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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: 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

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.

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.

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:

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.

Objective: This study assessed cardiovascular health (CVH) in young adults using the 2022 AHA Life's Essential 8 (LE8) score and compared it with the Life's Simple 7 (LS7) score. Methods: Individuals aged 18 to 44 years without a history of cardiovascular disease in the National Health and Nutrition Examination Survey (NHANES) cycles were included. Data from 2007-2008 to 2017-2018 were combined to create 3 groups (2007-2010, 2011-2014, and 2015-2018) for analysis. The LE8 score and its components were computed in the overall population and stratified by sex and race/ethnicity. Trends for the LE8 score were analyzed using adjusted linear regression models. Results: Among 12,197 young adults, representing an estimated 89.4 million individuals, from the NHANES 2007-2018, the CVH in the overall population and across all subgroups was stable (Ptrend >0.05). The blood lipid score improved across all subgroups (Ptrend:

Abstract Aims We sought to compare the generalizability and prognostic implications of heart failure with preserved ejection fraction (HFpEF) scores (HFA‐PEFF and H2FPEF score) in Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) and Phosphodiesterase‐5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (RELAX) trial participants and matched controls from the Atherosclerosis Risk in Community (ARIC) study. Methods and results Based on the respective scores, the study participants from the TOPCAT (N = 356), RELAX (N = 216), and ARIC (N = 379) studies were categorized as having a low, intermediate, or high likelihood of HFpEF. Age, sex, and race matched controls free of cardiovascular disease who had unexplained dyspnoea were used to evaluate the diagnostic performance. The prognostic value of scores was assessed using multivariable‐adjusted Cox regression analyses. The median HFA‐PEFF scores in the TOPCAT, RELAX, and ARIC studies were 5.0 [interquartile range (IQR): 5.0–6.0], 4.0 (IQR: 2.0–4.0), and 3.0 (IQR: 2.0–4.0), respectively. The median H2FPEF scores in the three studies were 5.5 (IQR: 4.0–7.0), 6.0 (IQR: 4.0–7.0), and 3.0 (IQR: 2.0–5.0), respectively. A low HFA‐PEFF and H2FPEF score can rule out HFpEF with high sensitivity (99.5% and 99.6%, respectively) and negative predictive value (95.7% and 98.3%, respectively). A high HFA‐PEFF and H2FPEF score can rule‐in HFpEF with good specificity (82.8% and 95.6%, respectively) and positive predictive value (79.9% and 90.4%, respectively). Among TOPCAT participants, the hazard for adverse cardiovascular events per point increase in HFA‐PEFF and H2FPEF score was 1.26 (95% confidence interval: 0.98–1.63) and 1.01 (95% confidence interval: 0.88–1.15), respectively. A higher H2FPEF score was associated with lower peak oxygen intake in RELAX trial participants (adjusted P = 0.01). Conclusions The HFA‐PEFF and the H2FPEF scores are reliable diagnostic tools for HFpEF. The prognostic utility of HFpEF scores requires further validation in larger rigorously phenotyped populations.

Objective: There has been a substantial decline in patients presenting for emergent and routine cardiovascular care in the United States after the onset of the coronavirus disease 2019 (COVID-19) pandemic. We sought to assess the risk of adverse clinical outcomes among patients undergoing coronary artery bypass graft (CABG) surgery during the 2020 COVID-19 pandemic period and compare the risks with those undergoing CABG before the pandemic in the year 2019. Methods: A retrospective cross-sectional analysis of the TriNetX Research Network database was performed. Patients undergoing CABG between January 20, 2019, and September 15, 2019, contributed to the 2019 cohort, and those undergoing CABG between January 20, 2020, and September 15, 2020, contributed to the 2020 cohort. Propensity-score matching was performed, and the odds of mortality, acute kidney injury, stroke, acute respiratory distress syndrome, and mechanical ventilation occurring by 30 days were evaluated. Results: The number of patients undergoing CABG in 2020 declined by 35.5% from 5534 patients in 2019 to 3569 patients in 2020. After propensity-score matching, 3569 patient pairs were identified in the 2019 and the 2020 cohorts. Compared with those undergoing CABG in 2019, the odds of mortality by 30 days were 0.96 (95% confidence interval [CI], 0.69-1.33; P = .80) in those undergoing CABG in 2020. The odds for stroke (odds ratio [OR], 1.201; 95% CI, 0.96-1.39), acute kidney injury (OR, 0.76; 95% CI, 0.59-1.08), acute respiratory distress syndrome (OR, 1.01; 95% CI, 0.60-2.42), and mechanical ventilation (OR, 1.11; 95% CI, 0.94-1.30) were similar between the 2 cohorts. Conclusions: The number of patients undergoing CABG in 2020 has substantially declined compared with 2019. Similar odds of adverse clinical outcomes were seen among patients undergoing CABG in the setting of COVID-19 compared with those in 2019.

Abstract Children and adolescents account for ~ 13% of total COVID-19 cases in the United States. However, little is known about the nature of the illness in children. The reopening of schools underlines the importance of understanding the epidemiology of pediatric COVID-19 infections. We sought to assess the clinical characteristics and outcomes in pediatric COVID-19 patients. We conducted a retrospective cross-sectional analysis of pediatric patients diagnosed with COVID-19 from healthcare organizations in the United States. The study outcomes (hospitalization, mechanical ventilation, critical care) were assessed using logistic regression. The subgroups of sex and race were compared after propensity score matching. Among 12,306 children with lab-confirmed COVID-19, 16.5% presented with respiratory symptoms (cough, dyspnea), 13.9% had gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal pain), 8.1% had dermatological symptoms (rash), 4.8% had neurological (headache), and 18.8% had other non-specific symptoms (fever, malaise, myalgia, arthralgia and disturbances of smell or taste). In the study cohort, the hospitalization frequency was 5.3%, with 17.6% needing critical care services and 4.1% requiring mechanical ventilation. Following propensity score matching, the risk of all outcomes was similar between males and females. Following propensity score matching, the risk of hospitalization was greater in non-Hispanic Black (RR 1.97 [95% CI 1.49–2.61]) and Hispanic children (RR 1.31 [95% CI 1.03–1.78]) compared with non-Hispanic Whites. In the pediatric population infected with COVID-19, a substantial proportion were hospitalized due to the illness and developed adverse clinical outcomes.

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

Objective: To evaluate the race-stratified state-level prevalence of health determinants and the racial disparities in coronavirus disease 2019 (COVID-19) cumulative incidence and mortality in the United States. Patients and Methods: The age-adjusted race-stratified prevalence of comorbidities (hypertension, diabetes, dyslipidemia, and obesity), preexisting medical conditions (pulmonary disease, heart disease, stroke, kidney disease, and malignant neoplasm), poor health behaviors (smoking, alcohol abuse, and physical inactivity), and adverse socioeconomic factors (education, household income, and health insurance) was computed in 435,139 American adult participants from the 2017 Behavioral Risk Factor Surveillance System survey. Correlation was assessed between health determinants and the race-stratified COVID-19 crude mortality rate and infection-fatality ratio computed from respective state public health departments in 47 states. Results: Blacks had a higher prevalence of comorbidities (63.3%; 95% CI, 62.4% to 64.2% vs 55.1%; 95% CI, 54.7% to 55.5%) and adverse socioeconomic factors (47.0%; 95% CI, 46.0% to 47.9% vs 30.9%; 95% CI, 30.6% to 31.3%) than did whites. The prevalence of preexisting medical conditions was similar in blacks (30.4%; 95% CI, 28.8% to 32.1%) and whites (30.8%; 95% CI, 30.2% to 31.4%). The prevalence of poor health behaviors was higher in whites (57.2%; 95% CI, 56.3% to 58.0%) than in blacks (50.2%; 95% CI,46.2% to 54.2%). Comorbidities and adverse socioeconomic factors were highest in the southern region, and poor health behaviors were highest in the western region. The cumulative incidence rate (per 100,000 persons) was 3-fold higher in blacks (1546.4) than in whites (540.4). The crude mortality rate (per 100,000 persons) was 2-fold higher in blacks (83.2) than in whites (33.2). However, the infection-fatality ratio (per 100 cases) was similar in whites (6.2) and blacks (5.4). Within racial groups, the geographic distribution of health determinants did not correlate with the state-level COVID-19 mortality and infection-fatality ratio (P>.05 for all). Conclusion: Racial disparities in COVID-19 are largely driven by the higher cumulative incidence of infection in blacks. There is a discordance between the geographic dispersion of COVID-19 mortality and the regional distribution of health determinants.

Abstract Aims Prior evidence has implicated leucocyte expansion in several cardiovascular disorders, including heart failure (HF) with reduced ejection fraction (rEF). However, the prognostic importance of leucocyte count in HF with preserved EF (HFpEF) remains largely unexplored. Methods and results The Americas cohort of the treatment of preserved cardiac function heart failure with an aldosterone antagonist (TOPCAT‐Americas) was used to evaluate the association between total leucocyte count and clinical outcomes in HFpEF. The primary outcome was a composite of aborted cardiac arrest, cardiovascular mortality, or hospitalization for HF. Secondary outcomes were hospitalization for HF, aborted cardiac arrest, stroke, non‐fatal myocardial infarction (MI), cardiovascular mortality, non‐cardiovascular mortality, and all‐cause mortality. Survival models were used to identify the risk of the primary and secondary outcomes in those with leucocyte count above the median (7100 cells/μL), as compared to those with leucocyte count below the median, during the follow‐up period. A total of 1746 (out of 1767; 99%) patients from TOPCAT‐Americas were available for the analyses with a median follow up of 2.4 (25th to 75th percentile 1.4–3.9) years. Patients with leucocyte count >7100 cells/μL were 36% more likely to experience the primary endpoint compared to those with ≤7100 cells/μL (hazard ratio: 1.36, 95% confidence interval: 1.14–1.61). This association remained significant after extensive adjustment for potential confounders (hazard ratio: 1.27, 95% confidence interval: 1.06–1.52). We also observed a greater incidence of HF hospitalization and non‐fatal MI in patients with higher leucocyte count. These associations remained robust on sensitivity analyses, suggesting a low probability of confounding. Exploratory analyses suggested that both higher leucocyte count (integrating the combined influence of both myeloid and lymphoid immune cells) and augmented platelet count (as a surrogate for myeloid immune cell expansion) in the same model were associated with the primary outcome (both P 7100 cells/μL was independently associated with adverse clinical outcomes in HFpEF patients from TOPCAT‐Americas. These results were primarily driven by the HF hospitalization outcome but were also accompanied by an excess of non‐fatal MI. Further research is needed to define the mechanisms underlying our findings and their prognostic implications.

Abstract Aims Immunomodulation in heart failure (HF) has been studied in several randomized controlled trials (RCTs) with variable effects on cardiac structure, function, and outcomes. We sought to determine the effect of immunomodulation on left ventricular ejection fraction (LVEF), LV end‐diastolic dimension (LVEDD), and all‐cause mortality in patients with HF with reduced ejection fraction (HFrEF) through meta‐analyses and trial sequential analyses (TSAs) of RCTs. Methods and results PubMed, Embase®, Cochrane CENTRAL, and ClinicalTrials.gov were systematically reviewed to identify RCTs that studied the effects of immunomodulation in patients with HFrEF. The primary endpoint in this analysis was change in LVEF. Secondary outcomes were changes in LVEDD and all‐cause mortality. TSA was used to quantify the statistical reliability of data in the cumulative meta‐analyses. Nineteen RCTs with 1341 HFrEF subjects were eligible for analyses. The aetiology of HF, specific immunomodulation strategy, and treatment duration were variable across trials. Immunomodulation led to a greater improvement in LVEF [mean difference: +5.7% 95% confidence interval (CI): 3.0–8.5%, P < 0.001] and reduction in LVEDD (mean difference: −3.7 mm, 95% CI: −7.0 to −0.4 mm, P = 0.028) than no immunomodulation in meta‐analyses and TSAs. We observed a non‐significant decrease in all‐cause mortality among those on immumomodulation (risk ratio: 0.7, 95% CI: 0.4–1.3, P = 0.234), but the Z‐curve for cumulative treatment effect of immunomodulation in the TSA did not cross the boundary of futility. Conclusions Immunomodulation led to improved cardiac structure and function in patients with HFrEF. While these benefits did not translate into a significant improvement in mortality, our analysis suggests that larger studies of targeted immunomodulation are needed to understand the true benefits.

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

Introduction: The interplay between sleep duration and inflammation on the baseline and incident cardiovascular (CV) risk is unknown. We sought to evaluate the association between sleep duration, C-reactive protein (CRP), baseline CV risk, and incident CV mortality. Methods: We used data from the National Health and Nutrition Examination Survey 2005–2010 linked with the cause of death data from the National Center for Health Statistics for adults aged ≥18 years. The associations between self-reported sleep duration and CRP, 10-year atherosclerotic CV disease risk score (ASCVD) and CV mortality were assessed using Linear, Poisson and Cox proportional hazard modeling as appropriate. Results: There were 17,635 eligible participants with a median age of 46 years (interquartile range [IQR] 31, 63). Among them, 51.3% were women and 46.9% were non-Hispanic Whites. Over a median follow-up of 7.5 years (IQR 6.0, 9.1), 350 CV deaths occurred at an incident rate of 2.7 per 1000-person years (IQR 2.4, 3.0). We observed a U–shaped associations between sleep duration and incident CV mortality rate (P-trend=0.011), sleep duration and 10-year ASCVD risk (P-trend 7 hours of sleep had higher risk of CV death attributable to inflammation after accounting for confounders. Conclusions: There was a U-shaped relationship of incident CV mortality, 10-year ASCVD risk, and CRP with sleep duration. These findings suggest an interplay between sleep duration, inflammation, and CV risk.

The rising incidence and recognition of cardiogenic shock has led to an increase in the use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). As clinical experience with this therapy has increased, there has also been a rapid growth in the body of observational and randomized data describing the clinical and logistical considerations required to institute a VA-ECMO program with successful clinical outcomes. The aim of this review is to summarize this contemporary data in the context of four key themes that pertain to VA-ECMO programs: the principles of patient selection; basic hemodynamic and technical principles underlying VA-ECMO; contraindications to VA-ECMO therapy; and common complications and intensive care considerations that are encountered in the setting of VA-ECMO therapy.

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.

Background Obese patients have lower NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) levels. The prognostic implications of achieving NT‐proBNP levels ≤1000 pg/mL in obese patients with heart failure (HF) receiving biomarker‐guided therapy are not completely known. We evaluated the prognostic implications of obesity and having NT‐proBNP levels (≤1000 pg/mL) in the GUIDE‐IT (Guiding Evidence‐Based Therapy Using Biomarker‐Intensified Treatment in HF) trial participants. Methods and Results The risk of adverse cardiovascular events (HF hospitalization or cardiovascular mortality) was assessed using multivariable‐adjusted Cox proportional hazard models based on having NT‐proBNP ≤1000 pg/mL (taken as a time‐varying covariate), stratified by obesity status. The study outcome was also assessed on the basis of the body mass index at baseline. The predictive ability of NT‐proBNP for adverse cardiovascular events was assessed using the likelihood ratio test. Compared with nonobese patients, obese patients were mostly younger, Black race, and more likely to be women. NT‐proBNP levels were 59.0% (95% CI, 39.5%–83.5%) lower among obese individuals. The risk of adverse cardiovascular events was lower in obese (hazard ratio [HR], 0.48; 95% CI, 0.29–0.59) and nonobese (HR, 0.32; 95% CI, 0.19–0.57) patients with HF who had NT‐proBNP levels ≤1000 pg/mL, compared with those who did not. There was no interaction between obesity and having NT‐proBNP ≤1000 pg/mL on the study outcome (P>0.10). Obese patients had a greater risk of developing adverse cardiovascular events (HR, 1.39; 95% CI, 1.01–1.90) compared with nonobese patients. NT‐proBNP was the strongest predictor of adverse cardiovascular event risk in both obese and nonobese patients. Conclusions On‐treatment NT‐proBNP level ≤1000 pg/mL has favorable prognostic implications, irrespective of obesity status. NT‐proBNP levels were the strongest predictor of cardiovascular events in both obese and nonobese individuals in this trial. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01685840.

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

Background Pulmonary arterial hypertension (PAH) is a lethal disease. In resource‐limited countries PAH outcomes are worse because therapy costs are prohibitive. To improve global outcomes, noninvasive and widely available biomarkers that identify high‐risk patients should be defined. Serum chloride is widely available and predicts mortality in left heart failure, but its prognostic utility in PAH requires further investigation. Methods and Results In this study 475 consecutive PAH patients evaluated at the University of Minnesota and Vanderbilt University PAH clinics were examined. Clinical characteristics were compared by tertiles of serum chloride. Both the Kaplan‐Meier method and Cox regression analysis were used to assess survival and predictors of mortality, respectively. Categorical net reclassification improvement and relative integrated discrimination improvement compared prediction models. PAH patients in the lowest serum chloride tertile (≤101 mmol/L: hypochloremia) had the lowest 6‐minute walk distance and highest right atrial pressure despite exhibiting no differences in pulmonary vascular disease severity. The 1‐, 3‐, and 5‐year survival was reduced in hypochloremic patients when compared with the middle‐ and highest‐tertile patients (86%/64%/44%, 95%/78%/59%, and, 91%/79%/66%). After adjustment for age, sex, diuretic use, serum sodium, bicarbonate, and creatinine, the hypochloremic patients had increased mortality when compared with the middle‐tertile and highest‐tertile patients. The Minnesota noninvasive model (functional class, 6‐minute walk distance, and hypochloremia) was as effective as the French noninvasive model (functional class, 6‐minute walk distance, and elevated brain natriuretic peptide or N‐terminal pro–brain natriuretic peptide) for predicting mortality. Conclusions Hypochloremia (≤101 mmol/L) identifies high‐risk PAH patients independent of serum sodium, renal function, and diuretic use.

BackgroundRecent trends of hospitalizations and in‐hospital mortality are not well defined in sarcoidosis. We examined aforementioned trends and prevalence of cardiovascular manifestations and explored rates of implantable cardioverter‐defibrillator implantation in hospitalizations with sarcoidosis. Methods and ResultsUsing data from the National Inpatient Sample, a retrospective population cohort from 2005 to 2014 was studied. To identify sarcoidosis, an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD‐9‐CM) diagnosis code was used. We excluded hospitalizations with myocardial infarction, coronary artery disease, and ischemic cardiomyopathy. Cardiovascular manifestations were defined by the presence of diagnosis codes for conduction disorders, arrhythmias, heart failure, nonischemic cardiomyopathy, and pulmonary hypertension. A total of 609 051 sarcoidosis hospitalizations were identified, with an age of 55±14 years, 67% women, and 50% black. The number of sarcoidosis hospitalizations increased from 2005 through 2014 (138 versus 175 per 100 000, Ptrend

Repair of congenital heart disease in the presence of high pulmonary pressure has always been a contentious issue. Pulmonary vascular resistance (PVR) is considered important for establishing operability in these patients. However, PVR estimation is not always accurate and cannot solely be relied upon to make critical decision of operability. Clinical examination, chest X-ray, and echocardiography are also important indicators of pulmonary vascular disease. Knowledge of pits and falls of each investigation is important for appropriate management in these patients. We present a case report of successfully operated, 6-year-old child with anomalous origin of the right pulmonary artery from aorta, deemed inoperable on the basis of PVR estimation.

Sub-mitral aneurysms are rarely reported clinical entity. Though a variety of etiologies are proposed, congenital weakness of the mitral valve annulus is the most widely accepted one. A 17-year-old boy with sub-mitral aneurysm presented with severe mitral regurgitation, which was diagnosed by echocardiography and successfully managed surgically. The aneurysm wall was positive for Staphylococcus aureus, and patient was treated with intensive antibiotics.

Multiple novel oral anticoagulants and left atrial appendage closure devices (WATCHMAN) have been tested against dose-adjusted vitamin K antagonists in randomized controlled trials for stroke prophylaxis in non-valvular atrial fibrillation. No direct comparisons of these strategies are available from randomized controlled trials. We conducted the current analyses by combining efficacy and safety characteristics of all FDA approved stroke prophylaxis treatment strategies for patients with non-valvular atrial fibrillation.We searched SCOPUS from 1945 till October 2015 for randomized controlled trials comparing these strategies and reporting efficacy and safety outcomes. Six randomized controlled trials were identified and included in the final analyses and review. We followed PRISMA guidelines for network meta-analyses while reporting the current analyses. We collected data on ischemic stroke, major bleeding, and the composite primary safety endpoint as defined by various randomized controlled trials. Network meta-analyses were conducted using consistency and inconsistency models for efficacy and safety outcomes. Surface under the cumulative ranking curve were then utilized to cluster rank these treatments for safety and efficacy.Six randomized controlled trials with 59,627 patients comparing six treatment strategies were eligible for the analyses. All prophylaxis strategies had comparable rates of ischemic stroke. Apixaban was associated with the least number of primary safety endpoint events as compared with all other treatments. In the cluster analyses assessing safety and efficacy, apixaban, edoxaban and dabigatran ranked best followed by vitamin K antagonists and rivaroxaban, whereas the WATCHMAN left atrial appendage closure device ranked last.Dose-adjusted vitamin K antagonists, novel oral anticoagulants, and the WATCHMAN left atrial appendage closure devices are equally efficacious for ischemic stroke prevention but these treatments have different safety profiles. More randomized controlled trials are needed to directly compare these strategies.

Background Significant controversy exists regarding the best approach for nonculprit vessel revascularization in patients with multivessel coronary artery disease presenting with ST‐segment elevation myocardial infarction. We conducted a systematic investigation to pool data from current randomized controlled trials (RCTs) to assess optimal treatment strategies in this patient population. Methods and Results A comprehensive search of SCOPUS from inception through May 2015 was performed using predefined criteria. We compared efficacy and safety outcomes of different approaches by categorizing the studies into 3 groups: (1) complete revascularization (CR) versus culprit lesion revascularization (CL) at index hospitalization, (2) CR at index hospitalization versus staged revascularization (SR) of nonculprit vessels at a separate hospitalization, and (3) comparison of SR versus CL. Eight eligible RCTs met the inclusion criteria: (1) CR versus CL (6 RCTs, n=1727) (2) CR versus SR (3 RCTs, n=311), and (3) SR versus CL (1 RCT, n=149). We observed significantly lower rates of major adverse cardiovascular events, revascularization, and repeat percutaneous coronary interventions among patients treated with CR and SR compared with a CL approach (P