Postcardiotomy Shock Syndrome: A Narrative Review of Perioperative Diagnosis and Management.

Postcardiotomy shock (PCS) is generally described as the inability to separate from cardiopulmonary bypass due to ineffective cardiac output after cardiotomy, which is caused by a primary cardiac disorder, resulting in inadequate tissue perfusion. Postcardiotomy shock occurs in 0.5% to 1.5% of contemporary cardiac surgery cases, and is accompanied by an in-hospital mortality of approximately 67%. In the last 2 decades, the incidence of PCS has increased, likely due to the increased age and baseline morbidity of patients requiring cardiac surgery. In this narrative review, the authors discuss the epidemiology and pathophysiology of PCS, the rationale and evidence behind the initiation, continuation, escalation, and discontinuation of mechanical support devices in PCS, and the anesthetic implications.

Triangulating evidence from observational and Mendelian randomization studies of ketone bodies for cognitive performance.

BACKGROUND: Ketone bodies (KBs) are an alternative energy supply for brain functions when glucose is limited. The most abundant ketone metabolite, 3-ß-hydroxybutyrate (BOHBUT), has been suggested to prevent or delay cognitive impairment, but the evidence remains unclear. We triangulated observational and Mendelian randomization (MR) studies to investigate the association and causation between KBs and cognitive function. METHODS: In observational analyses of 5506 participants aged ≥ 45 years from the Whitehall II study, we used multiple linear regression to investigate the associations between categorized KBs and cognitive function scores. Two-sample MR was carried out using summary statistics from an in-house KBs meta-analysis between the University College London-London School of Hygiene and Tropical Medicine-Edinburgh-Bristol (UCLEB) Consortium and Kettunen et al. (N = 45,031), and publicly available summary statistics of cognitive performance and Alzheimer's disease (AD) from the Social Science Genetic Association Consortium (N = 257,841), and the International Genomics of Alzheimer's Project (N = 54,162), respectively. Both strong (P < 5 × 10-8) and suggestive (P < 1 × 10-5) sets of instrumental variables for BOHBUT were applied. Finally, we performed cis-MR on OXCT1, a well-known gene for KB catabolism. RESULTS: BOHBUT was positively associated with general cognitive function (ß = 0.26, P = 9.74 × 10-3). In MR analyses, we observed a protective effect of BOHBUT on cognitive performance (inverse variance weighted: ßIVW = 7.89 × 10-2, PIVW = 1.03 × 10-2; weighted median: ßW-Median = 8.65 × 10-2, PW-Median = 9.60 × 10-3) and a protective effect on AD (ßIVW = - 0.31, odds ratio: OR = 0.74, PIVW = 3.06 × 10-2). Cis-MR showed little evidence of therapeutic modulation of OXCT1 on cognitive impairment. CONCLUSIONS: Triangulation of evidence suggests that BOHBUT has a beneficial effect on cognitive performance. Our findings raise the hypothesis that increased BOHBUT may improve general cognitive functions, delaying cognitive impairment and reducing the risk of AD.

Potential Impact of the 2019 ACC/AHA Guidelines on the Primary Prevention of Cardiovascular Disease Recommendations on the Inappropriate Routine Use of Aspirin and Aspirin Use Without a Recommended Indication for Primary Prevention of Cardiovascular Disease in Cardiology Practices: Insights From the NCDR PINNACLE Registry.

BACKGROUND: Aspirin is recommended in patients with atherosclerotic cardiovascular disease for secondary prevention. In patients without atherosclerotic cardiovascular disease and not at high 10-year risk, there is no evidence aspirin reduces adverse cardiovascular events and it could increase bleeding. The 2019 American College of Cardiology/American Heart Association Guidelines on Primary Prevention of Cardiovascular Disease state that aspirin may be considered for primary prevention (class IIb) in patients 40 to 70 years that are at higher risk of atherosclerotic cardiovascular disease and that routine use of aspirin should be avoided (class III:Harm) for patients >70 years. We examined the frequency of patients on aspirin for primary prevention that would have been considered unindicated or potentially harmful per the recent guideline where aspirin discontinuation may be beneficial. METHODS: To assess the potential impact, within the National Cardiovascular Disease Registry Practice Innovation and Clinical Excellence Registry, we assessed 855 366 patients from 400 practices with encounters between January 1, 2018 and March 31, 2019, that were receiving aspirin for primary prevention. We defined inappropriate use as the use of aspirin in patients <40 or >70 years and use without a recommended indication as use of aspirin in patients 40 to 70 years with low, borderline, or intermediate 10-year atherosclerotic cardiovascular disease risk. Frequency of inappropriate use and use without a recommended indication were calculated and practice-level variation was evaluated using the median rate ratio. RESULTS: Inappropriate use occurred in 27.6% (193 674/701 975) and use without a recommended indication in 26.0% (31 810/122 507) with significant practice-level variation in inappropriate use (predicted median practice-level rate 33.5%, interquartile range, 24.1% to 40.8%; median rate ratio, 1.71 [95% CI, 1.67-1.76]). CONCLUSIONS: Immediately before the 2019 American College of Cardiology/American Heart Association Guidelines on Primary Prevention of Cardiovascular Disease, over one-fourth of patients in this national registry were receiving aspirin for primary prevention inappropriately or without a recommended indication with significant practice-level variation. These findings help to determine the potential impact of guideline recommendations on contemporary use of aspirin for primary prevention.

Validation of lipid-related therapeutic targets for coronary heart disease prevention using human genetics.

Drug target Mendelian randomization (MR) studies use DNA sequence variants in or near a gene encoding a drug target, that alter the target's expression or function, as a tool to anticipate the effect of drug action on the same target. Here we apply MR to prioritize drug targets for their causal relevance for coronary heart disease (CHD). The targets are further prioritized using independent replication, co-localization, protein expression profiles and data from the British National Formulary and clinicaltrials.gov. Out of the 341 drug targets identified through their association with blood lipids (HDL-C, LDL-C and triglycerides), we robustly prioritize 30 targets that might elicit beneficial effects in the prevention or treatment of CHD, including NPC1L1 and PCSK9, the targets of drugs used in CHD prevention. We discuss how this approach can be generalized to other targets, disease biomarkers and endpoints to help prioritize and validate targets during the drug development process.

Cardiac Rehabilitation for Patients With Heart Failure: JACC Expert Panel.

Cardiac rehabilitation is defined as a multidisciplinary program that includes exercise training, cardiac risk factor modification, psychosocial assessment, and outcomes assessment. Exercise training and other components of cardiac rehabilitation (CR) are safe and beneficial and result in significant improvements in quality of life, functional capacity, exercise performance, and heart failure (HF)-related hospitalizations in patients with HF. Despite outcome benefits, cost-effectiveness, and strong practice guideline recommendations, CR remains underused. Clinicians, health care leaders, and payers should prioritize incorporating CR as part of the standard of care for patients with HF.

Professional Societies' Role in Addressing Member Burnout and Promoting Well-Being.

Rationale: Critical care clinicians have high burnout rates. Previous studies have explored individual and organizational solutions to address burnout, but existing literature has not considered how professional societies can prevent burnout and promote member well-being. Objectives: The Critical Care Society Collaborative convened a task force to document professional society initiatives to address burnout, explore perspectives on the role of societies to address burnout, and develop recommendations that could guide critical care societies' efforts to promote well-being. Methods: We conducted a multiphase evaluation of 17 major U.S. professional societies whose members regularly work in critical care settings. We asked representatives from each society to document their existing well-being initiatives, and we conducted semistructured interviews to explore perspectives on the role of professional societies to address burnout. The task force members then met to discuss phase one and two findings to develop recommendations that could act as a roadmap to guide future society efforts. Results: All society representatives agreed that professional societies have a responsibility to address burnout, and they described various well-being initiatives that could act as examples for future efforts. We developed a roadmap with the following recommendations: 1) Acknowledge the problem of burnout; 2) Commit to supporting member well-being; 3) Create collaborations to promote well-being; 4) Educate and advocate for change; 5) Foster innovation through research; and 6) Support organizational and individual solutions. Conclusions: Our findings highlight a clear role for professional societies to address burnout and promote members' well-being.

Genome-wide association study of circulating interleukin 6 levels identifies novel loci.

Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10-11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10-10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10-122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.

Establishing reference intervals for triglyceride-containing lipoprotein subfraction metabolites measured using nuclear magnetic resonance spectroscopy in a UK population.

BACKGROUND: Nuclear magnetic resonance (NMR) spectroscopy allows triglycerides to be subclassified into 14 different classes based on particle size and lipid content. We recently showed that these subfractions have differential associations with cardiovascular disease events. Here we report the distributions and define reference interval ranges for 14 triglyceride-containing lipoprotein subfraction metabolites. METHODS: Lipoprotein subfractions using the Nightingale NMR platform were measured in 9073 participants from four cohort studies contributing to the UCL-Edinburgh-Bristol consortium. The distribution of each metabolite was assessed, and reference interval ranges were calculated for a disease-free population, by sex and age group (<55, 55-65, >65 years), and in a subgroup population of participants with cardiovascular disease or type 2 diabetes. We also determined the distribution across body mass index and smoking status. RESULTS: The largest reference interval range was observed in the medium very-low density lipoprotein subclass (2.5th 97.5th percentile; 0.08 to 0.68 mmol/L). The reference intervals were comparable among male and female participants, with the exception of triglyceride in high-density lipoprotein. Triglyceride subfraction concentrations in very-low density lipoprotein, intermediate-density lipoprotein, low-density lipoprotein and high-density lipoprotein subclasses increased with increasing age and increasing body mass index. Triglyceride subfraction concentrations were significantly higher in ever smokers compared to never smokers, among those with clinical chemistry measured total triglyceride greater than 1.7 mmol/L, and in those with cardiovascular disease, and type 2 diabetes as compared to disease-free subjects. CONCLUSION: This is the first study to establish reference interval ranges for 14 triglyceride-containing lipoprotein subfractions in samples from the general population measured using the nuclear magnetic resonance platform. The utility of nuclear magnetic resonance lipid measures may lead to greater insights for the role of triglyceride in cardiovascular disease, emphasizing the importance of appropriate reference interval ranges for future clinical decision making.

Metabolic profiles of socio-economic position: a multi-cohort analysis.

BACKGROUND: Low socio-economic position (SEP) is a risk factor for multiple health outcomes, but its molecular imprints in the body remain unclear. METHODS: We examined SEP as a determinant of serum nuclear magnetic resonance metabolic profiles in ∼30 000 adults and 4000 children across 10 UK and Finnish cohort studies. RESULTS: In risk-factor-adjusted analysis of 233 metabolic measures, low educational attainment was associated with 37 measures including higher levels of triglycerides in small high-density lipoproteins (HDL) and lower levels of docosahexaenoic acid (DHA), omega-3 fatty acids, apolipoprotein A1, large and very large HDL particles (including levels of their respective lipid constituents) and cholesterol measures across different density lipoproteins. Among adults whose father worked in manual occupations, associations with apolipoprotein A1, large and very large HDL particles and HDL-2 cholesterol remained after adjustment for SEP in later life. Among manual workers, levels of glutamine were higher compared with non-manual workers. All three indicators of low SEP were associated with lower DHA, omega-3 fatty acids and HDL diameter. At all ages, children of manual workers had lower levels of DHA as a proportion of total fatty acids. CONCLUSIONS: Our work indicates that social and economic factors have a measurable impact on human physiology. Lower SEP was independently associated with a generally unfavourable metabolic profile, consistent across ages and cohorts. The metabolites we found to be associated with SEP, including DHA, are known to predict cardiovascular disease and cognitive decline in later life and may contribute to health inequalities.

Association of human immunodeficiency virus and hepatitis C virus infection with long-term outcomes post-ST segment elevation myocardial infarction in a disadvantaged urban community.

BACKGROUND: HIV and HCV have been linked to an increased risk of cardiovascular disease (CVD). Their impact on long-term outcomes following ST-segment myocardial infarction (STEMI) has not been previously studied. METHODS: We leveraged data from a STEMI registry (n = 1208) at an inner-city health system to assess the influence of HIV and HCV on post-STEMI outcomes. Cox regression was used to compare HIV-monoinfected (n = 22), HCV-monoinfected (n = 26) and HIV-HCV-coinfected patients (n = 8) with the neither-infected group (n = 1152) with regard to death, death or any readmission, and death or CVD readmission. RESULTS: The cohort was majority black or Hispanic. Median follow-up was 4.3 years. Compared to the neither-infected group, the HIV-monoinfected group showed near-significantly higher risks of death or any readmission (HR = 1.62, 95% CI = 0.96, 2.74) and death or CVD readmission (HR = 1.82, 95% CI = 0.98, 3.39) after full adjustment. On similar comparison, the HCV-monoinfected group exhibited significantly higher risks of death (HR = 2.09, 95% CI = 1.05, 4.15) and death or any readmission (HR = 1.68, 95% CI = 1.07, 2.65), whereas the HIV-HCV-coinfected group showed higher risk of death (HR = 6.51, 95% CI = 2.28, 18.61). CONCLUSIONS: In this cohort composed mostly of race-ethnic minorities, HIV monoinfection tended to be associated with 1.6-to-1.8-fold higher risk of death or readmission for any cause or CVD over long-term follow-up compared to neither infection, whereas HCV monoinfection was associated with 1.7-to-2.1-fold higher risk of death and death or any readmission, and HIV-HCV coinfection with 6.5-fold higher risk of death. These associations require further study in larger populations, but highlight the importance of identifying and treating HIV and HCV in patients presenting with STEMI.

Obesity and the paradox of mortality and heart failure hospitalization in heart failure with preserved ejection fraction.

BACKGROUND: Limited data exist on the association of obesity with both hospitalization and mortality in patients with heart failure with preserved ejection fraction (HFpEF), especially in the real-world ambulatory setting. We hypothesized that increasing body-mass index (BMI) in ambulatory heart failure with preserved ejection fraction would have a protective effect on these patients leading to decreased mortality and hospitalizations. METHODS: We studied the relationship between BMI and the time to all-cause mortality, time to heart failure (HF) hospitalization, and time to all-cause hospitalization over a 2-year follow-up in a national cohort of 2501 ambulatory HFpEF patients at 153 Veterans Affairs medical centers. RESULTS: Compared with normal BMI, overweight (HR 0.72; 95% CI 0.57-0.91), obesity class I (HR 0.59; 95% CI 0.45-0.77), obesity class II (HR 0.56; 95% CI 0.40-0.77), and obesity class III (HR 0.53; 95% CI 0.36-0.77) were associated with improved survival after adjustment for demographics and comorbidities. In contrast, the time to HF hospitalization showed an inverse relationship, with shorter time to HF hospitalization with increasing BMI compared with normal BMI; overweight (adjusted HR 1.30; 95% CI 0.88-1.90), obesity class I (HR 1.57; 95% CI 1.05-2.34), obesity class II (HR 1.79; 95% CI 1.15-2.78), and obesity class III (HR 1.96; 95% CI 1.23-3.12). However, time to first all-cause hospitalization was not significantly different by BMI groups. CONCLUSIONS: In a large, national ambulatory HFpEF cohort, despite the presence of the obesity paradox with respect to survival, increasing BMI was independently associated with an increased risk of HF hospitalization and similar risk of all-cause hospitalization. Future longer-term prospective trials evaluating the safety and efficacy of weight loss on morbidity and mortality, in patients with severe obesity and HFpEF are needed.

Addressing Burnout Syndrome From a Critical Care Specialty Organization Perspective.

BACKGROUND: Health care specialty organizations are an important resource for their membership; however, it is not clear how specialty societies should approach combating stress and burnout on an organizational scale. OBJECTIVE: To understand the prevalence of burnout syndrome in American Thoracic Society members, identify specialty-specific risk factors, and generate strategies for health care societies to combat burnout. METHODS: Cross-sectional, mixed-methods survey in a sample of 2018 American Thoracic Society International Conference attendees to assess levels of burnout syndrome, work satisfaction, and stress. RESULTS: Of the 130 respondents, 69% reported high stress, 38% met burnout criteria, and 20% confirmed chaotic work environments. Significant associations included sex and stress level; clinical time and at-home electronic health record work; and US practice and at-home electronic health record work. There were no significant associations between burnout syndrome and the selected demographics. Participants indicated patient care as the most meaningful aspect of work, whereas the highest contributors to burnout were workload and electronic health record documentation. Importantly, most respondents were unaware of available resources for burnout. CONCLUSIONS: Health care specialty societies have access to each level of the health system, creating an opportunity to monitor trends, disseminate resources, and influence the direction of efforts to reduce workplace stress and enhance clinician well-being.

Support, technology and mental health: correlates of trainee workplace satisfaction.

INTRODUCTION: Low physician workplace satisfaction may negatively impact patient care. Dissatisfaction may begin during residency training, where trainees face lower autonomy and less control over work conditions. The theoretical and empirical literature on trainees is couched mainly in terms of burnout. Theories of satisfaction, a different construct, are derived from studies of independent physicians. Identifying specific correlates of trainee satisfaction may be a clearer path to preparing a sustainable physician workforce. METHODS: We surveyed 3300 residents and fellows (response rate of 7.2% to 46,574 surveys sent) across multiple specialties and institutions in the US. The instrument was adapted from a previous large-scale survey of physician satisfaction, with changes reflecting factors theorized to specifically affect trainee satisfaction. We applied generalized linear regression to identify correlates of higher satisfaction. RESULTS: A total of 1444 (44%) residents/fellows reported they were very satisfied and 1311 (40%) reported being somewhat satisfied. Factors associated with satisfaction included positive perceptions of supporting clinical staff, the electronic health record, and stability of personal mental health. Surprisingly, a strong negative perception of completing insurance and/or disability forms was also associated with higher satisfaction. Factors often presumed to correlate with satisfaction, such as duty hours, debt load, and specialty, did not show significant associations. DISCUSSION: Multiple workplace factors are correlated with trainee satisfaction, but they are not the factors (such as financial debt) that we initially hypothesized. The factors we identified, including clinical staff support and personal mental health, may be targets for further study and/or pilot interventions aimed at improving satisfaction.

Triglyceride-containing lipoprotein sub-fractions and risk of coronary heart disease and stroke: A prospective analysis in 11,560 adults.

AIMS: Elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular disease; however, there is uncertainty about the role of total triglycerides and the individual triglyceride-containing lipoprotein sub-fractions. We measured 14 triglyceride-containing lipoprotein sub-fractions using nuclear magnetic resonance and examined associations with coronary heart disease and stroke. METHODS: Triglyceride-containing sub-fraction measures were available in 11,560 participants from the three UK cohorts free of coronary heart disease and stroke at baseline. Multivariable logistic regression was used to estimate the association of each sub-fraction with coronary heart disease and stroke expressed as the odds ratio per standard deviation increment in the corresponding measure. RESULTS: The 14 triglyceride-containing sub-fractions were positively correlated with one another and with total triglycerides, and inversely correlated with high-density lipoprotein cholesterol (HDL-C). Thirteen sub-fractions were positively associated with coronary heart disease (odds ratio in the range 1.12 to 1.22), with the effect estimates for coronary heart disease being comparable in subgroup analysis of participants with and without type 2 diabetes, and were attenuated after adjustment for HDL-C and LDL-C. There was no evidence for a clear association of any triglyceride lipoprotein sub-fraction with stroke. CONCLUSIONS: Triglyceride sub-fractions are associated with increased risk of coronary heart disease but not stroke, with attenuation of effects on adjustment for HDL-C and LDL-C.

Hyperglycaemia, adverse outcomes and impact of intravenous insulin therapy in patients presenting with acute ST-elevation myocardial infarction in a socioeconomically disadvantaged urban setting: The Montefiore STEMI Registry.

BACKGROUND: Hyperglycaemia occurs frequently in ST-elevation myocardial infarction (STEMI) and is associated with poor outcomes, for which continuous insulin infusion therapy (CIIT) may be beneficial. Information is limited regarding hyperglycaemia in acute STEMI affecting urban minority populations, or how CIIT fares in such real-world settings. METHODS AND RESULTS: We assembled an acute STEMI registry at an inner-city health system, focusing on patients with initial blood glucose ≥180 mg/dL to determine the impact of CIIT vs usual care. Clinical and outcomes data were added through linkage to electronic records. Inverse-probability-of-treatment weighting using propensity scores (PS) was used to compare CIIT vs no CIIT. The 1067 patients included were mostly Hispanic or African American; 356 had blood glucose ≥180 mg/dL. Such pronounced hyperglycaemia was related to female sex, minority race-ethnicity and lower socioeconomic score, and associated with increased death and death or CVD readmission. CIIT was preferentially used in patients with marked hyperglycaemia and was associated with in-hospital hypoglycaemia (21% vs 11%, P = .019) and, after PS weighting, with increased in-hospital (RR 3.23, 95% CI 0.94, 11.06) and 1-year (RR 2.26, 95% CI 1.02, 4.98) mortality. No significant differences were observed for death at 30 days or throughout follow-up, or death and readmission at any time point. CONCLUSIONS: Pronounced hyperglycaemia was common and associated with adverse prognosis in this urban population. CIIT met with selective use and was associated with hypoglycaemia, together with increased mortality at specific time points. Given the burden of metabolic disease, particularly among race-ethnic minorities, assessing the benefits of CIIT is a prerogative that requires evaluation in large-scale randomized trials.

Role of Coronary Calcium Score to Identify Candidates for ASCVD Prevention.

PURPOSE OF REVIEW: In this review, we describe the mechanism behind coronary artery calcification formation and detection, as well as its implication in cardiovascular disease (CVD) risk stratification, intervention, and prognosis in asymptomatic individuals. RECENT FINDINGS: Multiple cohort and population studies have shown that coronary artery calcium scoring is effective and reproducible in predicting the risk for cardiovascular disease. The updated 2018 ACC/AHA guideline has incorporated consideration of coronary artery calcification testing into cardiovascular disease risk stratification and therapy guidance. Coronary artery calcification's evidence-based role in detection, risk stratification, and ultimately its unique influence on therapeutic intervention and prognosis of cardiovascular disease in asymptomatic population is increasingly being recognized..

Liver Function and Risk of Type 2 Diabetes: Bidirectional Mendelian Randomization Study.

Liver dysfunction and type 2 diabetes (T2D) are consistently associated. However, it is currently unknown whether liver dysfunction contributes to, results from, or is merely correlated with T2D due to confounding. We used Mendelian randomization to investigate the presence and direction of any causal relation between liver function and T2D risk including up to 64,094 T2D case and 607,012 control subjects. Several biomarkers were used as proxies of liver function (i.e., alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], and γ-glutamyl transferase [GGT]). Genetic variants strongly associated with each liver function marker were used to investigate the effect of liver function on T2D risk. In addition, genetic variants strongly associated with T2D risk and with fasting insulin were used to investigate the effect of predisposition to T2D and insulin resistance, respectively, on liver function. Genetically predicted higher circulating ALT and AST were related to increased risk of T2D. There was a modest negative association of genetically predicted ALP with T2D risk and no evidence of association between GGT and T2D risk. Genetic predisposition to higher fasting insulin, but not to T2D, was related to increased circulating ALT. Since circulating ALT and AST are markers of nonalcoholic fatty liver disease (NAFLD), these findings provide some support for insulin resistance resulting in NAFLD, which in turn increases T2D risk.