Non-ischaemic cardiomyopathy, sudden death and implantable defibrillators: a review and meta-analysis

Objective: The recent Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH) trial suggested that implantable cardioverter defibrillators (ICDs) do not reduce overall mortality in patients with non-ischaemic cardiomyopathy (NICM), despite reducing sudden cardiac death. We performed an updated meta-analysis to examine the impact of ICD therapy on mortality in NICM patients. Methods: A systematic search for studies that examined the effect of ICDs on outcomes in NICM was performed. Our analysis compared patients randomised to an ICD with those randomised to no ICD, and examined the endpoint of overall mortality. Results: Six primary prevention trials and two secondary prevention trials were identified that met the pre-specified search criteria. Using a fixed-effects model, analysis of primary prevention trials revealed a reduction in overall mortality with ICD therapy (RR 0.76, 95% CI 0.65 to 0.91). Conclusions: Although our updated meta-analysis demonstrates a survival benefit of ICD therapy, the effect is substantively weakened by the inclusion of the DANISH trial—which is both the largest and most recent of the analysed trials—indicating that the residual pooled benefit of ICDs may reflect the risk of sudden death in older trials which included patients treated sub-optimally by contemporary standards. As such, these data must be interpreted cautiously. The results of the DANISH trial emphasise that there is no ‘one size fits all’ indication for primary prevention ICDs in NICM patients, and clinicians must consider age and comorbidity on an individual basis when determining whether a defibrillator is appropriate

Who benefits from a defibrillator—balancing the risk of sudden versus non-sudden death

Purpose of Review: Treatment with a defibrillator can reduce the risk of sudden death by terminating ventricular arrhythmias. The identification of patient groups in whom this function reduces overall mortality is challenging. In this review, we summarise the evidence for who benefits from a defibrillator. Recent Findings: Recent evidence suggests that contemporary pharmacologic and non-defibrillator device therapies are altering the potential risks and benefits of a defibrillator. Summary: Who benefits from a defibrillator is determined by both the risk of sudden death and the competing risk of other, non-sudden causes of death. The balance of these risks is changing, which calls into question whether historic evidence for the use of defibrillators remains robust in the modern era

Anticoagulation therapy in heart failure and sinus rhythm: a systematic review and meta-analysis

Objective: Heart failure is a prothrombotic state, and it has been hypothesised that thrombosis and embolism cause non-fatal and fatal events in heart failure and reduced ejection fraction (HFrEF). We sought to determine the effect of anticoagulant therapy on clinical outcomes in patients with HFrEF who are in sinus rhythm. Methods: We conducted an updated systematic review and meta-analysis to examine the effect of anticoagulation therapy in patients with HFrEF in sinus rhythm. Our analysis compared patients randomised to anticoagulant therapy with those randomised to antiplatelet therapy, placebo or control, and examined the endpoints of all-cause mortality, (re)hospitalisation for worsening heart failure, non-fatal myocardial infarction, non-fatal stroke of any aetiology and major haemorrhage. Results: Five trials were identified that met the prespecified search criteria. Compared with control therapy, anticoagulant treatment did not reduce all-cause mortality (risk ratio [RR] 0.99, 95% CI 0.90 to 1.08), (re)hospitalisation for heart failure (RR 0.97, 95% CI 0.82 to 1.13) or non-fatal myocardial infarction (RR 0.92, 95% CI 0.75 to 1.13). Anticoagulation did reduce the rate of non-fatal stroke (RR 0.63, 95% CI 0.49 to 0.81, p=0.001), but this was offset by an increase in the incidence of major haemorrhage (RR 1.88, 95% CI 1.49 to 2.38, p=0.001). Conclusions: Our meta-analysis provides evidence to oppose the hypothesis that thrombosis or embolism plays an important role in the morbidity and mortality associated with HFrEF, with the exception of stroke-related morbidity

Palliative care needs in patients hospitalized with heart failure (PCHF) study: rationale and design

Abstract Aims The primary aim of this study is to provide data to inform the design of a randomized controlled clinical trial (RCT) of a palliative care (PC) intervention in heart failure (HF). We will identify an appropriate study population with a high prevalence of PC needs defined using quantifiable measures. We will also identify which components a specific and targeted PC intervention in HF should include and attempt to define the most relevant trial outcomes. Methods An unselected, prospective, near-consecutive, cohort of patients admitted to hospital with acute decompensated HF will be enrolled over a 2-year period. All potential participants will be screened using B-type natriuretic peptide and echocardiography, and all those enrolled will be extensively characterized in terms of their HF status, comorbidity, and PC needs. Quantitative assessment of PC needs will include evaluation of general and disease-specific quality of life, mood, symptom burden, caregiver burden, and end of life care. Inpatient assessments will be performed and after discharge outpatient assessments will be carried out every 4 months for up to 2.5 years. Participants will be followed up for a minimum of 1 year for hospital admissions, and place and cause of death. Methods for identifying patients with HF with PC needs will be evaluated, and estimates of healthcare utilisation performed. Conclusion By assessing the prevalence of these needs, describing how these needs change over time, and evaluating how best PC needs can be identified, we will provide the foundation for designing an RCT of a PC intervention in HF

Efficacy of implantable haemodynamic monitoring in heart failure across ranges of ejection fraction: a systematic review and meta-analysis

Aims: We conducted a meta-analysis of randomised controlled trials (RCTs) of implantable haemodynamic monitoring (IHM)-guided care. Methods: PubMed and Ovid MEDLINE were searched for RCTs of IHM in patients with heart failure (HF). Outcomes were examined in total (first and recurrent) event analyses. Results: Five trials comparing IHM-guided care with standard care alone were identified and included 2710 patients across ejection fraction (EF) ranges. Data were available for 628 patients (23.2%) with heart failure with preserved ejection fraction (HFpEF) (EF ≥50%) and 2023 patients (74.6%) with heart failure with a reduced ejection fraction (HFrEF) (EF <50%). Chronicle, CardioMEMS and HeartPOD IHMs were used. In all patients, regardless of EF, IHM-guided care reduced total HF hospitalisations (HR 0.74, 95% CI 0.66 to 0.82) and total worsening HF events (HR 0.74, 95% CI 0.66 to 0.84). In patients with HFrEF, IHM-guided care reduced total worsening HF events (HR 0.75, 95% CI 0.66 to 0.86). The effect of IHM-guided care on total worsening HF events in patients with HFpEF was uncertain (fixed-effect model: HR 0.72, 95% CI 0.59 to 0.88; random-effects model: HR 0.60, 95% CI 0.32 to 1.14). IHM-guided care did not reduce mortality (HR 0.92, 95% CI 0.71 to 1.20). IHM-guided care reduced all-cause mortality and total worsening HF events (HR 0.80, 95% CI 0.72 to 0.88). Conclusions: In patients with HF across all EFs, IHM-guided care reduced total HF hospitalisations and worsening HF events. This benefit was consistent in patients with HFrEF but not consistent in HFpEF. Further trials with pre-specified analyses of patients with an EF of ≥50% are required. PROSPERO registration number: CRD42021253905

Characterization of and structural insight into struvite-K, MgKPO4·6H2O, an analogue of struvite

Struvite-K (MgKPO4·6H2O) is a magnesium potassium phosphate mineral with naturally cementitious properties, which is finding increasing usage as an inorganic cement for niche applications including nuclear waste management and rapid road repair. Struvite-K is also of interest in sustainable phosphate recovery from wastewater and, as such, a detailed knowledge of the crystal chemistry and high-temperature behavior is required to support further laboratory investigations and industrial applications. In this study, the local chemical environments of synthetic struvite-K were investigated using high-field solid-state 25Mg and 39K MAS NMR techniques, alongside 31P MAS NMR and thermal analysis. A single resonance was present in each of the 25Mg and 39K MAS NMR spectra, reported here for the first time alongside the experimental and calculated isotropic chemical shifts, which were comparable to the available data for isostructural struvite (MgNH4PO4·6H2O). An in situ high-temperature XRD analysis of struvite-K revealed the presence of a crystalline–amorphous–crystalline transition that occurred between 30 and 350 °C, following the single dehydration step of struvite-K. Between 50 and 300 °C, struvite-K dehydration yielded a transient disordered (amorphous) phase identified here for the first time, denoted δ-MgKPO4. At 350 °C, recrystallization was observed, yielding β-MgKPO4, commensurate with an endothermic DTA event. A subsequent phase transition to γ-MgKPO4 was observed on further heating, which reversed on cooling, resulting in the α-MgKPO4 structure stabilized at room temperature. This behavior was dissimilar from that of struvite exposed to high temperature, where NH4 liberation occurs at temperatures >50 °C, indicating that struvite-K could potentially withstand high temperatures via a transition to MgKPO4

Reduction of quartz to silicon monoxide by methane-hydrogen mixtures

The reduction of quartz was studied isothermally in a fluidized bed reactor using continuously flowing methane-hydrogen gas mixture in the temperature range from 1623 K to 1773 K (1350 °C to 1500 °C). The CO content in the off-gas was measured online using an infrared gas analyzer. The main phases of the reduced samples identified by XRD analysis were quartz and cristobalite. Significant weight loss in the reduction process indicated that the reduction products were SiO and CO. Reduction of SiO2 to SiO by methane starts with adsorption and dissociation of CH4 on the silica surface. The high carbon activity in the CH4-H2 gas mixture provided a strongly reducing condition. At 1623 K (1350 °C), the reduction was very slow. The rate and extent of reduction increased with the increasing temperature to 1723 K (1450 °C). A further increase in temperature to 1773 K (1500 °C) resulted in a decrease in the rate and extent of reduction. An increase in the gas flow rate from 0.4 to 0.8 NL/min and an increase in the methane content in the CH4-H2 gas mixture from 0 to 5 vol pct facilitated the reduction. Methane content in the gas mixture should be maintained at less than 5 vol pct in order to suppress methane cracking

Adherence to prescribed medications in patients with heart failure – insights from liquid chromatography-tandem mass spectrometry-based urine analysis

Aims: None of the existing studies on adherence have directly measured levels of medications (or their metabolites) in patients with heart failure. Methods and Results: We used liquid chromatography-tandem mass spectrometry to measure the presence of prescribed drugs (diuretics, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists) in the urine of patients reviewed 4 to 6 weeks after hospitalisation with heart failure. Patients were unaware that adherence was being assessed. Of the 341 patients studied, 281 (82.4%) were adherent i.e. had all prescribed drugs of interest detectable in their urine. Conversely, 60 patients (17.6%) were partially or completely non-adherent. Notably, 24 of the 60 were non-adherent to only diuretic therapy and only 7 out of all 341 patients studied (2.1%) were completely non-adherent to all prescribed heart failure drugs. There were no major differences in baseline characteristics between adherent and non-adherent patients. Conclusion: Non-adherence, assessed using a single spot urine measurement of drug levels, was confirmed in 1 of 5 patients evaluated 4 to 6 weeks after hospitalisation with heart failure

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Psychology and aggression

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68264/2/10.1177_002200275900300301.pd