Phenotyping heart failure by cardiac magnetic resonance imaging of cardiac macro- and microscopic structure: state of the art review.

Heart failure demographics have evolved in past decades with the development of improved diagnostics, therapies, and prevention. Cardiac magnetic resonance (CMR) has developed in a similar timeframe to become the gold-standard non-invasive imaging modality for characterizing diseases causing heart failure. CMR techniques to assess cardiac morphology and function have progressed since their first use in the 1980s. Increasingly efficient acquisition protocols generate high spatial and temporal resolution images in less time. This has enabled new methods of characterizing cardiac systolic and diastolic function such as strain analysis, exercise real-time cine imaging and four-dimensional flow. A key strength of CMR is its ability to non-invasively interrogate the myocardial tissue composition. Gadolinium contrast agents revolutionized non-invasive cardiac imaging with the late gadolinium enhancement technique. Further advances enabled quantitative parametric mapping to increase sensitivity at detecting diffuse pathology. Novel methods such as diffusion tensor imaging and artificial intelligence-enhanced image generation are on the horizon. Magnetic resonance spectroscopy (MRS) provides a window into the molecular environment of the myocardium. Phosphorus (31P) spectroscopy can inform the status of cardiac energetics in health and disease. Proton (1H) spectroscopy complements this by measuring creatine and intramyocardial lipids. Hyperpolarized carbon (13C) spectroscopy is a novel method that could further our understanding of dynamic cardiac metabolism. CMR of other organs such as the lungs may add further depth into phenotypes of heart failure. The vast capabilities of CMR should be deployed and interpreted in context of current heart failure challenges.

Myocardial Metabolism in Heart Failure.

PURPOSE OF REVIEW: Myocardial metabolism is intricately linked to cardiac function. Perturbations of cardiac energy metabolism result in an energy-starved heart and the development of contractile dysfunction. In this review, we discuss alterations in myocardial energy supply, transcriptional changes in response to different energy demands, and mitochondrial function in the development of heart failure. RECENT FINDINGS: Recent studies on substrate modulation through modifying energy substrate supply have shown cardioprotective properties. In addition, large cardiovascular outcome trials of anti-diabetic agents have demonstrated prognostic benefit, suggesting the importance of myocardial metabolism in cardiac function. Understanding molecular and transcriptional controls of cardiac metabolism promises new research avenues for metabolic treatment targets. Future studies assessing the impact of substrate modulation on cardiac energetic status and function will better inform development of metabolic therapies.

Perceived workplace support and mental health, well-being and burnout among health care professionals during the COVID-19 pandemic: a cohort analysis.

BACKGROUND: Little is known about the relationship between workplace support and mental health and burnout among health care professionals (HCPs) during the COVID-19 pandemic. In this cohort study, we sought to evaluate the association between perceived level of (and changes to) workplace support and mental health and burnout among HCPs, and to identify what constitutes perceived effective workplace support. METHODS: Online surveys at baseline (July-September 2020) and follow-up 4 months later assessed the presence of generalized anxiety disorder (using the 7-item Generalized Anxiety Disorder scale [GAD-7]), clinical insomnia, major depressive disorder (using the 9-item Patient Health Questionnaire), burnout (emotional exhaustion and depersonalization) and mental well-being (using the Short Warwick-Edinburgh Mental Wellbeing Score). Both surveys assessed self-reported level of workplace support (single-item Likert scale). For baseline and follow-up, independently, we developed separate logistic regression models to evaluate the association of the level of workplace support (tricohotomized as unsupported, neither supported nor unsupported and supported) with mental health and burnout. We also developed linear regression models to evaluate the association between the change in perceived level of workplace support and the change in mental health scores from baseline and follow-up. We used thematic analyses on free-text entries of the baseline survey to evaluate what constitutes effective support. RESULTS: At baseline (n = 1422) and follow-up (n = 681), HCPs who felt supported had reduced risk of anxiety, depression, clinical insomnia, emotional exhaustion and depersonalization, compared with those who felt unsupported. Among those who responded to both surveys (n = 681), improved perceived level of workplace support over time was associated with significantly improved scores on measures of anxiety (adjusted ß -0.13, 95% confidence interval [CI] -0.25 to -0.01), depression (adjusted ß -0.17, 95% CI -0.29 to -0.04) and mental well-being (adjusted ß 0.19, 95% CI 0.10 to 0.29), independent of baseline level of support. We identified 5 themes constituting effective workplace support, namely concern or understanding for welfare, information, tangible qualities of the workplace, leadership and peer support. INTERPRETATION: We found a significant association between perceived level of (and changes in) workplace support and mental health and burnout of HCPs, and identified potential themes that constitute perceived workplace support. Collectively, these findings can inform changes in guidance and national policies to improve mental health and burnout among HCPs. Trial registration: ClinicalTrials.gov, no. NCT04433260.

Improved lifestyle is associated with improved depression, anxiety and well-being over time in UK healthcare professionals during the COVID-19 pandemic: insights from the CoPE-HCP cohort study.

Background: One potential modifiable factor to improve the mental health of healthcare professionals (HCPs) during the pandemic is lifestyle. Aims: This study aimed to assess whether an improved lifestyle during the pandemic is associated with improved mental health symptoms and mental well-being in HCPs over time. Methods: This was a cohort study involving an online survey distributed at two separate time points during the pandemic (baseline (July-September 2020) and follow-up (December 2020-March 2021)) to HCPs working in primary or secondary care in the UK. Both surveys assessed for major depressive disorder (MDD) (Patient Health Questionnaire-9 (PHQ-9)), generalised anxiety disorder (GAD) (Generalised Anxiety Disorder-7 (GAD-7)), mental well-being (Short Warwick-Edinburgh Mental Well-being Score (SWEMWBS)) and self-reported lifestyle change (compared with the start of the pandemic) on multiple domains. Cumulative scores were calculated to estimate overall lifestyle change compared with that before the pandemic (at both baseline and follow-up). At each time point, separate logistic regression models were constructed to relate the lifestyle change score with the presence of MDD, GAD and low mental well-being. Linear regression models were also developed relating the change in lifestyle scores from baseline to follow-up to changes in PHQ-9, GAD-7 and SWEMWBS scores. Results: 613 HCPs completed both baseline assessment and follow-up assessment. Consistent significant cross-sectional associations between increased lifestyle change scores and a reduced risk of MDD, GAD and low mental well-being were observed at both baseline and follow-up. Over the study period, a whole unit increase in the change in novel scores (ie, improved overall lifestyle) over 4 months was inversely associated with changes in PHQ-9 (adjusted coefficient: -0.51, 95% confidence interval (CI): -0.73 to -0.30, p<0.001) and GAD-7 scores (adjusted coefficient: -0.32, 95% CI: -0.53 to -0.10, p=0.004) and positively associated with the change in SWEMWBS scores (adjusted coefficient: 0.37, 95% CI: 0.18 to 0.55, p<0.001). Conclusions: Improved lifestyle over time is associated with improved mental health and mental well-being in HCPs during the pandemic. Improving lifestyle could be a recommended intervention for HCPs to help mitigate the mental health impact during the current and future pandemics. Trial registration number: NCT04433260.

Feasibility, diagnostic performance and clinical value of an abbreviated echocardiography protocol in an out-patient cardiovascular setting: a pilot study.

BACKGROUND: There has been a growing demand for echocardiography services over the last 5 years, with this supply-demand mismatch exacerbated by the COVID-19 pandemic. Prior studies have suggested a high proportion of normal findings among echocardiograms requested for patients without known cardiovascular disease, particularly in low-risk cohorts. This pilot study investigates the role of an abbreviated echocardiography protocol in improving access to echocardiography services in a low-risk outpatient setting within the rapid access chest pain (RACP) clinic. METHOD: A retrospective review of electronic medical records and transthoracic echocardiography (TTE) studies for 212 patients from RACP clinic in 2019 (cohort A), prior to the introduction of the abbreviated echocardiography protocol, and 175 patients seen in the RACP clinic in 2021 (cohort B) was performed. The outcomes measured include the echocardiography referral burden from RACP clinic, waiting time for a TTE and echocardiography findings. RESULTS: 33% and 45% of patients seen in the RACP clinic in 2019 and 2021, respectively, were referred for a TTE. The most common indications include chest pain (50%), dyspnoea (19%) and palpitations (11%). Abnormal findings were identified in 36% of TTEs performed in cohort A and 13% in cohort B. The median echocardiogram study time was significantly shorter in cohort B (7 min vs 13 min, p < 0.00001), with a lower number of images acquired (43 vs. 62, p < 0.00001). The median waiting time for an echocardiography in cohort B was significantly shorter (median: 14 days vs. 42 days in 2019, p < 0.00001). No major pathologies were missed on a retrospective review of these images. CONCLUSION: Our study demonstrates that an abbreviated echocardiography protocol has potential to improve access to echocardiography services through increasing scheduling capacity, without compromising diagnostic performance in a low-risk outpatient population.

Longitudinal comparisons of mental health, burnout and well-being in patient-facing, non-patient-facing healthcare professionals and non-healthcare professionals during the COVID-19 pandemic: findings from the CoPE-HCP study.

BACKGROUND: The COVID-19 pandemic may disproportionately affect the mental health of healthcare professionals (HCPs), especially patient-facing HCPs. AIMS: To longitudinally examine mental health in HCPs versus non-HCPs, and patient-facing HCPs versus non-patient-facing HCPs. METHOD: Online surveys were distributed to a cohort at three phases (baseline, July to September 2020; phase 2, 6 weeks post-baseline; phase 3, 4 months post-baseline). Each survey contained validated assessments for depression, anxiety, insomnia, burnout and well-being. For each outcome, we conducted mixed-effects logistic regression models (adjusted for a priori confounders) comparing the risk in different groups at each phase. RESULTS: A total of 1574 HCPs and 147 non-HCPs completed the baseline survey. Although there were generally higher rates of various probable mental health issues among HCPs versus non-HCPs at each phase, there was no significant difference, except that HCPs had 2.5-fold increased risk of burnout at phase 2 (emotional exhaustion: odds ratio 2.50, 95% CI 1.15-5.46, P = 0.021), which increased at phase 3 (emotional exhaustion: odds ratio 3.32, 95% CI 1.40-7.87, P = 0.006; depersonalisation: odds ratio 3.29, 95% CI 1.12-9.71, P = 0.031). At baseline, patient-facing HCPs (versus non-patient-facing HCPs) had a five-fold increased risk of depersonalisation (odds ratio 5.02, 95% CI 1.65-15.26, P = 0.004), with no significant difference in the risk for other outcomes. The difference in depersonalisation reduced over time, but patient-facing HCPs still had a 2.7-fold increased risk of emotional exhaustion (odds ratio 2.74, 95% CI 1.28-5.85, P = 0.009) by phase 3. CONCLUSIONS: The COVID-19 pandemic had a huge impact on the mental health and well-being of both HCPs and non-HCPs, but there is disproportionately higher burnout among HCPs, particularly patient-facing HCPs.

Quantifying the Excess Risk of Adverse COVID-19 Outcomes in Unvaccinated Individuals With Diabetes Mellitus, Hypertension, Ischaemic Heart Disease or Myocardial Injury: A Meta-Analysis.

Background: More than 80% of individuals in low and middle-income countries (LMICs) are unvaccinated against coronavirus disease 2019 (COVID-19). In contrast, the greatest burden of cardiovascular disease is seen in LMIC populations. Hypertension (HTN), diabetes mellitus (DM), ischaemic heart disease (IHD) and myocardial injury have been variably associated with adverse COVID-19 outcomes. A systematic comparison of their impact on specific COVID-19 outcomes is lacking. We quantified the impact of DM, HTN, IHD and myocardial injury on six adverse COVID-19 outcomes: death, acute respiratory distress syndrome (ARDS), invasive mechanical ventilation (IMV), admission to intensive care (ITUadm), acute kidney injury (AKI) and severe COVID-19 disease (SCov), in an unvaccinated population. Methodology: We included studies published between 1st December 2019 and 16th July 2020 with extractable data on patients ≥18 years of age with suspected or confirmed SARS-CoV-2 infection. Odds ratios (OR) for the association between DM, HTN, IHD and myocardial injury with each of six COVID-19 outcomes were measured. Results: We included 110 studies comprising 48,809 COVID-19 patients. Myocardial injury had the strongest association for all six adverse COVID-19 outcomes [death: OR 8.85 95% CI (8.08-9.68), ARDS: 5.70 (4.48-7.24), IMV: 3.42 (2.92-4.01), ITUadm: 4.85 (3.94-6.05), AKI: 10.49 (6.55-16.78), SCov: 5.10 (4.26-6.05)]. HTN and DM were also significantly associated with death, ARDS, ITUadm, AKI and SCov. There was substantial heterogeneity in the results, partly explained by differences in age, gender, geographical region and recruitment period. Conclusion: COVID-19 patients with myocardial injury are at substantially greater risk of death, severe disease and other adverse outcomes. Weaker, yet significant associations are present in patients with HTN, DM and IHD. Quantifying these associations is important for risk stratification, resource allocation and urgency in vaccinating these populations. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, registration no: CRD42020201435 and CRD42020201443.

Early and Mid-Term Implications of the COVID-19 Pandemic on the Physical, Behavioral and Mental Health of Healthcare Professionals: The CoPE-HCP Study Protocol.

INTRODUCTION: The COVID-19 pandemic has led to unprecedented strain to healthcare systems worldwide and posed unique challenges to the healthcare professionals (HCPs) and the general public. OBJECTIVES: The aim of this study is to evaluate the impact of COVID-19 on the mental health, behavioral, and physical wellbeing of HCPs in the early and mid-term periods of the pandemic in comparison to non-HCPs. Thus, facilitating and guiding optimum planning and delivery of support to HCPs. METHODS AND ANALYSIS: An observational cross-sectional survey and cohort study aiming to enroll over 1050 participants (minimum, 800 HCPs and 250 controls). Study questionnaires will be completed at baseline and after 6-weeks and 4-months. Recruitment initiated July 2020. The study was designed in London, United Kingdom, but open to participants worldwide. Baseline: Questionnaires comprising of validated self-administered screening tools for depression, anxiety, sleep-related issues, wellbeing, and burnout. The questionnaires also explore changes in behavior and physical wellbeing of the participants. In addition, associations of these mental health and behavioral factors with work-related factors and support will be explored. Six-weeks and 4-months follow-up: Follow-up questionnaires will assess change in symptoms of anxiety and depression, sleep disorders, use of alcohol and other substances, behavioral or interpersonal relationship changes. Physical wellbeing will be assessed through the presence of suspected or confirmed COVID-19 infection and absence from work. We will also evaluate the impact of variable provision of personal protection equipment (supply and training), extended working hours, and concern for the wellbeing of family members, anxiety levels, and evidence of burnout. STATISTICAL CONSIDERATIONS: The study has 80% power to detect a 10% difference of combined depression and/or anxiety symptoms between the groups using two-sided type 1 error at 0.05 at baseline. Assuming that only 50% of these HCPs agree to be a part of a cohort survey, we will have 80% power to detect around 12% difference in the two groups in reported physical symptoms (20% vs. 32.3%), or prevalence of depression and/or anxiety at the end of the study. ETHICS: The study was approved by the Cambridge East, Research Ethics Committee (20/EE/0166). TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT04433260.

Current Perspectives on Coronavirus Disease 2019 and Cardiovascular Disease: A White Paper by the JAHA Editors.

Coronavirus Disease 2019 (COVID-19) has infected more than 3.0 million people worldwide and killed more than 200,000 as of April 27, 2020. In this White Paper, we address the cardiovascular co-morbidities of COVID-19 infection; the diagnosis and treatment of standard cardiovascular conditions during the pandemic; and the diagnosis and treatment of the cardiovascular consequences of COVID-19 infection. In addition, we will also address various issues related to the safety of healthcare workers and the ethical issues related to patient care in this pandemic.

Neurocysticercosis in pregnancy: maternal and fetal outcomes.

Neurocysticercosis (NCC) is a parasitic infection with the larvae of Taenia solium from contaminated pork. It is a leading cause of seizures in the developing world. Symptoms may be secondary to live or degenerating cysts, or previous infection causing calcification or gliosis. Diagnosis is based on clinical presentation, radiological confirmation of intracranial lesions and immunological testing. Management involves symptom control with antiepileptics and antiparasitic agents. Few cases have been described of maternal NCC during pregnancy. We describe a 25-year-old female presenting to a London hospital with secondary generalized seizures. MRI of the brain confirmed a calcified lesion in the right parietal lobe, and she gave a corroborative history of NCC during her childhood in India. She was stabilized initially on antiepileptics, but during her pregnancy presented with breakthrough seizures and radiological evidence of NCC reactivation. She was managed symptomatically with antiepileptics and completed the pregnancy to term with no fetal complications.

Human-derived natural antibodies: biomarkers and potential therapeutics.

The immune system generates antibodies and antigen-specific T-cells as basic elements of the immune networks that differentiate self from non-self in a finely tuned manner. The antigen-specific nature of immune responses ensures that normal immune activation contains non-self when tolerating self. Here we review the B-1 subset of lymphocytes which produce self-reactive antibodies. By analyzing the IgM class of natural antibodies that recognize antigens from the nervous system, we emphasize that natural antibodies are biomarkers of how the immune system monitors the host. The immune response activated against self can be detrimental when triggered in an autoimmune genetic background. In contrast, tuning immune activity with natural antibodies is a potential therapeutic strategy.

Fundamental studies of hybrid poly(2-(diisopropylamino)ethyl methacrylate)/poly(N-vinylpyrrolidone) films and capsules.

Hybrid and multicompartment carriers are of significant interest for the development of next-generation therapeutic drug carriers. Herein, fundamental investigations on layer-by-layer (LbL) capsules consisting of two different polymers are presented. The hybrid systems were designed to have pH-responsive, charge-shifting poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) inner layers and low-fouling poly(N-vinylpyrrolidone) (PVPON) outer layers. Planar hybrid films with different layer ratios were studied by quartz crystal microgravimetry (QCM) and atomic force microscopy (AFM). The information obtained was translated to particulate templates to prepare hybrid capsules, which were stabilized by click chemistry. The charge-shifting behavior of PDPA improved the cargo encapsulation and initial retention of a model CpG cargo, while outer layers of PVPON improved biofouling properties compared to single-component PDPA capsules. The results demonstrate the need to understand and design multifunctional systems that can successfully embody different functionalities in a single, stable construct for the fabrication of next-generation drug and gene delivery carriers aimed at overcoming the challenges encountered in biological systems.

Clickable Poly(2-oxazoline) Architectures for the Fabrication of Low-Fouling Polymer Capsules.

Hollow polymer capsules were prepared from linear as well as brushlike poly(2-oxazoline)s (POxs). Linear POxs containing alkene functionalities were obtained by cationic ring-opening polymerization (CROP), whereas the brush POxs bearing alkyne moieties were synthesized by a combination of CROP and reversible addition-fragmentation chain transfer (RAFT) polymerization. Multilayers consisting of POx/poly(methacrylic acid) (PMA) were sequentially deposited onto silica particle templates, and the films were stabilized either by thiol-ene (TE) chemistry or copper-catalyzed azide-alkyne cycloaddition (CuAAc). Stable, monodisperse capsules were formed after removal of the silica particles with hydrofluoric acid and were observed using fluorescence and atomic force microscopy (AFM). Both architectures exhibited low-fouling behavior, an essential criteria for therapeutic carriers to be utilized in bioapplications. In particular, the brush-like POx capsules show potential as a viable alternative material for the fabrication of low-fouling capsules.

Controlled release of DNA from poly(vinylpyrrolidone) capsules using cleavable linkers.

The design of polymer carriers with tunable degradation and cargo release is fundamental for applications in drug and gene delivery. In this study, we report low-fouling poly(N-vinyl pyrrolidone) (PVPON) capsules assembled via hydrogen bonding and stabilized using covalent cross-linking. We first investigated the effects of pH and ionic strength to optimize the assembly conditions. A model therapeutic cargo (plasmid DNA) was then loaded in the capsules and used for encapsulation and release studies. Two bisazide cross-linkers that contain a disulfide bond, termed PEG8 (poly(ethylene glycol)) and PEG(16), were employed to stabilize the multilayer films, and used to tune the degradation and cargo release behavior of the capsules in simulated cytoplasmic conditions. The results suggest that PEG8-stabilized capsules were more efficiently cross-linked, and hence displayed higher plasmid encapsulation. Consequently, the capsules cross-linked with PEG8 also showed a two-fold reduction in degradation rate. This ability to achieve controlled carrier degradation and cargo release makes these capsules of potential interest for drug and gene delivery.

Thin multilayer films and microcapsules containing DNA quadruplex motifs.

The assembly of multifunctional nanostructures bearing G-quadruplex motifs broadens the prospects of using G-quadruplexes as therapeutic carriers. Herein, we report the synthesis and characterization of an oligodeoxyguanosine, G15-mer polymer conjugate. We demonstrate that G15-mer oligonucleotides grafted to a polymer chain preserve the ability to self-assemble into ordered structures. The G-quadruplex-polymer conjugates were assembled onto a surface via hybridization with 30-mer cytosine strands, C30-mer, using a layer-by-layer approach to form microcapsules. A mechanism for the sequential assembly of the multilayer films and microcapsules is presented. We further investigate the photophysical behavior of porphyrin TMPyP4 bound to multilayer-coated particles. This study shows that the multilayer films bear residual and functional quadruplex moieties that can be used to effectively bind therapeutic agents.