Selecting patients with nonischemic dilated cardiomyopathy for ICDs

No abstract available

When can heart failure treatment be stopped safely? – Authors' reply

No abstract available

Personalizing sudden death risk stratification in dilated cardiomyopathy: past, present and future

Results from the DANISH Study (Danish Study to Assess the Efficacy of ICDs in Patients with Nonischemic Systolic Heat Failure on Mortality) suggest that, for many patients with dilated cardiomyopathy (DCM), implantable cardioverter defibrillators (ICD) do not increase longevity. Accurate identification of patients who are more likely to die of an arrhythmia and less likely to die from other causes is required to ensure improvement in outcomes and wise use of resources. Until now, left ventricular ejection fraction (LVEF) has been used as a key criterion for selecting patients with DCM for an ICD for primary prevention purposes. However, registry data suggest that many patients with DCM and an out-of-hospital cardiac arrest do not have a markedly reduced LVEF. Additionally, many patients with reduced LVEF die from non-sudden causes of death. Methods to predict a higher or lower risk of sudden death include the detection of myocardial fibrosis (a substrate for ventricular arrhythmia), microvolt T-wave alternans (MTWA; a marker of electrophysiological vulnerability) and genetic testing. Mid-wall fibrosis is identified by late gadolinium enhancement cardiovascular magnetic resonance imaging in around 30% of patients and provides incremental value in addition to LVEF for the prediction of SCD events. MTWA represents another promising predictor, supported by large meta-analyses that have highlighted the negative predictive value of this test. However, neither of these strategies has been routinely adopted for risk stratification in clinical practice. More convincing data from randomized trials are required to inform the management of patients with these features. Understanding of the genetics of DCM and how specific mutations affect arrhythmic risk is also rapidly increasing. The finding of a mutation in LMNA, the cause of around 6% of idiopathic DCM, commonly underpins more aggressive management due to the malignant nature of the associated phenotype. With the expansion of genetic sequencing, the identification of further high-risk mutations appears likely, leading to better informed clinical decision-making as well as providing insight into disease mechanisms. Over the next 5-10 years we expect these techniques to be integrated into the existing algorithm to form a more sensitive, specific and cost-effective approach to the selection of DCM patients for ICD implantation

Case Study -Creating the WCRM Concept of Operations

Abstract. This paper describes our experience in defining a suitable style, structure, content and set of features for the West Coast Route Modernisation (WCRM) Concept of Operations. The ability to capture the operational context of the future West Coast Main Line (WCML) railway is a critical integration activity, and key to the successful delivery of the WCRM, in particular as operational improvements contribute to a large part of the performance improvements on a railway. In the absence of guidance or standards for the production of operational concepts documents for a subject as vast and complex, we have applied rich traceability and requirements engineering best practice, with the aim to produce fit for purpose, clear and useable documentation. This paper also presents the relation between the Concept of Operations and the rest of the WCRM Systems Engineering activities, in particular its influence on the Systems Design Specification. It summarises the lessons learned and planned future developments

Donor-recipient HLA-A mismatching is associated with hepatic artery thrombosis, sepsis, graft loss and reduced survival after liver transplantation

HLA matching is not routinely performed for liver transplantation as there is no consistent evidence of benefit, however the impact of HLA mismatching remains uncertain. We explored the effect of class I and II HLA mismatching on graft failure and mortality. 1042 liver transplants performed at a single centre, between 1999 and 2016 with available HLA typing data were included. Median follow up period was 9.38 years (IQR 4.9-14) and 350/1042 (33.6%) transplants resulted in graft loss and 280/1042 (26.9%) in death. Graft loss and mortality were not associated with the overall number of mismatches at HLA-A, -B, -C, -DR and -DQ loci. However, graft failure and mortality were both increased in the presence of one (p = 0.004 and p = 0.01) and two (p = 0.01 and p = 0.04) HLA-A mismatches. Elevated hazard ratios for graft failure and death were observed with HLA-A mismatches in univariate and multivariate Cox proportional hazard models. Excess graft loss with HLA-A mismatch (138/940 (14.7%) of mismatched compared to 6/102 (5.9%) matched transplants) occurred within the first-year following transplantation (OR 2.75, p = 0.02). Strikingly, all grafts lost due to hepatic artery thrombosis were in HLA-A mismatched transplants (31/940 vs. 0/102), as were those lost due to sepsis (35/940 vs. 0/102). In conclusion, HLA-A mismatching was associated with increased graft loss and mortality. The poorer outcome for The HLA mismatched group was due to hepatic artery thrombosis and sepsis and these complications occurred exclusively with HLA-A mismatched transplants. This suggests that HLA-A mismatching is important for post-transplant outcomes and knowledge of HLA-A status may enable enhanced surveillance and interventions to reduce risk of complications or stratified HLA-A matching in high-risk recipients

Study Protocol For Clinical Trial of the Fit Families Multicomponent Obesity intervention For african american adolescents and their Caregivers: Next Step From the orbit initiative

INTRODUCTION: This study will test the effectiveness of FIT Families (FIT), a multicomponent family-based behavioural intervention, against a credible attention control condition, Home-Based Family Support (HBFS). This protocol paper describes the design of a randomised clinical trial testing the efficacy of the FIT intervention. The protocol will assess the efficacy of FIT to improve health status in African American adolescents with obesity (AAAO) and their primary caregivers on primary (percent body fat) and secondary (physical activity, metabolic control, weight loss) outcomes and its cost-effectiveness. METHODS: 180 youth/caregiver dyads are randomised into FIT or HBFS, stratified by age, gender and baseline per cent overweight. The proposed study follows a two condition (FIT, HBFS) by four assessment time points. Tests will be conducted to identify potential relationship of baseline demographic and clinical variables to our dependent variables and see whether they are balanced between groups. It is hypothesised that youth/caregiver dyads randomised to FIT will show significantly greater reductions in percent body fat over a 12-month follow-up period compared with AAAO receiving HBFS. Preliminary findings are expected by November 2023. ETHICS: This protocol received IRB approval from the Medical University of South Carolina (Pro00106021; see \u27MUSC IRB 106021 Main Approval.doxc\u27 in online supplemental materials). DISSEMINATION: Dissemination activities will include summary documents designed for distribution to the broader medical community/family audience and submission of manuscripts, based on study results, to relevant peer-reviewed scientific high-impact journals. TRIAL REGISTRATION NUMBER: NCT04974554