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Background: Prognostic models incorporate multiple prognostic factors to estimate the likelihood of future events for individual patients based on their prognostic factor values. Evaluating these models crucially involves conducting studies to assess their predictive performance, like discrimination. Systematic reviews and meta-analyses of these validation studies play an essential role in selecting models for clinical practice., Methods: In this paper, we outline 3 thresholds to determine the target for certainty rating in the discrimination of prognostic models, as observed across a body of validation studies., Results and Conclusion: We propose 3 thresholds when rating the certainty of evidence about a prognostic model's discrimination. The first threshold amounts to rating certainty in the model's ability to classify better than random chance. The other 2 approaches involve setting thresholds informed by other mechanisms for classification: clinician intuition or an alternative prognostic model developed for the same disease area and outcome. The choice of threshold will vary based on the context. Instead of relying on arbitrary discrimination cut-offs, our approach positions the observed discrimination within an informed spectrum, potentially aiding decisions about a prognostic model's practical utility., Competing Interests: Declaration of competing interest All authors declare they did not receive support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years exist or do other relationships or activities that could appear to have influenced the submitted work. All authors are members of the GRADE working group., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Induction therapy (IT) utility in heart transplantation (HT) remains contested. Commissioned by a clinical-practice guidelines panel to evaluate the effectiveness and safety of IT in adult HT patients, we conducted this systematic review and network meta-analysis (NMA)., Methods: We searched for studies from January 2000 to October 2022, reporting on the use of any IT agent in adult HT patients. Based on patient-important outcomes, we performed frequentist NMAs separately for RCTs and observational studies with adjusted analyses, and assessed the certainty of evidence using the GRADE framework., Results: From 5156 publications identified, we included 7 RCTs and 12 observational studies, and report on two contemporarily-used IT agents-basiliximab and rATG. The RCTs provide only very low certainty evidence and was uninformative of the effect of the two agents versus no IT or one another. With low certainty in the evidence from observational studies, basiliximab may increase 30-day (OR 1.13; 95% CI 1.06-1.20) and 1-year (OR 1.11; 95% CI 1.02-1.22) mortality compared to no IT. With low certainty from observational studies, rATG may decrease 5-year cardiac allograft vasculopathy (OR .82; 95% CI .74-.90) compared to no IT, as well as 30-day (OR .85; 95% CI .80-.92), 1-year (OR .87; 95% CI .79-.96), and overall (HR .84; 95% CI .76-.93) mortality compared to basiliximab., Conclusion: With low and very low certainty in the synthetized evidence, these NMAs suggest possible superiority of rATG compared to basiliximab, but do not provide compelling evidence for the routine use of these agents in HT recipients., (© 2024 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Background: A recent study showed that the accuracy of heart failure (HF) cardiologists and family doctors to predict mortality in outpatients with HF proved suboptimal, performing less well than models., Objectives: The authors sought to evaluate patient and physician factors associated with physician accuracy., Methods: The authors included outpatients with HF from 11 HF clinics. Family doctors and HF cardiologists estimated patient 1-year mortality. They calculated predicted mortality using the Seattle HF Model and followed patients for 1 year to record mortality (or urgent heart transplant or ventricular assist device implant as mortality-equivalent events). Using multivariable logistic regression, the authors evaluated associations among physician experience and confidence in estimates, duration of patient-physician relationship, patient-physician sex concordance, patient race, and predicted risk, with concordant results between physician and model predictions., Results: Among 1,643 patients, 1-year event rate was 10% (95% CI: 8%-12%). One-half of the estimates showed discrepant results between model and physician predictions, mainly owing to physician risk overestimation. Discrepancies were more frequent with increasing patient risk from 38% in low-risk to ∼75% in high-risk patients. When making predictions on male patients, female HF cardiologists were 26% more likely to have discrepant predictions (OR: 0.74; 95% CI: 0.58-0.94). HF cardiologist estimates in Black patients were 33% more likely to be discrepant (OR: 0.67; 95% CI: 0.45-0.99). Low confidence in predictions was associated with discrepancy. Analyses restricted to high-confidence estimates showed inferior calibration to the model, with risk overestimation across risk groups., Conclusions: Discrepant physician and model predictions were more frequent in cases with perceived increased risk. Model predictions outperform physicians even when they are confident in their predictions. (Predicted Prognosis in Heart Failure [INTUITION]; NCT04009798)., Competing Interests: Funding Support and Author Disclosures This study received funding from a Grant-in-Aid offered by the Heart and Stroke Foundation of Canada. Dr Alba has received funding by the Heart and Stroke Foundation of Canada Clinician-Scientist Program. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Exercise training post-transplant has been shown to improve physical function and quality of life in solid organ transplant (SOT) recipients. Online resources in the form of websites and videos are commonly used to provide education and instruction on exercise and physical activity in SOT; however, the content and quality of these online resources has not been evaluated., Methods: The first 200 websites and videos identified on Google and YouTube using the English search term "exercise and physical activity in solid organ transplantation" were analyzed. Website and video content was evaluated based on 25 key components of exercise and physical activity in SOT as described in established exercise program recommendations. Website and video quality was determined using DISCERN, Global Quality Scale (GQS), and Patient Education Materials and Assessment Tool (PEMAT; threshold for which material is deemed understandable or actionable is >70%). Parametric and non-parametric tests were used to assess website and video characteristics, content, and quality metrics., Results: Forty-nine unique SOT websites ( n  = 15) and videos ( n  = 34) were identified, with the two most common categories being foundation/advocacy organizations and scientific resources. The average reading grade level of websites was 13 ± 3. Website and video content scores varied significantly (websites 11.3 ± 6.4; videos 8.4 ± 5.3). DISCERN total score and GQS score were low (median range for DISCERN 2.5-3.0; median for GQS 2.0 for both websites and videos, out of 5). PEMAT understandability and actionability scores were also low across websites and videos (mean range 57%-67% and 47%-65%, respectively). Foundation/advocacy websites had higher content and quality scores compared to scientific organizations and news/media articles., Conclusions: To our knowledge, this is the first comprehensive assessment of online content and quality of website and video resources on physical activity and exercise in adult SOT recipients. There were a limited number of online English patient-directed resources related to physical activity in SOT, most of which only partly captured items outlined in consensus exercise program recommendations and were of low quality and understandability and actionability. This work provides important insight to the English-speaking transplant community on the current state of online exercise health information and provides future direction for resource development., Competing Interests: The 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Da Silva, Momen, Al Kaabi, Masrur, Holdsworth, Prevost, Logan, Santa Mina, Mucsi, Bhat, Alba, Reid, Ferreira, Mathur, Janaudis-Ferreira, Wickerson and Rozenberg.)

Background: The use of induction therapy (IT) agents in the early post-heart transplant period remains controversial. The following recommendations aim to provide guidance on the use of IT agents, including Basiliximab and Thymoglobulin, as part of routine care in heart transplantation (HTx)., Methods: We recruited an international, multidisciplinary panel of 15 stakeholders, including patient partners, transplant cardiologists and surgeons, nurse practitioners, pharmacists, and methodologists. We commissioned a systematic review on benefits and harms of IT on patient-important outcomes, and another on patients' values and preferences to inform our recommendations. We used the GRADE framework to summarize our findings, rate certainty in the evidence, and develop recommendations. The panel considered the balance between benefits and harms, certainty in the evidence, and patient's values and preferences, to make recommendations for or against the routine post-operative use of Thymoglobulin or Basiliximab., Results: The panel made recommendations on three major clinical problems in HTx: (1) We suggest against the routine post-operative use of Basiliximab compared to no IT, (2) we suggest against the routine use of Thymoglobulin compared to no IT, and (3) for those patients for whom IT is deemed desirable, we suggest for the use of Thymoglobulin as compared to Basiliximab., Conclusion: This report highlights gaps in current knowledge and provides directions for clinical research in the future to better understand the clinical utility of IT agents in the early post heart transplant period, leading to improved management and care., (© 2024 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Understanding how visitors spend time in zoo exhibits is important as zoological facilities work to enhance visitor experience and conservation education outcomes. We explored a variety of factors we hypothesized would influence visitor stay times in two aviaries at Disney's Animal Kingdom®. Within these aviaries, visitors could utilize educational materials, listen to staff-led demonstrations, or talks, view animal training sessions, or speak directly with animal care or education staff. We observed visitors and recorded the opportunities they utilized in the exhibit. Visitors to either aviary who conversed with exhibit-specific staff stayed between 67% and 89% longer than visitors who did not. In addition, visitors who used a bird guide while in either aviary stayed between 59% and 82% longer than those who did not. Those who listened to an animal care talk or engaged with a staff-led demonstration stayed between 50% and 68% longer than those who did not have the option to participate in such activities. This study provides insight into how exhibit offerings can influence visitor behavior. Implementing strategies used in this study to increase visitors' time in an exhibit may enhance visitor experience and improve learning outcomes., (© 2023 Disney's Animals, Science and Environment. Zoo Biology published by Wiley Periodicals LLC.)

Aims: Mathematical models previously developed to predict outcomes in patients with heart failure (HF) generally have limited performance and have yet to integrate complex data derived from cardiopulmonary exercise testing (CPET), including breath-by-breath data. We aimed to develop and validate a time-to-event prediction model using a deep learning framework using the DeepSurv algorithm to predict outcomes of HF., Methods and Results: Inception cohort of 2490 adult patients with high-risk cardiac conditions or HF underwent CPET with breath-by-breath measurements. Potential predictive features included known clinical indicators, standard summary statistics from CPETs, and mathematical features extracted from the breath-by-breath time series of 13 measurements. The primary outcome was a composite of death, heart transplant, or mechanical circulatory support treated as a time-to-event outcomes. Predictive features ranked as most important included many of the features engineered from the breath-by-breath data in addition to traditional clinical risk factors. The prediction model showed excellent performance in predicting the composite outcome with an area under the curve of 0.93 in the training and 0.87 in the validation data sets. Both the predicted vs. actual freedom from the composite outcome and the calibration of the prediction model were excellent. Model performance remained stable in multiple subgroups of patients., Conclusion: Using a combined deep learning and survival algorithm, integrating breath-by-breath data from CPETs resulted in improved predictive accuracy for long-term (up to 10 years) outcomes in HF. DeepSurv opens the door for future prediction models that are both highly performing and can more fully use the large and complex quantity of data generated during the care of patients with HF., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Diaphragm atrophy can contribute to dyspnea in patients with heart failure (HF) with its link to central neurohormonal overactivation. HF medications that cross the blood-brain barrier could act centrally and improve respiratory function, potentially alleviating diaphragmatic atrophy. Therefore, we compared the benefit of central- vs peripheral-acting HF drugs on respiratory function, as assessed by a single cardiopulmonary exercise test (CPET) and outcomes in HF patients., Methods: A retrospective study was conducted of 624 ambulatory adult HF patients (80% male) with reduced left ventricular ejection fraction ≤ 40% and a complete CPET, followed at a single institution between 2001 and 2017. CPET parameters, and the outcomes all-cause death, a composite endpoint (all-cause death, need for left ventricular assist device, heart transplantation), and all-cause and/or HF hospitalizations, were compared in patients receiving central-acting (n = 550) vs peripheral-acting (n = 74) drugs., Results: Compared to patients who receive peripheral-acting drugs, patients who receive central-acting drugs had better respiratory function (peak breath-by breath oxygen uptake [VO 2 ], P  = 0.020; forced expiratory volume in 1 second [FEV1], P  = 0.007), and ventilatory efficiency (minute ventilation / carbon dioxide production [VE/VCO 2 ], P < 0.001; end-tidal carbon dioxide tension [PETCO 2 ], P  = 0.015; and trend for forced vital capacity [FVC], P  = 0.056). Many of the associations between the CPET parameters and drug type remained significant after multivariate adjustment. Moreover, patients receiving central-acting drugs had fewer composite events ( P  = 0.023), and HF hospitalizations ( P  = 0.044), although significance after multivariant correction was not achieved, despite the hazard ratio being 0.664 and 0.757, respectively., Conclusions: Central-acting drugs were associated with better respiratory function as measured by CPET parameters in HF patients. This could extend to clinically meaningful composite outcomes and hospitalizations but required more power to be definitive in linking to drug effect. Central-acting HF drugs show a role in mitigating diaphragm weakness., (© 2024 The Authors.)

Introduction: We evaluated the effect of relative changes in combined tacrolimus and sirolimus (drug) levels, following sirolimus initiation, on outcomes in ambulatory heart transplantation (HTx) recipients., Methods: We performed a retrospective analysis of HTx recipients who received tacrolimus, followed by sirolimus initiation, any time after HTx. We calculated the relative change in combined drug levels 1-month post-sirolimus initiation, relative to tacrolimus levels pre-initiation, and categorized patients into decreased (≥15% decrease), stable (<15% decrease to <15% increase), or increased (≥15% increase) groups. We compared, across the three groups, changes in post-initiation estimated glomerular filtration rate (eGFR) and left ventricular ejection fraction (LVEF) using one-way ANOVA and Šidák's post-hoc analysis, as well as the individual and composite outcomes of new donor specific antibodies (DSA), acute cellular rejection (ACR), and all-cause mortality using Fisher's exact test., Results: Amongst 99 HTx recipients included, the median age was 53 years, time to sirolimus initiation was 1.5 years post-HTx, and pre-sirolimus eGFR was 52 mL/min/1.73 m 2 . Nine patients had decreased, 15 stable, and 75 increased, relative combined drug levels. Relative change in eGFR was significantly higher in patients with decreased levels compared to patients with increased levels at 6 months post-initiation (P < .05), but this was not sustained at 12 months. There were no differences in LVEF change or in individual and composite risks for developing DSA, ACR, and all-cause mortality at 12 months across the groups., Conclusion: Post-sirolimus initiation, a relative decrease in combined drug levels, compared to increased levels, was associated with temporarily improved renal function., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Studies evaluating the effectiveness of care based on patients' risk of adverse outcomes (risk-guided care) use a variety of study designs. In this scoping review, using examples, we review characteristics of relevant studies and present key design features to optimize the trustworthiness of results., Study Design and Setting: We searched five online databases for studies evaluating the effect of risk-guided care among adults on clinical outcomes, process, or cost. Pairs of reviewers independently performed screening and data abstraction. We descriptively summarized the study design and characteristics., Results: Among 14,561 hits, we identified 116 eligible studies. Study designs included randomized controlled trials (RCTs), post hoc analysis of RCTs, and retrospective or prospective cohort studies. Challenges and sources of bias in the design included limited performance of predictive models, contamination, inadequacy to address the credibility of subgroup effects, absence of differences in care across risk strata, reporting only process measures as opposed to clinical outcomes, and failure to report benefits and harms., Conclusion: To assess the benefit of risk-guided care, RCTs provide the most trustworthy evidence. Observational studies offer an alternative but are hampered by confounding and other limitations. Reaching valid conclusions when testing risk-guided care requires addressing the challenges identified in our review., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Endomyocardiofibrosis (EMF) is a restrictive cardiomyopathy characterized by subendocardial fibrosis due to eosinophilic myocardial infiltration. EMF may commonly present with heart failure (HF) or atrial fibrillation (AF). Immunosuppression can be effective in early stages, but not in the chronic phase. Our objective was to describe the characteristics of EMF patients in the Americas. This registry is a retrospective multicenter cross-sectional study including patients ≥18 years-old with EMF diagnosed by imaging methods, according to the Mocumbi criteria. Clinical, biochemical, and imaging variables were analyzed. On the 54 patients included, 28 (52%) were male with an age of 47 years. The etiology was idiopathic in 47 (87%) patients, familial in 4 (7%), and secondary to chemotherapy in 2 (3.5%). We detected a history of HF in 41 patients (76%), AF in 19 (35%), and ischemic stroke in 8 (15%). The diagnosis was made by echocardiography in all patients, and 38% had Cardiac Resonance or Computed Tomography. Thirty-five patients (65%) presented a left ventricular ejection fraction ≥50%, 11 (21%) severe mitral regurgitation, and 18 (33%) severe tricuspid regurgitation. In 17 patients (32%) the diagnosis was confirmed by endomyocardial biopsy. Among medical therapy, 72% received beta-blockers, 63% vasodilators, 65% mineralocorticoid antagonists, 7.4% SGLT2 inhibitors, and 11% corticosteroids. Subendocardial resection was performed in 9 (16%) patients and mitral valve replacement in 11 (20%) patients. In conclusion, EMF patients had a high prevalence of HF, AF, and embolic events. The diagnosis was frequently made in an advanced stage when HF management and surgery were the only effective treatments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Limited data integrating waitlist and postheart transplant (HT) mortality have evaluated outcomes of left ventricular assist device (LVAD)-bridged strategy vs no LVAD according to patient characteristics. We evaluated waitlist and post-HT mortality in LVAD-bridged vs nonbridged patients based on body mass index (BMI)., Methods: We included linked adults listed for HT in Organ Procurement and Transplant Network/United Network for Organ Sharing and patients receiving durable LVAD as bridge to HT or candidacy in Society of Thoracic Surgeons/Interagency Mechanical Circulatory Support databases (2010-2019). Using BMI at listing or LVAD implant, we categorized patients as underweight (<18.5 kg/m 2 ), normal weight (18.5-24.99 kg/m 2 ), overweight (25-29.99 kg/m 2 ), and obese (≥30 kg/m 2 ). Kaplan-Meier analysis and multivariable Cox proportional hazards models informed the effect of LVAD-bridged and nonbridged strategy by BMI on waitlist, post-HT, and overall mortality (including waitlist and post-HT mortality)., Results: Among 11,216 LVAD-bridged and 17,122 nonbridged candidates, bridged candidates were more frequently obese (37.3% vs 28.6%) (p < 0.001). Multivariable analysis indicated increased waitlist mortality in LVAD-bridged vs nonbridged with overweight (Hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.02-1.36) or obesity (HR 1.35, 95%CI 1.17-1.56) in comparison to normal weight candidates (HR 1.02, 95%CI 0.88-1.19) (p-interaction < 0.001). Post-transplant mortality was not statistically different in LVAD-bridged vs nonbridged patients across BMI categories (p-interaction = 0.26). There was a nonsignificant graded increase in overall mortality in LVAD-bridged with overweight (HR 1.53, 95%CI 1.39-1.68) or obesity (HR 1.61, 95%CI 1.46-1.78) compared to nonbridged patients (p-interaction = 0.13)., Conclusions: LVAD-bridged candidates with obesity had higher waitlist mortality compared to nonbridged candidates with obesity. Post-transplant mortality was similar in LVAD-bridged and nonbridged patients, but obesity remained associated with increased mortality in both groups. This study may aid clinicians and advanced heart failure patients with obesity in decision-making., (Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: COVID-19 acute respiratory distress syndrome (ARDS) is often managed with mechanical ventilation (MV), requiring sedation and paralysis, with associated risk of complications. There is limited evidence on the use of high flow nasal cannula (HFNC). We hypothesized that management of COVID-19 ARDS without MV is feasible., Methods: Included were all adult patients diagnosed with COVID-19 ARDS, with PaO2/FiO2 ratio <100 at admission, and whose management was initially performed without MV. We evaluated need for intubation during ICU stay, mortality and hospital/ICU length of stay (LOS)., Results: Out of 118 patients, 41 were managed only with HFNC from hospital admission (and at least during first 24 hours in ICU) and had a PaO2/FiO2 ratio <100 (72.9±13.0). Twenty-nine out of 41 patients never required MV: 24 of them survived and were discharged home. Their median ICU LOS was 11 (7-17) days, and their hospital LOS was 29 (18-45) days. We identified PaO2/FiO2 ratio at ICU admission as the only significant predictor for need for MV during ICU stay. We also identified age, length of non-invasive respiratory support before ICU admission, mean value of PaO2/FiO2 ratio during first half and whole ICU stay as predictors of mortality., Conclusions: It is safe to monitor in ICU and use HFNC in patients affected by COVID-19 ARDS who initially present data suggesting an early need for intubation. The 41 patients admitted with a PaO2/FiO2 ratio <100 and initially treated only with HFNC show a 22% mortality that is in the lower range of what is reported in recent literature.

Background: Many studies have demonstrated that physicians often err in estimating patient prognosis. No studies have directly compared physician to model predictive performance in heart failure (HF). We aimed to compare the accuracy of physician versus model predictions of 1-year mortality., Methods: This multicenter prospective cohort study on 11 HF clinics in 5 provinces in Canada included consecutive consented outpatients with HF with reduced left ventricular ejection fraction (<40%). By collecting clinical data, we calculated predicted 1-year mortality using the Seattle HF Model (SHFM), the Meta-Analysis Global Group in Chronic HF score, and the HF Meta-Score. HF cardiologists and family doctors, blinded to model predictions, estimated patient 1-year mortality. During 1-year follow-up, we recorded the composite end point of mortality, urgent ventricular assist device implant, or heart transplant. We compared physicians and model discrimination (C statistic), calibration (observed versus predicted event rate), and risk reclassification., Results: The study included 1643 patients with ambulatory HF with a mean age of 65 years, 24% female, and mean left ventricular ejection fraction of 28%. Over 1-year follow-up, 9% had an event. The SHFM had the best discrimination (SHFM C statistic 0.76; HF Meta-Score 0.73; Meta-Analysis Global Group in Chronic Heart Failure 0.70) and calibration. Physicians' discrimination differed little (0.75 for HF cardiologists and 0.73 for family doctors) but both physician groups substantially overestimated risk by >10% in both low- and high-risk patients (poor calibration). In risk reclassification analysis, among patients without events, the SHFM better classified 51% in comparison to HF cardiologists and 43% in comparison to family doctors. In patients with events, the SHFM erroneously assigned lower risk to 44% in comparison to HF cardiologists and 34% in comparison to family doctors., Conclusions: Family doctors and HF cardiologists showed adequate risk discrimination, with however substantial overestimation of absolute risk. Predictive models showed higher accuracy. Incorporating models in family and HF cardiology practices may improve patient care and resource use in HF with reduced left ventricular ejection fraction., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT04009798., Competing Interests: Disclosures None.

Objectives: To update previous Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance by addressing inconsistencies and interpreting subgroup analyses., Study Design and Setting: Using an iterative process, we consulted with members of the GRADE working group through multiple rounds of written feedback and discussions at GRADE working group meetings., Results: The guidance complements previous guidance with clarification in two areas: (1) assessing inconsistency and (2) assessing the credibility of possible effect modifiers that might explain inconsistency. Specifically, the guidance clarifies that inconsistency refers to variability in results, not in study characteristics; that inconsistency assessment for binary outcomes requires consideration of both relative and absolute effects; how to decide between narrower and broader questions in systematic reviews and guidelines; that, with the same evidence, ratings of inconsistency may differ depending on the target of certainty rating; and how GRADE inconsistency ratings relate to a statistical measure of inconsistency I 2 depending on the context in which one views results. The second part of the guidance illustrates, based on a worked example, the use of the instrument to assess the credibility of effect modification analyses. The guidance explains the stepwise process of moving from a subgroup analysis to assessing the credibility of effect modification and, if found credible, to subgroup-specific effect estimates and GRADE certainty ratings., Conclusion: This updated guidance addresses specific conceptual and practical issues that systematic review authors frequently face when considering the degree of inconsistency in estimates of treatment effects across studies., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The incidence of hospitalizations for cardiovascular events has been associated with specific weather conditions and air pollution. A comprehensive model including the interactions between various environmental factors remains to be developed., Objectives: The purpose of this study was to develop a comprehensive model of the association between weather patterns and the incidence of cardiovascular events and use this model to forecast near-term spatiotemporal risk., Methods: We present a spatiotemporal analysis of the association between atmospheric data and the incidence rate of hospital admissions related to heart failure (922,132 episodes), myocardial infarction (521,988 episodes), and ischemic stroke (263,529 episodes) in ∼24 million people in Canada between 2007 and 2017. Our hierarchical Bayesian model captured the spatiotemporal distribution of hospitalizations and identified weather and air pollution-related factors that could partially explain fluctuations in incidence., Results: Models that included weather and air pollution variables outperformed models without those covariates for most event types. Our results suggest that environmental factors may interact in complex ways on human physiology. The impact of environmental factors was magnified with increasing age. The weather and air pollution variables included in our models were predictive of the future incidence of heart failure, myocardial infarction, and ischemic strokes., Conclusions: The increasing importance of environmental factors on cardiovascular events with increasing age raises the need for the development of educational materials for older patients to recognize environmental conditions where exacerbations are more likely. This model could be the basis of a forecasting system used for local, short-term clinical resource planning based on the anticipated incidence of events., Competing Interests: This study was funded by the Ted Rogers Centre for Heart Research, 10.13039/100009663University Health Network, Toronto, Ontario, Canada. The study funder had no involvement in study design, data analysis, or in the decision to publish the results of this study. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Though lion-tailed macaques are managed ex situ as an assurance population, little information is available on the relationship between behavior and reproductive physiology to ensure successful management and evaluate welfare. To facilitate social and reproductive management in a group of one male and three female lion-tailed macaques at Disney's Animal Kingdom®, we observed behaviors associated with dominance and reproduction, rated genital swellings, recorded menses, tracked ovarian cycles as determined by measurement of fecal immunoreactive progesterone (P4) and estradiol (E2), and monitored fecal cortisol (CORT). We analyzed the dominance hierarchy of females, compared hormone patterns of ovarian cycles with genital swellings and copulations relative to menses, and tested for correlations between hormones and behavior. The strength of the dominance hierarchy indicated moderate linearity, but relaxed after the dominant female received anxiolytic medications to reduce intraspecific aggression. Fecal P4 and E2 patterns revealed ovarian cycle lengths averaging 29.7 ± 0.8 days. The timing of single-day E2 peaks varied between and within females' cycles. However, on average, E2 peaks occurred 6-10 days after the first day of menses, with maximum genital swellings and copulations occurring slightly thereafter in uncontracepted females. Female-to-female aggression and sexual behaviors with the male were related to ovarian cycle phase, but correlations between behaviors and hormones varied between females. Initiated aggression was positively correlated with E2 in the dominant and mid-ranked females, while aggression received was positively correlated with P4 or negatively correlated with E2 in the mid-ranked and subordinate females. In one uncontracepted female, sexual behaviors with the male were negatively correlated to P4. CORT was positively correlated to aggression in the dominant and mid-ranked females and negatively correlated to grooming in the subordinate female. Results indicate observations of visual and behavioral cues can be used to track ovarian cycles and evaluate social dynamics and welfare in zoo-housed lion-tailed macaques., (© 2022 Wiley Periodicals LLC.)

Introduction: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a prevailing option for the management of severe early graft dysfunction. This systematic review and individual patient data (IPD) meta-analysis aims to evaluate (1) mortality, (2) rates of major complications, (3) prognostic factors, and (4) the effect of different VA-ECMO strategies on outcomes in adult heart transplant (HT) recipients supported with VA-ECMO., Methods and Results: We conducted a systematic search and included studies of adults (≥18 years) who received VA-ECMO during their index hospitalization after HT and reported on mortality at any timepoint. We pooled data using random effects models. To identify prognostic factors, we analysed IPD using mixed effects logistic regression. We assessed the certainty in the evidence using the GRADE framework. We included 49 observational studies of 1477 patients who received VA-ECMO after HT, of which 15 studies provided IPD for 448 patients. There were no differences in mortality estimates between IPD and non-IPD studies. The short-term (30-day/in-hospital) mortality estimate was 33% (moderate certainty, 95% confidence interval [CI] 28%-39%) and 1-year mortality estimate 50% (moderate certainty, 95% CI 43%-57%). Recipient age (odds ratio 1.02, 95% CI 1.01-1.04) and prior sternotomy (OR 1.57, 95% CI 0.99-2.49) are associated with increased short-term mortality. There is low certainty evidence that early intraoperative cannulation and peripheral cannulation reduce the risk of short-term death., Conclusions: One-third of patients who receive VA-ECMO for early graft dysfunction do not survive 30 days or to hospital discharge, and one-half do not survive to 1 year after HT. Improving outcomes will require ongoing research focused on optimizing VA-ECMO strategies and care in the first year after HT., Competing Interests: Conflict of Interest The authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Fulminant myocarditis (FM) may lead to cardiogenic shock requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Results of effectiveness studies of VA-ECMO have been contradictory. We evaluated the aggregate short-term mortality after VA-ECMO and predictive factors in patients with FM. We systematically searched in electronic databases (February 2022) to identify studies evaluating short-term mortality (defined as mortality at 30 days or in-hospital) after VA-ECMO support for FM. We included studies with 5 or more patients published after 2009. We assessed the quality of the evidence using the QUIPS and GRADE tools. Mortality was pooled using random effect models. We performed meta-regression to explore heterogeneity based on a priori defined factors. We included 54 observational studies encompassing 2388 FM patients supported with VA-ECMO. Median age was 41 years (25th to 75th percentile 37-47), and 50% were female. The pooled short-term mortality was 35% (95% CI 29-40%, I 2  = 69%; moderate certainty). By meta-regression, studies with younger populations showed lower mortality. Female sex, receiving a biopsy, cardiac arrest, left ventricular unloading, and earlier recruitment time frame, did not explain heterogeneity. These results remained consistent regardless of continent and the risk of bias category. In individual studies, low pH value, high lactate, absence of functional cardiac recovery on ECMO, increased burden of malignant arrhythmia, high peak coronary markers, and IVIG use were identified as independent predictors of mortality. When conventional therapies have failed, especially in younger patients, cardiopulmonary support with VA-ECMO should be considered in the treatment of severe FM., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Early right heart failure (RHF) remains a major source of morbidity and mortality after left ventricular assist device (LVAD) implantation, yet efforts to predict early RHF have proven only modestly successful. Pharmacologic unloading of the left ventricle may be a risk stratification approach allowing for assessment of right ventricular and hemodynamic reserve., Methods: We performed a multicenter, retrospective analysis of patients who had undergone continuous-flow LVAD implantation from October 2011 to April 2020. Only those who underwent vasodilator testing with nitroprusside during their preimplant right heart catheterization were included (n = 70). Multivariable logistic regression was used to determine independent predictors of early RHF as defined by Mechanical Circulatory Support-Academic Research Consortium., Results: Twenty-seven patients experienced post-LVAD early RHF (39%). Baseline clinical characteristics were similar between patients with and without RHF. Patients without RHF, however, achieved higher peak stroke volume index (SVI) (30.1 ± 8.8 vs 21.7 ± 7.4 mL/m 2 ; p < 0.001; AUC: 0.78; optimal cut-point: 22.1 mL/m 2 ) during nitroprusside administration. Multivariable analysis revealed that peak SVI was significantly associated with early RHF, demonstrating a 16% increase in risk of early RHF per 1 ml/m 2 decrease in SVI. A follow up cohort of 10 consecutive patients from July 2020 to October 2021 resulted in all patients being categorized appropriately in regards to early RHF versus no RHF according to peak SVI., Conclusion: Peak SVI with nitroprusside administration was independently associated with post-LVAD early RHF while resting hemodynamics were not. Vasodilator testing may prove to be a strong risk stratification tool when assessing LVAD candidacy though additional prospective validation is needed., Competing Interests: Financial disclosures No grants, contracts, or other financial support was received for this manuscript., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Coronavirus disease 2019 (COVID-19) has resulted in a reduction in patients seeking timely consultation for illnesses that are not related to COVID-19. Previously, we reported a decline in the number of emergency department (ED) visits and hospitalizations for acute decompensated heart failure (ADHF) during the 2020 COVID-19 pandemic vs that in 2019. We aimed to determine the consequences of these early trends on ADHF-patient morbidity and mortality., Methods: We compared consecutive patients presenting with ADHF to 3 academic medical centres in Toronto, Canada from March 1-September 28, 2020, vs those from the same time period in 2019. We used multivariate logistic regression models to evaluate whether the odds of hospitalization after presenting to the ED, recurrent ED visits or readmission within 30 days, and in-hospital all-cause mortality differed by timeframe., Results: We observed that, during the COVID-19 pandemic, a lower total number of patients presented to the hospital with ADHF, vs that in 2019. Despite this difference, the probability of being admitted to the hospital did not differ for patients seen in 2020 vs 2019. Among ADHF patients admitted to the hospital, however, we observed a significantly higher proportion being admitted to the intensive care unit, and a relative 66% increase in in-hospital mortality during the 2020 COVID-19 era, compared to that in 2019., Conclusions: Our findings suggest that improved messaging may be needed for patients living with chronic health conditions, including HF, during the pandemic, to educate and encourage them to present to hospital services when in need., (© 2022 The Authors.)

Introduction: Predicted heart mass (PHM) was neither derived nor evaluated in an obese population. Our objective was to evaluate size mismatch using actual body weight or ideal body weight (IBW)-adjusted PHM on mortality and risk assessment., Methods: We conducted a retrospective cohort study of adult recipients with BMI ≥30 kg/m 2 or recipients of donors with BMI≥30 kg/m 2 from the ISHLT registry. We used multivariable Cox proportional hazard models to evaluate 30-day and 1-year mortality. The two models were compared using net reclassification index., Results: 10,817 HT recipients, age 55 (IQR 46-62) years, 23% female, BMI 31 kg/m 2 (IQR 28-33) were included. Donors were age 34 (IQR 24-44) years, 31% female, and BMI 31 kg/m 2 (IQR 26-34). There was a significant nonlinear association between mortality and actual PHM but not IBW-adjusted PHM. Undersizing using actual PHM was associated with higher 30-day and 1-year mortality (p < .01), not seen with IBW-adjusted PHM. Actual PHM better risk classified .6% (95% CI .3-.8) patients compared to IBW-adjusted PHM., Conclusion: Actual PHM can be used for size matching when assessing mortality risk in obese recipients or recipients of obese donors. There is no advantage to re-calculating PHM using IBW to define candidate risk at the time of organ allocation., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-related disease (COVID-19) is an infectious disease characterized by systemic inflammation, which might enhance baseline thrombotic risk, especially in hospitalized patients. Little is, however, known about predictors of thrombotic complications in patients with COVID-19., Methods: We prospectively followed up 180 hospitalized COVID-19 patients. Demographics, clinical and laboratory features at presentation and past medical history were tested as predictors of the first thrombotic complication through multivariate Cox regression analysis and a categorical score generated based on the results., Results: Sixty-four thromboses were recorded in 54 patients, of whom seven with thrombosis on admission and 47 with thrombosis during hospitalization. Patients with thrombosis were mainly Caucasian and diabetic, had marked baseline signs of inflammation and organ damage, lower PaO2/FiO2 ratio, higher D-dimer levels and history of major hemorrhages. The latter three variables were independently associated to thrombotic complications and concurred to a 0-5 score, which accounted for 80% of the total sample variability. Patients with three or more points of the newly generated score were at higher risk for thrombotic complications (HR=4.9, P<0.001). Patients with thrombotic complications were more likely to be admitted to intensive care and/or to die (HR=1.9, P=0.036). Five of 180 patients were diagnosed with disseminated intravascular coagulation and three of them died. Eleven minor and no major bleeding events were observed., Conclusions: Patients with COVID-19 are at increased risk for thrombosis and might be stratified on admission based on lower Pao2/FiO2 ratio, higher D-dimer levels and history of major hemorrhages.

The impact of right ventricular (RV) dysfunction on long-term post-HTx outcomes remains uncertain. We assessed the impact of serial measurements of Tricuspid Annular Plane Systolic Excursion (TAPSE) on post-HTx mortality and morbidity. This two-center retrospective cohort study included consecutive adult HTx recipients (2000-2017). We used multivariable extended hazard regression models to evaluate the association between TAPSE and left ventricular ejection fraction (LVEF), entered as time-dependent variables, and all-cause mortality, cardiac allograft vasculopathy (CAV), acute cellular rejection (ACR), and chronic kidney disease (CKD). TAPSE was modelled using cubic splines. We included 485 HTx recipients (9461 TAPSE measurements), median (25th- 75th percentile) 19 (10-27) mm; median age was 52 (41-59) years, and 71.3% were male. During a follow-up of 6.7 (3.0-10.8) years, 92 patients died, 225 had ACR >2R, 234 CAV, and 91 CKD. By multivariable analysis, for each 1-mm decrease in patients with a TAPSE value <15mm, mortality increased by 22% (P<.001). For the average HTx recipient with a TAPSE of 15mm, 10mm, and 6mm, 1-year mortality was 3%, 7%, and 17%, and 5-year mortality was 8%, 20%, and 43%, respectively. Reduced TAPSE was significantly associated with increased CAV but notACR and CKD. A decrease in TAPSE below 15mm represents clinically significant graft dysfunction, warranting close monitoring., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Mortality for patients on veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for cardiogenic shock (CS) complicating acute myocardial infarction (AMI) remains high. This meta-analysis aims to identify factors that predict higher risk of mortality after VA-ECMO for AMI., Methods: We meta-analyzed mortality after VA-ECMO for CS complicating AMI and the effect of factors from systematically selected studies published after 2009., Results: 72 studies (10,276 patients) were included with a pooled mortality estimate of 58 %. With high confidence in estimates, failure to achieve TIMI III flow and left main culprit were identified as factors associated with higher mortality. With low-moderate confidence, older age, high BMI, renal dysfunction, increasing lactate, prothrombin activity < 50%, VA-ECMO implantation after revascularization, and non-shockable ventricular arrythmias were identified as factors associated with mortality., Conclusion: These results provide clinicians with a framework for selecting patients for VA-ECMO for CS complicating AMI., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Exploring the association between frailty and mortality in a cohort of patients with COVID-19 respiratory insufficiency treated with continuous positive airway pressure., Methods: Frailty was measured using a Frailty Index (FI) created by using the baseline assessment data on comorbidities and body mass index and baseline blood test results (including pH, lactate dehydrogenase, renal and liver function, inflammatory indexes and anemia). FI > 0.25 identified frail individuals., Results: Among the 159 included individuals (81% men, median age of 68) frailty was detected in 69% of the patients (median FI score 0.3 ± 0.08). Frailty was associated to an increased mortality (adjusted HR 1.99, 95% CI 1.02-3.88, p = 0.04)., Conclusions: Frailty is highly prevalent among patients with COVID-19, predicts poorer outcomes independently of age. A personalization of care balancing the risk and benefit of treatments (especially the invasive ones) in such complex patients is pivotal., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Extracorporeal cardiopulmonary resuscitation (eCPR) can improve survival in selected patients with cardiac arrest (CA). In this meta-analysis, we evaluated factors associated with short-term survival and favorable neurologic outcome (FNO) post-eCPR. In June 2019, we systematically searched electronic databases for studies reporting on survival and predictors associated with short-term survival or FNO post-eCPR using multivariable analysis. We meta-analyzed outcomes and predictors using the inverse variance method with a random-effects model. We identified 92 studies with 13 factors amenable to meta-analysis. Pooled short-term survival and FNO were 25% and 16% respectively. Lower lactate, return of spontaneous circulation, shockable rhythm, shorter CPR duration, baseline pH, shorter low-flow time, and history of hypertension were significantly associated with short-term survival. In addition, shockable rhythm, lower lactate, and use of targeted temperature management were associated with FNO. The identified factors associated with short-term survival and FNO post-eCPR could guide prognosis prediction at the time of CA., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Risk models, informing optimal long-term medical management, seldom use natriuretic peptides (NP) in ascertaining the absolute risk of outcomes for HF patients. Individual studies evaluating the prognostic value of NPs in HF patients have reported varying effects, arriving at best estimates requires a systematic review. We systematically summarized the best evidence regarding the prognostic value of brain natriuretic peptide (BNP) and NT-proBNP in predicting mortality and hospitalizations in ambulatory heart failure (HF) patients. We searched bibliographic databases from 2005 to 2018 and included studies evaluating the association of BNP or NT-proBNP with mortality or hospitalization using multivariable Cox proportional hazard models. We pooled hazard ratios using random-effect models, explored heterogeneity using pre-specified subgroup analyses, and evaluated the certainty of evidence using the Grading of Recommendations and Development Evaluation framework. We identified 67 eligible studies reporting on 76,178 ambulatory HF patients with a median BNP of 407 pg/mL (261-574 pg/mL). Moderate to high-quality evidence showed that a 100-pg/mL increase in BNP was associated with a 14% increased hazard of mortality (HR 1.14, 95% CI 1.06-1.22); a 1-log-unit increase was associated with a 51% increased hazard of mortality (HR 1.51, 95% CI 1.41-1.61) and 48% increased hazard of mortality or hospitalization (HR 1.48, 95% CI 1.29-1.69). With moderate to high certainty, we observed a 14% independent relative increase in mortality, translating to a clinically meaningful increase in absolute risk even for low-risk patients. The observed associations may help in developing more accurate risk models that incorporate NPs and accurately prognosticate HF patients., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Previous primary studies have explored the association between blood pressure (BP) and mortality in ambulatory heart failure (HF) patients reporting varying and contrasting associations. The aim is to determine the pooled BP prognostic value and explore potential reasons for between-study inconsistency. We searched Medline, Cochrane, EMBASE and CINAHL from January 2005 to October 2018 for studies with ≥ 50 events (mortality and/or hospitalization) and included BP in a multivariable model in ambulatory HF patients. We pooled hazard ratios (random effects model) for systolic BP (SBP) or diastolic BP (DBP) effect on mortality and/or hospitalization risk. We used a priori defined sub-group analyses to explore heterogeneity and GRADE approach to assess the certainty of the evidence. Seventy-one eligible articles (239,467 screened) at low to moderate risk of bias included 235,752 participants. Higher SBP was associated with reduced all-cause mortality (HR 0.93, 95%CI 0.91-0.95, I 2  = 87.13%, moderate certainty), all-cause hospitalization events (HR 0.91, 95%CI 0.88-0.93, I 2  = 44.4%, high certainty) and their composite endpoint (HR 0.93 per 10 mmHg, 95%CI 0.91-0.94, I 2  = 86.3%, high certainty). DBP did not demonstrate a statistically significant effect for all outcomes. The association strength was significantly weaker in studies following patients with either LVEF > 40%, higher average SBP (> 130 mmHg), increasing age and diabetes. All other a priori subgroup hypotheses did not explain between study differences. Higher ambulatory SBP is associated with reduced risk of all-cause mortality and hospitalization. Patients with lower BP and reduced LVEF are in a high-risk group of developing adverse events with moderate certainty of evidence., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Prognostic models combine several prognostic factors to provide an estimate of the likelihood (or risk) of future events in individual patients, conditional on their prognostic factor values. A fundamental part of evaluating prognostic models is undertaking studies to determine whether their predictive performance, such as calibration and discrimination, is reproduced across settings. Systematic reviews and meta-analyses of studies evaluating prognostic models' performance are a necessary step for selection of models for clinical practice and for testing the underlying assumption that their use will improve outcomes, including patient's reassurance and optimal future planning., Methods: In this paper, we highlight key concepts in evaluating the certainty of evidence regarding the calibration of prognostic models., Results and Conclusion: Four concepts are key to evaluating the certainty of evidence on prognostic models' performance regarding calibration. The first concept is that the inference regarding calibration may take one of two forms: deciding whether one is rating certainty that a model's performance is satisfactory or, instead, unsatisfactory, in either case defining the threshold for satisfactory (or unsatisfactory) model performance. Second, inconsistency is the critical GRADE domain to deciding whether we are rating certainty in the model performance being satisfactory or unsatisfactory. Third, depending on whether one is rating certainty in satisfactory or unsatisfactory performance, different patterns of inconsistency of results across studies will inform ratings of certainty of evidence. Fourth, exploring the distribution of point estimates of observed to expected ratio across individual studies, and its determinants, will bear on the need for and direction of future research., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To date, long-term graft dysfunction, an important cause of death after heart transplantation, has been defined as a left ventricular ejection fraction (LVEF) of ≤40% or right atrial pressure (RAP) of ≥15 mm Hg. Empirical associations between measures of cardiac function and mortality post-transplant remain, however, unestablished., Methods: We conducted a retrospective two-centre cohort study of consecutive adults who underwent heart transplant between 2002 and 2017. We evaluated the association between LVEF and RAP and mortality, including rejection and cardiac allograft vasculopathy as additional time-dependent covariates using Cox proportional hazard models. We applied restricted cubic splines to both LVEF and RAP., Results: Of 590 eligible heart transplant recipients, of whom 72% were male with a mean age of 49 years, 410 received their transplant at Toronto General Hospital and 180 at Rigshospitalet. We observed a 5% absolute risk increase for 1-year mortality, from 11% to 16%, when the LVEF dropped to 53% (HR 1.71 for LVEF of 53% compared with 60%, 95% CI 1.36 to 2.14) or when the RAP increased to 12 mm Hg (HR 1.49 for RAP of 12 mm Hg compared with 5 mm Hg, 95% CI 1.04 to 2.13)., Conclusion: In this study, we observed that small changes in graft function at any time post-transplant are associated with an increased mortality. Our results suggest that the current definition of graft dysfunction may underestimate patient risk of adverse outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

The trade and private ownership of non-domesticated animals has detrimental effects on individual animals and their wild populations. Therefore, there is a need to understand the conditions that motivate and dissuade interest in non-domesticated pet ownership. Past research has demonstrated that the way in which non-domesticated animals are portrayed in images influences the public's perception that they are suitable as pets. We conducted an online survey of people residing in the United States to investigate how viewing images that could be realistically captured in the zoo and broader tourism industries impact the degree to which people report interest in having that animal as a pet. We focused on two species, reticulated pythons (Malayopython reticulatus) and two-toed sloths (Choloepus hoffmanni), and presented each species in six different visual contexts. After viewing an image, respondents reported interest in pet ownership on a four-point Likert scale. Each species was studied separately in a between-subjects design and results were analyzed using ordinal logistic regression models. Thirty-nine percent of respondents reported interest in sloth pet ownership, and 21% reported interest in python pet ownership. However, contrary to our hypotheses, we found that viewing these species in different visual contexts did not significantly affect survey respondents' reported interest in having either species as a pet. Generation was a significant predictor of interest in both sloth and python pet ownership, with younger generations reporting more interest in having these species as pets. Male respondents reported more interest in python pet ownership, whereas there were no significant differences between genders regarding interest in sloth ownership. We consider how modern media exposure to animals in unnatural contexts may relate to the generational effect and discuss priorities for future research to better understand the development of individual interests in non-domesticated pet ownership., Competing Interests: The authors have declared that no competing interests exist.

Here, we evaluated if visual barriers could reduce intraspecific agonism in an all-male group of Nile crocodiles ( Crocodylus niloticus ) living in a zoo. Crocodiles were monitored for nearly 100 h, and four "hotspots" of aggression within their exhibit were identified. Within these four locations, visual barriers were placed at the surface of the water with the goal of reducing agonism by targeting sight lines associated with their species-typical minimum exposure posture, where crocodiles submerge their body but maintain facial sensory organs above the water line. Crocodile behavior was then monitored for 226 h, evaluating both short- and long-term effects of the visual barriers. In both observation periods, intraspecific agonism was unaffected by visual barriers. However, crocodiles were more likely to be on land and closer together, after the barriers were installed, showing the barriers affected nonagonistic behaviors. Monitoring of such unintended effects is significant to ensure no welfare concerns are created in any exhibit or husbandry modification attempt. Additionally, time of day and temperature were significant predictors of behavior, highlighting the importance of such factors in the analysis of reptilian behavior. While ineffective at reducing agonism, this is the first published study evaluating exhibit design and behavior of crocodilians in zoos and aquariums. The methodologies and findings here should provide useful information for future behavioral and welfare studies of this understudied taxa.

Background and Aim of Study: There exists controversy regarding the impact of infection in patients with a left ventricular assist device (LVAD) on post-heart transplant outcomes. This study evaluated the association between infections during LVAD support and the risk of early and late post-heart transplant infection, rejection, and mortality in transplant recipients bridged with an LVAD., Methods: This is a single-center retrospective observational cohort study of consecutive adults supported with a continuous flow LVAD undergoing heart transplant between 2006 and 2019 at the Toronto General Hospital. The grade of LVAD infection was classified as per International Society of Heart and Lung Transplantation guidelines. Patients were divided into three groups: (1) patients with LVAD-specific infection confirmed with positive cultures requiring long-term antibiotic use until the time of transplant; (2) patients with any type of infection in whom antibiotics were stopped at least 1 month before transplant; (3) patients without any infections between LVAD implant and transplant. Logistic regression and Cox proportional hazard models were used to evaluate early- and late-post transplant outcomes, respectively., Results: We included 75 LVAD recipients: 16 (21%) patients had a chronic LVAD-related infection on suppressive antibiotics, 30 (40%) had a resolved infection, and 29 (39%) had no infections. During a median post-transplant follow-up time of 4 (2 to 7) years, 65 (87%) patients developed infections, 43 (64%) rejections, and 17 (23%) deaths. Both short- and long-term risks of infection, rejection, and mortality did not differ significantly among the groups., Conclusion: LVAD patients with infections did not have a significantly higher risk of infection, rejection, or mortality at any time point after transplant., (© 2021 Wiley Periodicals LLC.)

Background: In Europe, Italy and Lombardy, in autumn 2020, there was a steep increase in reported cases due to the second epidemic wave of SARS-Cov-2 infection. We aimed to evaluate the appropriateness of COVID-19 patients' admissions to the ED of the San Raffaele Hospital., Methods: We compared data between the inter-wave period (IWP, from 1st to 30th September) and the second wave period (WP, 1st October to 15th November) focusing on the ED presentation, discharge priority colour code and outcomes., Results: Out of 977 admissions with a SARS-Cov-2 positive swab, 6% were in the IWP and 94% in the WP. Red, yellow and white code increased (these latter from 1.8% to 5.4%) as well as self-presented in yellow and white code. Discharges home increased from 1.8% to 5.4%, while hospitalizations decreased from 63% to 51%., Discussion: We found a rise in white codes (among self-presented patients), indicating inappropriateness of admissions. The increase in discharges suggests that several patients did not require hospitalization., Conclusions: The pandemic brought out the fundamental role of primary care to manage patients with low-intensity needs. The important increase in ED admissions of COVID-19 patients caused a reduction of NO-COVID-19 patients, with possible inadequate treatment.

Cardiac sarcoidosis (CS) with clinical manifestation occurs in about 5-8% of patients with sarcoidosis. CS may be clinically suspected by the presence of ventricular arrhythmia, conduction abnormalities, and heart failure (HF). However, 20%-25% of patients may present with silent CS, having asymptomatic cardiac involvement. The diagnosis of CS is based on findings from nuclear studies, cardiac magnetic resonance, and extra-cardiac tissue biopsy. Due to the inflammatory nature of the disease, immunosuppressive medications are a cornerstone of therapy. The treatment also includes recommended HF medical therapies. Since CS patients are at risk of sudden cardiac death resulting from progression of cardiac dysfunction or the presence of scar originating from fatal arrhythmias, implantable cardioverter-defibrillators should be considered, with special indication beyond accepted recommendations in HF. In CS, the extent of left ventricular dysfunction is the most important mortality predictor. Heart transplant or mechanical circulatory support may represent life saving strategies in selective CS patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Primary graft dysfunction (PGD) is a leading cause of early mortality after heart transplant (HTx). To identify PGD incidence and impact on mortality, and to elucidate risk factors for PGD, we systematically reviewed studies using the ISHLT 2014 Consensus Report definition and reporting the incidence of PGD in adult HTx recipients., Methods: We conducted a systematic search in January 2020 including studies reporting the incidence of PGD in adult HTx recipients. We used a random effects model to pool the incidence of PGD among HTx recipients and, for each PGD severity, the mortality rate among those who developed PGD. For prognostic factors evaluated in ≥2 studies, we used random effects meta-analyses to pool the adjusted odds ratios for development of PGD. The GRADE framework informed our certainty in the evidence., Results: Of 148 publications identified, 36 observational studies proved eligible. With moderate certainty, we observed pooled incidences of 3.5%, 6.6%, 7.7%, and 1.6% and 1-year mortality rates of 15%, 21%, 41%, and 35% for mild, moderate, severe and isolated right ventricular-PGD, respectively. Donor factors (female sex, and undersized), recipient factors (creatinine, and pre-HTx use of amiodarone, and temporary or durable mechanical support), and prolonged ischemic time proved associated with PGD post-HTx., Conclusion: Our review suggests that the incidence of PGD may be low but its risk of mortality high, increasing with PGD severity. Prognostic factors, including undersized donor, recipient use of amiodarone pre-HTx and recipient creatinine may guide future studies in exploring donor and/or recipient selection and risk mitigation strategies., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: The Heart Failure (HF) Meta-score may be useful in predicting prognosis in patients with primary prevention cardiac resynchronization defibrillators (CRT-D) considering the competing risk of appropriate defibrillator shock versus mortality., Methods: Data from 648 consecutive patients from two centers were used for the evaluation of the performance of the HF Meta-score. The primary endpoint was mortality and the secondary endpoint was time to first appropriate implantable cardioverter-defibrillator (ICD) shock or death without prior appropriate ICD shock. Fine-Gray model was used for competing risk regression analysis., Results: In the entire cohort, 237 patients died over a median follow-up of 5.2 years. Five-year cumulative incidence of mortality ranged from 12% to 53%, for quintiles 1 through 5 of the HF Meta-score, respectively (log-rank P < 0.001). Compared with the lowest quintile, mortality risk was higher in the highest quintile (HR 6.9; 95%CI 3.7-12.8). The HF Meta-score had excellent calibration, accuracy, and good discrimination in predicting mortality (C-statistic 0.76 at 1-year and 0.71 at 5-year). The risk of death without appropriate ICD shock was higher in risk quintile 5 compared to quintile 1 (sub HR 5.8; 95%CI 3.1-11.0, P < 0.001)., Conclusions: Our study demonstrated a good ability of the HF Meta-score to predict survival in HF patients treated with CRT-D as primary prevention. The HF Meta-score proved to be useful in identifying a subgroup with a significantly poor prognosis despite a CRT-D., Competing Interests: Declaration of Competing Interest Dr. Theuns has received research grants from Biotronik and Boston Scientific and consulting fees from Boston Scientific. Dr. Schaer is listed on the speaker's bureau for Medtronic. Dr. Sticherling has received speaker fees from Boston Scientific, Biotronik and Microport CRM and consulting fees from Biotronik, Boston Scientific, and Medtronic. Dr. Yap is listed as an ad hoc consultant for Medtronic and Boston Scientific and has been a speaker for Medtronic. The other authors have nothing to disclose., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

The benefit of exercise training in cardiac resynchronization therapy (CRT) recipients is not well established. We conducted a systematic review and meta-analysis to determine the effect of exercise training on clinical outcomes in CRT recipients.A comprehensive search until 2019 was conducted of MEDLINE, Epub, Embase, CINAHL and Cochrane databases as well as a bibliographic hand search to identify additional studies. We included all studies that compared aerobic exercise interventions in adults treated with CRT devices with adults treated with usual CRT care. These studies evaluated patient clinical characteristics, exercise testing measures, hemodynamic measures, echocardiography parameters, biomarkers and adverse events. Independent reviewers evaluated study eligibility, abstracted data and assessed risk of bias in duplicate. We used random-effect meta-analysis methods to estimate mean differences and odds ratios. Grades of Recommendation, Assessment, Development and Evaluation system were used to quantify absolute effects and quality of evidence. I 2 was used to evaluate heterogeneity.We identified seven studies, six randomized control trials and one observational study, totaling 332 CRT patients in the exercise intervention and 534 patients receiving usual care. Peak VO 2 was 2.4 ml/kg/min higher in the exercise group in comparison with the control group (pooled mean difference 2.26, 95% CI 1.38-3.13, I 2  = 53%, high quality). AT-VO 2 improved with exercise rehabilitation, and heterogeneity was considered low (pooled mean difference 3.96, 95% CI 2.68-5.24, I 2  = 0.0%, moderate quality).Peak VO 2 and AT-VO 2 are increased with aerobic exercise in CRT recipients, demonstrating a significant improvement in functional capacity.

Background: Venoarterial extracorporeal membrane oxygenation (VA ECMO) is associated with variable outcomes. In this meta-analysis, we evaluated the mortality after VA ECMO across multiple etiologies of cardiogenic shock (CS)., Methods: In June 2019, we performed a systematic search selecting observational studies with ≥10 adult patients reporting on short-term mortality (30-day or mortality at discharge) after initiation of VA ECMO by CS etiology published after 2009. We performed meta-analyses using random effect models and used metaregression to evaluate mortality across CS etiology., Results: We included 306 studies (29,289 patients): 25 studies on after heart transplantation (HTx) (771 patients), 13 on myocarditis (906 patients), 33 on decompensated heart failure (HF) (3,567 patients), 64 on after cardiotomy shock (8,231 patients), 10 on pulmonary embolism (PE) (221 patients), 80 on acute myocardial infarction (AMI) (7,774 patients), and 113 on after cardiac arrest [CA] (7,814 patients). With moderate certainty on effect estimates, we observed significantly different mortality estimates for various etiologies (p < 0.001), which is not explained by differences in age and sex across studies: 35% (95% CI: 29-42) for after HTx, 40% (95% CI: 33-46) for myocarditis, 53% (95% CI: 46-59) for HF, 52% (95% CI: 38-66) for PE, 59% (95% CI: 56-63) for cardiotomy, 60% (95% CI: 57-64) for AMI, 64% (95% CI: 59-69) for post‒in-hospital CA, and 76% (95% CI: 69-82) for post-out‒of-hospital CA. Univariable metaregression showed that variation in mortality estimates within etiology group was partially explained by population age, proportion of females, left ventricle venting, and CA., Conclusions: Using an overall estimate of mortality for patients with CS requiring VA ECMO is inadequate given the differential outcomes by etiology. To further refine patient selection and management to improve outcomes, additional studies evaluating patient characteristics impacting outcomes by specific CS etiology are needed., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)