Impaired Antibody Response Is Associated with Histone-Release, Organ Dysfunction and Mortality in Critically Ill COVID-19 Patients.

PURPOSE: the pathophysiologic mechanisms explaining differences in clinical outcomes following COVID-19 are not completely described. This study aims to investigate antibody responses in critically ill patients with COVID-19 in relation to inflammation, organ failure and 30-day survival. METHODS: All patients with PCR-verified COVID-19 and gave consent, and who were admitted to a tertiary Intensive care unit (ICU) in Sweden during March-September 2020 were included. Demography, repeated blood samples and measures of organ function were collected. Analyses of anti-SARS-CoV-2 antibodies (IgM, IgA and IgG) in plasma were performed and correlated to patient outcome and biomarkers of inflammation and organ failure. RESULTS: A total of 115 patients (median age 62 years, 77% male) were included prospectively. All patients developed severe respiratory dysfunction, and 59% were treated with invasive ventilation. Thirty-day mortality was 22.6% for all included patients. Patients negative for any anti-SARS-CoV-2 antibody in plasma during ICU admission had higher 30-day mortality compared to patients positive for antibodies. Patients positive for IgM had more ICU-, ventilator-, renal replacement therapy- and vasoactive medication-free days. IgA antibody concentrations correlated negatively with both SAPS3 and maximal SOFA-score and IgM-levels correlated negatively with SAPS3. Patients with antibody levels below the detection limit had higher plasma levels of extracellular histones on day 1 and elevated levels of kidney and cardiac biomarkers, but showed no signs of increased inflammation, complement activation or cytokine release. After adjusting for age, positive IgM and IgG antibodies were still associated with increased 30-day survival, with odds ratio (OR) 7.1 (1.5-34.4) and 4.2 (1.1-15.7), respectively. CONCLUSION: In patients with severe COVID-19 requiring intensive care, a poor antibody response is associated with organ failure, systemic histone release and increased 30-day mortality.

Income is associated with the probability to receive early coronary angiography after out-of-hospital cardiac arrest.

INTRODUCTION: Low socioeconomic status has been associated with worse outcome after cardiac arrest. This study aims to investigate if patients´ income influences the probability to receive early coronary angiography in out-of-hospital cardiac arrest (OHCA) patients. METHODS: In this nationwide retrospective observational study, 3906 OHCA patients admitted alive and registered in the Swedish Registry for Cardiopulmonary Resuscitation were included. Individual data on income and educational level, prehospital parameters, coronary angiography results and comorbidity were linked from SWEDEHEART and other national registers. RESULTS: Patients were divided into quarters depending on their income level. In the unadjusted model there was a strong correlation between income level and rate of early coronary angiography where 35.5% of patients in the highest income quarters received early angiography compared to 15.4% in the lowest income quarters. When adjusting for educational level, sex, age, comorbidity and hospital type, there were still higher chance of receiving early coronary angiography with increasing income, OR 1.31 (CI 1.01-1.68) and 1.67 (CI 1.29-2.16) for the two highest income quarters respectively compared to the lowest income quarter. When adding potential mediators to the model (first recorded ECG rhythm by the EMS, location, response time, bystander cardiopulmonary resuscitation and if the arrest was witnessed) no difference in early angiography related to income level where found. The main mediator was first recorded ECG rhythm. CONCLUSION: Income level is associated with the probability to undergo early coronary angiography in OHCA patients. This association seems to be mediated by the initial ECG rhythm.

Post-resuscitation myocardial dysfunction in out-of-hospital cardiac arrest patients randomized to immediate coronary angiography versus standard of care.

BACKGROUND: Immediate coronary angiography with subsequent percutaneous coronary intervention (PCI) has the potential to reduce post-resuscitation myocardial dysfunction in out-of-hospital cardiac arrest (OHCA) patients. The aim of this study was to see if immediate coronary angiography, with potential PCI, in patients without ST-elevation on the ECG, influenced post-resuscitation myocardial function and cardiac biomarkers. METHODS: A secondary analysis of the Direct or Subacute Coronary Angiography in Out-of-Hospital Cardiac Arrest (DISCO) trial (ClinicalTrials.gov ID: NCT02309151). Patients with bystander-witnessed OHCA, without ST-elevations on the ECG were randomly assigned to immediate coronary angiography within two hours of cardiac arrest (n = 38) versus standard-of-care with deferred angiography (n = 40). Outcome measures included left ventricle ejection fraction (LVEF) at 24 h, peak Troponin T levels, lactate clearance and NT-proBNP at 72 h. RESULTS: In the immediate-angiography group, median LVEF at 24 h was 47% (Q1-Q3; 30-55) vs. 46% (Q1-Q3; 35-55) in the standard-of-care group. Peak Troponin-T levels during the first 24 h were 362 ng/L (Q1-Q3; 174-2020) in the immediate angiography group and 377 ng/L (Q1-Q3; 205-1078) in the standard-of-care group. NT-proBNP levels at 72 h were 931 ng/L (Q1-Q3; 396-2845) in the immediate-angiography group and 1913 ng/L (Q1-Q3; 489-3140) in the standard-of-care group. CONCLUSION: In this analysis of OHCA patients without ST-elevation on the ECG randomized to immediate coronary angiography or standard-of-care, no differences in post-resuscitation myocardial dysfunction parameters between the two groups were found. This finding was consistent also in patients randomized to immediate coronary angiography where PCI was performed compared to those where PCI was not performed.

Gender differences in utilization of coronary angiography and angiographic findings after out-of-hospital cardiac arrest: A registry study.

INTRODUCTION: We investigated the impact of gender in performance and findings of early coronary angiography (CAG) and percutaneous coronary intervention (PCI), comorbidity and outcome in a large population of out-of-hospital cardiac arrest (OHCA) patients with an initially shockable rhythm. METHODS: Retrospective cohort study. Data retrieved 2008-2013 from the Swedish Register for Cardio-Pulmonary Resuscitation, Swedeheart Registry and National Patient Register. RESULTS: We identified 1498 patients of whom 78% were men. Men and women had the same pathology on the first registered electrocardiogram (ECG): 30% vs. 29% had ST-elevation and 10% vs. 9% had left bundle branch block (LBBB) (P = 0.97). Proportions of performed CAG did not differ between genders. Among patients without ST-elevation/LBBB men more often had at least one significant stenosis, 78% vs. 54% (P = 0.001), more multi-vessel disease (P = 0.01), had normal coronary angiography less often, 22% vs. 46% and PCI more often, 59% vs. 42% (P = 0.03). Among patients without ST-elevation/LBBB on the initial ECG, more men had previously known ischaemic heart disease, 27% vs. 19% (P = 0.02) and a presumed cardiac origin of the cardiac arrest, 86% vs. 72% (P < 0.001). Multivariable analysis showed no association between gender and evaluation by early CAG. In men and women, 1-year survival was 56% vs. 50% (P = 0.22) in patients with ST-elevation/LBBB and 48% vs. 51% (P = 0.50) in patients without. CONCLUSION: Despite no gender differences in ECG findings indicating an early CAG, men had more severe coronary artery disease while women more frequently had normal coronary angiography. However, this did not influence 1-year survival.

Direct or subacute coronary angiography in out-of-hospital cardiac arrest (DISCO)-An initial pilot-study of a randomized clinical trial.

BACKGROUND: The clinical importance of immediate coronary angiography, with potentially subsequent percutaneous coronary intervention (PCI), in out-of-hospital cardiac arrest (OHCA) patients without ST-elevation on the ECG is unclear. In this study, we assessed feasibility and safety aspects of performing immediate coronary angiography in a pre-specified pilot phase of the 'DIrect or Subacute Coronary angiography in Out-of-hospital cardiac arrest' (DISCO) randomized controlled trial (ClinicalTrials.gov ID: NCT02309151). METHODS: Resuscitated bystander witnessed OHCA patients >18 years without ST-elevation on the ECG were randomized to immediate coronary angiography versus standard of care. Event times, procedure related adverse events and safety variables within 7 days were recorded. RESULTS: In total, 79 patients were randomized to immediate angiography (n = 39) or standard of care (n = 40). No major differences in baseline characteristics between the groups were found. There were no differences in the proportion of bleedings and renal failure. Three patients randomized to immediate angiography and six patients randomized to standard care died within 24 h. The median time from EMS arrival to coronary angiography was 135 min in the immediate angiography group. In patients randomized to immediate angiography a culprit lesion was found in 14/38 (36.8%) and PCI was performed in all these patients. In 6/40 (15%) patients randomized to standard of care, coronary angiography was performed before the stipulated 3 days. CONCLUSION: In this out-of-hospital cardiac arrest population without ST-elevation, randomization to a strategy to perform immediate coronary angiography was feasible although the time window of 120 min from EMS arrival at the scene of the arrest to start of coronary angiography was not achieved. No significant safety issues were reported.

Coronary angiography in out-of-hospital cardiac arrest without ST elevation on ECG-Short- and long-term survival.

BACKGROUND: The potential benefit of early coronary angiography in out-of-hospital cardiac arrest (OHCA) patients without ST elevation on ECG is unclear. The aim of this study was to evaluate the association between early coronary angiography and survival in these patients. METHODS: Nationwide observational study between 2008 and 2013. Included were patients admitted to hospital after witnessed OHCA, with shockable rhythm, age 18 to 80 years and unconscious. Patients with ST-elevation on ECG were excluded. Patients that underwent early CAG (within 24 hours) were compared with no early CAG (later during the hospital stay or not at all). Outcomes were survival at 30 days, 1 year, and 3 years. Multivariate analysis included pre-hospital factors, comorbidity and ECG-findings. RESULTS: In total, 799 OHCA patients fulfilled the inclusion criteria, of which 275 (34%) received early CAG versus 524 (66%) with no early CAG. In the early CAG group, the proportion of patients with an occluded coronary artery was 27% and 70% had at least one significant coronary stenosis (defined as narrowing of coronary lumen diameter of ≥50%). The 30-day survival rate was 65% in early CAG group versus 52% with no early CAG (P < .001). The adjusted OR was 1.42 (95% CI 1.00-2.02). The one-year survival rate was 62% in the early CAG group versus 48% in the no early CAG group with the adjusted hazard ratio of 1.35 (95% CI 1.04-1.77). CONCLUSION: In this population of bystander-witnessed cases of out-of-hospital cardiac arrest with shockable rhythm and ECG without ST elevation, early coronary angiography may be associated with improved short and long term survival.

Design of DISCO-Direct or Subacute Coronary Angiography in Out-of-Hospital Cardiac Arrest study.

BACKGROUND: Acute coronary syndrome is a common cause of out-of-hospital cardiac arrest (OHCA). In patients with OHCA presenting with ST elevation, immediate coronary angiography and potential percutaneous coronary intervention (PCI) after return of spontaneous circulation are recommended. However, the evidence for this invasive strategy in patients without ST elevation is limited. Observational studies have shown a culprit coronary artery occlusion in about 30% of these patients, indicating the electrocardiogram's (ECG's) limited sensitivity. The aim of this study is to determine whether immediate coronary angiography and subsequent PCI will provide outcome benefits in OHCA patients without ST elevation. METHODS/DESIGN: We describe the design of the DIrect or Subacute Coronary angiography in Out-of-hospital cardiac arrest study (DISCO)-a pragmatic national, multicenter, randomized, clinical study. OHCA patients presenting with no ST elevation on their first recorded ECG will be randomized to a strategy of immediate coronary angiography or to standard of care with admission to intensive care and angiography after 3days at the earliest unless the patient shows signs of acute ischemia or hemodynamic instability. Primary end point is 30-day survival. An estimated 1,006 patients give 80% power (α = .05) to detect a 20% improved 30-day survival rate from 45% to 54%. Secondary outcomes include good neurologic recovery at 30days and 6months, and cognitive function and cardiac function at 6months. CONCLUSION: This randomized clinical study will evaluate the effect of immediate coronary angiography after OHCA on 30-day survival in patients without ST elevation on their first recorded ECG.