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Medical examiners and coroners (ME/Cs) are essential public health partners for terrorism preparedness and response. These medicolegal investigators support both public health and public safety functions and investigate deaths that are sudden, suspicious, violent, unattended, and unexplained. Medicolegal autopsies are essential for making organism-specific diagnoses in deaths caused by biologic terrorism. This report has been created to 1) help public health officials understand the role of ME/Cs in biologic terrorism surveillance and response efforts and 2) provide ME/Cs with the detailed information required to build capacity for biologic terrorism preparedness in a public health context. This report provides background information regarding biologic terrorism, possible biologic agents, and the consequent clinicopathologic diseases, autopsy procedures, and diagnostic tests as well as a description of biosafety risks and standards for autopsy precautions. ME/Cs' vital role in terrorism surveillance requires consistent standards for collecting, analyzing, and disseminating data. Familiarity with the operational, jurisdictional, and evidentiary concerns involving biologic terrorism-related death investigation is critical to both ME/Cs and public health authorities. Managing terrorism-associated fatalities can be expensive and can overwhelm the existing capacity of ME/Cs. This report describes federal resources for funding and reimbursement for ME/C preparedness and response activities and the limited support capacity of the federal Disaster Mortuary Operational Response Team. Standards for communication are critical in responding to any emergency situation. This report, which is a joint collaboration between CDC and the National Association of Medical Examiners (NAME), describes the relationship between ME/Cs and public health departments, emergency management agencies, emergency operations centers, and the Incident Command System. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess left ventricular (LV) function and brain-type natriuretic peptide (BNP) in patients with first-time flash pulmonary edema (FPE). PATIENTS AND METHODS: We retrospectively studied all patients presenting to Mayo Clinic's site in Rochester, MN, from January 5, 2000, to December 30, 2004, with FPE. Only patients with first-time FPE who had undergone BNP assessment and echocardiography within 24 hours of presentation were included. Patients were divided into 2 groups: those with reduced LV ejection fraction (LVEF) (less than 50%) and those with preserved LVEF (equals 50%). RESULTS: Thirty-seven patients met the inclusion criteria (22 female, 15 male). Mean plus or minus SD LVEF was 41% plus or minus 13%. The LVEF was reduced in 73% (group 1, n equals 27; mean plus or minus SD age, 75 plus or minus 8 years) and preserved in 27% (group 2, n equals 10; mean plus or munus SD age, 75 plus or minus 13 years). Most frequent underlying causes for first-time FPE were coronary artery disease and hypertension. Patients with preserved LVEF had significantly lower BNP levels at presentation (535 pg/mL [interquartile range, 352-1210 pg/mL]) vs 1320 pg/mL (interquartile range, 768-2000 pg/mL; P equals .01), despite similar elevated LV filling pressures as measured by echocardiography. The mean plus or minus SD ratio of early diastolic mitral valve inflow velocity to early diastolic mitral annulus velocity was 23 plus or minus 8 vs 22 plus or minus 10; P equals .78. Early diastolic mitral annulus velocity, a surrogate measurement for myocardial relaxation, was reduced in all patients with preserved LVEF and in 95% of patients with reduced LVEF. CONCLUSION: Coronary artery disease and hypertension are the most common precipitating factors for first-time FPE. Reduced myocardial relaxation in almost all patients regardless of LVEF supports the notion that diastolic dysfunction is a prerequisite for FPE. Levels of BNP were elevated in every patient regardless of LVEF but were significantly lower in patients with preserved LVEF despite similarly elevated LV filling pressures. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To determine the clinical and angiographic characteristics of patients who underwent coronary artery bypass graft (CABG) surgery before the availability of drug-eluting stents (DES) and to project the potential impact of percutaneous coronary intervention using DES. PATIENTS AND METHODS: We reviewed the coronary angiograms obtained between March 1999 and December 2001 of 192 consecutive patients from Olmsted County, Minnesota, who had undergone isolated CABG surgery for the first time. Three interventional cardiologists categorized the patients into 1 of 4 groups on the basis of technical feasibility of complete revascularization by percutaneous coronary intervention with DES. RESULTS: The study population consisted primarily of men (78%), with a mean age of 67 years. Of the 192 patients, 58 (30%) had diabetes mellitus, and 124 (65%) had 3-vessel disease. Twelve patients (6%) had lesions suitable for stents that matched the inclusion criteria for DES in recently published trials; 77 (40%) had lesions suitable for stents but had lesion characteristics not included in the initial DES trials. Thirty-two patients (17%) had target lesions considered technically difficult, but feasible, for stent placement. Seventy-one patients (37%) had lesions unsuitable for percutaneous coronary intervention (75% of these due to chronic occlusions) with the current stent delivery technology. CONCLUSION: This population-based analysis suggests that only a small proportion of patients undergoing CABG surgery meets the strict angiographic eligibility criteria for DES on the basis of recent trials. However, up to 46% of current CABG patients may ultimately undergo conversion to DES. The remaining 54% of this patient population may still not be ideal candidates for DES with the current stent delivery technology. [ABSTRACT FROM AUTHOR]

Objective: To compare left ventricular (LV) systolic and diastolic function in patients with apical ballooning syndrome (ABS) and those with acute myocardial infarction (AMI) using 2-dimensional Doppler echocardiography and strain rate imaging (SRI).Patients and Methods: We prospectively enrolled patients with newly diagnosed AMI and ABS who had akinetic apical walls. Both 2-dimensional Doppler echocardiography and SRI were performed on hospital day 1 or within 24 hours of primary percutaneous coronary intervention.Results: Twenty-four patients with AMI and 13 patients with ABS (mean +/- SD age, 63+/-15 vs 73+/-12 years; P=.03) were prospectively enrolled in the study from October 3, 2005 through July 12, 2006. The mean +/- SD LV end-diastolic volume was larger (58.1+/-9.1 vs 45.2+/-10.6 mL/m(2); P<.001) and the mean +/- SD LV ejection fraction was lower (35%+/-6% vs 43%+/-9%; P=.006) in patients with ABS compared with patients with AMI. The early diastolic mitral annular velocity was similar (0.06+/-0.02 vs 0.06+/-0.02 m/s; P=.85) in both groups, but the ratio of early diastolic mitral valve inflow velocity to early diastolic mitral annulus velocity was higher in patients with AMI than in patients with ABS (16.3+/-6.9 vs 12.2+/-3.2; P=.05). The systolic strain rate was decreased at the apex in both groups (P=.98). Both the early diastolic strain rate of the apex (0.64+/-0.24 vs 0.48+/-0.30 s(-1); P=.04) and the postsystolic shortening index of the apex (61%+/-15% vs 45%+/-23%; P=.006) were higher in the patients with ABS than in those with AMI. However, early diastolic SR was higher in the akinetic apical walls of patients with AMI with recovery than those with no recovery (0.64+/-0.35 vs 0.43+/-0.25 s(-1); P=.04) and was similar between akinetic apical walls of patients with AMI with recovery and the akinetic apical walls of ABS.Conclusion: Compared with patients with AMI, those with ABS showed the functional paradox of worse initial LV systolic function with larger LV size but better LV diastolic function. The early systolic strain rate and postsystolic shortening were greater in patients with ABS than in those with AMI; hence, these measurements can be helpful in distinguishing ABS from AMI and in detecting myocardial viability. [ABSTRACT FROM AUTHOR]

Objectives: To determine the frequency of urgent coronary angiography in patients with acute pericarditis and to examine clinical characteristics associated with coronary angiography.Patients and Methods: This is a retrospective analysis of all incident cases of acute viral or idiopathic pericarditis evaluated at Mayo Clinic's site in Rochester, MN, between January 1, 2000, and December 31, 2006. The main outcome measures were use of urgent coronary angiography and rate of concomitant coronary artery disease in patients with pericarditis.Results: There were 238 patients with a final diagnosis of acute pericarditis (mean age, 47.7+/-17.9 years; 157 [66.0%] were male). On the initial electrocardiogram, 146 patients (61.3%) had ST-segment elevation, and 92 (38.7%) had no ST-segment elevation. Coronary angiography was performed in 40 patients (16.8% of all patients); the frequency was 5-fold higher among those with ST-segment elevation (24.7% vs 4.3%; P<.001). Additionally, 7 patients (4.8%) with ST-segment elevation received thrombolytics before transfer to our institution; no patients without ST-segment elevation received thrombolysis (P=.05). Characteristics associated with a higher likelihood of coronary angiography included typical anginal chest pain, ST-segment elevation, previous percutaneous coronary intervention, elevated troponin T values, diaphoresis, and male sex. Coronary angiography revealed concomitant mild to moderate coronary artery disease in 14 (35.0%) of the 40 patients who underwent this procedure.Conclusion: Urgent coronary angiography is commonly performed in patients with acute pericarditis, particularly those with ST-segment elevation, typical myocardial infarction symptoms, and elevated troponin T values. Coronary artery disease was present angiographically in one-third of patients undergoing the procedure. Although patients with ST-segment elevation myocardial infarction must receive prompt reperfusion, clinicians must also consider the diagnosis of pericarditis to avoid unneeded coronary angiography. [ABSTRACT FROM AUTHOR]

Objectives: Our aim was to examine whether gender-based differences in mortality after percutaneous coronary interventions (PCIs) have changed in the past 25 years.Background: Women with coronary artery disease have a higher risk of adverse outcomes after PCIs than do men. Recent temporal trends in short-term and long-term mortality in women after PCIs are unknown.Methods: We performed a retrospective cohort study of 18,885 consecutive, unique patients who underwent PCIs between 1979 and 1995 (early group, n = 7,904, 28% women) and between 1996 and 2004 (recent group, n = 10,981, 31% women). Thirty-day and long-term mortality were compared by gender.Results: Compared with men, women undergoing PCIs were older and more likely to have diabetes mellitus, hypertension, or hypercholesterolemia. Overall, PCI was successful in 89% of women and 90% of men. In the recent group, 30-day mortality was significantly reduced compared with that in the early group in women (2.9% vs. 4.4%, p = 0.002) and men (2.2% vs. 2.8%, p = 0.04). However, long-term survival was similar between the early and recent groups among both men and women. After adjustment for risk factors, there was no difference between men and women from 1994 onward for either 30-day or long-term outcomes.Conclusions: The 30-day mortality after PCI in men and women has decreased in the past 25 years. After accounting for baseline risks, no differences in short-term or long-term mortality were observed between men and women. [ABSTRACT FROM AUTHOR]

Objective: To compare outcomes among patients receiving eptifibatide or abciximab during primary percutaneous coronary intervention (PCI) for acute myocardial infarction (MI) with ST elevation or new left bundle branch block.Patients and Methods: From January 1999 through January 2004, 576 patients underwent primary PCI and received adjunctive glycoprotein IIb/IIIa receptor antagonists. Propensity scores were used to adjust for baseline differences between groups. Logistic regression and Cox proportional hazards were used to model the association between choice of glycoprotein IIlb/IIIa receptor antagonist and adverse events.Results: Abciximab was given to 327 patients (57%) and eptifibatide to 249 (43%). Observed rates of in-hospital death or MI did not differ between groups (eptifibatide, 6%; abciximab, 5%; P = .95). This result persisted with adjustment for various patient characteristics (adjusted odds ratio, 1.03; 95% confidence interval, 0.40-2.65; P = .95). Kaplan-Meier estimated rates of death, MI, or target vessel revascularization at 1-year follow-up were 20.9% with eptifibatide and 22.3% with abciximab. The adjusted hazard ratio for the composite end point during a median follow-up of 12 months was 1.36 (95% confidence interval, 0.89-2.07; P = -.16).Conclusion: In this observational analysis, outcomes were similar with use of either abciximab or eptifibatide among patients undergoing primary PCI for acute MI. Additional comparative research is warranted to confirm these results. [ABSTRACT FROM AUTHOR]

Objective: To test the feasibility and safety of genotype guidance in the selection of P2Y 12 monotherapy within 1 week of percutaneous coronary interventions (PCIs) among patients with high bleeding risk (HBR)., Patient and Methods: The study was a single-center, open-label, pilot trial. Patients (n=100) with HBR (as defined by an academic research consortium) after successful PCI received dual antiplatelet therapy with clopidogrel and aspirin. Following availability of cytochrome P450 2C19 (CYP2C19) genotype results (mean, 2.9 days), aspirin was discontinued. Normal, rapid, or ultrarapid CYP2C19 metabolizers continued clopidogrel monotherapy for 90 days whereas loss-of-function allele carriers switched to prasugrel or ticagrelor monotherapy. The primary safety endpoints were a composite of post-dismissal cardiac death/spontaneous myocardial infarction less than 30 days or stent thrombosis <90 days of discharge. The subjects also underwent post-dismissal assessment for BARC (Bleeding Academic Research Consortium) type 3 or 5 bleeding, all-cause death, any MI, and/or repeat revascularization up to 90 days., Results: There were 98 patients with complete data (median age, 76.5 years, 36% women; 49% acute coronary syndrome). Sixty-nine (70.4%) were normal, rapid, or ultrarapid metabolizers and continued clopidogrel monotherapy, and 29 (29.6%) were intermediate CYP2C19 metabolizers and received monotherapy with prasugrel (n=21) or ticagrelor (n=8). The mean duration of dual antiplatelet therapy was 5.1 days. During 90-day follow-up, no patient died, there was one possible stent thrombosis, and three patients on clopidogrel had Bleeding Academic Research Consortium type 3 bleeding events., Conclusion: Genotype-guided P2Y 12 inhibitor monotherapy within a week of PCI is feasible and likely safe in patients with HBR (CHAMP [Clopidogrel With High Bleeding Risk and Adverse Events With Monotherapy in Patients Undergoing Percutaneous Coronary Interventions]; NCT05223335)., (Copyright © 2024 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objectives: Early coronary angiography (CAG) has been recommended in selected patients following out-of-hospital-cardiac-arrest (OHCA). We aimed to identify clinical features associated with acute coronary occlusion (ACO) and evaluate the associations between ACO, successful percutaneous coronary intervention (PCI) and outcomes in this population., Methods: We included comatose OHCA patients treated with targeted temperature management (TTM) between December 2005 and September 2016 who underwent early CAG within 24 hours. The co-primary outcomes were all-cause 30-day mortality and good neurological outcome (modified Rankin Score [mRS] ≤2) at hospital discharge., Results: Among 155 patients (93% shockable arrest rhythm, 55% with ST elevation), 133 (86%) had coronary artery stenosis ≥50% and 65 (42%) had ACO. ST elevation (sensitivity 74%, specificity 59%, OR 4.0, 95% CI 2.0-8.1) and elevated first troponin (sensitivity 88%, specificity 26%, OR 2.5, 95% CI 1.1-6.1) had limited sensitivity and specificity for ACO. Unadjusted 30-day mortality did not differ significantly by coronary disease severity or ACO. Successful PCI was associated with a lower risk of 30-day mortality (adjusted HR 0.5, 95% CI 0.2-0.9, P=.03), especially among patients with ACO (adjusted HR 0.4, 95% CI 0.1-0.9, P=0.03). After adjustment, ACO and PCI were not associated with the probability of good neurological outcome., Conclusions: In this select cohort of resuscitated OHCA patients undergoing CAG, unstable coronary disease is highly prevalent and successful PCI was associated with a higher probability of 30-day survival, especially among those with ACO. Neither ACO nor successful PCI were independently associated with good neurological outcome.

Background: Genetic-guided P2Y 12 inhibitor selection has been proposed to reduce ischemic events by identifying CYP2C19 loss-of-function (LOF) carriers at increased risk with clopidogrel treatment after percutaneous coronary intervention (PCI). A prespecified analysis of TAILOR-PCI (Tailored Antiplatelet Therapy Following PCI) evaluated the effect of genetic-guided P2Y 12 inhibitor therapy on cumulative ischemic and bleeding events., Objectives: Here, the authors detail a prespecified analysis of cumulative endpoints. The primary endpoint was cumulative incidence rate of ischemic events at 12 months. Cumulative incidence of major and minor bleeding was a secondary endpoint. Cox proportional hazards models as adapted by Wei, Lin, and Weissfeld were used to estimate the effect of this strategy on all observed events., Methods: The TAILOR-PCI trial was a prospective trial including 5,302 post-PCI patients with acute and stable coronary artery disease (CAD) who were randomized to genetic-guided P2Y 12 inhibitor or conventional clopidogrel therapy. In the genetic-guided group, LOF carriers were prescribed ticagrelor, whereas noncarriers received clopidogrel. TAILOR-PCI's primary analysis was time to first event in LOF carriers., Results: Among 5,276 patients (median age 62 years; 25% women; 82% acute CAD; 18% stable CAD), 1,849 were LOF carriers (903 genetic-guided; 946 conventional therapy). The cumulative primary endpoint was significantly reduced in the genetic-guided group compared with the conventional therapy (HR: 0.61; 95% CI: 0.41-0.89; P = 0.011) with no significant difference in cumulative incidence of major or minor bleeding (HR: 1.36; 95% CI: 0.67-2.76; P = 0.39)., Conclusions: Among CYP2C19 LOF carriers undergoing PCI, a genetic-guided strategy resulted in a statistically significant reduction in cumulative ischemic events without a significant difference in bleeding. (Tailored Antiplatelet Therapy Following PCI [TAILOR-PCI]; NCT01742117)., Competing Interests: Funding Support and Author Disclosures Funding for this research was provided by the National Institutes of Health (NIH) grants U01HL128606 to Drs Pereira and Farkouh and U01HL128626 to Dr Bailey. The content of this manuscript is solely the responsibility of the authors and does not necessarily reflect the views of the National Heart, Lung, and Blood Institute (NHLBI) or the National Institutes of Health. Dr Farkouh has received grants from NHLBI, Amgen, Novartis, and Novo Nordisk. Mr Lennon has received grants from the National Institutes of Health (NIH)/NHLBI and receiving nonfinancial support from Spartan Biosciences. Dr So has received grants from Eli Lilly Canada, Spartan Biosciences, Roche Diagnostics, and Aggredyne Inc; and has received personal fees from AstraZeneca Canada, Bayer Canada, and Servier Canada. Dr Goodman has received research grant support (eg, steering committee or data and safety monitoring committee) and/or speaker/consulting honoraria (eg, advisory boards) from Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, Daiichi Sankyo/American Regent, Eli Lilly, Esperion, Ferring Pharmaceuticals, HLS Therapeutics, JAMP Pharma, Merck, Novartis, Novo Nordisk A/C, Pendopharm/Pharmascience, Pfizer, Regeneron, Sanofi, Servier, Tolmar Pharmaceuticals, and Valeo Pharma; and has received salary support/honoraria from the Heart and Stroke Foundation of Ontario/University of Toronto (Polo) Chair, Canadian Heart Research Centre and MD Primer, Canadian VIGOUR Centre, Cleveland Clinic Coordinating Centre for Clinical Research, Duke Clinical Research Institute, New York University Clinical Coordinating Centre, PERFUSE Research Institute, and the TIMI Study Group (Brigham Health). Dr Lerman has received personal fees from Itamar Medical, Phillips/Volcano, Shahal, and Wei Jian RC Inc. Dr Tanguay has received personal fees from Mayo Clinic, AstraZeneca, Bayer, Daiichi Sankyo, Servier, Novartis, and BMS-Pfizer Alliance. Dr Welsh has received grants and/or personal fees from AstraZeneca, Pfizer, Bayer, Canadian Cardiac Society, Mayo Clinic, Boehringer Ingelheim, and Novartis. Dr Bailey has received grants from NIH. Dr Pereira has received grants from the NHLBI. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Despite numerous clinically available vaccines and therapeutics, aged patients remain at increased risk for COVID-19 morbidity. Furthermore, various patient populations, including the aged can have suboptimal responses to SARS-CoV-2 vaccine antigens. Here, we characterized vaccine-induced responses to SARS-CoV-2 synthetic DNA vaccine antigens in aged mice. Aged mice exhibited altered cellular responses, including decreased IFNγ secretion and increased TNFα and IL-4 secretion suggestive of T H 2-skewed responses. Aged mice exhibited decreased total binding and neutralizing antibodies in their serum but significantly increased T H 2-type antigen-specific IgG1 antibody compared to their young counterparts. Strategies to enhance vaccine-induced immune responses are important, especially in aged patient populations. We observed that co-immunization with plasmid-encoded adenosine deaminase (pADA)enhanced immune responses in young animals. Ageing is associated with decreases in ADA function and expression. Here, we report that co-immunization with pADA enhanced IFNγ secretion while decreasing TNFα and IL-4 secretion. pADA expanded the breadth and affinity SARS-CoV-2 spike-specific antibodies while supporting T H 1-type humoral responses in aged mice. scRNAseq analysis of aged lymph nodes revealed that pADA co-immunization supported a T H 1 gene profile and decreased FoxP3 gene expression. Upon challenge, pADA co-immunization decreased viral loads in aged mice. These data support the use of mice as a model for age-associated decreased vaccine immunogenicity and infection-mediated morbidity and mortality in the context of SARS-CoV-2 vaccines and provide support for the use of adenosine deaminase as a molecular adjuvant in immune-challenged populations., Competing Interests: DW has received grant funding, participates in industry collaborations, has received speaking honoraria, and has received fees for consulting, including serving on scientific review committees. Remunerations received by DW include direct payments and equity/options. DW also discloses the following associations with commercial partners: Geneos consultant/advisory board, AstraZeneca advisory board, speaker, Inovio board of directors, consultant, Sanofi advisory board, BBI advisory board, Pfizer advisory Board, Flagship consultant, and Advaccine consultant. SW is a scientific founder of Avamab Pharma Inc., a pre-clinical, pre-revenue stage company dedicated to research and development of AAV gene therapies for the treatment and prevention of infectious diseases. SW is a co-founder and Chief Scientific Officer of Inspire Biotherapeutics, a pre-clinical, pre-revenue stage gene therapy company developing AAV-based therapies for monogenic lung diseases. SW is an inventor on issued patents in Canada and US for the AAV6.2FF capsid, which are owned by the University of Guelph, and licensed to Avamab Pharma Inc., Inspire Biotherapeutics, and Cellastra Inc. From 2020 to February 2023, SW was an unpaid scientific advisor for Cellastra Inc., which is dedicated to research and development of gene therapies targeting root causes of scarring. SW is a co-inventor on a pending US and Canadian patent for the Engineered Newcastle disease virus vector and uses thereof, filed/owned by the University of Guelph. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gary, Tursi, Warner, Cuismano, Connors, Parzych, Griffin, Bell, Ali, Frase, Hojecki, Canziani, Chaiken, Kannan, Moffat, Embury-Hyatt, Wooton, Kossenkov, Patel, Kobasa, Kutzler, Haddad and Weiner.)

Herein, we studied the impact of empty LNP (eLNP), component of mRNA-based vaccine, on anti-viral pathways and immune function of cells from young and aged individuals. eLNP induced maturation of monocyte derived dendritic cells (MDDCs). We further show that eLNP upregulated CD40 and induced cytokine production in multiple DC subsets and monocytes. This coincided with phosphorylation of TANK binding kinase 1 (pTBK1) and interferon response factor 7 (pIRF7). In response to eLNP, healthy older adults (>65 yrs) have decreased CD40 expression, and IFN-γ output compared to young adults (<65 yrs). Additionally, cells from older adults have a dysregulated anti-viral signaling response to eLNP stimulation, measured by the defect in type I IFN production, and phagocytosis. Overall, our data show function of eLNP in eliciting DC maturation and innate immune signaling pathways that is impaired in older adults resulting in lower immune responses to SARS-CoV-2 mRNA-based vaccines., (© 2023. The Author(s).)

Background: Aminophylline, an adenosine antagonist, can be used to prevent adenosine-mediated bradyarrhythmias., Methods: Retrospective, observational, descriptive analysis of patients undergoing rotational atherectomy with intravenous (IV) aminophylline pretreatment during a 10-year period (2010-2020). The primary composite outcome was the occurrence of a documented bradyarrhythmia requiring pharmacologic intervention and/or temporary pacemaker (TPM) implantation., Results: A total of 296 patients received IV aminophylline pretreatment. The primary composite outcome occurred in 1.7% (n = 5) of patients. None of the patients required rescue TPM. Bradyarrhythmias were documented in 2.4% (n = 7) of patients. Pharmacologic interventions, typically with IV atropine, were used in 15% (n = 43) of patients. Per-vessel analyses demonstrated that patients undergoing atherectomy to the circumflex and right coronary arteries were more likely than those undergoing atherectomy to other vessels to have bradyarrhythmias requiring pharmacologic intervention (3.4% vs 0%, P = .01)., Conclusions: In this 10-year single-center experience using IV aminophylline pretreatment to prevent major bradyarrhythmias in patients undergoing coronary atherectomy, none of the patients required rescue TPM implantation. These data demonstrate that coronary atherectomy can be performed safely without prophylactic TPM, with aminophylline pretreatment and selective use of atropine representing an effective noninvasive approach., (© 2023 The Authors.)

Introduction: Healthcare organizations faced unique operational challenges during the COVID-19 pandemic. Assuring the safety of both patients and healthcare workers in hospitals has been the primary focus during the COVID-19 pandemic., Methods: The NIH Vaccine Program (VP) with the Vaccine Management System (VMS) was created based on the commitment of NIH leadership, program leadership, the development team, and the program team; defining Key Performance Indicators (KPIs) of the VP and the VMS; and the NIH Clinical Center's (NIH CC) interdisciplinary approach to deploying the VMS., Results: This article discusses the NIH business requirements of the VP and VMS, the target KPIs of the VP and the VMS, and the NIH CC interdisciplinary approach to deploying an organizational VMS for vaccinating the NIH workforce. The use of the DCRI Spiral-Agile Software Development Life Cycle enabled the development of a system with stakeholder involvement that could quickly adapt to changing requirements meeting the defined KPIs for the program and system. The assessment of the defined KPIs through a survey and comments from the survey support that the VP and VMS were successful., Conclusion: A comprehensive program to maintain a healthy workforce includes asymptomatic COVID testing, symptomatic COVID testing, contact tracing, vaccinations, and policy-driven education. The need to develop systems during the pandemic resulted in changes to build software quickly with the input of many more users and stakeholders then typical in a decreased amount of time., Competing Interests: No competing financial interests exist., (Copyright 2022, ABSA International 2022.)

The progressive impairment of immunity to pathogens and vaccines with aging is a significant public health problem as the world population shifts to an increased percentage of older adults (> 65). We have previously demonstrated that cells obtained from older volunteers have delayed and defective induction of type I interferons and T cell and B cell helper cytokines in response to TLR ligands when compared to those from adult subjects. However, the underlying intracellular mechanisms are not well described. Herein, we studied two critical pathways important in the production of type I interferon (IFN), the interferon response factor 7 (pIRF7), and TANK-binding kinase (pTBK-1). We show a decrease in pIRF7 and pTBK-1 in cross-priming dendritic cells (cDC1s), CD4 + T cell priming DCs (cDC2s), and CD14 dim CD16 + vascular patrolling monocytes from older adults (n = 11) following stimulation with pathway-specific agonists in comparison with young individuals (n = 11). The decrease in these key antiviral pathway proteins correlates with decreased phagocytosis, suggesting impaired function in Overall, our findings describe molecular mechanisms which explain the innate functional impairment in older adults and thus could inform us of novel approaches to restore these defects., (© 2022. The Author(s).)

Background: Previous percutaneous coronary intervention risk models were focused on single outcome, such as mortality or bleeding, etc, limiting their applicability. Our objective was to develop contemporary percutaneous coronary intervention risk models that not only determine in-hospital mortality but also predict postprocedure bleeding, acute kidney injury, and stroke from a common set of variables., Methods: We built risk models using logistic regression from first percutaneous coronary intervention for any indication per patient (n=19 322, 70.6% with acute coronary syndrome) using the Mayo Clinic registry from January 1, 2000 to December 31, 2016. Approval for the current study was obtained from the Mayo Foundation Institutional Review Board. Patients with missing outcomes (n=4183) and those under 18 (n=10) were removed resulting in a sample of 15 129. We built both models that included procedural and angiographic variables (Models A) and precatheterization model (Models B)., Results: Death, bleeding, acute kidney injury, and stroke occurred in 247 (1.6%), 650 (4.3%), 1184 (7.8%), and 67 (0.4%), respectively. The C statistics from the test dataset for models A were 0.92, 0.70, 0.77, and 0.71 and for models B were 0.90, 0.67, 0.76, and 0.71 for in-hospital death, bleeding, acute kidney injury, and stroke, respectively. Bootstrap analysis indicated that the models were not overfit to the available dataset. The probabilities estimated from the models matched the observed data well, as indicated by the calibration curves. The models were robust across many subgroups, including women, elderly, acute coronary syndrome, cardiogenic shock, and diabetes., Conclusions: The new risk scoring models based on precatheterization variables and models including procedural and angiographic variables accurately predict in-hospital mortality, bleeding, acute kidney injury, and stroke. The ease of its application will provide useful prognostic and therapeutic information to both patients and physicians.

Background: There are limited data on uninsured patients presenting with acute myocardial infarction-cardiogenic shock (AMI-CS). This study sought to compare the management and outcomes of AMI-CS between uninsured and privately insured individuals., Methods: Using the National Inpatient Sample (2000-2016), a retrospective cohort of adult (≥18 years) uninsured admissions (primary payer-self-pay or no charge) were compared with privately insured individuals. Interhospital transfers were excluded. Outcomes of interest included in-hospital mortality, temporal trends in admissions, use of cardiac procedures, do-not-resuscitate status, palliative care referrals, and resource utilization., Results: Of 402 182 AMI-CS admissions, 21 966 (5.4%) and 93 814 (23.3%) were uninsured and privately insured. Compared with private insured individuals, uninsured admissions were younger, male, from a lower socioeconomic status, had lower comorbidity, higher rates of acute organ failure, ST-segment elevation AMI-CS (77.3% versus 76.4%), and concomitant cardiac arrest (33.8% versus 31.9%; all P <0.001). Compared with 2000, in 2016, there were more uninsured (adjusted odds ratio, 1.15 [95% CI, 1.13-1.17]; P <0.001) and less privately insured admissions (adjusted odds ratio, 0.85 [95% CI, 0.83-0.87]; P <0.001). Uninsured individuals received less frequent coronary angiography (79.5% versus 81.0%), percutaneous coronary intervention (60.8% versus 62.2%), mechanical circulatory support (54% versus 55.5%), and had higher palliative care (3.8% versus 3.2%) and do-not-resuscitate status use (4.4% versus 3.2%; all P <0.001). Uninsured admissions had higher in-hospital mortality (adjusted odds ratio, 1.62 [95% CI, 1.55-1.68]; P <0.001) and resource utilization., Conclusions: Uninsured individuals have higher in-hospital mortality and lower use of guideline-directed therapies in AMI-CS compared with privately insured individuals.

A one-pot strategy for functionalizing pyranoside 1,2- cis -diols with two different ester protecting groups is reported. The approach employs regioselective acylation via orthoester hydrolysis promoted by a carboxylic acid, e.g., levulinic acid, acetic acid, benzoic acid, or chloroacetic acid. Upon removal of water and introduction of a coupling agent, the carboxylic acid is esterified to the hydroxyl group liberated during hydrolysis. Although applied to 1,2- cis -diols on pyranoside scaffolds, the method should be applicable to such motifs on any six-membered ring.

Background: There are limited data on the temporal trends, incidence, and outcomes of ST-segment-elevation myocardial infarction-cardiogenic shock (STEMI-CS)., Methods: Adult (>18 years) STEMI-CS admissions were identified using the National Inpatient Sample (2000-2017) and classified by tertiles of admission year (2000-2005, 2006-2011, 2012-2017). Outcomes of interest included temporal trends, acute organ failure, cardiac procedures, in-hospital mortality, hospitalization costs, and length of stay., Results: In ∼4.3 million STEMI admissions, CS was noted in 368,820 (8.5%). STEMI-CS incidence increased from 5.8% in 2000 to 13.0% in 2017 (patient and hospital characteristics adjusted odds ratio [aOR] 2.45 [95% confidence interval {CI} 2.40-2.49]; P < 0.001). Multiorgan failure increased from 55.5% (2000-2005) to 74.3% (2012-2017). Between 2000 and 2017, coronary angiography and percutaneous coronary intervention use increased from 58.8% to 80.1% and 38.6% to 70.6%, whereas coronary artery bypass grafting decreased from 14.9% to 10.4% (all P < 0.001). Over the study period, the use of intra-aortic balloon pump (40.6%-37.6%) decreased, and both percutaneous left ventricular assist devices (0%-12.9%) and extra-corporeal membrane oxygenation (0%-2.8%) increased (all P < 0.001). In hospital mortality decreased from 49.6% in 2000 to 32.7% in 2017 (aOR 0.29 [95% CI 0.28-0.31]; P < 0.001). During the 18-year period, hospital lengths of stay decreased, hospitalization costs increased and use of durable left ventricular assist device /cardiac transplantation remained stable (P > 0.05)., Conclusions: In the United States, incidence of CS in STEMI has increased 2.5-fold between 2000 and 2017, while in-hospital mortality has decreased during the study period. Use of coronary angiography and PCI increased during the study period., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by the Shock Society.)

Background: Coronary endothelial dysfunction (CED) causes angina/ischemia in patients with nonobstructive coronary artery disease (NOCAD). Patients with CED have decreased number and function of CD34+ cells involved in normal vascular repair with microcirculatory regenerative potential and paracrine anti-inflammatory effects. We evaluated safety and potential efficacy of intracoronary autologous CD34+ cell therapy for CED., Methods: Twenty NOCAD patients with invasively diagnosed CED and persistent angina despite maximally tolerated medical therapy underwent baseline exercise stress test, GCSF (granulocyte colony stimulating factor)-mediated CD34+ cell mobilization, leukapheresis, and selective 1×10 5 CD34+ cells/kg infusion into left anterior descending. Invasive CED evaluation and exercise stress test were repeated 6 months after cell infusion. Primary end points were safety and effect of intracoronary autologous CD34+ cell therapy on CED at 6 months of follow-up. Secondary end points were change in Canadian Cardiovascular Society angina class, as-needed sublingual nitroglycerin use/day, Seattle Angina Questionnaire scores, and exercise time at 6 months. Change in CED was compared with that of 51 historic control NOCAD patients treated with maximally tolerated medical therapy alone., Results: Mean age was 52±13 years; 75% were women. No death, myocardial infarction, or stroke occurred. Intracoronary CD34+ cell infusion improved microvascular CED (%acetylcholine-mediated coronary blood flow increased from 7.2 [-18.0 to 32.4] to 57.6 [16.3-98.3]%; P =0.014), decreased Canadian Cardiovascular Society angina class (3.7±0.5 to 1.7±0.9, Wilcoxon signed-rank test, P =0.00018), and sublingual nitroglycerin use/day (1 [0.4-3.5] to 0 [0-1], Wilcoxon signed-rank test, P =0.00047), and improved all Seattle Angina Questionnaire scores with no significant change in exercise time at 6 months of follow-up. Historic control patients had no significant change in CED., Conclusions: A single intracoronary autologous CD34+ cell infusion was safe and may potentially be an effective disease-modifying therapy for microvascular CED in humans. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03471611.

Objective: To study associations between the Minnesota coronavirus disease 2019 (COVID-19) mitigation strategies on incidence rates of acute myocardial infarction (MI) or revascularization among residents of Southeast Minnesota., Methods: Using the Rochester Epidemiology Project, all adult residents of a nine-county region of Southeast Minnesota who had an incident MI or revascularization between January 1, 2015, and December 31, 2020, were identified. Events were defined as primary in-patient diagnosis of MI or undergoing revascularization. We estimated age- and sex-standardized incidence rates and incidence rate ratios (IRRs) stratified by key factors, comparing 2020 to 2015-2019. We also calculated IRRs by periods corresponding to Minnesota's COVID-19 mitigation timeline: "Pre-lockdown" (January 1-March 11, 2020), "First lockdown" (March 12-May 31, 2020), "Between lockdowns" (June 1-November 20, 2020), and "Second lockdown" (November 21-December 31, 2020)., Results: The incidence rate in 2020 was 32% lower than in 2015-2019 (24 vs 36 events/100,000 person-months; IRR, 0.68; 95% CI, 0.62-0.74). Incidence rates were lower in 2020 versus 2015-2019 during the first lockdown (IRR, 0.54; 95% CI, 0.44-0.66), in between lockdowns (IRR, 0.70; 95% CI, 0.61-0.79), and during the second lockdown (IRR, 0.54; 95% CI, 0.41-0.72). April had the lowest IRR (IRR 0.48; 95% CI, 0.34-0.68), followed by August (IRR, 0.55; 95% CI, 0.40-0.76) and December (IRR, 0.56; 95% CI, 0.41-0.77). Similar declines were observed across sex and all age groups, and in both urban and rural residents., Conclusion: Mitigation measures for COVID-19 were associated with a reduction in hospitalizations for acute MI and revascularization in Southeast Minnesota. The reduction was most pronounced during the lockdown periods but persisted between lockdowns., (© 2021 The Authors.)

We introduce a new chamfering paradigm, locally connecting pixels to produce path distances that approximate Euclidean space by building a small network (a replacement product) inside each pixel. These " RE -grid graphs" maintain near-Euclidean polygonal distance contours even in noisy data sets, making them useful tools for approximation when exact numerical solutions are unobtainable or impractical. The RE -grid graph creates a modular global architecture with lower pixel-to-pixel valency and simplified topology at the cost of increased computational complexity due to its internal structure. We present an introduction to chamfering replacement products with a number of case study examples to demonstrate the potential of these graphs for path-finding in high frequency and low resolution image spaces which motivate further study. Possible future applications include morphology, watershed segmentation, halftoning, neural network design, anisotropic image processing, image skeletonization, dendritic shaping, and cellular automata.

Objective: To analyze outcomes of patients with ST-segment elevation myocardial infarction (STEMI) after successful primary percutaneous coronary intervention (PCI) triaged to the cardiac intensive care unit (CICU) vs a general telemetry unit by a Zwolle risk score-based algorithm., Methods: We introduced a quality improvement protocol in 2014 encouraging admission of STEMI patients with Zwolle score of 3 or less to general telemetry units unless they were hemodynamically unstable. We subsequently conducted a retrospective single-center cohort study of consecutive STEMI patients who had undergone primary PCI from January 1, 2014, to December 31, 2018. Outcomes studied include immediate complications, need for urgent unplanned intervention, need for CICU care, length of hospitalization, and survival., Results: We identified 547 patients, 406 with a Zwolle score of 3 or less. Of these, 192 (47.3%) were admitted to general telemetry and 214 (52.7%) to the CICU. Reasons for CICU admission included persistent chest pain, late presentation, and procedural complications. The average hospital length of stay was 2.1±1.4 days for non-CICU patients and 3.3±2.8 days for low-risk CICU patients ( P <.001). Two patients initially admitted to general telemetry required transfer to the CICU. There were 26 patients who required unplanned cardiovascular intervention within 30 days, 5 from the general telemetry unit; 540 patients survived to discharge. One in-hospital death occurred among those initially triaged to the general telemetry unit, and this was due to a noncardiac cause., Conclusion: A Zwolle score-based algorithm can be used to safely triage post-PCI STEMI patients to a general telemetry unit.

Objective: To determine whether the Mayo Cardiac Intensive Care Unit (CICU) Admission Risk Score (M-CARS) is associated with CICU resource utilization., Patients and Methods: Adult patients admitted to our CICU from 2007 to 2018 were retrospectively reviewed, and M-CARS was calculated from admission data. Groups were compared using Wilcoxon test for continuous variables and χ 2 test for categorical variables., Results: We included 12,428 patients with a mean age of 67±15 years (37% female patients). The mean M-CARS was 2.1±2.1, including 5890 (47.4%) patients with M-CARS less than 2 and 644 (5.2%) patients with M-CARS greater than 6. Critical care restricted therapies were frequently used, including mechanical ventilation in 28.0%, vasoactive medications in 25.5%, and dialysis in 4.8%. A higher M-CARS was associated with greater use of critical-care therapies and longer CICU and hospital length of stay. The low-risk cohort with M-CARS less than 2 was less likely to require critical-care-restricted therapies, including invasive or noninvasive mechanical ventilation (8.0% vs 46.1%), vasoactive medications (10.1% vs 38.8%), or dialysis (1.0% vs 8.2%), compared with patients with M-CARS greater than or equal to 2 (all P <.001)., Conclusion: Patients with M-CARS less than 2 infrequently require critical-care resources and have extremely low mortality, suggesting that the M-CARS could be used to facilitate the triage of critically ill cardiac patients., (© 2021 THE AUTHORS.)

Objective: To determine whether the Mayo Cardiac Intensive Care Unit (CICU) Admission Risk Score (M-CARS) accurately predicts 1-year mortality., Methods: We retrospectively reviewed adult CICU patients admitted from January 1, 2007, through April 30, 2018, and calculated M-CARS using admission data. We examined the association between admission M-CARS, as continuous and categorical variables, and 1-year mortality., Results: This study included 12,428 unique patients with a mean age of 67.6±15.2 years (4686 [37.7%] female). A total of 2839 patients (22.8%) died within 1 year of admission, including 1149 (9.2%) hospital deaths and 1690 (15.0%) of the 11,279 hospital survivors. The 1-year survival decreased incrementally as a function of increasing M-CARS (P<.001), and all components of M-CARS were significant predictors of 1-year mortality (P<.001). The 1-year survival among hospital survivors decreased incrementally as a function of increasing M-CARS for scores below 3 (all P<.001); however, there was no further decrease in 1-year survival for hospital survivors with M-CARS of 3 or more (P=.99). The M-CARS components associated with 1-year mortality among hospital survivors included blood urea nitrogen, red blood cell distribution width, Braden skin score, and respiratory failure (all P<.001)., Conclusion: M-CARS predicted 1-year mortality among CICU admissions, with a plateau effect at high M-CARS of 3 or more for hospital survivors. Significant added predictors of 1-year mortality among hospital survivors included markers of frailty and chronic illness., (Copyright © 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background There are limited contemporary data on the use of emergent coronary artery bypass grafting (CABG) in acute myocardial infarction. Methods and Results Adult (aged >18 years) acute myocardial infarction admissions were identified using the National (Nationwide) Inpatient Sample (2000-2017) and classified by tertiles of admission year. Outcomes of interest included temporal trends of CABG use; age-, sex-, and race-stratified trends in CABG use; in-hospital mortality; hospitalization costs; and hospital length of stay. Of the 11 622 528 acute myocardial infarction admissions, emergent CABG was performed in 1 071 156 (9.2%). CABG utilization decreased overall (10.5% [2000] to 8.7% [2017]; adjusted odds ratio [OR], 0.98 [95% CI, 0.98-0.98]; P <0.001), in ST-segment-elevation myocardial infarction (10.2% [2000] to 5.2% [2017]; adjusted OR, 0.95 [95% CI, 0.95-0.95]; P <0.001) and non-ST-segment-elevation myocardial infarction (10.8% [2000] to 10.0% [2017]; adjusted OR, 0.99 [95% CI, 0.99-0.99]; P <0.001), with consistent age, sex, and race trends. In 2012 to 2017, compared with 2000 to 2005, admissions receiving emergent CABG were more likely to have non-ST-segment-elevation myocardial infarction (80.5% versus 56.1%), higher rates of noncardiac multiorgan failure (26.1% versus 8.4%), cardiogenic shock (11.5% versus 6.4%), and use of mechanical circulatory support (19.8% versus 18.7%). In-hospital mortality in CABG admissions decreased from 5.3% (2000) to 3.6% (2017) (adjusted OR, 0.89; 95% CI, 0.88-0.89 [ P <0.001]) in the overall cohort, with similar temporal trends in patients with ST-segment-elevation myocardial infarction and non-ST-segment-elevation myocardial infarction. An increase in lengths of hospital stay and hospitalization costs was seen over time. Conclusions Utilization of CABG has decreased substantially in acute myocardial infarction admissions, especially in patients with ST-segment-elevation myocardial infarction. Despite an increase in acuity and multiorgan failure, in-hospital mortality consistently decreased in this population.

Aims: There are limited contemporary data on the use of initial fibrinolysis in ST-segment elevation myocardial infarction cardiogenic shock (STEMI-CS). This study sought to compare the outcomes of STEMI-CS receiving initial fibrinolysis vs. primary percutaneous coronary intervention (PPCI)., Methods: Using the National (Nationwide) Inpatient Sample from 2009 to 2017, a comparative effectiveness study of adult (>18 years) STEMI-CS admissions receiving pre-hospital/in-hospital fibrinolysis were compared with those receiving PPCI. Admissions with alternate indications for fibrinolysis and STEMI-CS managed medically or with surgical revascularization (without fibrinolysis) were excluded. Outcomes of interest included in-hospital mortality, development of non-cardiac organ failure, complications, hospital length of stay, hospitalization costs, use of palliative care, and do-not-resuscitate status., Results: During 2009-2017, 5297 and 110 452 admissions received initial fibrinolysis and PPCI, respectively. Compared with those receiving PPCI, the fibrinolysis group was more often non-White, with lower co-morbidity, and admitted on weekends and to small rural hospitals (all P < 0.001). In the fibrinolysis group, 95.3%, 77.4%, and 15.7% received angiography, PCI, and coronary artery bypass grafting, respectively. The fibrinolysis group had higher rates of haemorrhagic complications (13.5% vs. 9.9%; P < 0.001). The fibrinolysis group had comparable all-cause in-hospital mortality [logistic regression analysis: 28.8% vs. 28.5%; propensity-matched analysis: 30.8% vs. 30.3%; adjusted odds ratio 0.97 (95% confidence interval 0.90-1.05); P = 0.50]. The fibrinolysis group had comparable rates of acute organ failure, hospital length of stay, rates of palliative care referrals, do-not-resuscitate status use, and lesser hospitalization costs., Conclusions: The use of initial fibrinolysis had comparable in-hospital mortality than those receiving PPCI in STEMI-CS in the contemporary era in this large national observational study., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background The role of race and ethnicity in the outcomes of cardiac arrest (CA) complicating acute myocardial infarction (AMI) is incompletely understood. Methods and Results This was a retrospective cohort study of adult admissions with AMI-CA from the National Inpatient Sample (2012-2017). Self-reported race/ethnicity was classified as White, Black, and others (Hispanic, Asian or Pacific Islander, Native American, Other). Outcomes of interest included in-hospital mortality, coronary angiography, percutaneous coronary intervention, palliative care consultation, do-not-resuscitate status use, hospitalization costs, hospital length of stay, and discharge disposition. Of the 3.5 million admissions with AMI, CA was noted in 182 750 (5.2%), with White, Black, and other races/ethnicities constituting 74.8%, 10.7%, and 14.5%, respectively. Black patients admitted with AMI-CA were more likely to be female, with more comorbidities, higher rates of non-ST-segment-elevation myocardial infarction, and higher neurological and renal failure. Admissions of patients of Black and other races/ethnicities underwent coronary angiography (61.9% versus 70.2% versus 73.1%) and percutaneous coronary intervention (44.6% versus 53.0% versus 58.1%) less frequently compared to patients of white race ( p <0.001). Admissions of patients with AMI-CA had significantly higher unadjusted mortality (47.4% and 47.4%) as compared with White patients admitted (40.9%). In adjusted analyses, Black race was associated with lower in-hospital mortality (odds ratio [OR], 0.95; 95% CI, 0.91-0.99; P =0.007) whereas other races had higher in-hospital mortality (OR, 1.11; 95% CI, 1.08-1.15; P <0.001) compared with White race. Admissions of Black patients with AMI-CA had longer length of hospital stay, higher rates of palliative care consultation, less frequent do-not-resuscitate status use, and fewer discharges to home (all P <0.001). Conclusions Racial and ethnic minorities received less frequent guideline-directed procedures and had higher in-hospital mortality and worse outcomes in AMI-CA.

Objectives: The aim of this study was to examine the effect of CYP2C19 genotype on clinical outcomes in patients with coronary artery disease (CAD) who predominantly underwent percutaneous coronary intervention (PCI), comparing those treated with ticagrelor or prasugrel versus clopidogrel., Background: The effect of CYP2C19 genotype on treatment outcomes with ticagrelor or prasugrel compared with clopidogrel is unclear., Methods: Databases through February 19, 2020, were searched for studies reporting the effect of CYP2C19 genotype on ischemic outcomes during ticagrelor or prasugrel versus clopidogrel treatment. Study eligibility required outcomes reported for CYP2C19 genotype status and clopidogrel and alternative P2Y 12 inhibitors in patients with CAD with at least 50% undergoing PCI. The primary analysis consisted of randomized controlled trials (RCTs). A secondary analysis was conducted by adding non-RCTs to the primary analysis. The primary outcome was a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia. Meta-analysis was conducted to compare the 2 drug regimens and test interaction with CYP2C19 genotype., Results: Of 1,335 studies identified, 7 RCTs were included (15,949 patients, mean age 62 years; 77% had PCI, 98% had acute coronary syndromes). Statistical heterogeneity was minimal, and risk for bias was low. Ticagrelor and prasugrel compared with clopidogrel resulted in a significant reduction in ischemic events (relative risk: 0.70; 95% confidence interval: 0.59 to 0.83) in CYP2C19 loss-of-function carriers but not in noncarriers (relative risk: 1.0; 95% confidence interval: 0.80 to 1.25). The test of interaction on the basis of CYP2C19 genotype status was statistically significant (p = 0.013), suggesting that CYP2C19 genotype modified the effect. An additional 4 observational studies were found, and adding them to the analysis provided the same conclusions (p value of the test of interaction <0.001)., Conclusions: The effect of ticagrelor or prasugrel compared with clopidogrel in reducing ischemic events in patients with CAD who predominantly undergo PCI is based primarily on the presence of CYP2C19 loss-of-function carrier status. These results support genetic testing prior to prescribing P2Y 12 inhibitor therapy., Competing Interests: Funding Support and Author Disclosures Funding for this research was provided by National Institutes of Health grants U01HL128606 and 3U01HL128606-03S1. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. All rights reserved.)

Aims: There are limited data on the trends and outcomes of mechanical circulatory support (MCS)-assisted early percutaneous coronary intervention (PCI) in acute myocardial infarction with cardiogenic shock (AMI-CS). In this study, we sought to assess the use, temporal trends, and outcomes of percutaneous MCS-assisted early PCI in AMI-CS., Methods and Results: Using the National Inpatient Sample database from 2005-2014, a retrospective cohort of AMI-CS admissions receiving early PCI (hospital day zero) was identified. MCS use was defined as intra-aortic balloon pump (IABP), percutaneous left ventricular assist device (pLVAD) and extracorporeal membrane oxygenation (ECMO) support. Outcomes of interest included in-hospital mortality, resource utilisation, trends and predictors of MCS-assisted PCI. Of the 110,452 admissions, MCS assistance was used in 55%. IABP, pLVAD and ECMO were used in 94.8%, 4.2% and 1%, respectively. During 2009-2014, there was a decrease in MCS-assisted PCI due to a decrease in IABP, despite an increase in pLVAD and ECMO. Younger age, male sex, lower comorbidity, and cardiac arrest independently predicted MCS use. MCS-assisted PCI was predictive of higher in-hospital mortality (31% vs 26%, adjusted odds ratio 1.23 [1.19-1.27]; p<0.001) and greater resource utilisation. IABP-assisted PCI had lower in-hospital mortality and lesser resource utilisation compared to pLVAD/ECMO., Conclusions: MCS-assisted PCI identified a sicker AMI-CS cohort. There was a decrease in IABP and an increase in pLVAD/ECMO.

The SARS-CoV-2 pandemic has almost 56 million confirmed cases resulting in over 1.3 million deaths as of November 2020. This infection has proved more deadly to older adults (those >65 years of age) and those with immunocompromising conditions. The worldwide population aged 65 years and older is increasing, and the total number of aged individuals will outnumber those younger than 65 years by the year 2050. Aging is associated with a decline in immune function and chronic activation of inflammation that contributes to enhanced viral susceptibility and reduced responses to vaccination. Here we briefly review the pathogenicity of the virus, epidemiology and clinical response, and the underlying mechanisms of human aging in improving vaccination. We review current methods to improve vaccination in the older adults using novel vaccine platforms and adjuvant systems. We conclude by summarizing the existing clinical trials for a SARS-CoV-2 vaccine and discussing how to address the unique challenges for vaccine development presented with an aging immune system.

Background: Previous studies have defined preshock as isolated hypotension or isolated hypoperfusion, whereas shock has been variably defined as hypoperfusion with or without hypotension. We aimed to evaluate the mortality risk associated with hypotension and hypoperfusion at the time of admission in a cardiac intensive care unit population., Methods: We analyzed Mayo Clinic cardiac intensive care unit patients admitted between 2007 and 2015. Hypotension was defined as systolic blood pressure <90 mm Hg or mean arterial pressure <60 mm Hg, and hypoperfusion as admission lactate >2 mmol/L, oliguria, or rising creatinine. Associations between hypotension and hypoperfusion with hospital mortality were estimated using multivariable logistic regression., Results: Among 10 004 patients with a median age of 69 years, 43.1% had acute coronary syndrome, and 46.1% had heart failure. Isolated hypotension was present in 16.7%, isolated hypoperfusion in 15.3%, and 8.7% had both hypotension and hypoperfusion. Stepwise increases in hospital mortality were observed with hypotension and hypoperfusion compared with neither hypotension nor hypoperfusion (3.3%; all P <0.001): isolated hypotension, 9.3% (adjusted odds ratio, 1.7 [95% CI, 1.4-2.2]); isolated hypoperfusion, 17.2% (adjusted odds ratio, 2.3 [95% CI, 1.9-3.0]); both hypotension and hypoperfusion, 33.8% (adjusted odds ratio, 2.8 [95% CI, 2.1-3.6]). Adjusted hospital mortality in patients with isolated hypoperfusion was higher than in patients with isolated hypotension ( P =0.02) and not significant different from patients with both hypotension and hypoperfusion ( P =0.18)., Conclusions: Hypotension and hypoperfusion are both associated with increased mortality in cardiac intensive care unit patients. Hospital mortality is higher with isolated hypoperfusion or concomitant hypotension and hypoperfusion (classic shock). We contend that preshock should refer to isolated hypotension without hypoperfusion, while patients with hypoperfusion can be considered to have shock, irrespective of blood pressure.

Background: There are limited contemporary data on the influence of primary payer status on the management and outcomes of ST-segment elevation myocardial infarction (STEMI)., Objective: To assess the influence of insurance status on STEMI outcomes., Methods: Adult (>18 years) STEMI admissions were identified using the National Inpatient Sample database (2000-2017). Expected primary payer was classified into Medicare, Medicaid, private, uninsured and others. Outcomes of interest included in-hospital mortality, use of coronary angiography and percutaneous coronary intervention (PCI), hospitalization costs, hospital length of stay and discharge disposition., Results: Of the 4,310,703 STEMI admissions, Medicare, Medicaid, private, uninsured and other insurances were noted in 49.0%, 6.3%, 34.4%, 7.2% and 3.1%, respectively. Compared to the others, the Medicare cohort was older (75 vs. 53-57 years), more often female (46% vs. 20-36%), of white race, and with higher comorbidity (all p<0.001). The Medicare and Medicaid population had higher rates of cardiogenic shock and cardiac arrest. The Medicare cohort had higher in-hospital mortality (14.2%) compared to the other groups (4.1-6.7%), p<0.001. In a multivariable analysis (Medicare referent), in-hospital mortality was higher in uninsured (adjusted odds ratio (aOR) 1.14 [95% confidence interval {CI} 1.11-1.16]), and lower in Medicaid (aOR 0.96 [95% CI 0.94-0.99]; p = 0.002), privately insured (aOR 0.73 [95% CI 0.72-0.75]) and other insurance (aOR 0.91 [95% CI 0.88-0.94]); all p<0.001. Coronary angiography (60% vs. 77-82%) and PCI (45% vs. 63-70%) were used less frequently in the Medicare population compared to others. The Medicare and Medicaid populations had longer lengths of hospital stay, and the Medicare population had the lowest hospitalization costs and fewer discharges to home., Conclusions: Compared to other types of primary payers, STEMI admissions with Medicare insurance had lower use of coronary angiography and PCI, and higher in-hospital mortality., Competing Interests: Conflicts of Interest: Dr. Jaffe has been a consultant for Beckman, Abbott, Siemens, ET Healthcare, Sphing6toec, Quidel, and Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: There are limited data on how sex influences the outcomes of acute myocardial infarction-cardiogenic shock (AMI-CS) in young adults., Methods: A retrospective cohort of AMI-CS admissions aged 18 to 55 years, during 2000 to 2017, was identified using the National Inpatient Sample. Use of coronary angiography, percutaneous coronary intervention, mechanical circulatory support and noncardiac interventions was identified. Outcomes of interest included in-hospital mortality, use of cardiac interventions, hospitalization costs, and length of stay., Results: A total 90 648 AMI-CS admissions ≤55 years of age were included, of which 26% were women. Higher rates of CS were noted in men (2.2% in 2000 to 4.8% in 2017) compared with women (2.6% in 2000 to 4.0% in 2017; P <0.001). Compared with men, women with AMI-CS were more frequently of Black race, from a lower socioeconomic status, with higher comorbidity, and admitted to rural and small hospitals (all P <0.001). Women had lower rates of ST-segment elevation presentation (73.0% versus 78.7%), acute noncardiac organ failure, cardiac arrest (34.3% versus 35.7%), and received less-frequent coronary angiography (78.3% versus 81.4%), early coronary angiography (49.2% versus 54.1%), percutaneous coronary intervention (59.2% versus 64.0%), and mechanical circulatory support (50.3% versus 59.2%; all P <0.001). Female sex was an independent predictor of in-hospital mortality (23.0% versus 21.7%; adjusted odds ratio, 1.11 [95% CI, 1.07-1.16]; P <0.001). Women had lower hospitalization costs ($156 372±$198 452 versus $167 669±$208 577; P <0.001) but comparable lengths of stay compared with men., Conclusions: In young AMI-CS admissions, women are treated less aggressively and experience higher in-hospital mortality than men.

Objective: To evaluate outcomes by sex in older adults with cardiogenic shock complicating acute myocardial infarction (AMI-CS)., Materials and Methods: A retrospective cohort of older (≥75 years) AMI-CS admissions during January 1, 2000, to December 31, 2014, was identified using the National Inpatient Sample. Interhospital transfers were excluded. Use of angiography, percutaneous coronary intervention (PCI), mechanical circulatory support (MCS), and noncardiac interventions was identified. The primary outcome was in-hospital mortality stratified by sex, and secondary outcomes included temporal trends of prevalence, in-hospital mortality, use of cardiac and noncardiac interventions, hospitalization costs, and length of stay., Results: In this 15-year period, there were 134,501 AMI-CS admissions 75 years or older, of whom 51.5% (n=69,220) were women. Women were on average older, were more often Hispanic or nonwhite race, and had lower comorbidity, acute organ failure, and concomitant cardiac arrest. Compared with older men (n=65,281), older women (n=69,220) had lower use of coronary angiography (55.4% [n=35,905] vs 49.2% [n=33,918]), PCI (36.3% [n=23,501] vs 34.4% [n=23,535]), MCS (34.3% [n=22,391] vs 27.2% [n=18,689]), mechanical ventilation, and hemodialysis (all P<.001). Female sex was an independent predictor of higher in-hospital mortality (adjusted odds ratio, 1.05; 95% CI, 1.02-1.08; P<.001) and more frequent discharges to a skilled nursing facility. In subgroup analyses of ethnicity, presence of cardiac arrest, and those receiving PCI and MCS, female sex remained an independent predictor of increased mortality., Conclusion: Female sex is an independent predictor of worse in-hospital outcomes in older adults with AMI-CS in the United States., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: There are limited data on the complications with a percutaneous left ventricular assist device (pLVAD) vs. intra-aortic balloon pump (IABP) in acute myocardial infarction-cardiogenic shock (AMI-CS)., Objective: To assess the trends, rates and predictors of complications., Methods: Using a 17-year AMI-CS population from the National Inpatient Sample, AMI-CS admissions receiving pLVAD and IABP support were evaluated for vascular, lower limb amputation, hematologic, neurologic and acute kidney injury (AKI) complications. In-hospital mortality, hospitalization costs and length of stay in pLVAD and IABP cohorts with complications was studied., Results: Of 168,645 admissions, 7,855 (4.7%) receiving pLVAD support. The pLVAD cohort had higher comorbidity, cardiac arrest (36.1% vs. 29.7%) and non-cardiac organ failure (74.7% vs. 56.9%) rates. Complications were higher in pLVAD compared to IABP cohort-overall 69.0% vs. 54.7%; vascular 3.8% vs. 2.1%; lower limb amputation 0.3% vs. 0.3%; hematologic 36.0% vs. 27.7%; neurologic 4.9% vs. 3.5% and AKI 55.4% vs. 39.1% (all p<0.001 except for amputation). Non-White race, higher comorbidity, organ failure, and extracorporeal membrane oxygen use were predictors of complications for both cohorts. The pLVAD cohort with complications had higher in-hospital mortality (45.5% vs. 33.1%; adjusted odds ratio 1.65 [95% confidence interval 1.55-1.75]), shorter duration of hospital stay, and higher hospitalization costs compared to the IABP cohort with complications (all p<0.001). These results were consistent in propensity-matched pairs., Conclusions: AMI-CS admissions receiving pLVAD had higher rates of complications compared to the IABP, with worse in-hospital outcomes in the cohort with complications., Competing Interests: The authors have declared that no competing interests exist.

Background: The optimal MAP target for patients with cardiogenic shock (CS) remains unknown. We sought to determine the relationship between mean arterial pressure (MAP) and mortality in the cardiac intensive care unit (CICU) patients with CS., Methods: Using a single-center database of CICU patients admitted between 2007 and 2015, we identified patients with an admission diagnosis of CS. MAP was measured every 15 min, and the mean of all MAP values during the first 24 h (mMAP 24 ) was recorded. Multivariable logistic regression determined the relationship between mMAP 24 and adjusted hospital mortality., Results: We included 1002 patients with a mean age of 68 ± 13.7 years, including 36% females. Admission diagnoses included acute coronary syndrome in 60%, heart failure in 74%, and cardiac arrest in 38%. Vasoactive drugs were used in 72%. The mMAP 24 was higher (75 vs. 71 mmHg, p < 0.001) among hospital survivors (66%) compared with non-survivors (34%). Hospital mortality was inversely associated with mMAP 24 (adjusted OR 0.9 per 5 mmHg higher mMAP 24 , p = 0.01), with a stepwise increase in hospital mortality at lower mMAP 24 . Patients with mMAP 24  < 65 mmHg were at higher risk of hospital mortality (57% vs. 28%, adjusted OR 2.0, 95% CI 1.4-3.0, p < 0.001); no differences were observed between patients with mMAP 24 65-74 vs. ≥ 75 mmHg (p > 0.1)., Conclusion: In patients with CS, we observed an inverse relationship between mMAP 24 and hospital mortality. The poor outcomes in patients with mMAP 24  < 65 mmHg provide indirect evidence supporting a MAP goal of 65 mmHg for patients with CS.

Background: Although extracorporeal membrane oxygenation (ECMO) is used for hemodynamic support for in-hospital cardiac arrest (IHCA) complicating acute myocardial infarction (AMI), there are limited data on the outcomes stratified by the timing of initiation of this strategy., Methods: Adult (>18 years) AMI admissions with IHCA were identified using the National Inpatient Sample (2000-2017) and the timing of ECMO with relation to IHCA was identified. Same-day vs. non-simultaneous ECMO support for IHCA were compared. Outcomes of interest included in-hospital mortality, temporal trends, hospitalization costs, and length of stay., Results: Of the 11.6 million AMI admissions, IHCA was noted in 1.5% with 914 (<0.01%) receiving ECMO support. The cohort receiving same-day ECMO (N = 795) was on average female, with lower comorbidity, higher rates of ST-segment-elevation AMI, shockable rhythm, and higher rates of complications. Compared to non-simultaneous ECMO, the same-day ECMO cohort had higher rates of coronary angiography (67.5% vs. 51.3%; p = 0.001) and comparable rates of percutaneous coronary intervention (58.9% vs. 63.9%; p = 0.32). The same-day ECMO cohort had higher in-hospital mortality (63.1% vs. 44.5%; adjusted odds ratio 3.98 (95% confidence interval 2.34-6.77); p < 0.001), shorter length of stay, and lower hospitalization costs. Older age, minority race, non-ST-segment elevation AMI, multiorgan failure, and complications independently predicted higher in-hospital mortality in IHCA complicating AMI., Conclusions: Same-day ECMO support for IHCA was associated with higher in-hospital mortality compared to those receiving non-simultaneous ECMO support. Though ECMO-assisted CPR is being increasingly used, careful candidate selection is key to improving outcomes in this population.