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Objective: Ischemic mitral regurgitation is prevalent and associated with high surgical risk. With the less-invasive option of transcatheter edge-to-edge repair, the optimal patient selection for mitral valve operation for ischemic mitral regurgitation remains unclear. We sought to identify high-risk features in this group to guide patient selection. Methods: Using the Cardiothoracic Surgery Trial Network's severe ischemic mitral regurgitation trial data, we identified patient and echocardiographic characteristics associated with an increased risk of 2-year mortality using the support vector classifier and Cox proportional hazards model. We identified 6 high-risk features associated with 2-year survival. Patients were categorized into 3 groups, each having 1 or less, 2, or 3 or more of the 6 identified high-risk features. Results: Among the 251 patients, the median age was 69 (Q1 62, Q3 75) years, and 96 (38%) were female. Two-year mortality was 21% (n = 53). We identified 6 high-risk preoperative features: age 75 years or more (n = 69, 28%), prior sternotomy (n = 49, 20%), renal insufficiency (n = 69, 28%), gastrointestinal bleeding (n = 15, 6%), left ventricular ejection fraction less than 40% (n = 131, 52%), and ventricular end-systolic volume index less than 50 mL/m2 (n = 93, 37%). In patients who had 1 or less, 2, and 3 or more high-risk features, 90-day mortality was 4.2% (n = 5), 9.9% (n = 4), and 20.0% (n = 10), respectively (P = .006), and 2-year mortality was 10% (n = 12), 22% (n = 18), and 46% (n = 23) (P

Background Gender‐ and sex‐based disparities in mitral valve disease exist; however the factors associated with these differences are unknown. Identifying these differences is essential in devising mitigating strategies. We evaluated gender and sex differences among patients with severe primary mitral regurgitation (MR) across treatment phases. Methods and Results We conducted a retrospective cohort study of patients with new diagnoses of severe primary MR between 2016 and 2020. We compared multidisciplinary evaluation incidence and 2‐year survival between men and women. We analyzed a subgroup meeting class 1 indications for intervention, which includes severe symptomatic MR or severe asymptomatic MR with ejection fraction 40 mm. Logistic regression models identified predictors associated with the likelihood of multidisciplinary evaluation. Among 330 patients meeting class 1 indications, women were older (79 versus 76 years, P=0.01) and had higher Society of Thoracic Surgeons risk scores for mitral valve repair than men (2.5% versus 1.4%, P=0.003). Women were less likely to undergo multidisciplinary evaluation (57% versus 84%, P

Background Multidisciplinary heart team (HT) evaluation is recommended for patients with severe primary mitral regurgitation to optimize treatment decisions. However, its impact on patient outcomes remains unknown. We evaluated the impact of implementing mitral HT on patient survival. Methods and Results We conducted a retrospective cohort study of patients with new diagnoses of severe primary mitral regurgitation in a large healthcare network echocardiogram database between 2016 and 2020. We compared the incidence of multidisciplinary evaluation by structural cardiology and cardiac surgery services and 2‐year survival before and after mitral HT implementation. The 1:1 propensity‐score matching between pre‐ and post‐mitral HT used Society of Thoracic Surgeons Predicted Risk of Mortality for mitral repair, age, sex, race, heart failure symptoms, inpatient setting, history of MI, and dementia as covariates. Logistic regression identified variables associated with the likelihood of undergoing multidisciplinary evaluation. Among 70 510 echocardiograms performed, 391 patients had severe primary mitral regurgitation (median age, 77 years; 46% women). Multidisciplinary evaluation increased from 29% to 89% (P

Abstract The management and follow-up of moderate aortic stenosis (AS) lacks consensus as the progression patterns are not well understood. This study aimed to identify the hemodynamic progression of AS, and associated risk factors and outcomes. We included patients with moderate AS with at least three transthoracic echocardiography (TTE) studies performed between 2010 and 2021. Latent class trajectory modeling was used to classify AS groups with distinctive hemodynamic trajectories, which were determined by serial systolic mean pressure gradient (MPG) measurements. Outcomes were defined as all-cause mortality and aortic valve replacement (AVR). A total of 686 patients with 3093 TTE studies were included in the analysis. Latent class model identified two distinct AS trajectory groups based on their MPG: a slow progression group (44.6%) and a rapid progression group (55.4%). Initial MPG was significantly higher in the rapid progression group (28.2 ± 5.6 mmHg vs. 22.9 ± 2.8 mmHg, P

Abstract In patients with bicuspid aortic valves, guidelines call for regular follow-up to monitor disease progression and guide intervention. We aimed to evaluate how closely these recommendations are followed at a tertiary care center. Among 48,504 patients who received echocardiograms (2013–2018) at a tertiary care center, 245 patients were identified to have bicuspid aortic valve. Bivariate analyses compared characteristics between patients who did and did not receive follow-up by a cardiovascular specialist. During a median follow-up of 3.5 ± 2.2 years (mean age 55.2 ± 15.6 years, 30.2% female), 72.7% of patients had at least one visit with a cardiovascular specialist after diagnosis of bicuspid aortic valve. These patients had a higher proportion of surveillance by echocardiogram (78.7% vs. 34.3%, p

Abstract Understanding postoperative recovery is critical for guiding efforts to improve post-acute phase care. How recovery evolves during the first 30 days after cardiac surgery is not well-understood. A digital platform may enable granular quantification of recovery by frequently capturing patient-reported outcome measures (PROM) that can be clinically implemented to support recovery. We conduct a prospective cohort study using a digital platform to measure recovery after cardiac surgery using a PROM sent every 3 days for 30 days after surgery to characterize recovery in multiple domains (e.g., pain, sleep, activities of daily living, anxiety) and to identify factors related to the patient’s perception of overall recovery. We enroll patients who underwent cardiac surgery at a tertiary center between January 2019 and March 2020 and automatically deliver PROMs and reminders electronically. Of the 10 surveys delivered per patient, 8 (IQR 6–10) are completed. Patients who experienced postoperative complications more commonly belong to the worst overall recovery trajectory. Of the 12 domains modeled, only the worst anxiety trajectory is associated with the worse overall recovery trajectory membership, suggesting that even when patients struggle in the recovery of other domains, the patient may still feel progress in their recovery. We demonstrate that using a digital platform, automated PROM data collection, and characterization of multi-domain recovery trajectories is feasible and likely implementable in clinical practice. Overall recovery may be impacted by complications, while slow progress in constituent domains may still allow for the perception of overall recovery progression.

Objective: Overprescribing of opioids has contributed to the opioid epidemic. Electronic medical records systems can auto-populate a default number of opioid pills that are prescribed at time of discharge. The aim of this study was to examine the association between lowered default pill counts with changed prescribing practices after cardiac surgery. Methods: On May 18, 2017, the default number of pills prescribers see in electronic medical records in the Yale New Haven Health System was lowered from 30 to 12. Patients undergoing coronary artery grafts, valve surgeries, and thoracic aortic aneurysm surgeries were included in this study. Data were gathered and stratified into 2 groups: 1 year before and 1 year following the default change. The amount of opioid prescribed was compared between the 2 groups. Results: A total of 1741 patient charts were reviewed, 832 before the change and 909 after the change. Significant changes were seen in prescribing practices, where the average amount of opioid prescribed was about 25% lower after the change. This amounted to about 15 fewer pills of 5 mg morphine for each patient. A linear regression model adjusting for other factors determined a prescribing difference of 75.2 morphine milligram equivalents per prescription (P

Abstract Background Prior studies on ascending thoracic aortic aneurysm (ATAA) growth rates have reported approximately 1 mm of growth per year but these studies are based on referral-based study populations which are biased towards the highest risk patients who may not represent the true natural history of aortic aneurysm disease. We aimed to characterize the growth rate of ATAAs in a non-referral-based population, using a large institutional database of computed tomography (CT) scans. Methods We queried the 21,325 CT scans performed at our institution between 2013 and 2016 on patients ages 50–85 years old for radiologic diagnosis of aortic aneurysm or dilatation. 560 patients were identified to have aortic dilatation > 4 cm, of which 207 had follow-up scan intervals > 6 months. This comprised our non-referral-based study population. Linearized annual aneurysm growth rates were calculated by dividing the change in aortic size by the time interval between CT scans. Results The median time interval between scans was 2.7 years (interquartile range [IQR] 1.5–4.2) for the 207 patients included in the study. The median initial aneurysm size was 4.3 cm (IQR 4.1–4.5). 38.2% (n = 79) of patients did not experience aortic dilatation. The median growth rate was 0.13 mm/year (IQR − 0.24 to 0.49). Of patients in the top quartile of growth rates, 26.9% of patients were female whereas 12.9% of patients were female in the bottom three quartiles of growth rates. Conclusion While some patients’ ATAAs may grow at previously published rates of around 1 mm/year, this is not the predominant pattern in a non-referral-based population and may over-estimate the overall growth rate of ATAAs.

Abstract Medial degeneration is a common histopathological finding in aortopathy and is considered a mechanism for dilatation. We investigated if medial degeneration is specific for sporadic thoracic aortic aneurysms versus nondilated aortas. Specimens were graded by pathologists, blinded to the clinical diagnosis, according to consensus histopathological criteria. The extent of medial degeneration by qualitative (semi-quantitative) assessment was not specific for aneurysmal compared to nondilated aortas. In contrast, blinded quantitative assessment of elastin amount and medial cell number distinguished aortic aneurysms and referent specimens, albeit with marked overlap in results. Specifically, the medial fraction of elastin decreased from dilution rather than loss of protein as cross-sectional amount was maintained while the cross-sectional number, though not density, of smooth muscle cells increased in proportion to expansion of the media. Furthermore, elastic lamellae did not thin and interlamellar distance did not diminish as expected for lumen dilatation, implying a net gain of lamellar elastin and intralamellar cells or extracellular matrix during aneurysmal wall remodeling. These findings support the concepts that: (1) medial degeneration need not induce aortic aneurysms, (2) adaptive responses to altered mechanical stresses increase medial tissue, and (3) greater turnover, not loss, of mural cells and extracellular matrix associates with aortic dilatation.

BackgroundNatural history of atrial and ventricular secondary mitral regurgitation (SMR) is poorly understood. We compared the impact of the degree of SMR on survival between atrial and ventricular dysfunction.MethodsWe conducted a retrospective cohort study of patients who underwent echocardiography in a healthcare network between 2013-2018. We compared the survival of patients with atrial and ventricular dysfunction, using propensity scores developed from differences in patient demographics and comorbidities within SMR severity strata (none, mild, moderate or severe). We fitted Cox proportional hazards models to estimate the risk-adjusted hazards of death across different severities of SMR between patients with atrial and ventricular dysfunction.ResultsOf 11,987 patients included (median age 69 years [IQR 58-80]; 46% women), 6,254 (52%) had isolated atrial dysfunction, and 5,733 (48%) had ventricular dysfunction. 3,522 patients were matched from each arm using coarsened exact matching. Hazard of death in atrial dysfunction without SMR was comparable to ventricular dysfunction without SMR (HR 1.1, 95% CI 0.9-1.3). Using ventricular dysfunction without SMR as reference, hazards of death remained higher in ventricular dysfunction than in atrial dysfunction across increasing severities of SMR: mild SMR (HR 2.1, 95% CI 1.8-2.4 in ventricular dysfunction versus HR 1.7, 95%CI 1.5-2.0 in atrial dysfunction) and moderate/severe SMR (HR 2.8, 95%CI 2.4-3.4 versus HR 2.4, 95%CI 2.0-2.9).ConclusionsSMR across all severities were associated with better survival in atrial dysfunction than in ventricular dysfunction, though the magnitude of the diminishing survival were similar between atrial and ventricular dysfunction in increasing severity of SMRs.

Abstract Background Hypo-attenuated leaflet thickening (HALT) in bioprosthetic aortic valve has been studied, but its equivalent in bioprosthetic mitral valve (bMV) remains uncharacterized. We sought to identify the prevalence, hemodynamic characteristics, and significance of anticoagulation therapy in bMV HALT. Methods A single-center cross-sectional study of 53 consecutive patients who underwent mitral valve replacement (MVR) with bMV between 2007 and 2017 was conducted. Cardiac-gated contrasted CT scans were obtained. Anticoagulant and antiplatelet therapy use were ascertained at the time of hospital discharge and CT scanning. Patient characteristics, postoperative stroke, and hemodynamic profile by echocardiogram were obtained to descriptively characterize the prevalence and characteristics associated with bMV HALT. Results Three patients (5.7%) were found to have a HALT on bMV. The mean time from index MVR to CT scan was 3.4 ± 0.8 years in HALT cohort and 3.4 ± 2.7 years in non-HALT cohort. Fifty patients (94.3%) were discharged on warfarin, and 37 patients (69.8%) were on warfarin at the time of CT scans. One patient with HALT was on therapeutic warfarin at the time of the CT scan that identified HALT. All three patients were asymptomatic at the time of CT scan. In patients with HALT, mean transmitral pressure gradient were 8, 5, and 2.7 mmHg, all with trivial or mild mitral regurgitation. Conclusions In this study, the prevalence of HALT was low at 5.7%, all presenting without symptoms. One patient presented with HALT while on therapeutic oral anticoagulation, which may suggest thrombotic etiology may not adequately explain HALT.

Background Patients with obesity and advanced heart failure face unique challenges on the path to heart transplantation. There are limited data on waitlist and transplantation outcomes in this population. We aimed to evaluate the impact of obesity on heart transplantation outcomes, and to investigate the effects of the new organ procurement and transplantation network allocation system in this population. Methods and Results This cohort study of adult patients listed for heart transplant used the United Network for Organ Sharing database from January 2006 to June 2020. Patients were stratified by body mass index (BMI) (18.5–24.9, 25–29.9, 30–34.9, 35–39.9, and 40–55 kg/m2). Recipient characteristics and donor characteristics were analyzed. Outcomes analyzed included transplantation, waitlist death, and posttransplant death. BMI 18.5 to 24.9 kg/m2 was used as the reference compared with progressive BMI categories. There were 46 645 patients listed for transplantation. Patients in higher BMI categories were less likely to be transplanted. The lowest likelihood of transplantation was in the highest BMI category, 40 to 55 kg/m2 (hazard ratio [HR], 0.19 [0.05–0.76]; P=0.02). Patients within the 2 highest BMI categories had higher risk of posttransplantation death (HR, 1.29; P

Background Screening protocols do not exist for ascending thoracic aortic aneurysms (ATAAs). A risk prediction algorithm may aid targeted screening of patients with an undiagnosed ATAA to prevent aortic dissection. We aimed to develop and validate a risk model to identify those at increased risk of having an ATAA, based on readily available clinical information. Methods and Results This is a cross‐sectional study of computed tomography scans involving the chest at a tertiary care center on unique patients aged 50 to 85 years between 2013 and 2016. These criteria yielded 21 325 computed tomography scans. The double‐oblique technique was used to measure the ascending thoracic aorta, and an ATAA was defined as >40 mm in diameter. A logistic regression model was fitted for the risk of ATAA, with readily available demographics and comorbidity variables. Model performance was characterized by discrimination and calibration metrics via split‐sample testing. Among the 21 325 patients, there were 560 (2.6%) patients with an ATAA. The multivariable model demonstrated that older age, higher body surface area, history of arrhythmia, aortic valve disease, hypertension, and family history of aortic aneurysm were associated with increased risk of an ATAA, whereas female sex and diabetes were associated with a lower risk of an ATAA. The C statistic of the model was 0.723±0.016. The regression coefficients were transformed to scores that allow for point‐of‐care calculation of patients' risk. Conclusions We developed and internally validated a model to predict patients' risk of having an ATAA based on demographic and clinical characteristics. This algorithm may guide the targeted screening of an undiagnosed ATAA.

Background Although current guidelines recommend dual antiplatelet therapy (DAPT) for 3 to 6 months following transcatheter aortic valve replacement (TAVR), there are no studies directly comparing outcomes of different durations of DAPT following TAVR. Methods and Results PubMed, EMBASE, and Cochrane Database were searched through November 2020 to identify clinical studies that investigated single antiplatelet therapy versus DAPT use following TAVR. Studies using oral anticoagulants and antiplatelet therapy concomitantly were excluded. The DAPT group was subdivided by the duration of DAPT. We extracted the risk ratios (RRs) of major or life‐threatening bleeding, stroke, and all‐cause mortality. Four randomized controlled trials, 2 propensity‐score matched studies, and 1 observational study were identified, yielding a total of 2498 patients who underwent TAVR assigned to the single antiplatelet therapy group (n=1249), 3‐month DAPT group (n=485), or 6‐month DAPT group (n=764). Pooled analyses demonstrated that when compared with the single antiplatelet therapy group, the rates of major or life‐threatening bleeding were significantly higher in the 3‐ and 6‐month DAPT groups (RR [95% CI]=2.13 [1.33–3.40], P=0.016; RR [95% CI]=2.54 [1.49–4.33], P=0.007, respectively) with no difference between the 3‐month DAPT versus 6‐month DAPT groups. The rates of stroke and all‐cause mortality were similar among the 3 groups. Conclusions In this network meta‐analysis of antiplatelet therapy following TAVR, single antiplatelet therapy with aspirin had lower bleeding without increasing stroke or death when compared with either 3‐ or 6‐month DAPT.

Abstract Background Elevated white blood cell counts and leukocyte ratios are recognized markers of systemic inflammation associated with poor surgical outcomes. We analyzed the temporal stability and prognostic value of the preoperative Neutrophil-to-Lymphocyte ratio (NLR) and Lymphocyte-to-Neutrophil ratio (LNR) in patients undergoing coronary artery bypass grafts and/or valve surgery. Methods We retrospectively reviewed 558 patients who underwent elective cardiac surgery between July 2014 and December 2016, excluding patients with immunosuppressed status. The stability of NLR and LNR was evaluated using interclass correlation coefficients. The patients were dichotomized into two groups, high NLR and low NLR, based on the median value of preoperative NLR in our cohort. A logistic regression model compared preoperative NLR and LNR values to clinical outcomes, including a composite of perioperative events and mid-term mortality. Results We identified that NLR reliability over time was good (ICC = .592; R-squared = .351), and LNR reliability over time was excellent (ICC = .761; R-squared = .601). Furthermore, an increased duration between collection dates was not significantly correlated with increased variability in NLR (Pearson Correlation Coefficient: −.111, p = .117). On multivariate model, neither high NLR (OR = .879, p = .168) nor low LNR (OR = 3.30, p = .214) was significantly associated with a composite of perioperative events, but increased LNR was associated with lower mid-term mortality (HR .001, p = .026). Conclusions Both NLR and LNR were stable over time, up to 100 days, but LNR values were more consistent compared to NLR. High LNR was significantly associated with decreased risk of mid-term mortality, and LNR showed a stronger relationship with mid-term mortality than its NLR counterpart. Both of these findings indicate that LNR may be a more useful and valuable clinical marker.

BackgroundPatients with restrictive or hypertrophic cardiomyopathy (RCM/HCM) and congenital heart disease (CHD) do not derive clinical benefit from inotropes and mechanical circulatory support. Concerns were expressed that the new heart allocation system implemented in October 2018 would disadvantage these patients. This paper aimed to examine the impact of the new adult heart allocation system on transplantation and outcomes among patients with RCM/HCM/CHD.MethodsWe identified adult patients with RCM/HCM/CHD in the United Network for Organ Sharing (UNOS) database who were listed for or received a cardiac transplant from April 2017-June 2020. The cohort was separated into those listed before and after allocation system changes. Demographics and recipient characteristics, donor characteristics, waitlist survival, and post-transplantation outcomes were analyzed.ResultsThe number of patients listed for RCM/HCM/CHD increased after the allocation system change from 429 to 517. Prior to the change, the majority RCM/HCM/CHD patients were Status 1A at time of transplantation; afterwards, most were Status 2. Wait times decreased significantly for all: RCM (41 days vs 27 days; PConclusionsThe new allocation system has had a positive impact on time to transplantation of patients with RCM, HCM, and CHD without negatively influencing survival.

Background The likelihood of undergoing reoperative coronary artery bypass graft surgery (CABG) is important for older patients who are considering first‐time CABG. Trends in the reoperative CABG for these patients are unknown. Methods and Results We used the Medicare fee‐for‐service inpatient claims data of adults undergoing isolated first‐time CABG between 1998 and 2017. The primary outcome was time to first reoperative CABG within 5 years of discharge from the index surgery, treating death as a competing risk. We fitted a Cox regression to model the likelihood of reoperative CABG as a function of patient baseline characteristics. There were 1 666 875 unique patients undergoing first‐time isolated CABG and surviving to hospital discharge. The median (interquartile range) age of patients did not change significantly over time (from 74 [69–78] in 1998 to 73 [69–78] in 2017); the proportion of women decreased from 34.8% to 26.1%. The 5‐year rate of reoperative CABG declined from 0.77% (95% CI, 0.72%–0.82%) in 1998 to 0.23% (95% CI, 0.19%–0.28%) in 2013. The annual proportional decline in the 5‐year rate of reoperative CABG overall was 6.6% (95% CI, 6.0%–7.1%) nationwide, which did not differ across subgroups, except the non‐white non‐black race group that had an annual decline of 8.5% (95% CI, 6.2%–10.7%). Conclusions Over a recent 20‐year period, the Medicare fee‐for‐service patients experienced a significant decline in the rate of reoperative CABG. In this cohort of older adults, the rate of declining differed across demographic subgroups.

Introduction Improving postoperative patient recovery after cardiac surgery is a priority, but our current understanding of individual variations in recovery and factors associated with poor recovery is limited. We are using a health-information exchange platform to collect patient-reported outcome measures (PROMs) and wearable device data to phenotype recovery patterns in the 30-day period after cardiac surgery hospital discharge, to identify factors associated with these phenotypes and to investigate phenotype associations with clinical outcomes.Methods and analysis We designed a prospective cohort study to enrol 200 patients undergoing valve, coronary artery bypass graft or aortic surgery at a tertiary centre in the USA. We are enrolling patients postoperatively after the intensive care unit discharge and delivering electronic surveys directly to patients every 3 days for 30 days after hospital discharge. We will conduct medical record reviews to collect patient demographics, comorbidity, operative details and hospital course using the Society of Thoracic Surgeons data definitions. We will use phone interview and medical record review data for adjudication of survival, readmission and complications. We will apply group-based trajectory modelling to the time-series PROM and device data to classify patients into distinct categories of recovery trajectories. We will evaluate whether certain recovery pattern predicts death or hospital readmissions, as well as whether clinical factors predict a patient having poor recovery trajectories. We will evaluate whether early recovery patterns predict the overall trajectory at the patient-level.Ethics and dissemination The Yale Institutional Review Board approved this study. Following the description of the study procedure, we obtain written informed consent from all study participants. The consent form states that all personal information, survey response and any medical records are confidential, will not be shared and are stored in an encrypted database. We plan to publish our study findings in peer-reviewed journals.

Background To evaluate changes in patient characteristics and outcomes for infective endocarditis (IE) related to opioid use disorder (OUD), we used the National (Nationwide) Inpatient Sample (NIS) to characterize the trend in hospitalizations for patients with IE with and without OUD and those treated medically and surgically. Methods and Results Temporal trends in hospitalization characteristics for patients with IE with and without OUD and those treated medically and surgically were estimated via the NIS data in 2005–2014. Hospitalizations for OUD and IE increased from 119 to 202 and from 12 to 15 cases per 100 000 between 2005 and 2014, respectively. Hospitalizations with OUD among all IE hospitalizations increased from 6.3% in 2005 to 11.6% in 2014. Among all IE hospitalizations, patients being admitted for IE in the setting of OUD were younger compared with the cohort of IE without OUD (aged 37.6±0.21 years versus 60.9±0.16 years). Myocardial infarction, diabetes mellitus, chronic kidney disease, peripheral vascular disease, and heart failure were more common in patients without OUD. The OUD cohort more frequently had liver disease (46.0% versus 10.8%) and immunosuppressed status (4.3% versus 2.1%). Valve operations for IE accounted for 10.2% of all valve operations in 2005, and this increased to 12.7% in 2014. These proportions were similar between OUD (11.4%) and non‐OUD (11.1%) cohorts. Operative mortality was lower in patients with OUD (4.3% versus 9.4%, P

ImportancePatient outcomes in heart failure clinical trials are generally better than those observed in real-world settings. This may be related to stricter inclusion and exclusion criteria in clinical trials.ObjectiveWe study sought to characterize the clinical implications of differences between patients in clinical trials and those in a real-world registry of patients receiving left ventricular assist devices (LVADs).Design, setting, and participantsThis retrospective cohort study included all patients in INTERMACS (the Interagency Registry for Mechanically Assisted Circulatory Support) who were implanted with an axial flow LVAD from 2010 to 2015 to allow for equivalent comparisons.Main outcomes and measuresDifferences in patient characteristics and 2-year rates of adverse outcomes with those reported in the ENDURANCE and MOMENTUM 3 clinical trials. Survival analyses were used to assess the relationships between prespecified patient factors and clinical outcomes.ResultsOf the 10,937 LVAD recipients identified in INTERMACS between 2010-2015, 44% met at least 1 clinical trial exclusion criterion. The 2-year incidence of stroke and death amongst LVAD recipients in INTERMACS and the landmark clinical trials differed significantly (PConclusions and relevanceMost exclusion criteria used in LVAD clinical trials did not afford a substantially greater risk to patients in the real-world setting. In the relatively infrequent cases of end stage renal disease, thrombocytopenia, respiratory failure, and need for ECMO, the risks and benefits of LVAD therapy need careful weighting and further study.

Background Improving postoperative recovery is important, with a national focus on postacute care, but the volume and quality of evidence in this area are not well characterized. We conducted a systematic review to characterize studies on postoperative recovery after adult cardiac surgery using patient‐reported outcome measures. Methods and Results From MEDLINE and Web of Science, studies were included if they prospectively assessed postoperative recovery on adult patients undergoing cardiac surgery using patient‐reported outcome measures. Six recovery domains were defined by prior literature: nociceptive symptoms, mental health, physical function, activities of daily living, sleep, and cognitive function. Of the 3432 studies, 105 articles met the inclusion criteria. The studies were small (median sample size, 119), and mostly conducted in single‐center settings (n=81; 77%). Study participants were predominantly men (71%) and white (88%). Coronary artery bypass graft was included in 93% (n=98). Studies commonly selected for elective cases (n=56; 53%) and patients with less comorbidity (n=67; 64%). Median follow‐up duration was 91 (interquartile range, 42–182) days. Studies most commonly assessed 1 domain (n=42; 40%). The studies also varied in the instruments used and differed in their reporting approach. Studies commonly excluded patients who died during the follow‐up period (n=48; 46%), and 45% (n=47) did not specify how those patients were analyzed. Conclusions Studies of postoperative patient‐reported outcome measures are low in volume, most often single site without external validation, varied in their approach to missing data, and narrow in the domains and diversity of patients. The evidence base for postoperative patient‐reported outcome measures needs to be strengthened.

With a view to investigate whether in-ovo cadmium (Cd) exposure can attribute toxic effects in developing avian embryo, the fertile eggs of Japanese quail were injected with Cd and the mortality during incubation and the body weights of day-old hatchlings were measured. The Cd toxicity in the embryo were also assessed by evaluating some well-known oxidative stress markers such as metallothionein (MT) mRNA expression, catalase activity and malondialdehyde (MDA) production in day-10 male and female embryos exposed to Cd with or without ascorbic acid. Results showed that as minimum as 1μg/egg of in-ovo Cd administration increased the embryonic death and decreased the hatchling body weights. A slightly higher mortality rate was found in the 1μg Cd/egg received male embryos than in the female embryos. Compare to the control, higher MT mRNA expression and MDA generation were observed in 1μg Cd/egg received live embryos irrespective of sex. Co-exposure of 50μg ascorbic acid with 1μg Cd/egg inhibited the increse in MDA production in embryos of both sexes but the augment of MT mRNA expression was supressed only in female embryos. These results suggested that in-ovo Cd pollution in avian species might cause the embryonic toxicity leading to death, and the sensitivity of developing quail embryo to antioxidant protection against Cd toxicity is not exactly similar in both sexes of embryos.

Cellular glutathione peroxidase has important antioxidant and detoxification functions by protecting cells from oxidative damage induced by reactive oxygen species. To investigate the expression of cellular glutathione peroxidase mRNA during embryogenesis in Japanese quail, livers were collected at day 6, 9, 12, 15 and 17 of incubation for measurement of mRNA levels by RT-PCR. The result showed that cellular glutathione peroxidase mRNA expresses in all stages during embryonic development. To observe the effect of selenium in maternal diet on the hatchability and cellular glutathione peroxidase mRNA expression in the liver of hatchlings, mother quail were fed regular diet (0.24ppm selenium) with 0, 0.25, 0.5 or 1ppm selenium. After 2 weeks of feeding, fertilized eggs were collected and incubated. Livers of the mothers and the hatchlings were collected for measurement of cellular glutathione peroxidase mRNA expression. The results showed that the hatchability was high in eggs from quail fed 0.25ppm selenium, but it was decreased in eggs from quail fed 0.5 or 1ppm selenium. Cellular glutathione peroxidase mRNA levels of female quail fed 0.25, 0.5 or 1ppm selenium were higher than those fed regular diet. Cellular glutathione peroxidase mRNA levels of the hatchlings originating from the quail fed 0.25ppm selenium were higher than those of the hatchlings from the quail fed regular diet. These results indicated that although selenium is important for embryonic development through antioxidant defense system by cellular glutathione peroxidase, high level of selenium in the maternal diet has an adverse effect on embryonic development.

Glutathione peroxidase 1 (cellular glutathione peroxidase, EC 1.11.1.9 (GPX1)) is an antioxidant enzyme that plays an important role in scavenging reactive oxygen species to protect cells from oxidative damage. To clone the quail GPX1, total RNA was extracted from mature female quail liver. Degenerated primers were designed based on conserved sequences among five species (human, monkey, cattle, rat, and mouse) to amplify the quail fragment GPX1 with reverse transcription polymerase chain reaction. The cDNA sequence of partial Japanese quail GPX1 is 212 nucleotides in length. The rapid amplification of cDNA ends system (5′ and 3′ RACE) was used to obtain the full-length Japanese quail GPX1 cDNA. The 843-nucleotide quail GPX1 cDNA contains a 153 amino acid open reading frame, a 7bp 5′-untranslated region, and a 377bp 3′-untranslated region containing the poly A tail. It contains putative selenocysteine residue which is encoded by an unusual stop codon TGA. Comparison of amino acid sequences showed that Japanese quail GPX1 shares 65-74% identity with GPX1 of other animals, suggesting that our clone is an authentic member of GPX1. GPX1 mRNA was expressed in all tissues examined including kidney, adrenal gland, liver, small follicle, small intestine, heart, and breast muscle; the highest level was detected in liver. This quail GPX1 cDNA will provide a tool for further studies of GPX1 expression in the quail.

In aves, the perivitelline membrane is an extracellular matrix surrounding the oocyte at the time of ovulation, and is composed of several glycoproteins belonging to the zona pellucida (ZP) gene family. ZP1 and ZPC have been identified as the major components of the perivitelline membrane in quail and chicken. In addition, ZPD has been identified as a component of the chicken perivitelline membrane, and is synthesized in ovarian granulosa cells as ZPC. In contrast, ZP1 is synthesized in the liver and transported by blood circulation. In the present study, we isolated complementary DNA of turkey ZP1 from the liver and analyzed the turkey perivitelline membrane and serum using antiserum for quail ZP1. Turkey ZP1 encodes a protein of 943 amino acids containing a signal peptide, glutamine rich repeat, trefoil domain, ZP domain and consensus furin cleavage site, like quail and chicken counterparts. N-glycosylation sites, which have been proposed as important for interaction with sperm, are completely conserved among the birds. Turkey ZP1 shares 93% and 88% sequence identity with quail and chicken ZP1, respectively. In particular, sequence identity of the ZP domain among birds was higher than overall, probably due to the important role of the ZP domain in construction of the perivitelline membrane. Western blot analysis using anti-ZP1 antiserum detected a band which was almost the same molecular mass as quail ZP1, in the lysate of the perivitelline membrane and in the serum of turkey. These results suggest that turkey ZP1 is synthesized in the liver, and is transported by blood circulation to the ovary as reported in quail and chicken.

To explore the possible endocrine-disrupting effect of cadmium (Cd), we have tested its role on very-low-density apolipoprotein II mRNA (apoVLDL II) expression by diethylstilbestrol (DES) in Japanese quail. Three-week-old immature male quail were intraperitoneally injected with DES (10mg/kg body wt and 24hrs before sacrifice) to induce apoVLDL II mRNA in the liver. The same birds were intraperitoneally injected with 0.001, 0.01, 0.1, 1 or 3mg/kg body wt of CdCl2 at 48hrs before DES injection. A reverse-transcription polymerase chain reaction (RT-PCR) was applied to quantify the mRNA level. We found that 0.1mg/kg body wt of Cd injection contributed an additive effect in DES-stimulated apoVLDL II mRNA expression, whereas Cd injection above this level suppressed the effect. The present results suggest that Cd has biphasic effects on estrogen-dependent gene transcription, and 0.1mg/kg body wt of Cd administration can mimic the estrogen functions in Japanese quail.

The effects of a single dosage of cadmium (Cd) administration on the survival rate, body weight (BW), egg production, egg quality characteristics and hatching outputs in 0, 0.1, 0.3, 1, 3 and 10mg CdCl2/kg BW injected laying quail were studied. It was found that a 10mg Cd injection induced 41.7% mortality. A retainable significant BW loss in the 3mg dosed birds and a decreased egg production in the 1mg and 3mg dosed birds were observed during the first 3 days after injection, and the recovering of the egg production rate was delayed as the doses of Cd injection increased. Cd administration significantly increased the shell membrane weight in 0.1mg and 0.3mg injection, decreased the eggshell thickness in 0.3mg injection, and lowered the fertility rate in 0.3mg injection during the first 3 days of injection. The present study suggests that exposure to Cd, even by a single dosage, can hamper quail reproduction for a very short time, mainly by decreasing egg production and thinning the eggshell.

In order to examine the binding affinity of various estrogenic compounds to estrogen receptor β (ERβ), the cDNA encoding the hinge domain, the ligand-binding domain, and the C-terminal domain of quail ERβ was constructed and transfected into competent Escherichia coli. The binding assay performed using the supernatant of the cell lysates showed that bacterially-expressed ERβ has one single class of binding site for estradiol-17β with a dissociation constant of 4.90±0.16×10-9M. The competition studies indicated that the relative binding affinities for the synthetic estrogens, diethylstilbestrol and ethinyl estradiol, are very high, while those for the xenoestrogens, bisphenol A and nonylphenol, are very low. Coumestrol, known as one of phytoestrogens, can compete with estradiol-17β with higher binding affinity for ERβ than ERα.

The extracellular matrix surrounding the oocyte before ovulation is called perivitelline membrane (PL) in avian species. We previously reported that one of its components, ZPC, is produced in the ovarian granulosa cells by the stimulation of follicle-stimulating hormone and testosterone. Another component, ZP1, is synthesized in the liver, and might be transported to surface of the oocyte in the follicles. These glycoproteins are assembled to form a three-dimensional network of coarse fiber between the granulosa cells and the oocyte. In order to address the mode of PL formation, we investigated the progressive changes in contents of ZP1 and ZPC in PL during the follicular development in quail ovary. Western blot analysis using specific antisera indicated that ZP1 band was first appeared as 97kDa in molecular mass when the granulosa layer was isolated from the fourth largest follicle, and the intensity of the band was dramatically increased after the follicle matured to the third largest one. On the other hand, immunoreactive ZPC appeared as early as in the granulosa layer obtained from the small yellow follicles (SYF), and the intensity of the immunoreactive band increased progressively during follicular development. The immunohistochemical analysis indicated that the immunoreactive ZP1 and ZPC were not detected on the sections of follicular wall of the very small stroma-embedded white follicles. The immunoreactive ZPC was detected in the PL of SYF sections, whereas no detectable ZP1 was seen in the SYF sections. These results demonstrated that the accumulation of ZP1 was not synchronized to that of ZPC in the PL during follicular development. Alternatively, the accumulation of ZPC in the PL was preceded to that of ZP1 during follicular development in quail ovary.

Estrogenic compounds must bind to estrogen receptors (ER) and modulate estrogen-sensitive gene expression. However, various in vivo and in vitro assays have established that xenoestrogens and phytoestrogens are rather weak estrogens, with a 5,000- to 10,000-fold lower binding affinity to ER than estradiol-17β (E2). The purpose of this study was to determine the binding affinity of various estrogen-like chemicals to bacterially expressed quail ERα. The first-strand cDNA was synthesized from total RNA isolated from mature female quail liver with oligo-dT primed reverse transcription. The cDNA included the hinge region, the ligand-binding domain, and the C-terminal domain of quail ERα. It was amplified by PCR, and the PCR product was ligated into GST fusion protein expression vector, and transfected to the E. coli DH5α strain. A binding assay using the supernatant of the cell lysate was performed by incubation with [3H] E2 and increasing concentrations of competitor at 4°C for 18h. Unbound steroids were removed by the addition of dextran-coated charcoal, followed by centrifugation for 15min. The radioactivity of the supernatant was determined with a liquid scintillation counter. Quail ERα expressed bacterially showed binding affinity to E2 with a dissociation constant of 1.74±0.34 X10-10M. The competition studies indicated that the relative binding affinities for the synthetic estrogens, diethylstilbestrol and ethynylestradiol, are very high, but that of the xenoestrogens, bisphenol A and nonylphenol, are very low. The phytoestrogens, coumestrol and genistein, can compete with E2 with a significant binding affinity.

Avian perivitelline membrane, an investment homologous to the zona pellucida of mammalian oocytes, is composed of two glycoproteins. Previous studies have indicated that one of the components, a glycoprotein homologous to mammalian ZPC, is produced and secreted by the granulosa cells of maturing follicles in quail ovary. In the present study, to investigate the hormonal regulation of ZPC production, [3H] leucine incorporation into ZPC was compared in granulosa cells cultured in a medium containing follicle-stimulating hormone (FSH), luteinizing hormone, or prolactin, and a stimulatory effect of FSH was observed. By measuring ZPC protein in the medium and mRNA in the cells with Western blotting and Northern blotting analyses, respectively, we found that addition of FSH stimulated not only ZPC protein production but also ZPC mRNA expression in the granulosa cells. These results suggested that FSH stimulates ZPC protein production at the gene transcription level.

Recent studies suggest that action video game players exhibit superior performance in visuospatial cognitive tasks compared with non-game players. However, the neural basis underlying this visuospatial cognitive performance advantage remains largely unknown. The present human behavioral and imaging study compared gray matter volume in action video game experts and non-experts using structural magnetic resonance imaging and voxel-based morphometry analysis. The results revealed significantly larger gray matter volume in the right posterior parietal cortex in experts compared with non-experts. Furthermore, the larger gray matter volume in the right posterior parietal cortex significantly correlated with individual performance in a visual working memory task in experts. These results suggest that differences in brain structure may be linked to extensive video game play, leading to superior visuospatial cognitive performance in action video game experts.