Improving Outcomes After Post-Cardiac Arrest Brain Injury: A Scientific Statement From the International Liaison Committee on Resuscitation.

This scientific statement presents a conceptual framework for the pathophysiology of post-cardiac arrest brain injury, explores reasons for previous failure to translate preclinical data to clinical practice, and outlines potential paths forward. Post-cardiac arrest brain injury is characterized by 4 distinct but overlapping phases: ischemic depolarization, reperfusion repolarization, dysregulation, and recovery and repair. Previous research has been challenging because of the limitations of laboratory models; heterogeneity in the patient populations enrolled; overoptimistic estimation of treatment effects leading to suboptimal sample sizes; timing and route of intervention delivery; limited or absent evidence that the intervention has engaged the mechanistic target; and heterogeneity in postresuscitation care, prognostication, and withdrawal of life-sustaining treatments. Future trials must tailor their interventions to the subset of patients most likely to benefit and deliver this intervention at the appropriate time, through the appropriate route, and at the appropriate dose. The complexity of post-cardiac arrest brain injury suggests that monotherapies are unlikely to be as successful as multimodal neuroprotective therapies. Biomarkers should be developed to identify patients with the targeted mechanism of injury, to quantify its severity, and to measure the response to therapy. Studies need to be adequately powered to detect effect sizes that are realistic and meaningful to patients, their families, and clinicians. Study designs should be optimized to accelerate the evaluation of the most promising interventions. Multidisciplinary and international collaboration will be essential to realize the goal of developing effective therapies for post-cardiac arrest brain injury.

Improving Outcomes After Post-Cardiac Arrest Brain Injury: A Scientific Statement From the International Liaison Committee on Resuscitation.

This scientific statement presents a conceptual framework for the pathophysiology of post-cardiac arrest brain injury, explores reasons for previous failure to translate preclinical data to clinical practice, and outlines potential paths forward. Post-cardiac arrest brain injury is characterized by 4 distinct but overlapping phases: ischemic depolarization, reperfusion repolarization, dysregulation, and recovery and repair. Previous research has been challenging because of the limitations of laboratory models; heterogeneity in the patient populations enrolled; overoptimistic estimation of treatment effects leading to suboptimal sample sizes; timing and route of intervention delivery; limited or absent evidence that the intervention has engaged the mechanistic target; and heterogeneity in postresuscitation care, prognostication, and withdrawal of life-sustaining treatments. Future trials must tailor their interventions to the subset of patients most likely to benefit and deliver this intervention at the appropriate time, through the appropriate route, and at the appropriate dose. The complexity of post-cardiac arrest brain injury suggests that monotherapies are unlikely to be as successful as multimodal neuroprotective therapies. Biomarkers should be developed to identify patients with the targeted mechanism of injury, to quantify its severity, and to measure the response to therapy. Studies need to be adequately powered to detect effect sizes that are realistic and meaningful to patients, their families, and clinicians. Study designs should be optimized to accelerate the evaluation of the most promising interventions. Multidisciplinary and international collaboration will be essential to realize the goal of developing effective therapies for post-cardiac arrest brain injury.

Long-term cardiovascular, cerebrovascular, and thrombotic complications after SARS-CoV-2-Omicron infection: a retrospective cohort study.

OBJECTIVES: Evidence suggests that some COVID-19 survivors experience a wide range of post-COVID-19 sequelae; however, the majority of studies were conducted prior to emergence of the milder Omicron variant. We examined the post-acute risk of new incident cardiovascular complications after SARS-CoV-2 infection in a multi-ethnic Asian population, during Omicron predominance. METHODS: This cohort study used national testing and healthcare claims databases in Singapore to build a cohort of individuals with confirmed SARS-CoV-2 infection during Omicron BA.1/2 transmission, and a contemporaneous test-negative group. Participants in both groups were followed up for a median of 300 days. We estimated risks of new-incident cardiovascular complications using doubly robust competing-risks survival analysis. Risks were reported using two measures: hazard ratio (HR) and excess burden (EB). RESULTS: We included 375,903 test-positive, infected individuals (mean age 48 years) and 619,379 test-negative controls (mean age 47 years). The majority (97.5%, 366,593/375,903) of infected individuals had mild infection not requiring hospitalisation. There was no overall increased risk of new-incident cardiovascular complications, (adjusted-hazards-ratio, aHR = 1.01 [0.97-1.07]) amongst COVID-19 survivors when compared against test-negatives. A modestly increased risk and excess burden of dysrhythmias amongst COVID-19 survivors (aHR=1.09 [1.01- 1.19]) was observed. Risk and burdens of new-incident cardiovascular complications predominantly accrued in hospitalised (aHR=5.52 [3.76-8.10]) and severe (aHR=5.52 [3.76-8.10]) COVID-19 cases. CONCLUSIONS: No significantly increased overall risk of any cardiovascular complication was observed in the 300 days following COVID-19 infection during the Omicron-dominant period when compared against test-negatives, with the exception of a small increased occurrence of dysrhythmias.

Predictors of Mortality in Acute Myocardial Infarction Complicated by Cardiogenic Shock despite Intra-Aortic Balloon Pump: Opportunities for Advanced Mechanical Circulatory Support in Asia.

Introduction: Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) mortality remains high despite revascularization and the use of the intra-aortic balloon pump (IABP). Advanced mechanical circulatory support (MCS) devices, such as catheter-based ventricular assist devices (cVAD), may impact mortality. We aim to identify predictors of mortality in AMI-CS implanted with IABP and the proportion eligible for advanced MCS in an Asian population. Methods: We retrospectively analyzed a cohort of Society for Cardiovascular Angiography and Intervention (SCAI) stage C and above AMI-CS patients with IABP implanted from 2017-2019. We excluded patients who had IABP implanted for indications other than AMI-CS. Primary outcome was 30-day mortality. Binary logistic regression was used to calculate adjusted odds ratios (aOR) for patient characteristics. Results: Over the 3-year period, 242 patients (mean age 64.1 ± 12.4 years, 88% males) with AMI-CS had IABP implanted. 30-day mortality was 55%. On univariate analysis, cardiac arrest (p < 0.001), inotrope/vasopressor use prior to IABP (p = 0.004) was more common in non-survivors. Non-survivors were less likely to be smokers (p = 0.001), had lower ejection fraction, higher creatinine/ lactate and lower pH (all p < 0.001). On multi-variate analysis, predictors of mortality were cardiac arrest prior to IABP (aOR 4.00, CI 2.28-7.03), inotrope/vasopressor prior to IABP (aOR 2.41, CI 1.18-4.96), lower arterial pH (aOR 0.02, CI 0.00-0.31), higher lactate (aOR 2.42, CI 1.00-1.19), and lower hemoglobin (aOR 0.83, CI 0.71-0.98). Using institutional MCS criteria, 106 patients (44%) would have qualified for advanced MCS. Conclusions: Early mortality in AMI-CS remains high despite IABP. Many patients would have qualified for higher degrees of MCS.

Predictors and outcomes of withholding and withdrawal of life-sustaining treatments in intensive care units in Singapore: a multicentre observational study.

BACKGROUND: Clinical practice guidelines on limitation of life-sustaining treatments (LST) in the intensive care unit (ICU), in the form of withholding or withdrawal of LST, state that there is no ethical difference between the two. Such statements are not uniformly accepted worldwide, and there are few studies on LST limitation in Asia. This study aimed to evaluate the predictors and outcomes of withholding and withdrawal of LST in Singapore, focusing on the similarities and differences between the two approaches. METHODS: This was a multicentre observational study of patients admitted to 21 adult ICUs across 9 public hospitals in Singapore over an average of three months per year from 2014 to 2019. The primary outcome measures were withholding and withdrawal of LST (cardiopulmonary resuscitation, invasive mechanical ventilation, and vasopressors/inotropes). The secondary outcome measure was hospital mortality. Multivariable generalised mixed model analysis was used to identify independent predictors for withdrawal and withholding of LST and if LST limitation predicts hospital mortality. RESULTS: There were 8907 patients and 9723 admissions. Of the former, 80.8% had no limitation of LST, 13.0% had LST withheld, and 6.2% had LST withdrawn. Common independent predictors for withholding and withdrawal were increasing age, absence of chronic kidney dialysis, greater dependence in activities of daily living, cardiopulmonary resuscitation before ICU admission, higher Acute Physiology and Chronic Health Evaluation (APACHE) II score, and higher level of care in the first 24 h of ICU admission. Additional predictors for withholding included being of Chinese race, the religions of Hinduism and Islam, malignancy, and chronic liver failure. The additional predictor for withdrawal was lower hospital paying class (with greater government subsidy for hospital bills). Hospital mortality in patients without LST limitation, with LST withholding, and with LST withdrawal was 10.6%, 82.1%, and 91.8%, respectively (p < 0.001). Withholding (odds ratio 13.822, 95% confidence interval 9.987-19.132) and withdrawal (odds ratio 38.319, 95% confidence interval 24.351-60.298) were both found to be independent predictors of hospital mortality on multivariable analysis. CONCLUSIONS: Differences in the independent predictors of withholding and withdrawal of LST exist. Even after accounting for baseline characteristics, both withholding and withdrawal of LST independently predict hospital mortality. Later mortality in patients who had LST withdrawn compared to withholding suggests that the decision to withdraw may be at the point when medical futility is recognised.

Mechanical circulatory support for cardiogenic shock: a network meta-analysis of randomized controlled trials and propensity score-matched studies.

PURPOSE: Cardiogenic shock is associated with high mortality. In refractory shock, it is unclear if mechanical circulatory support (MCS) devices improve survival. We conducted a network meta-analysis to determine which MCS devices confers greatest benefit. METHODS: We searched MEDLINE, Embase, and Scopus databases through 27 August 2023 for relevant randomized controlled trials (RCTs) and propensity score-matched studies (PSMs). We conducted frequentist network meta-analysis, investigating mortality (either 30 days or in-hospital) as the primary outcome. We assessed risk of bias (Cochrane risk of bias 2.0 tool/Newcastle-Ottawa Scale) and as sensitivity analysis reconstructed survival data from published survival curves for a one-stage unadjusted individual patient data (IPD) meta-analysis using a stratified Cox model. RESULTS: We included 38 studies (48,749 patients), mostly reporting on patients with Society for Cardiovascular Angiography and Intervention shock stages C-E cardiogenic shock. Compared with no MCS, extracorporeal membrane oxygenation with intra-aortic balloon pump (ECMO-IABP; network odds ratio [OR]: 0.54, 95% confidence interval (CI): 0.33-0.86, moderate certainty) was associated with lower mortality. There were no differences in mortality between ECMO, IABP, microaxial ventricular assist device (mVAD), ECMO-mVAD, centrifugal VAD, or mVAD-IABP and no MCS (all very low certainty). Our one-stage IPD survival meta-analysis based on the stratified Cox model found only ECMO-IABP was associated with lower mortality (hazard ratio, HR, 0.55, 95% CI 0.46-0.66). CONCLUSION: In patients with cardiogenic shock, ECMO-IABP may reduce mortality, while other MCS devices did not reduce mortality. However, this must be interpreted within the context of inter-study heterogeneity and limited certainty of evidence.

Association between Conversion to Shockable Rhythms and Survival with Favorable Neurological Outcomes for Out-of-Hospital Cardiac Arrests.

BACKGROUND: The initial cardiac rhythm in out-of-hospital cardiac arrest (OHCA) portends different prognoses and affects treatment decisions. Initial shockable rhythms are associated with good survival and neurological outcomes but there is conflicting evidence for those who initially present with non-shockable rhythms. The aim of this study is to evaluate if OHCA with conversion from non-shockable (i.e., asystole and pulseless electrical activity) rhythms to shockable rhythms compared to OHCA remaining in non-shockable rhythms is associated with better survival and neurological outcomes. METHOD: OHCA cases from the Pan-Asian Resuscitation Outcomes Study registry in 13 countries between January 2009 and February 2018 were retrospectively analyzed. Cases with missing initial rhythms, age <18 years, presumed non-medical cause of arrest, and not conveyed by emergency medical services were excluded. Multivariable logistic regression analysis was performed to evaluate the relationship between initial and subsequent shockable rhythm, survival to discharge, and survival with favorable neurological outcomes (cerebral performance category 1 or 2). RESULTS: Of the 116,387 cases included. 11,153 (9.6%) had initial shockable rhythms and 9,765 (8.4%) subsequently converted to shockable rhythms. Japan had the lowest proportion of OHCA patients with initial shockable rhythms (7.3%). For OHCA with initial shockable rhythm, the adjusted odds ratios (aOR) for survival and good neurological outcomes were 8.11 (95% confidence interval [CI] 7.62-8.63) and 15.4 (95%CI 14.1-16.8) respectively. For OHCA that converted from initial non-shockable to shockable rhythms, the aORs for survival and good neurological outcomes were 1.23 (95%CI 1.10-1.37) and 1.61 (95%CI 1.35-1.91) respectively. The aORs for survival and good neurological outcomes were 1.48 (95%CI 1.22-1.79) and 1.92 (95%CI 1.3 - 2.84) respectively for initial asystole, while the aOR for survival in initial pulseless electrical activity patients was 0.83 (95%CI 0.71-0.98). Prehospital adrenaline administration had the highest aOR (2.05, 95%CI 1.93-2.18) for conversion to shockable rhythm. CONCLUSION: In this ambidirectional cohort study, conversion from non-shockable to shockable rhythm was associated with improved survival and neurologic outcomes compared to rhythms that continued to be non-shockable. Continued advanced resuscitation may be beneficial for OHCA with subsequent conversion to shockable rhythms.

Temporal trends in out-of-hospital cardiac arrest with an initial non-shockable rhythm in Singapore.

Aim: Out-of-hospital cardiac arrest (OHCA) with an initial non-shockable rhythm is the predominant form of OHCA in adults. We evaluated its 10-year trends in epidemiology and management in Singapore. Methods: Using the national OHCA registry we studied the trends of 20,844 Emergency Medical Services-attended adult OHCA from April 2010 to December 2019. Survival to hospital discharge was the primary outcome. Trends and outcomes were analyzed using linear and logistic regression, respectively. Results: Incidence rates of adult OHCAs increased during the study period, driven by non-shockable OHCA. Compared to shockable OHCA, non-shockable OHCAs were significantly older, had more co-morbidities, unwitnessed and residential arrests, longer no-flow time, and received less bystander cardiopulmonary resuscitation (CPR) and in-hospital interventions (p < 0.001). Amongst non-shockable OHCA, age, co-morbidities, residential arrests, no-flow time, time to patient, bystander CPR and epinephrine administration increased during the study period, while presumed cardiac etiology decreased (p < 0.05). Unlike shockable OHCA, survival for non-shockable OHCA did not improve (p < 0.001 for trend difference). The likelihood of survival for non-shockable OHCA significantly increased with witnessed arrest (adjusted odds ratio (aOR) 2.02) and bystander CPR (aOR 3.25), but decreased with presumed cardiac etiology (aOR 0.65), epinephrine administration (aOR 0.66), time to patient (aOR 0.93) and age (aOR 0.98). Significant two-way interactions were observed for no-flow time and residential arrest with bystander CPR (aOR 0.96 and 0.40 respectively). Conclusion: The incidence of non-shockable OHCA increased between 2010 and 2019. Despite increased interventions, survival did not improve for non-shockable OHCA, in contrast to the improved survival for shockable OHCA.

Blood Pressure Targets for Out-of-Hospital Cardiac Arrest: A Systematic Review and Meta-Analysis.

BACKGROUND: With ideal mean arterial pressure (MAP) targets in resuscitated out-of-hospital cardiac arrest (OHCA) patients unknown, we performed a meta-analysis of randomised controlled trials (RCTs) to compare the effects of higher versus lower MAP targets. METHODS: We searched four databases until 1 May 2023 for RCTs reporting the effects of higher MAP targets (>70 mmHg) in resuscitated OHCA patients and conducted random-effects meta-analyses. The primary outcome was mortality while secondary outcomes were neurological evaluations, arrhythmias, acute kidney injury, and durations of mechanical ventilation and ICU stay. We conducted inverse-variance weighted strata-level meta-regression against a proportion of non-survivors to assess differences between reported MAPs. We also conducted a trial sequential analysis of RCTs. RESULTS: Four RCTs were included. Higher MAP was not associated with reduced mortality (OR: 1.09, 95%-CI: 0.84 to 1.42, p = 0.51), or improved neurological outcomes (OR: 0.99, 95%-CI: 0.77 to 1.27, p = 0.92). Such findings were consistent despite additional sensitivity analyses. Our robust variance strata-level meta-regression revealed no significant associations between mean MAP and the proportion of non-survivors (B: 0.029, 95%-CI: -0.023 to 0.081, p = 0.162), and trial sequential analysis revealed no meaningful survival benefit for higher MAPs. CONCLUSIONS: A higher MAP target was not significantly associated with improved mortality and neurological outcomes in resuscitated OHCA patients.

Measurement Properties of the 15-Item Singapore Caregiver Quality of Life Scale (SCQOLS-15) in Family Caregivers of Patients with Heart Diseases.

PURPOSE: To evaluate the measurement properties of the 15-item Singapore Caregiver Quality of Life Scale (SCQOLS-15) in family caregivers of patients with heart diseases. METHODS: The SCQOLS-15 survey was self-administered by family caregivers of patients with chronic heart diseases, at baseline and 1 week later. The criterion validity of SCQOLS-15 and its domain scores was assessed by calculating the Spearman correlation coefficient (ρ) with the Brief Assessment Scale for Caregivers (BASC), Caregiver Reaction Assessment (CRA), and their sub-scores. Known-group validity was assessed using the New York Heart Association (NYHA) functional class. Test-retest reliability was evaluated using the intraclass correlation coefficient (ICC). RESULTS: Of the 327 caregivers included, 65% were adult children and 28% were spouses. The distribution of NYHA classes of the patients was I: 27%, II: 40%, III: 24%, and IV: 9%. There was a positive correlation between the SCQOLS-15 and BASC total scores (ρ = 0.7). SCQOLS-15 domain scores were also correlated with BASC and CRA sub-scores as per a priori hypotheses, with absolute values of ρ ranging from 0.4 to 0.6. The mean values of SCQOLS-15 total and all domain scores were lower among caregivers of patients with NYHA class III/IV compared to those of class I/II patients (each P < 0.05). Among 146 caregivers who completed the follow-up and self-rated a stable quality-of-life, ICCs for test-retest reliability of SCQOLS-15 total and all domain scores were ≥ 0.8. CONCLUSION: The SCQOLS-15 is a valid and reliable instrument for measuring the quality of life in caregivers of heart disease patients.

Determinants of health-related quality of life after out-of-hospital cardiac arrest (OHCA): A systematic review.

OBJECTIVE: With a growing number of out-of-hospital cardiac arrest (OHCA) survivors globally, the focus of OHCA management has now broadened to survivorship. An outcome central to survivorship is health-related quality of life (HRQoL). This systematic review aimed to synthesise evidence related to the determinants of HRQoL of OHCA survivors. METHODS: We systematically searched MEDLINE, Embase, and Scopus from inception to 15 August 2022 to identify studies investigating the association of at least one determinant and HRQoL in adult OHCA survivors. All articles were independently reviewed by two investigators. We abstracted data pertaining to determinants and classified them using a well-established HRQoL theoretical framework - the Wilson and Cleary (revised) model. RESULTS: 31 articles assessing a total of 35 determinants were included. Determinants were classified into the five domains in the HRQoL model. 26 studies assessed determinants related to individual characteristics (n = 3), 12 studied biological function (n = 7), nine studied symptoms (n = 3), 16 studied functioning (n = 5), and 35 studied characteristics of the environment (n = 17). In studies that included multivariable analyses, most reported that individual characteristics (older age, female sex), symptoms (anxiety, depression), and functioning (impaired neurocognitive function) were significantly associated with poorer HRQoL. CONCLUSIONS: Individual characteristics, symptoms, and functioning played significant roles in explaining the variability in HRQoL. Significant non-modifiable determinants such as age and sex could be used to identify populations at risk of poorer HRQoL, while significant modifiable determinants such as psychological health and neurocognitive functioning could serve as targets for post-discharge screening and rehabilitation plans. PROSPERO registration number: CRD42022359303.

Did lockdown influence bystanders' willingness to perform cardiopulmonary resuscitation? A worldwide registry-based perspective.

AIM: Bystander cardiopulmonary resuscitation (CPR) significantly increases the survival rate after out-of-hospital cardiac arrest. Using population-based registries, we investigated the impact of lockdown due to Covid-19 on the provision of bystander CPR, taking background changes over time into consideration. METHODS: Using a registry network, we invited all registries capable of delivering data from 1. January 2017 to 31. December 2020 to participate in this study. We used negative binominal regression for the analysis of the overall results. We also calculated the rates for bystander CPR. For every participating registry, we analysed the incidence per 100000 inhabitants of bystander CPR and EMS-treated patients using Poisson regression, including time trends. RESULTS: Twenty-six established OHCA registries reported 742 923 cardiac arrest patients over a four-year period covering 1.3 billion person-years. We found large variations in the reported incidence between and within continents. There was an increase in the incidence of bystander CPR of almost 5% per year. The lockdown in March/April 2020 did not impact this trend. The increase in the rate of bystander CPR was also seen when analysing data on a continental level. We found large variations in incidence of bystander CPR before and after lockdown when analysing data on a registry level. CONCLUSION: There was a steady increase in bystander CPR from 2017 to 2020, not associated with an increase in the number of ambulance-treated cardiac arrest patients. We did not find an association between lockdown and bystanders' willingness to start CPR before ambulance arrival, but we found inconsistent patterns of changes between registries.

The Effect of Building-Level Socioeconomic Status on Bystander Cardiopulmonary Resuscitation: A Retrospective Cohort Study.

OBJECTIVE: Understanding the social determinants of bystander cardiopulmonary resuscitation (CPR) receipt can inform the design of public health interventions to increase bystander CPR. The association of socioeconomic status with bystander CPR is generally poorly understood. We evaluated the relationship between socioeconomic status and bystander CPR in cases of out-of-hospital cardiac arrest (OHCA). METHODS: This was a retrospective cohort study based on the Singapore cohort of the Pan-Asian Resuscitation Outcomes Study registry between 2010 and 2018. We categorized patients into low, medium, and high Singapore Housing Index (SHI) levels-a building-level index of socioeconomic status. The primary outcome was receipt of bystander CPR. The secondary outcomes were prehospital return of spontaneous circulation and survival to discharge. RESULTS: A total of 12,730 OHCA cases were included, the median age was 71 years, and 58.9% were male. The bystander CPR rate was 56.7%. Compared to patients in the low SHI category, those in the medium and high SHI categories were more likely to receive bystander CPR (medium SHI: adjusted odds ratio [aOR] 1.48, 95% CI 1.30-1.69; high SHI: aOR 1.93, 95% CI 1.67-2.24). High SHI patients had higher survival compared to low SHI patients on unadjusted analysis (OR 1.79, 95% CI 1.08-2.96), but not adjusted analysis (adjusted for age, sex, race, witness status, arrest time, past medical history of cancer, and first arrest rhythm). When comparing high with low SHI, females had larger increases in bystander CPR rates than males. CONCLUSIONS: Lower building-level socioeconomic status was independently associated with lower rate of bystander CPR, and females were more susceptible to the effect of low socioeconomic status on lower rate of bystander CPR.

Association of anticoagulation use during continuous kidney replacement therapy and 90-day outcomes: A multicentre study.

Introduction: Anticoagulation is recommended during continuous kidney replacement therapy (CKRT) to prolong the filter lifespan for optimal filter performance. We aimed to evaluate the effect of anticoagulation during CKRT on dialysis dependence and mortality within 90 days of intensive care unit (ICU) admission. Method: Our retrospective observational study evaluated the first CKRT session in critically ill adults with acute kidney injury (AKI) in Singapore from April to September 2017. The primary outcome was a composite of dialysis dependence or death within 90 days of ICU admission; the main exposure variable was anticoagulation use (regional citrate anticoagulation [RCA] or systemic heparin). Multivariable logistic regression was performed to adjust for possible confounders: age, female sex, Acute Physiology and Chronic Health Evaluation (APACHE II) score, liver dysfunction, coagulopathy (international normalised ratio[INR] >1.5) and platelet counts of less than 100,000/uL). Results: The study cohort included 276 patients from 14 participating adult ICUs, of whom 176 (63.8%) experienced dialysis dependence or death within 90 days of ICU admission (19 dialysis dependence, 157 death). Anticoagulation significantly reduced the odds of the primary outcome (adjusted odds ratio [AOR] 0.47, 95% confidence interval [CI] 0.27-0.83, P=0.009). Logistic regression analysis using anticoagulation as a 3-level indicator variable demonstrated that RCA was associated with mortality reduction (AOR 0.46, 95% CI 0.25-0.83, P=0.011), with heparin having a consistent trend (AOR 0.51, 95% CI 0.23-1.14, P=0.102). Conclusion: Among critically ill patients with AKI, anticoagulation use during CKRT was associated with reduced dialysis or death at 90 days post-ICU admission, which was statistically significant for regional citrate anticoagulation and trended in the same direction of benefit for systemic heparin anticoagulation. Anticoagulation during CKRT should be considered whenever possible.

Prior Cancer Is Associated with Lower Atherosclerotic Cardiovascular Disease Risk at First Acute Myocardial Infarction.

Background: Patients with cancer are at increased risk of acute myocardial infarction (AMI). It is unclear if the Atherosclerotic Cardiovascular Disease (ASCVD) risk score at incident AMI is reflective of this higher risk in patients with prior cancer than those without. Methods: We linked nationwide AMI and cancer registries from 2008 to 2019. A total of 18,200 eligible patients with ASCVD risk score calculated at incident AMI were identified (1086 prior cancer; 17,114 no cancer). Results: At incident AMI, age-standardized mean ASCVD risk was lower in the prior cancer group (18.6%) than no cancer group (20.9%) (p < 0.001). Prior to incident AMI, smoking, hypertension, hyperlipidemia and diabetes mellitus were better controlled in the prior cancer group. However post-AMI, prior cancer was associated with lower guideline-directed medical therapy usage and higher all-cause mortality (adjusted hazard ratio 1.85, 95% confidence interval 1.66−2.07). Conclusions: AMI occurred despite better control of cardiovascular risk factors and lower age-standardized estimated mean 10-year ASCVD risk among patients with prior cancer than no cancer. Prior cancer was associated with lower guideline-directed medical therapy post-AMI and higher mortality.

Effects of Carotid Artery Stiffness on Cerebral Small-Vessel Disease and Cognition.

Background Carotid artery stiffness is associated with cognitive impairment and dementia, but the underlying mechanisms remain unknown. We examined the associations of carotid artery stiffness with cerebral small-vessel disease markers, cognition, and dementia subtypes in a memory clinic cohort. Methods and Results A total of 272 participants underwent carotid ultrasonography, 3 Tesla brain magnetic resonance imaging, and neuropsychological assessment. Carotid ultrasonography was used to assess ß-index, pressure-strain elastic modulus, and pulse-wave velocity-ß. Brain magnetic resonance images were graded for cerebral small-vessel disease markers, including white matter hyperintensities, lacunes, and cerebral microbleeds. Participants were classified as having no cognitive impairment, cognitive impairment and no dementia, or dementia subtyped as Alzheimer disease and vascular dementia. Cognition was assessed using National Institute of Neurological Disorders and Stroke-Canadian Stroke Network harmonization battery. After adjusting for age, sex, cardiovascular risk factors, and diseases, multivariable models showed that ß-index (ß=0.69; P=0.002), elastic modulus (ß=0.78; P<0.001), and pulse-wave velocity-ß (ß=0.80; P<0.001) were associated with white matter hyperintensities, and elastic modulus (odds ratio [OR], 1.39 [95% CI, 1.04-1.85]) and pulse-wave velocity-ß (OR, 1.47 [95% CI, 1.10-1.98]) were independently associated with lacunes. Similarly, ß-index (OR, 2.04 [95% CI, 1.14-4.13]), elastic modulus (OR, 2.22 [95% CI, 1.25-4.42]), and pulse-wave velocity-ß (OR, 2.50 [95% CI, 1.36-5.18]) were independently associated with vascular dementia. Carotid stiffness measures were independently associated with worse performance in global cognition, visuomotor speed, visuospatial function, and executive function. These associations became largely nonsignificant after further adjusting for cerebral small-vessel disease markers. Conclusions In memory clinic patients, carotid artery stiffness was associated with white matter hyperintensities and lacunes, impairment in global and domain-specific cognition, and causative subtypes of dementia, particularly vascular. The effects of carotid stiffness on cognition were not independent of, and were partially mediated by, cerebral small-vessel disease.

Impact of COVID-19 on barriers to dispatcher-assisted cardiopulmonary resuscitation in adult out-of-hospital cardiac arrests in Singapore.

OBJECTIVE: Fewer out-of-hospital cardiac arrest (OHCA) patients received bystander cardiopulmonary resuscitation during the COVID-19 pandemic in Singapore. We investigated the impact of COVID-19 on barriers to dispatcher-assisted cardiopulmonary resuscitation (DA-CPR). METHODS: We reviewed audio recordings of all calls to our national ambulance service call centre during the pandemic (January-June 2020) and pre-pandemic (January-June 2019) periods. Our primary outcome was the presence of barriers to DA-CPR. Multivariable logistic regression was used to assess the effect of COVID-19 on the likelihood of barriers to and performance of DA-CPR, adjusting for patient and event characteristics. RESULTS: There were 1241 and 1118 OHCA who were eligible for DA-CPR during the pandemic (median age 74 years, 61.6 % males) and pre-pandemic (median age 73 years, 61.1 % males) periods, respectively. Compared to pre-pandemic, there were more residential and witnessed OHCA during the pandemic (87 % vs 84.9 % and 54 % vs 38.1 %, respectively); rates of DA-CPR were unchanged (57.3 % vs 61.1 %). COVID-19 increased the likelihood of barriers to DA-CPR (aOR 1.47, 95 % CI: 1.25-1.74) but not performance of DA-CPR (aOR 0.86, 95 % CI: 0.73 - 1.02). Barriers such as 'patient status changed' and 'caller not with patient' increased during COVID-19 pandemic. 'Afraid to do CPR' markedly decreased during the pandemic; fear of COVID-19 transmission made up 0.5 % of the barriers. CONCLUSION: Barriers to DA-CPR were encountered more frequently during the COVID-19 pandemic but did not affect callers' willingness to perform DA-CPR. Distancing measures led to more residential arrests with increases in certain barriers, highlighting opportunities for public education and intervention.

Microaxial Left Ventricular Assist Device in Cardiogenic Shock: A Systematic Review and Meta-Analysis.

Microaxial left ventricular assist devices (LVAD) are increasingly used to support patients with cardiogenic shock; however, outcome results are limited to single-center studies, registry data and select reviews. We conducted a systematic review and meta-analysis, searching three databases for relevant studies reporting on microaxial LVAD use in adults with cardiogenic shock. We conducted a random-effects meta-analysis (DerSimonian and Laird) based on short-term mortality (primary outcome), long-term mortality and device complications (secondary outcomes). We assessed the risk of bias and certainty of evidence using the Joanna Briggs Institute and the GRADE approaches, respectively. A total of 63 observational studies (3896 patients), 6 propensity-score matched (PSM) studies and 2 randomized controlled trials (RCTs) were included (384 patients). The pooled short-term mortality from observational studies was 46.5% (95%-CI: 42.7-50.3%); this was 48.9% (95%-CI: 43.8-54.1%) amongst PSM studies and RCTs. The pooled mortality at 90 days, 6 months and 1 year was 41.8%, 51.1% and 54.3%, respectively. Hemolysis and access-site bleeding were the most common complications, each with a pooled incidence of around 20%. The reported mortality rate of microaxial LVADs was not significantly lower than extracorporeal membrane oxygenation (ECMO) or intra-aortic balloon pumps (IABP). Current evidence does not suggest any mortality benefit when compared to ECMO or IABP.

Management of Out-of-Hospital Cardiac Arrest during COVID-19: A Tale of Two Cities.

Variations in the impact of the COVID-19 pandemic on out-of-hospital cardiac arrest (OHCA) have been reported. We aimed to, using population-based registries, compare community response, Emergency Medical Services (EMS) interventions and outcomes of adult, EMS-treated, non-traumatic OHCA in Singapore and metropolitan Atlanta, before and during the pandemic. Associations of OHCA characteristics, pre-hospital interventions and pandemic with survival to hospital discharge were analyzed using logistic regression. There were 2084 cases during the pandemic (17 weeks from the first confirmed COVID-19 case) and 1900 in the pre-pandemic period (corresponding weeks in 2019). Compared to Atlanta, OHCAs in Singapore were older, received more bystander interventions (cardiopulmonary resuscitation (CPR): 65.0% vs. 41.4%; automated external defibrillator application: 28.6% vs. 10.1%), yet had lower survival (5.6% vs. 8.1%). Compared to the pre-pandemic period, OHCAs in Singapore and Atlanta occurred more at home (adjusted odds ratio (aOR) 2.05 and 2.03, respectively) and were transported less to hospitals (aOR 0.59 and 0.36, respectively) during the pandemic. Singapore reported more witnessed OHCAs (aOR 1.96) yet less bystander CPR (aOR 0.81) during pandemic, but not Atlanta (p < 0.05). The impact of COVID-19 on OHCA outcomes did not differ between cities. Changes in OHCA characteristics and management during the pandemic, and differences between Singapore and Atlanta were likely the result of systemic and sociocultural factors.

Clustering of Environmental Parameters and the Risk of Acute Myocardial Infarction.

The association between days with similar environmental parameters and cardiovascular events is unknown. We investigate the association between clusters of environmental parameters and acute myocardial infarction (AMI) risk in Singapore. Using k-means clustering and conditional Poisson models, we grouped calendar days from 2010 to 2015 based on rainfall, temperature, wind speed and the Pollutant Standards Index (PSI) and compared the incidence rate ratios (IRR) of AMI across the clusters using a time-stratified case-crossover design. Three distinct clusters were formed with Cluster 1 having high wind speed, Cluster 2 high rainfall, and Cluster 3 high temperature and PSI. Compared to Cluster 1, Cluster 3 had a higher AMI incidence with IRR 1.04 (95% confidence interval 1.01-1.07), but no significant difference was found between Cluster 1 and Cluster 2. Subgroup analyses showed that increased AMI incidence was significant only among those with age ≥65, male, non-smokers, non-ST elevation AMI (NSTEMI), history of hyperlipidemia and no history of ischemic heart disease, diabetes or hypertension. In conclusion, we found that AMI incidence, especially NSTEMI, is likely to be higher on days with high temperature and PSI. These findings have public health implications for AMI prevention and emergency health services delivery during the seasonal Southeast Asian transboundary haze.