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Background Nasal decolonization with mupirocin has been a commonly used strategy for the prevention of surgical site infections (SSIs) due to SA. We recently noted an increase in SSIs due to SA despite the use of mupirocin, including a case of post-operative mupirocin-resistant MRSA infection despite intranasal mupirocin. We therefore evaluated the mupirocin susceptibility of SA at Stamford Hospital to determine the optimal regimen for decolonization. Methods SA isolates were recovered from clinical and screening samples received in the microbiology laboratory from 8/1/2020 to 2/28/2022. Mupirocin susceptibility was determined using e-tests and a standardized inoculum on Mueller-Hinton agar. Isolates were categorized as “susceptible” (MuS) with minimum inhibitory concentrations (MIC) ≤4 mcg/ml or resistant (MuR) with MIC values ≥8mcg/ml. Resistant strains were further divided into low-level resistance, with MIC values from 8 to 256 mcg/ml, and high-level resistance, with MIC values >256/ml. SA isolates were identified and tested for susceptibility by usual Clinical Laboratory Standards Institute (CLSI) criteria. Results 223 unique SA isolates from 218 patients were tested. Patients ranged in age from newborn to 94 years. Twenty-four SA isolates (10.8%) were resistant to mupirocin (20 MRSA and 4 MSSA). Of the 24 MuR strains, 19 (79.2%) isolates demonstrated high-level resistance. MRSA strains were more likely to be resistant (22.5% were MuR) than MSSA strains (3.0% were MuR) (p< 0.001). MuR strains did not differ from MuS strains with respect to patient age, sex, race, site of isolation, infected versus colonized, community-acquired versus hospital-acquired or inpatient/out-patient location. Conclusion Preventing surgical site infections is challenging. Decolonization with mupirocin nasal ointment has been a common component of preoperative optimization. However, the emergence of resistance would render mupirocin suboptimal and other regimens might be preferred. In our study, less than 80% of MRSA strains were MuS. These findings are concerning and have led us to reevaluate our current decolonization strategy. In patients colonized with MRSA at high risk for infection (e.g. total joint replacement), intranasal povidone iodine may be preferable to mupirocin. Disclosures All Authors: No reported disclosures.

OBJECTIVES A paucity of point-of-care ultrasound (POCUS) databases limits machine learning (ML). Assess feasibility of training ML algorithms to visually estimate left ventricular ejection fraction (EF) from a subxiphoid (SX) window using only apical 4-chamber (A4C) images. METHODS Researchers used a long-short-term-memory algorithm for image analysis. Using the Stanford EchoNet-Dynamic database of 10,036 A4C videos with calculated exact EF, researchers tested 3 ML training permeations. First, training on unaltered Stanford A4C videos, then unaltered and 90° clockwise (CW) rotated videos and finally unaltered, 90° rotated and horizontally flipped videos. As a real-world test, we obtained 615 SX videos from Harbor-UCLA (HUCLA) with EF calculations in 5% ranges. Researchers performed 1000 randomizations of EF point estimation within HUCLA EF ranges to compensate for ML and HUCLA EF mismatch, obtaining a mean value for absolute error (MAE) comparison and performed Bland-Altman analyses. RESULTS The ML algorithm EF mean MAE was estimated at 23.0, with a range of 22.8-23.3 using unaltered A4C video, mean MAE was 16.7, with a range of 16.5-16.9 using unaltered and 90° CW rotated video, mean MAE was 16.6, with a range of 16.3-16.8 using unaltered, 90° CW rotated and horizontally flipped video training. Bland-Altman showed weakest agreement at 40-45% EF. CONCLUSIONS Researchers successfully adapted unrelated ultrasound window data to train a POCUS ML algorithm with fair MAE using data manipulation to simulate a different ultrasound examination. This may be important for future POCUS algorithm design to help overcome a paucity of POCUS databases.

BackgroundEpidemiological studies show increased cardiovascular disease (CVD) risk amongst individuals with psychiatric disorders; however, sex differences in comorbidity have been inconsistent. This study examined the sex-specific association between higher genetic risk of three psychiatric disorders [major depression (MD), schizophrenia and bipolar disorder] and the risk of three CVDs [coronary artery disease (CAD), heart failure (HF) and atrial fibrillation].Methods and FindingsSex-specific association between polygenic scores (PGS) for psychiatric disorders and CVD outcomes was assessed in 345,201 European-ancestry individuals (UK Biobank) using logistic regression, with analyses replicated in an independent BioVU cohort (N = 62,641).In the UK Biobank cohort, a 1-standard-deviation increase in PGSMDwas associated with a 1.11- (95% CI: 1.06 - 1.16; p = 5E-06) and 1.09-fold (95% CI: 1.04 - 1.14; p = 0.00038) higher risk of incident CAD and HF in females respectively, but only with a 1.04-fold (95% CI: 1.02 - 1.07; p = 0.0016) increased risk of incident CAD in males. These associations remained even in the absence of any psychiatric disorder diagnosis. The higher risk in females may potentially be mediated by greater BMI increase in females. The risk increase of HF was consistent between females who were pre-menopausal at baseline (mean age = 44.9 years) and post-menopausal at baseline (mean age = 60.8 years), while the risk increase of CAD was only observed in the baseline post- menopausal cohort. No significant association with CVD risks was observed for the genetic risk of schizophrenia or bipolar disorder. The greater increase in CAD risk in females was replicated in the BioVU cohort.ConclusionsGenetic predisposition to MD confers a greater risk of CAD and HF in females compared to males, even in the absence of any depression diagnosis. In addition to depression diagnosis, this study highlights the importance of considering predisposition to depression in heart health checks, especially in women.

Nasal decolonization with mupirocin has been a common strategy for the prevention of surgical site infections (SSIs) and recurrent skin and soft tissue infections due to Staphylococcus aureus (SA). We recently noted an increase in SSIs due to SA, including a case of post-operative mupirocin-resistant methicillin-resistant SA (MRSA) infection despite attempted preoperative decolonization with mupirocin. We therefore evaluated the mupirocin susceptibility of SA at our hospital to determine the optimal regimen for decolonization.SA isolates were recovered from clinical and screening samples received in the microbiology laboratory. Mupirocin susceptibility was determined using e-tests and isolates were categorized as susceptible or resistant using a breakpoint MIC value of 4mcg/ml.223 unique SA isolates from 218 patients were tested. Twenty-four SA isolates (10.8%) were resistant to mupirocin (20 MRSA and 4 methicillin-sensitive SA [MSSA]). MRSA strains were more likely to be resistant to mupirocin than MSSA strains (22.5% vs 3.0%, P.001).The emergence of drug resistance makes the policy of decolonization with nasal mupirocin a suboptimal strategy for the prevention of MRSA infections. In our study, less than 80% of MRSA strains were mupirocin susceptible. In patients colonized with MRSA at high risk for infection (eg, total joint replacement), other regimens such as intranasal povidone iodine may be preferable to mupirocin for patient decolonization.

Background: Transcatheter closure is the preferred treatment for atrial septal defects. The available devices are effective and safe though concerns persist over cardiac erosion risk. A review of t...

Background Depression is a significant concern after cardiac surgery and has not been studied in patients undergoing transcatheter aortic valve replacement (TAVR). We sought to examine the prevalence of pre-procedure depression and anxiety symptoms and explore whether brief bedside cognitive behavioral therapy (CBT) could prevent post-TAVR psychological distress. Methods We prospectively recruited consecutive TAVR patients and randomized them to receive brief CBT or treatment as usual (TAU) during their hospitalization. Multi-level regression techniques were used to evaluate changes by treatment arm in depression, anxiety, and quality of life from baseline to 1 month post-TAVR adjusted for sex, race, DM, CHF, MMSE, and STS score. Results One hundred and forty six participants were randomized. The mean age was 82 years, and 43% were female. Self-reported depression and anxiety scores meeting cutoffs for clinical level distress were 24.6% and 23.2% respectively. Both TAU and CBT groups had comparable improvements in depressive symptoms at 1-month (31% reduction for TAU and 35% reduction for CBT, p = .83). Similarly, both TAU and CBT groups had comparable improvements in anxiety symptoms at 1-month (8% reduction for TAU and 11% reduction for CBT, p = .1). Quality of life scores also improved and were not significantly different between the two groups. Conclusions Pre-procedure depression and anxiety may be common among patients undergoing TAVR. However, TAVR patients show spontaneous improvement in depression and anxiety scores at 1-month follow up, regardless of brief CBT. Further research is needed to determine whether more tailored CBT interventions may improve psychological and medical outcomes.

BackgroundBased on observational studies and small-scale randomized controlled trials, it is uncertain whether cholesterol-lowering statins have any beneficial or adverse effects on depressive symptoms. In this study we investigate this question using a genomics approach.MethodsTo compare the pharmacological effects of statin and antidepressant exposure and identify commonly perturbed biological pathways, we interrogated Connectivity Map (CMap), a database of gene expression signatures from drug-treated human cell lines. We used Mendelian randomization, a statistical genomics approach, to investigate the potential causal on-target (HMGCR inhibition) and off-target effects of statin exposure on depression, depressive symptoms, and traits related to the shared pathways identified from CMap analysis.ResultsCompounds inducing highly similar gene expression responses to statins (as indicated by an average CMap connectivity score with statins > 90) were enriched for antidepressants (12 out of 38 antidepressants; p < 1E-05). Genes perturbed in the same direction by both statins and antidepressants were significantly enriched for diverse cellular and metabolic pathways, and various immune activation, development and response processes. Genetically proxied HMGCR inhibition was significantly associated with monocyte and platelet-related metrics.ConclusionsOur study is the first to directly compare gene expression responses to statins and antidepressants, demonstrating perturbation of shared immune pathways. We further show that statin exposure is strongly associated with alterations in monocyte and platelet measures, both of which have previously been implicated in depression. Our findings warrant further investigation into the use of statins for treating depression, particularly in patients with raised blood biomarkers of inflammation.

OBJECTIVES: Our objective was to evaluate patient-reported oxygen saturation (SpO2 ) using pulse oximetry as a home monitoring tool for patients with initially nonsevere COVID-19 to identify need for hospitalization. METHODS: Patients were enrolled at the emergency department (ED) and outpatient testing centers. Each patient was given a home pulse oximeter and instructed to record their SpO2 every 8 hours. Patients were instructed to return to the ED for sustained home SpO2

Background Accidental awareness during general anaesthesia (AAGA) is a complex and rare outcome to investigate in surgical patient populations, particularly obstetric patients. We report the protocol of the Direct Reporting of Awareness in Maternity patients (DREAMY) study, illustrating how the research was designed to address practical and methodological challenges for investigating AAGA in an obstetric cohort. Methods This is the trial protocol of a prospective, multicentre cohort study of patients undergoing obstetric surgery under general anaesthesia. Accidental awareness during general anaesthesia will be detected using three repetitions of standardised direct questioning over 30 days, with responses indicating memories during general anaesthesia verified using structured interviews. Reports will be adjudicated, then classified, in accordance with pre-defined and pre-validated structures, including the Michigan Awareness Classification tool. Quantitative data will be collected on general anaesthesia conduct for all participants. This descriptive study is being conducted in England and aims to recruit a minimum of 2015 patients. Results The DREAMY study was prospectively registered (ClinicalTrials.gov Identifier: NCT03100396) and ethical approval granted. Participant recruitment began in May 2017 and one year follow up concluded in August 2019. Publication of the results is anticipated in 2020. Conclusions The DREAMY study will provide data on incidence, experience and implications of AAGA for obstetric patients, using a robust methodology that will reliably detect and translate subjective AAGA reports into objective outcomes. In addition, the study is expected to improve vigilance for AAGA in participating hospitals and encourage adoption of recommendations for support of patients experiencing AAGA.

Supranormal ejection fraction by echocardiography in clinically referred patient populations has been associated with an increased risk of cardiovascular disease (CVD). The prognostic implication of supranormal left ventricular ejection fraction (LVEF)-assessed by cardiac magnetic resonance (CMR)-in healthy, community-dwelling individuals is unknown.The purpose of this study is to investigate the prognostic implication of supranormal LVEF as assessed by CMR and its inter-relationship with stroke volume among community-dwelling adults without CVD.Participants from the MESA (Multi-Ethnic Study of Atherosclerosis) and DHS (Dallas Heart Study) cohorts free of CVD who underwent CMR with LVEF above the normal CMR cutoff (≥57%) were included. The association between cohort-specific LVEF categories and risk of clinically adjudicated major adverse cardiovascular events (MACE) was assessed using adjusted Cox models. Subgroup analysis was also performed to evaluate the association of LVEF and risk of MACE among individuals stratified by left ventricular stroke volume index.The study included 4,703 participants from MESA and 2,287 from DHS with 727 and 151 MACE events, respectively. In adjusted Cox models, the risk of MACE was highest among individuals in LVEF Q4 (vs Q1) in both cohorts after accounting for potential confounders (MESA: HR = 1.27 [95% CI: 1.01-1.60], P = 0.04; DHS: HR = 1.72 [95% CI: 1.05-2.79], P = 0.03). A significant interaction was found between the continuous measures of LVEF and left ventricular stroke volume index (P interaction = 0.02) such that higher LVEF was significantly associated with an increased risk of MACE among individuals with low but not high stroke volume.Among community-dwelling adults without CVD, LVEF in the supranormal range is associated with a higher risk of adverse cardiovascular outcomes, particularly in those with lower stroke volume.

Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure.Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 x 10(-8) under an additive genetic model.Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.

Connecticut saw its first multi-drug- and carbapenem-resistant Pseudomonas aeruginosa (CRPA) isolate in 2019. The global prevalence of such isolates has gradually increased over the past few years. Resistance was mediated in part by the presence of New Delhi metallo-beta-lactamase (NDM), a recently described carbapenemase that is more commonly found in members of the Enterobacterales, and is associated with travel to India and regions of the Middle East. We were asked to see a 32-year-old female with a urinary tract infection due to this pan-resistant Pseudomonas isolate. The patient presented a therapeutic challenge due to lack of available therapy in a complicated pregnancy.

We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species that are putatively in the mechanistic pathway to coronary artery disease (CAD). We quantified 596 lipid species in serum from 4,492 phenotyped individuals from the Busselton Health Study. In our discovery GWAS we identified 667 independent loci associations with these lipid species (479 novel), followed by meta-analysis and validation in two independent cohorts. Lipid endophenotypes (134) identified for CAD were associated with variation at 186 genomic loci. Associations between independent lipid-loci with coronary atherosclerosis were assessed in ∼456,000 individuals from the UK Biobank. Of the 53 lipid-loci that showed evidence of association (P−3), 43 loci were associated with at least one of the 134 lipid endophenotypes. The findings of this study illustrate the value of integrative biology to investigate the genetics and lipid metabolism in the aetiology of atherosclerosis and CAD, with implications for other complex diseases.

Importance Observational studies have reported associations between antihypertensive medication and psychiatric disorders, although the reported direction of association appears to be dependent on drug class. Objective To estimate the potential effect of different antihypertensive drug classes on schizophrenia, bipolar disorder, and major depressive disorder. Design, Setting, and Participants This 2-sample mendelian randomization study assessed the association between a single-nucleotide variant (SNV) and drug target gene expression derived from existing expression quantitative trait loci (eQTL) data in blood (sample 1) and the SNV-disease association from published case-control genome-wide association studies (sample 2). Significant associations were corroborated using published brain eQTL and protein QTL data. Participants included 40 675 patients with schizophrenia and 64 643 controls, 20 352 patients with bipolar disorder and 31 358 controls, and 135 458 patients with major depressive disorder and 344 901 controls. Blood eQTL levels were measured in 31 684 individuals from 37 cohorts (eQTLGen consortium); prefrontal cortex eQTLs were measured from the PsychENCODE resource in 1387 individuals; and protein QTLs were measured in cerebral spinal fluid from 544 individuals and plasma from 818 individuals. Data were collected from October 4, 2019, to June 1, 2020, and analyzed from October 14, 2019, to June 6, 2020. Exposures Expression levels of antihypertensive drug target genes as proxies for drug exposure, and genetic variants robustly associated with the expression of these genes as mendelian randomization instruments. Main Outcomes and Measures Risk for schizophrenia, bipolar disorder, and major depressive disorder. Results A 1-SD lower expression of the angiotensin-converting enzyme (ACE) gene in blood was associated with lower systolic blood pressure of 4.0 (95% CI, 2.7-5.3) mm Hg, but increased risk of schizophrenia (odds ratio [OR], 1.75; 95% CI, 1.28-2.38; P = 3.95 × 10−4). A concordant direction of association was also observed between ACE expression in prefrontal cortex (OR, 1.33; 95% CI, 1.13-1.56) and ACE protein levels in cerebral spinal fluid (OR per 1-SD decrease, 1.12; 95% CI, 1.05-1.19) and plasma (OR per 1-SD decrease, 1.04; 95% CI, 1.01-1.07). We found no evidence for an association between genetically estimated SBP and schizophrenia risk. Conclusions and Relevance Findings suggest an adverse association of lower ACE messenger RNA and protein levels with schizophrenia risk. These findings warrant greater pharmacovigilance and further investigation into the effect of ACE inhibitors, particularly those that are centrally acting, on psychiatric symptoms in patients with schizophrenia, as well as the role of ACE inhibitor use in late-onset schizophrenia.

BackgroundThere is growing evidence from observational studies that drugs used for the prevention and treatment of CVD may cause, exacerbate, or relieve neuropsychiatric symptoms.AimUse Mendelian randomisation (MR) analysis to investigate the potential effect of different antihypertensive drugs on schizophrenia, bipolar disorder and major depressive disorder.MethodsWe conduct two sample MR using expression quantitative trait loci (eQTLs) for antihypertensive drug target genes as genetic instruments, together with summary data from published genome-wide association studies, to investigate the causal effect of changes in drug target gene expression (as proxies of drug exposure) on psychiatric disorders.ResultsA 1 standard deviation lower expression of the ACE gene in blood was associated with 4.0 mmHg (95% CI = 2.7 – 5.3) lower systolic blood pressure, but increased risk of schizophrenia (OR (95% CI) = 1.75 (1.28 – 2.38)). A concordant direction of effect was observed with ACE expression in brain tissue.ConclusionsFindings suggest an adverse effect of lower ACE expression on schizophrenia risk. This warrants further investigation to determine if lowering ACE activity for treatment of hypertension using ACE inhibitors (particularly centrally-acting drugs) may worsen symptoms in patients with schizophrenia, and whether there is any association between ACE inhibitor use and risk of (mainly late-onset) schizophrenia.

Methicillin-resistant Staphylococcus aureus (MRSA) poses significant therapeutic challenges related to its frequency in clinical infections, innate virulence properties, and propensity for multiantibiotic resistance. MRSA is among the most common causes of endovascular infections, including infective endocarditis (IE). Our objective was to employ transthoracic echocardiography (TTE) to evaluate the effect of exebacase, a novel direct lytic agent, in experimental aortic valve MRSA IE. TTE was utilized to evaluate the in vivo effect of exebacase on MRSA-infected vegetation progression when combined with daptomycin (versus daptomycin alone). Primary intravegetation outcomes were maximum size, weights at sacrifice, and MRSA counts at infection baseline versus after 4 days of daptomycin treatment (alone or in addition to exebacase administered once on treatment day 1). A single dose of exebacase in addition to daptomycin cleared significantly more intravegetation MRSA than daptomycin alone. This was associated with a statistical trend toward reduced maximum vegetation size in the exebacase plus daptomycin versus the daptomycin alone therapy groups (P = 0.07). Also, mean vegetation weights in the exebacase-treated group were significantly lower than those of the daptomycin alone group (P < 0.0001). Maximum vegetation size by TTE correlated with vegetation weight (P = 0.005). In addition, intravegetation MRSA counts in the combination group were significantly lower than those of untreated controls (P < 0.0001) and the daptomycin alone group (P < 0.0001). This study suggests that exebacase has a salutary impact on MRSA-infected vegetation progression when combined with daptomycin, especially in terms of vegetation MRSA burden, size, and weight. Moreover, TTE appears to be an efficient noninvasive tool to assess therapeutic efficacies in experimental MRSA IE.

BackgroundNaturally occurring human genetic variants provide a valuable tool to identify drug targets and guide drug prioritization and clinical trial design. Ivabradine is a heart rate lowering drug with protective effects on heart failure despite increasing the risk of atrial fibrillation. In patients with coronary artery disease without heart failure, the drug does not protect against major cardiovascular adverse events prompting questions about the ability of genetics to have predicted those effects. This study evaluates the effect of a mutation in HCN4, ivabradine’s drug target, on safety and efficacy endpoints.MethodsWe used genetic association testing and Mendelian randomization to predict the effect of ivabradine and heart rate lowering on cardiovascular outcomes.ResultsUsing data from the UK Biobank and large GWAS consortia, we evaluated the effect of a heart rate-reducing genetic variant at the HCN4 locus encoding ivabradine’s drug target. These genetic association analyses showed increases in risk for atrial fibrillation (OR 1.09, 95% CI: 1.06-1.13, P=9.3 ×10−9) in the UK Biobank. In a cause-specific competing risk model to account for the increased risk of atrial fibrillation, the HCN4 variant reduced incident heart failure in participants that did not develop atrial fibrillation (HR 0.90, 95% CI: 0.83-0.98, P=0.013). In contrast, the same heart rate reducing HCN4 variant did not prevent a composite endpoint of myocardial infarction or cardiovascular death (OR 0.99, 95% CI: 0.93-1.04, P=0.61).ConclusionGenetic modelling of ivabradine recapitulates its benefits in heart failure, promotion of atrial fibrillation, and neutral effect on myocardial infarction.CONDENSED ABSTRACTThe effects of drugs can sometimes be predicted from the effects of mutations in genes encoding drug targets. We tested the effect of a heart rate reducing allele at the HCN4 locus encoding ivabradine’s drug target and found results coherent with the SHIFT and SIGNIFY clinical trials of ivabradine. The genetic variant increased the risk of atrial fibrillation and cardioembolic stroke and protected against heart failure in a competing risk model accounting for the increased risk of atrial fibrillation. The variant had a neutral effect on a composite of myocardial infarction and cardiovascular death.

Objectives The goal of this study was to investigate sex differences in adenosine-free coronary pressure indexes. Background Several adenosine-free coronary pressure wire indexes have been proposed to assess the functional significance of coronary artery lesions; however, there is a theoretical concern that sex differences may affect diagnostic performance because of differences in resting flow and distal myocardial mass. Methods In this CONTRAST (Can Contrast Injection Better Approximate FFR Compared to Pure Resting Physiology?) substudy, contrast fractional flow reserve (cFFR), obtained during contrast-induced submaximal hyperemia, the instantaneous wave-free ratio (iFR), and distal/proximal coronary pressure ratio (Pd/Pa) were compared with fractional flow reserve (FFR) in 547 men and 216 women. Using FFR ≤0.8 as a reference, the diagnostic performance of each index was compared. Results Men and women had similar diameter stenosis (p = 0.78), but women were less likely to have FFR ≤0.80 than men (42.5% vs. 51.5%, p = 0.04). Sensitivity was similar among cFFR, iFR, and Pd/Pa when comparing women and men, respectively (cFFR, 77.5% vs. 75.3%; p = 0.69; iFR, 84.9% vs. 79.4%; p = 0.30; Pd/Pa, 78.8% vs. 77.3%; p = 0.78). cFFR was more specific than iFR or Pd/Pa regardless of sex (cFFR, 94.3% vs. 95.8%; p = 0.56; iFR, 75.6% vs. 80.1%; p = 0.38; Pd/Pa, 80.6% vs. 78.7%; p = 0.69). By receiver-operating characteristic curve analysis, cFFR provided better diagnostic accuracy than resting indexes irrespective of sex (p ≤ 0.0001). Conclusions Despite the theoretical concern, the diagnostic sensitivity and specificity of cFFR, iFR, and Pd/Pa did not differ between the sexes. Irrespective of sex, cFFR provides the best diagnostic performance.

Staphylococcus warneri , a coagulase negative staphylococcus, has been isolated in prosthetic device-related infections and has been reported as a rare cause of endocarditis. We report a case of prosthetic aortic valve S. warneri endocarditis, in which the patient lacked typical infectious signs and symptoms, instead presenting with congestive heart failure due to perforation of the valve. Providers should consider endocarditis with a low virulence pathogen such as S. warneri when a patient with a prosthetic valve presents with heart failure, even in the absence of fever, leukocytosis and other infectious symptoms. Cardiol Res. 2017;8(5):236-240 doi: https://doi.org/10.14740/cr588w

Background: The prognostic impact of coronary microvascular dysfunction after percutaneous coronary intervention (PCI) remains unclear in patients with stable coronary artery disease. This study sought to investigate the prognostic value of microvascular function measured immediately after PCI in patients with stable coronary artery disease. Methods: We enrolled 572 patients with stable coronary artery disease who underwent PCI and elective measurement of the index of microcirculatory resistance (IMR) immediately after PCI from 8 centers in 4 countries. Impaired microvascular function was defined as IMR≥25 (high IMR). Major adverse cardiac events, including death, myocardial infarction (MI) and target vessel revascularization, were evaluated. Results: During a median follow-up duration of 4.0 years, the cumulative major adverse cardiac events rate was significantly higher in the high IMR group (n=66/148) compared with the low IMR group (n=128/424; hazard ratio [HR], 1.56; 95% CI, 1.16−2.105; P =0.001), primarily due to a higher rate of periprocedural MI (HR, 1.59; 95% CI, 1.11−2.28; P =0.004) but also due to higher rates of mortality (HR, 1.59; 95% CI, 0.76−3.35; P =0.22), spontaneous MI (HR, 2.10; 95% CI, 0.67−6.63; P =0.20) and target vessel revascularization (HR, 1.40; 95% CI, 0.77−2.54; P =0.27). Cumulative risk for death, spontaneous MI, and target vessel revascularization was higher in the high IMR group (HR, 1.55; 95% CI, 0.99−2.43; P =0.056), as was death and spontaneous MI alone (HR, 1.79; 95% CI, 0.96−3.36; P =0.065). On multivariable analysis, high IMR post-PCI was an independent predictor of major adverse cardiac events. Conclusions: IMR measured immediately after PCI predicts adverse events in patients with stable coronary artery disease.

Heart failure (HF) is a leading cause of morbidity and mortality worldwide1. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained2–4. We report the largest GWAS meta-analysis of HF to-date, comprising 47,309 cases and 930,014 controls. We identify 12 independent variant associations with HF at 11 genomic loci, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function suggesting shared genetic aetiology. Expression quantitative trait analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homeostasis (BAG3), and cellular senescence (CDKN1A). Using Mendelian randomisation analysis we provide new evidence supporting previously equivocal causal roles for several HF risk factors identified in observational studies, and demonstrate CAD-independent effects for atrial fibrillation, body mass index, hypertension and triglycerides. These findings extend our knowledge of the genes and pathways underlying HF and may inform the development of new therapeutic approaches.

Fungal endocarditis remains an uncommon clinical diagnosis, though is likely to become more frequent due to the global increase in transplantations and cardiac valvular surgery. A case of prosthetic valve endocarditis due to Aspergillus fumigatus is described that was diagnosed with serologic fungal markers and confirmed with positive blood cultures, an uncommon finding. Keywords: Fungal Endocarditis, Aspergillus fumigatus, Fungemia

Publisher's version (útgefin grein), Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans., The work was supported by the following grants: National Institute of Health grants: R21HL123677, R21-HL140385, DK104806-01A1, R01-MD012765-01A1 (NF), National Institutes of Health awards R01HG009120, R01HG006399, U01CA194393, T32NS048004 (CG), the American Heart Association Grant #17POST33350042 (PV), the British Heart Foundation (RG/13/5/30112) and the National Institute for Health Research University College London Hospitals Biomedical Research Centre (RCL and RPH), the British Heart Foundation FS/14/55/30806 (JCH), the German Federal Ministry of Education and Research (BMBF) in the context of the e:Med program (e:AtheroSysMed), the DFG as part of the CRC 1123 (B3), and the FP7/2007-2103 European Union project CVgenes@target (grant agreement number Health-F2-2013-601456). We thank Li-Ming Gan for assistance with the STARNET study and Jon White for assistance with UCLEB analyses. Additional acknowledgements are included in Supplementary Note 2.

Background: Despite advances in the representation of women in medical training, women continue to be underrepresented in cardiology, academic medicine, and more specifically, in senior positions within academic medicine. Identifying disparities in research productivity and acknowledgment can highlight barriers to female representation in academic cardiology leadership, as well as in academic promotion. Methods and Results: This bibliometric analysis included all authors of original research articles between 1980 and 2017 from 3 high-impact cardiology journals ( Journal of the American College of Cardiology , Circulation , and European Heart Journal ). We identified 71 345 unique authors of 55 085 primary research articles during our study period. Female authors accounted for 33.1% of all authors; however, they represented only 26.7% of first authors and 19.7% of senior authors. Looking at the most prolific authors within this time period, female authors were not well represented, accounting for only 5% of the top 100 authors. Articles with a female senior author had more female middle authors than articles with a male senior author (mean 1.41 versus 0.97, P P P Conclusions: Using a large database of published manuscripts, we found that female representation in published cardiology research has increased over the past 4 decades. However, women continue to be not well represented as first authors, senior authors, and in the number of publications. When women were senior authors, they published more articles with female first authors and had more female authors. In addition to recruiting more women into the field of cardiology, additional work is needed to identify and address barriers to academic advancement for female physician-scientists.