxygenation (VA ECMO). Patients with BMI > 30 (n = 133) had significantly prolonged CPR duration compared to their peers with BMI ≤ 30 kg/m2 (n = 150) and were significantly more likely to require support with VA ECMO (85.7% vs 73.3%, p = 0.015). Survival to hospital discharge was significantly higher in patients with BMI ≤ 30 kg/m2 (48% vs. 29.3%, p < 0.001). BMI was an independent predictor of mortality in a multivariable logistic regression analysis. The four-year mortality rate was low and not significantly different between the two groups (p = 0.32). CONCLUSION: ECPR yields clinically meaningful long-term survival in patients with BMI > 30 kg/m2. However, the resuscitation time is significantly prolonged, and the overall survival significantly lower compared to patients with BMI ≤ 30 kg/m2. ECPR should, therefore, not be withheld for this population, but faster transport to an ECMO capable centre is mandated to improve survival to hospital discharge.

Intraarrest transport, extracorporeal cardiopulmonary resuscitation, and early invasive management in refractory out-of-hospital cardiac arrest: an individual patient data pooled analysis of two randomised trials.

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.

Supraglottic airway devices are associated with asphyxial physiology after prolonged CPR in patients with refractory Out-of-Hospital cardiac arrest presenting for extracorporeal cardiopulmonary resuscitation.

BACKGROUND: Multiple randomized clinical trials have compared specific airway management strategies during ACLS with conflicting results. However, patients with refractory cardiac arrest died in almost all cases without the availability of extracorporeal cardiopulmonary resuscitation (ECPR). Our aim was to determine if endotracheal intubation (ETI) was associated with improved outcomes compared to supraglottic airways (SGA) in patients with refractory cardiac arrest presenting for ECPR. METHODS: We retrospectively studied 420 consecutive adult patients with refractory out-of-hospital cardiac arrest due to shockable presenting rhythms presenting to the University of Minnesota ECPR program. We compared outcomes between patients receiving ETI (n = 179) and SGA (n = 204). The primary outcome was the pre-cannulation arterial PaO2 upon arrival to the ECMO cannulation center. Secondary outcomes included neurologically favorable survival to hospital discharge and eligibility for VA-ECMO based upon resuscitation continuation criteria applied upon arrival to the ECMO cannulation center. RESULTS: Patients receiving ETI had significantly higher median PaO2 (71 vs. 58 mmHg, p = 0.001), lower median PaCO2 (55 vs. 75 mmHg, p < 0.001), and higher median pH (7.03 vs. 6.93, p < 0.001) compared to those receiving SGA. Patients receiving ETI were also significantly more likely to meet VA-ECMO eligibility criteria (85% vs. 74%, p = 0.008). Of patients eligible for VA-ECMO, patients receiving ETI had significantly higher neurologically favorable survival compared to SGA (42% vs. 29%, p = 0.02). CONCLUSIONS: ETI was associated with improved oxygenation and ventilation after prolonged CPR. This resulted in increased rate of candidacy for ECPR and increased neurologically favorable survival to discharge with ETI compared to SGA.

A Multi-omic and Multi-Species Analysis of Right Ventricular Failure.

Right ventricular failure (RVF) is a leading cause of morbidity and mortality in multiple cardiovascular diseases, but there are no approved treatments for RVF as therapeutic targets are not clearly defined. Contemporary transcriptomic/proteomic evaluations of RVF are predominately conducted in small animal studies, and data from large animal models are sparse. Moreover, a comparison of the molecular mediators of RVF across species is lacking. Here, we used transcriptomics and proteomics analyses to define the molecular pathways associated with cardiac MRI-derived values of RV hypertrophy, dilation, and dysfunction in pulmonary artery banded (PAB) piglets. Publicly available data from rat monocrotaline-induced RVF and pulmonary arterial hypertension patients with preserved or impaired RV function were used to compare the three species. Transcriptomic and proteomic analyses identified multiple pathways that were associated with RV dysfunction and remodeling in PAB pigs. Surprisingly, disruptions in fatty acid oxidation (FAO) and electron transport chain (ETC) proteins were different across the three species. FAO and ETC proteins and transcripts were mostly downregulated in rats, but were predominately upregulated in PAB pigs, which more closely matched the human data. Thus, the pig PAB metabolic molecular signature was more similar to human RVF than rodents. These data suggest there may be divergent molecular responses of RVF across species, and that pigs more accurately recapitulate the metabolic aspects of human RVF.