Use of Imaging-guided Decongestion for Reducing Heart Failure Readmission and Death in High-risk Patients: A Multi-site Randomized Trial of a Nurse-led Strategy at the Point of Care.

BACKGROUND: Nurse-led disease management programs (DMPs) decrease readmission after acute decompensated heart failure (HF). We sought whether readmissions could be further reduced by lung ultrasound (LUS)-guided decongestion before discharge and during DMP. METHODS AND RESULTS: Of 290 patients hospitalized with acute decompensated HF, 122 at high risk for readmission or mortality were randomized to receive usual care (UC) (n = 64) or UC plus intervention (DMP-Plus) (n = 58), comprising LUS-guided management before discharge and during at-home follow-up. Residual congestion was identified by ≥10 B-lines detected in 8 lung zones. The outcomes included a composite of readmission and/or mortality at 30 and 90 days, and 90-day HF readmission. Residual congestion was detected equally among the patient groups. The 30-day composite outcome occurred in 28% DMP-plus patients and 22% UC patients (odd ratio [OR], 1.36; 95% confidence interval [CI], 0.59-3.1; P = .5) and the 90-day HF readmission outcome occurred in 22% and 31%, respectively (odds ratio, 0.63; 95% CI, 0.28-1.43; P = .3). Residual congestion, identified at predischarge LUS examination in high-risk patients, was associated with early (<14-day) HF readmission (relative risk, 1.19; 95% CI, 1.06-1.32; P = .002) and multiple (≥2) readmissions over 90 days of follow-up (relative risk, 1.09; 95% CI, 1.01-1.16; P = .012), independent of demographics and comorbidities. CONCLUSIONS: Readmission in patients with incomplete decongestion before discharge occurs within the first 2 weeks. However, our DMP-plus strategy did not improve the primary outcome.

HeartMate 3 implantation with an emphasis on the biventricular configuration.

OBJECTIVES: Right ventricular failure following implantation of a durable left ventricular assist device (LVAD) is a major driver of mortality. Reported survival following biventricular (BiVAD) or total artificial heart (TAH) implantation remains substantially inferior to LVAD alone. We report our outcomes with LVAD and BiVAD HeartMate 3 (HM3). METHODS: Consecutive patients undergoing implantation of an HM3 LVAD between November 2014 and December 2021, at The Alfred, Australia were included in the study. Comparison was made between the BiVAD and LVAD alone groups. RESULTS: A total of 86 patients, 65 patients with LVAD alone and 21 in a BiVAD configuration underwent implantation. The median age of the LVAD and BiVAD groups was 56 years (Interquartile range 46-62) and 49 years (Interquartile range 37-55), respectively. By 4 years after implantation, 54% of LVAD patients and 43% of BiVAD patients had undergone cardiac transplantation. The incidence of stroke in the entire experience was 3.5% and pump thrombosis 5% (all in the RVAD). There were 14 deaths in the LVAD group and 1 in the BiVAD group. The actuarial survival for LVAD patients at 1 year was 85% and BiVAD patients at 1 year was 95%. CONCLUSIONS: The application of HM 3 BiVAD support in selected patients appears to offer a satisfactory solution to patients requiring biventricular support.

2024 Australia-New Zealand Expert Consensus Statement on Cardiac Amyloidosis.

Over the past 5 years, early diagnosis of and new treatments for cardiac amyloidosis (CA) have emerged that hold promise for early intervention. These include non-invasive diagnostic tests and disease modifying therapies. Recently, CA has been one of the first types of cardiomyopathy to be treated with gene editing techniques. Although these therapies are not yet widely available to patients in Australia and New Zealand, this may change in the near future. Given the rapid pace with which this field is evolving, it is important to view these advances within the Australian and New Zealand context. This Consensus Statement aims to update the Australian and New Zealand general physician and cardiologist with regards to the diagnosis, investigations, and management of CA.

Vasoplegia Following Orthotopic Heart Transplantation: Prevalence, Predictors and Clinical Outcomes.

BACKGROUND: Patients undergoing heart transplant are at high risk for postoperative vasoplegia. Despite its frequency and association with poor clinical outcomes, there remains no consensus definition for vasoplegia, and the predisposing risk factors for vasoplegia remain unclear. Accordingly, the aim of this study was to evaluate the prevalence, predictors, and clinical outcomes associated with vasoplegia in a contemporary cohort of patients undergoing heart transplantation. METHODS: This was a retrospective cohort study of patients undergoing heart transplantation from January 2015 to December 2019. A binary definition of vasoplegia of a cardiac index of 2.5 L/min/m2 or greater and requirement for norepinephrine (≥5 µg/min), epinephrine (≥4 µg/min), or vasopressin (≥1 unit/h) to maintain a mean arterial blood pressure of 65 mm Hg, for 6 consecutive hours during the first 48 hours postoperatively, was used in determining prevalence. Given the relatively low threshold for the binary definition of vasoplegia, patients were divided into tertiles based on their cumulative vasopressor requirement in the 48 hours following transplant. Outcomes included all-cause mortality, intubation time, intensive care unit length of stay, and length of total hospitalization. RESULTS: After exclusion of patients with primary cardiogenic shock, major bleeding, or overt sepsis, data were collected on 95 eligible patients. By binary definition, vasoplegia incidence was 66.3%. We separately stratified by actual vasopressor requirement tertile (high, intermediate, low). Stratified by tertile, patients with vasoplegia were older (52.7 ± 10.2 vs 46.8 ± 12.7 vs 44.4 ± 11.3 years, P = .02), with higher rates of chronic kidney disease (18.8% vs 32.3% vs 3.1%, P = .01) and were more likely to have been transplanted from left ventricular assist device support (n = 42) (62.5% vs 32.3% vs 37.5%, P = .03). Cardiopulmonary bypass time was prolonged in those that developed vasoplegia (155 min [interquartile range 135-193] vs 131 min [interquartile range 117-152] vs 116 min [interquartile range 102-155], P = .003). Intubation time and length of intensive care unit and hospital stay were significantly increased in those that developed vasoplegia; however, this difference did not translate to a significant increase in all-cause mortality at 30 days or 1 year. CONCLUSIONS: Vasoplegia occurs at a high rate after heart transplantation. Older age, chronic kidney disease, mechanical circulatory support, and prolonged bypass time are all associated with vasoplegia; however, this study did not demonstrate an associated increase in all-cause mortality LAY SUMMARY: Patients undergoing heart transplantation are at high risk of vasoplegia, a condition defined by low blood pressure despite normal heart function. We found that vasoplegia was common after heart transplant, occurring in 60%-70% of patients after heart transplant after excluding those with other causes for low blood pressure. Factors implicated included age, poor kidney function, prolonged cardiopulmonary bypass time and preoperative left ventricular assist device support. We found no increased risk of death in patients with vasoplegia despite longer lengths of stay in intensive care and in hospital.

Incidence and Predictors of Eosinophilic Myocardial Hypersensitivity in Patients Receiving Home Dobutamine.

ABSTRACT: We sought to examine incidence and predictors of eosinophilic myocardial hypersensitivity (EMH) in a cohort of patients in the home inotrope program of a quaternary cardiac transplant center. Patients on home inotropes with progression to heart transplantation or ventricular assist device (VAD) between January 2000 and May 2020 were included. EMH was diagnosed by the presence of an interstitial predominate eosinophilic infiltrate within the myocardium by experienced cardiac pathologists. From a cohort of 74 patients, 58% (43) were on dobutamine and 42% (31) were on milrinone. Dobutamine was associated with EMH incidence of 14% (6/43), with zero cases in the milrinone cohort. Mean age was 52 ± 12 years, 22% were female. More than half (62%) were nonischemic dilated cardiomyopathies, the remainder were ischemic cardiomyopathy. Dobutamine dose [250 (200-282) vs. 225 (200-291) µg/min] and duration of therapy [41 (23-79) vs. 53 (24-91) days] was similar between those with and without EMH. Median change in eosinophil count was 0.31 × 10 9 /L in the EMH group compared with only 0.03 × 10 9 /L in the non-EMH cohort, P = 0.02. Increase in peripheral eosinophil count of >0.20 × 10 9 /L demonstrated good discrimination between those with and without EMH, c-statistic 0.83 (95% CI 0.66-1.0). Heart failure hospitalization occurred in 83% of the EMH group versus 59% in the non-EMH group, P = 0.26. Requirement for VAD was significantly higher in the EMH group (83% vs. 41%, P = 0.05). In conclusion, EMH occurred in 14% of patients receiving home dobutamine. Rising eosinophil count should prompt physicians to consider EMH and switch to milrinone to avoid possible escalation to VAD.

Levosimendan and Continuous Outpatient Support With Inotropes in Patients With Advanced Heart Failure: A Single-Centre Descriptive Study.

ABSTRACT: To describe the use of levosimendan in a quaternary referral center with a dedicated heart failure service and compare its efficacy and safety to continuous outpatient support with inotropes (COSI) among patients with advanced heart failure (AHF) who require bridge-to-decision (BTD) or bridge-to-transplant (BTT) therapy. This study was a retrospective, single-center, descriptive study of patients with AHF who received either a single levosimendan infusion or COSI between 2018 and 2021. A total of 23 patients received a levosimendan infusion, and 14 were started on COSI. Three indications for levosimendan were identified: (1) to facilitate weaning of continuous inotropes, (2) to augment diuresis in cardiorenal syndrome, and (3) as first-line therapy for cardiogenic shock in selected patients. Eighty-three percent (19 of 23) of patients who received levosimendan survived to discharge, and there were few clinically significant adverse events. Overall survival at 12 months among patients who received levosimendan was 74%. No statistically significant difference in survival was observed at 12 months (P = 0.68) or beyond (P = 0.63) between patients who received levosimendan and were discharged with a plan for BTD or BTT and those who received COSI. Levosimendan is a safe and effective short-term therapy in AHF and offers comparable long-term survival to COSI in patients who require BTD or BTT therapy.

Current approaches to the diagnosis and management of amyloidosis.

Amyloidosis is a collection of diseases caused by the misfolding of proteins that aggregate into insoluble amyloid fibrils and deposit in tissues. While these fibrils may aggregate to form insignificant localised deposits, they can also accumulate in multiple organs to the extent that amyloidosis can be an immediately life-threatening disease, requiring urgent treatment. Recent advances in diagnostic techniques and therapies are dramatically changing the disease landscape and patient prognosis. Delays in diagnosis and treatment remain the greatest challenge, necessitating physician awareness of the common clinical presentations that suggest amyloidosis. The most common types are transthyretin (ATTR) amyloidosis followed by immunoglobulin light-chain (AL) amyloidosis. While systemic AL amyloidosis was previously considered a death sentence with no effective therapies, significant improvement in patient survival has occurred over the past 2 decades, driven by greater understanding of the disease process, risk-adapted adoption of myeloma therapies such as proteosome inhibitors (bortezomib) and monoclonal antibodies (daratumumab) and improved supportive care. ATTR amyloidosis is an underdiagnosed cause of heart failure. Technetium scintigraphy has made noninvasive diagnosis much easier, and ATTR is now recognised as the most common type of amyloidosis because of the increased identification of age-related ATTR. There are emerging ATTR treatments that slow disease progression, decrease patient hospitalisations and improve patient quality of life and survival. This review aims to update physicians on recent developments in amyloidosis diagnosis and management and to provide a diagnostic and treatment framework to improve the management of patients with all forms of amyloidosis.

Richardson's ground squirrel litter size-sex ratio trade-off reveals conditional adaptive sex allocation.

Trivers and Willard proposed that female mammals should adjust their investment in male versus female offspring relative to their ability to produce high-quality offspring. We tested whether litter size-sex ratio trade-offs predicted by Adaptive Sex Allocation (ASA) theory occur among Richardson's ground squirrel (Urocitellus richardsonii) dams over 10 distinct breeding years in a population where individuals experienced variability in food availability and habitat disruption. Litters of primiparous dams became increasingly female-biased with increasing litter size, but that trend waned among second litters born to dams, and reversed among third litters, with larger litters becoming more male-biased, suggesting that ASA is a product of interacting selection pressures. Trade-offs were not associated with habitat disruption, the availability of supplementary food, or dam age. An association between habitat disruption and male-biased sex ratios, the prevalence of litter size-sex ratio trade-offs and placental scar counts exceeding the number of juveniles at weaning in our population, but not in a geographically distinct population of conspecifics exposed to different environmental conditions reveal that the expression of ASA varies among populations and among years within populations, illustrating the conditional nature of ASA.

Reduction in mortality from implantable cardioverter-defibrillators in non-ischaemic cardiomyopathy patients is dependent on the presence of left ventricular scar.

Aims: In patients with non-ischaemic cardiomyopathy (NICM), the mortality benefit of a primary prevention implantable cardioverter-defibrillator (ICD) has been challenged. Left ventricular (LV) scar identified by cardiac magnetic resonance (CMR) imaging is associated with a high risk of malignant arrhythmia in NICM. We aimed to determine the impact of LV scar on the mortality benefit from a primary prevention ICD in NICM. Methods and results: We recruited 452 consecutive heart failure patients [New York Heart Association (NYHA) Class II/III] with NICM and LV ejection fraction ≤35% from a state-wide CMR service. All patients fulfilled European Society of Cardiology guidelines for primary prevention ICD implantation; however, the decision to implant was at the treating physician's discretion. Baseline clinical and CMR data were recorded prospectively and heart failure mortality risk (MAGGIC score) was calculated. The primary study outcome measurement was all-cause mortality based on presence or absence of ICD, stratified by LV scar. Median follow-up was 37.9 months and there was no difference in MAGGIC score between those who did and did not receive a primary prevention ICD (19.30 ± 5.46 vs. 18.90 ± 5.67, P = 0.50). In patients without LV scar, ICD implantation was not associated with improved mortality [hazard ratio (HR) = 1.22, 95% confidence interval (CI): 0.53-2.78, P = 0.64]. In patients with LV scar, ICD implantation was independently associated with reduced mortality (HR = 0.45, 95% CI: 0.26-0.77, P = 0.003). Conclusions: In patients with NICM, primary prevention ICD implantation is only associated with reduced mortality in patients with LV scar. This may enable more effective selection of NICM patients for ICD implantation compared with current guidelines.

Central distribution of oxytocin and vasopressin 1a receptors in juvenile Richardson's ground squirrels.

Oxytocin and vasopressin are well-conserved peptides important to the regulation of numerous aspects of social behavior, including sociality. Research exploring the distribution of the receptors for oxytocin (Oxtr) and for vasopressin (Avpr1a) in mammals has revealed associations between receptor distribution, sociality, and species' mating systems. Given that sociality and gregariousness can be tightly linked to reproduction, these nonapeptides unsurprisingly support affiliative behaviors that are important for mating and offspring care. We localized these receptors in juvenile Richardson's ground squirrel brains to determine whether distribution patterns of Oxtr and Avpr1a that are associated with promiscuous mating systems differ in rodents that also exhibit non-reproductive affiliation. These squirrels are social, colonial, and engage in nepotistic alarm calling behavior and affiliation outside of a reproductive context. Juveniles are the most affiliative age-class and are non-reproductive; making them ideal for examining these associations. We found that juveniles had dense Oxtr binding in the dentate gyrus of the hippocampus, amygdala, lateral septum, bed nucleus of the stria terminalis and medial geniculate nucleus. Juveniles had low to modest levels of Avpr1a binding in the medial preoptic area, olfactory bulbs, nucleus accumbens, superior colliculus, and inferior colliculus. We noted Oxtr and Avpr1a binding in the social behavior neural network (SBNN), further supporting a role of these nonapeptides in modulating social behavior across taxa. Oxtr and Avpr1a binding was also present in brain regions important to auditory processing that have known projections to the SBNN. We speculate that these neural substrates may be where these nonapeptides regulate communication.

Comparison of Magnetic Resonance Analysis of Myocardial Scarring With Biomarker Release Following S-T Elevation Myocardial Infarction.

BACKGROUND: Late gadolinium enhancement (LGE) with cardiac magnetic resonance (CMR) is commonly assumed to represent myocardial fibrosis; however, comparative human histological data are limited, and there is no consensus on the most accurate method for LGE quantitation. We evaluated the relationship between CMR assessment of regional fibrosis and infarct size assessment using serial biomarkers after ST elevation acute myocardial infarction (STEMI). METHODS: Ninety-three patients treated for STEMI (59±10 years, 86% male) underwent CMR 6 months after infarction. Infarct size was quantified by CMR-LGE using manual and range of semi-automated thresholds (range: 2-10 standard deviations [SD]) above reference myocardium and the full width-half maximum (FWHM) technique, and compared with the rise in serum biomarkers. The agreement between CMR and biomarker in the identification of large infarcts based on peak troponin (TnI) levels was also analysed. RESULTS: Quantification methods had a strong influence on the infarct size assessment with CMR-LGE. Significant correlations were observed between LGE and biomarkers across all of the signal intensity thresholds. Whilst there was a wide variation with respect to the estimation of total LGE size (from 6.8±7.7 to 32.1±11.3 grams), the variation in the correlation with peak troponin level was much smaller (r-values ranging from 0.670 to 0.876). There was good agreement between CMR-LGE and biomarker assessment of infarct size; the best agreement between CMR-LGE and large infarction using a threshold of 8SD for peak TnI>50ng/mL (Cohen's kappa (κ)=0.722), and a threshold of 4SD for peak TnI >95ng/mL (κ=0.761). CONCLUSIONS: The correlation between CMR-LGE quantification of infarct size and biomarker release following STEMI at a range of semi-automated thresholds was consistently strong, with good agreement between measures across a range of thresholds.

Effects of post-discharge management on rates of early re-admission and death after hospitalisation for heart failure.

OBJECTIVES: To investigate whether enrolment of patients in management programs after hospitalisation for heart failure (HF) reduces the likelihood of post-hospital adverse outcomes. DESIGN: Cohort study in which associations between adverse outcomes at 30 and 90 days for people hospitalised for HF and baseline clinical, socio-demographic and blood pathology factors, and with post-discharge management strategies, were assessed. Setting, participants: 906 patients with HF were prospectively enrolled in five Australian states at cardiology departments with expertise in treating people with HF. MAIN OUTCOME MEASURES: All-cause re-admissions and deaths at 30 and 90 days after discharge from the index admission. RESULTS: 58% of patients were men; the mean age was 72.5 years (SD, 13.9 years). By hospital, 30-day re-admission rates ranged from 17% to 33%, and 90-day rates from 40% to 55%; 30-day mortality rates were 0-13%, 90-day rates 4-24%. Factors associated with increased odds of re-admission or death at 30 or 90 days included living alone, cognitive impairment, depression, NYHA classification, left atrial volume index, and Charlson index score. Nurse-led disease management programs and reviews within 7 days were associated with reduced odds of re-admission (but not of death) at 30 and 90 days; exercise programs were associated with reduced odds at 90 days. Significant between-hospital differences in re-admission rates were reduced after adjustment for post-discharge management programs, and abolished by further adjustment for echocardiography findings. Between-hospital differences in mortality were largely explained by differences in echocardiographic findings. CONCLUSIONS: Differences in early re-admission rates after hospitalisation for HF are primarily explained by differences in post-discharge management.

Brain-liver connections: role of the preautonomic PVN neurons.

Diabetes mellitus and the coexisting conditions and complications, including hypo- and hyperglycemic events, obesity, high cholesterol levels, and many more, are devastating problems. Undoubtedly, there is a huge demand for treatment and prevention of these conditions that justifies the search for new approaches and concepts for better management of whole body metabolism. Emerging evidence demonstrates that the autonomic nervous system is largely involved in the regulation of glucose homeostasis; however, the underlying mechanisms are still under investigation. Within the hypothalamus, the paraventricular nucleus (PVN) is in a unique position to integrate neural and hormonal signals to command both the autonomic and neuroendocrine outflow. This minireview will provide a brief overview on the role of preautonomic PVN neurons and the importance of the PVN-liver pathway in the regulation of glucose homeostasis.

Diffuse Ventricular Fibrosis on Cardiac Magnetic Resonance Imaging Associates With Ventricular Tachycardia in Patients With Hypertrophic Cardiomyopathy.

INTRODUCTION: Non-sustained ventricular tachycardia (NSVT) is a risk factor for sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). We aimed to assess whether diffuse ventricular fibrosis on cardiac magnetic resonance (CMR) imaging could be a surrogate marker for ventricular arrhythmias in patients with HCM. METHODS: A total of 100 patients with HCM (mean age 51 ± 13 years, septal wall thickness 20 ± 5 mm) underwent CMR with a 1.5 T scanner to determine the presence of ventricular late gadolinium enhancement (LGE) for focal fibrosis, and post-contrast T1 mapping for diffuse ventricular fibrosis. The presence of NSVT was determined by Holter monitoring and a subset of high risk patients received an implantable cardioverter-defibrillator (ICD). RESULTS: NSVT was detected in 23 of 100 patients with HCM. Focal ventricular fibrosis (by LGE) was observed in 87%, with no significant difference between patients with (96%) or without NSVT (86%, P = 0.19). However, LGE mass was greater in patients with (16.5 ± 19.1 g) versus without NSVT (7.6 ± 10.2 g, P < 0.01). NSVT was associated with a significant reduction in ventricular T1 relaxation time (422 ± 54 milliseconds) versus patients without NSVT (512 ± 115 milliseconds; P < 0.001). There was significant reduction in ventricular T1 relaxation time in patients with (430 ± 48 milliseconds) versus without aborted SCD (495 ± 113 milliseconds; P = 0.01) over a mean follow-up of 40 ± 10 months. On multivariate analysis post-contrast ventricular T1 relaxation time and septal wall thickness were the only predictors of NSVT. CONCLUSION: Post-contrast T1 relaxation time on CMR is associated with ventricular arrhythmias in patients with HCM. Diffuse ventricular fibrosis may be an important marker of arrhythmic risk in patients with HCM.

Catch the wave: prairie dogs assess neighbours' awareness using contagious displays.

The jump-yip display of black-tailed prairie dogs (Cynomys ludovicianus) is contagious, spreading through a prairie dog town as 'the wave' through a stadium. Because contagious communication in primates serves to assess conspecific social awareness, we investigated whether instigators of jump-yip bouts adjusted their behaviour relative to the response of conspecifics recruited to display bouts. Increased responsiveness of neighbouring town members resulted in bout initiators devoting a significantly greater proportion of time to active foraging. Contagious jump-yips thus function to assess neighbours' alertness, soliciting social information to assess effective conspecific group size in real time and reveal active probing of conspecific awareness consistent with theory of mind in these group-living rodents.

The prudent parent meets old age: a high stress response in very old seabirds supports the terminal restraint hypothesis.

The reproductive success of wild animals usually increases with age before declining at the end of life, but the proximate mechanisms underlying those patterns remain elusive. Young animals are expected to invest less in current reproduction due to high prospects for future reproduction (the "restraint" hypothesis). The oldest animals may also show restraint when conditions are sub-optimal where even a small increase in reproductive investment may lead to death ("terminal restraint"). Alternatively, reproduction may be constrained by lack of experience and senescence (the "constraint" hypothesis). In two species of breeding seabirds, behavioural (time to return the offspring, calmness during restraint) and physiological (metabolism, glucose and corticosterone) parameters responded similarly to stress with advancing age, implying a generalized stress response. Across those parameters, birds were "shy" (high stress response) when young or old, and "bold" (low stress response) when middle-aged. Specifically, free corticosterone, the principal avian glucocorticoid responsible for directing energy away from reproduction and towards immediate survival following stress, was highest in both young and very old stressed birds. All age groups had a similar adrenal capacity to produce corticosterone, implying that middle-aged birds were showing restraint. Because the stress response, was highest at ages when the probability of current reproduction was lowest rather than at ages when the probability of future reproduction was highest we concluded that birds restrained reproductive investment based on current conditions rather than potential future opportunities. In particular, old birds showed terminal restraint when stressed. Hormonal cues promoted investment in adult survival over reproductive output at both the start and end of life consistent with the restraint hypothesis.

Age-related variation in energy expenditure in a long-lived bird within the envelope of an energy ceiling.

Energy expenditure in wild animals can be limited (i) intrinsically by physiological processes that constrain an animal's capacity to use energy, (ii) extrinsically by energy availability in the environment and/or (iii) strategically based on trade-offs between elevated metabolism and survival. Although these factors apply to all individuals within a population, some individuals expend more or less energy than other individuals. To examine the role of an energy ceiling in a species with a high and individually repeatable metabolic rate, we compared energy expenditure of thick-billed murres (Uria lomvia) with and without handicaps during a period of peak energy demand (chick-rearing, N = 16). We also compared energy expenditure of unencumbered birds (N = 260) across 8 years exhibiting contrasting environmental conditions and correlated energy expenditure with fitness (reproductive success and survival). Murres experienced an energy ceiling mediated through behavioural adjustments. Handicapped birds decreased time spent flying/diving and chick-provisioning rates such that overall daily energy expenditure remained unchanged across the two treatments. The energy ceiling did not reflect energy availability or trade-offs with fitness, as energy expenditure was similar across contrasting foraging conditions and was not associated with reduced survival or increased reproductive success. We found partial support for the trade-off hypothesis as older murres, where prospects for future reproduction would be relatively limited, did overcome an energy ceiling to invest more in offspring following handicapping by reducing their own energy reserves. The ceiling therefore appeared to operate at the level of intake (i.e. digestion) rather than expenditure (i.e. thermal constraint, oxidative stress). A meta-analysis comparing responses of breeding animals to handicapping suggests that our results are typical: animals either reduced investment in themselves or in their offspring to remain below an energy ceiling. Across species, whether a handicapped individual invested in its own energy stores or its offspring's growth was not explained by life history (future vs. current reproductive potential). Many breeding animals apparently experience an intrinsic energy ceiling, and increased energy costs lead to a decline in self-maintenance and/or offspring provisioning.

Asymptomatic myocarditis during clozapine re-titration, in a patient who had previously been stable on clozapine for 10 years.

OBJECTIVE: We present a case of confirmed clozapine-induced myocarditis in a patient who was not naïve to the drug. METHOD: This patient, who had been stable on clozapine for 10 years, relapsed following self-cessation. Asymptomatic throughout inpatient re-titration, serum cardiac enzymes were nonetheless routinely taken. RESULTS: Occult myocarditis was only discovered due to an elevated Troponin I, and was confirmed by cardiac imaging. CONCLUSIONS: Once thought to be the preserve of initial exposure to the medication, clozapine-induced myocarditis can occur at any re-titration point if the immunological milieu permits. We therefore recommend routine monitoring of serum cardiac enzymes with all patients undergoing titration of clozapine, regardless of whether they have previously been stable on the drug.

Long term follow up and outcomes of Covid-19 vaccine associated myocarditis in Victoria, Australia: A clinical surveillance study.

BACKGROUND: Myocarditis and myopericarditis are well described adverse events of special interest (AESI) following COVID-19 vaccinations. Although reports are reassuring regarding initial clinical outcomes, information about longer term outcomes remains limited. We aimed to further this knowledge and report outcomes to 6 months post diagnosis from a single population cohort. METHODS: Reports of myocarditis following COVID-19 vaccination were followed up by SAEFVIC (Surveillance of Adverse Events Following Vaccination in the Community), the state-wide vaccine safety service for Victoria, Australia. Confirmed myocarditis cases (Brighton Collaboration Criteria levels 1-3) were followed up via surveys at 1, 3 and 6 months post symptom onset. Responses received between 22 February 2021 and 30 September 2022 were analysed. RESULTS: 87.5 % (N = 182) of eligible participants completed at least 1 survey report. 377 reports were analysed. 76.9 % of completed reports were from male patients. The median age of patients was 21 years [IQR: 16 to 32]. 54.8 % (n = 74) of survey reports at 6 months, reported ongoing symptoms. At all follow-up time points, females were significantly more likely to have ongoing symptoms. At 6 months, 51.9 % of male respondents reported symptom resolution compared to 22.6 % of female patients (p = 0.002). Females were also more likely to continue medication and have ongoing exercise restrictions. However, males were significantly more likely to have higher initial peak troponin results and abnormal initial cardiac imaging investigations. CONCLUSIONS: There appears to be a significant proportion of patients who experience ongoing symptoms to 6 months post onset amongst patients that experience these AESI. Male patients were more likely to report earlier and more complete symptom recovery, despite significantly higher average initial peak troponin. This difference in phenotypic presentation in females compared to males warrants further investigation and there is a need for longer term follow up data.