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Sodium–glucose cotransporter 2 (SGLT2) inhibitors are effective antidiabetic therapies in patients with type 2 diabetes mellitus and are associated with improved glycaemic control as well as with reductions in body mass and blood pressure. In large cardiovascular outcome trials in patients with diabetes, SGLT2 inhibitors improve cardiovascular and renal outcomes, including hospitalization for heart failure, with this benefit extending to patients without diabetes who have heart failure with reduced ejection fraction. The possible mechanisms of benefit are being extensively investigated because they are unlikely to be related to improved glycaemic control. Early natriuresis with a reduction in plasma volume, a consequent rise in haematocrit, improved vascular function, a reduction in blood pressure and changes in tissue sodium handling are all likely to have a role. Additional mechanisms of SGLT2 inhibitors that might be beneficial include a reduction in adipose tissue-mediated inflammation and pro-inflammatory cytokine production, a shift towards ketone bodies as the metabolic substrate for the heart and kidneys, reduced oxidative stress, lowered serum uric acid level, reduced glomerular hyperfiltration and albuminuria, and suppression of advanced glycation end-product signalling. Further outcome trials and mechanistic studies, including in patients with heart failure with preserved ejection fraction or non-diabetic kidney disease, might identify other possible mechanisms of benefit of SGLT2-inhibitor therapy.SGLT2 inhibitors improve cardiovascular and renal outcomes even in patients without diabetes mellitus. In this Review, Cowie and Fisher describe the additional mechanisms of benefit of SGLT2 inhibitors, unrelated to improved glycaemic control.

In heart failure (HF), increased physical activity is associated with improved quality of life, reduced hospitalisation, and increased longevity and is an important aim of treatment. However, physical activity levels in individuals living with HF are typically extremely low. This qualitative study with one-to-one interviews systematically explores perceived clinical, environmental, and psychosocial barriers and enablers in older adults (≥70 years old) living with HF. Semi-structured interviews (N = 16) based on the Theoretical Domains Framework elicited 39 belief statements describing the barriers and enablers to physical activity. Theoretical domains containing these beliefs and corresponding constructs that were both pervasive and common were deemed most relevant. These were: concerns about physical activity (Beliefs about Consequences), self-efficacy (Beliefs about Capabilities), social support (Social Influences), major health event (Environmental Context and Resources), goal behavioural (Goal), action planning (Behavioural Regulation). This work extends the limited research on the modifiable barriers and enablers for physical activity participation by individuals living with HF. The research findings provide insights for cardiologists, HF-specialist nurses, and physiotherapists to help co-design and deliver a physical activity intervention more likely to be effective for individuals living with HF.

Today, with the advent of Large-scale generative Language Models (LLMs) it is now possible to simulate free responses to interview questions such as those traditionally analyzed using qualitative research methods. Qualitative methodology encompasses a broad family of techniques involving manual analysis of open-ended interviews or conversations conducted freely in natural language. Here we consider whether artificial “silicon participants” generated by LLMs may be productively studied using qualitative analysis methods in such a way as to generate insights that could generalize to real human populations. The key concept in our analysis is algorithmic fidelity , a validity concept capturing the degree to which LLM-generated outputs mirror human sub-populations’ beliefs and attitudes. By definition, high algorithmic fidelity suggests that latent beliefs elicited from LLMs may generalize to real humans, whereas low algorithmic fidelity renders such research invalid. Here we used an LLM to generate interviews with “silicon participants” matching specific demographic characteristics one-for-one with a set of human participants. Using framework-based qualitative analysis, we showed the key themes obtained from both human and silicon participants were strikingly similar. However, when we analyzed the structure and tone of the interviews we found even more striking differences. We also found evidence of a hyper-accuracy distortion. We conclude that the LLM we tested (GPT-3.5) does not have sufficient algorithmic fidelity to expect in silico research on it to generalize to real human populations. However, rapid advances in artificial intelligence raise the possibility that algorithmic fidelity may improve in the future. Thus we stress the need to establish epistemic norms now around how to assess the validity of LLM-based qualitative research, especially concerning the need to ensure the representation of heterogeneous lived experiences.

Background Prior to the Covid-19 pandemic, heart failure (HF) disease management programmes were predominantly delivered in-person, with telemedicine being uncommon. Covid-19 resulted in a rapid shift to “remote-by-default” clinic appointments in many organisations. We evaluated clinician and patient experiences of teleconsultations for HF. Methods From 16th March 2020, all HF appointments at a specialist centre in the UK were telemedicine-by-default through a mixture of telephone and video consultations, with rare in-person appointments. HF clinicians and patients with HF were invited to participate in semi-structured interviews about their experiences. A purposive sampling technique was used. Interviews were conducted using Microsoft Teams®, recorded and transcribed verbatim. Narrative data were explored by thematic analysis. Clinicians and patients were interviewed until themes saturated. Results Eight clinicians and eight patients with HF were interviewed before themes saturated. Five overarching themes emerged: 1) Time utilisation – telemedicine consultations saved patients time travelling to and waiting for appointments. Clinicians perceived them to be more efficient, but more administrative time was involved. 2) Clinical assessment – without physical examination, clinicians relied more on history, observations and test results; video calls were perceived as superior to telephone calls for remote assessment. Patients confident in self-monitoring tended to be more comfortable with telemedicine. 3) Communication and rapport – clinicians experienced difficulty establishing rapport with new patients by telephone, though video was better. Patients generally did not perceive that remote consultation affected their rapport with clinicians. 4) Technology – connection issues occasionally disrupted video consultations, but overall patients and clinicians found the technology easy to use. 5) Choice and flexibility – both patients and clinicians believed that the choice of modality should be situation-dependent. Conclusions Telemedicine HF consultations were more convenient for patients, saved them time, and were generally acceptable to clinicians, but changed workflows, consultation dynamics, and how clinical assessment was performed. Telemedicine should be used alongside in-person appointments in a “hybrid” model tailored to individual patients and settings.

Background Discrepancy exists amongst studies investigating the effect of comorbid heart failure (HF) on the morbidity and mortality of chronic obstructive pulmonary disease (COPD) patients. Methods MEDLINE and Embase were searched using a pre-specified search strategy for studies comparing hospitalisation, rehospitalisation, and mortality of COPD patients with and without HF. Studies must have reported crude and/or adjusted rate ratios, risk ratios, odds ratios (OR), or hazard ratios (HR). Results Twenty-eight publications, reporting 55 effect estimates, were identified that compared COPD patients with HF with those without HF. One study reported on all-cause hospitalisation (1 rate ratio). Two studies reported on COPD-related hospitalisation (1 rate ratio, 2 OR). One study reported on COPD- or cardiovascular-related hospitalisation (4 HR). One study reported on 90-day all-cause rehospitalisation (1 risk ratio). One study reported on 3-year all-cause rehospitalisation (2 HR). Four studies reported on 30-day COPD-related rehospitalisation (1 risk ratio; 5 OR). Two studies reported on 1-year COPD-related rehospitalisation (1 risk ratio; 1 HR). One study reported on 3-year COPD-related rehospitalisation (2 HR). Eighteen studies reported on all-cause mortality (1 risk ratio; 4 OR; 24 HR). Five studies reported on all-cause inpatient mortality (1 risk ratio; 4 OR). Meta-analyses of hospitalisation and rehospitalisation were not possible due to insufficient data for all individual effect measures. Meta-analysis of studies requiring spirometry for the diagnosis of COPD found that risk of all-cause mortality was 1.61 (pooled HR; 95%CI: 1.38, 1.83) higher in patients with HF than in those without HF. Conclusions In this systematic review, we investigated the effect of HF comorbidity on hospitalisation and mortality of COPD patients. There is substantial evidence that HF comorbidity increases COPD-related rehospitalisation and all-cause mortality of COPD patients. The effect of HF comorbidity may differ depending on COPD phenotype, HF type, or HF severity and should be the topic of future research.

Heart failure is a life‐threatening disease and addressing it should be considered a global health priority. At present, approximately 26 million people worldwide are living with heart failure. The outlook for such patients is poor, with survival rates worse than those for bowel, breast or prostate cancer. Furthermore, heart failure places great stresses on patients, caregivers and healthcare systems. Demands on healthcare services, in particular, are predicted to increase dramatically over the next decade as patient numbers rise owing to ageing populations, detrimental lifestyle changes and improved survival of those who go on to develop heart failure as the final stage of another disease. It is time to ease the strain on healthcare systems through clear policy initiatives that prioritize heart failure prevention and champion equity of care for all. Despite the burdens that heart failure imposes on society, awareness of the disease is poor. As a result, many premature deaths occur. This is in spite of the fact that most types of heart failure are preventable and that a healthy lifestyle can reduce risk. Even after heart failure has developed, premature deaths could be prevented if people were taught to recognize the symptoms and seek immediate medical attention. Public awareness campaigns focusing on these messages have great potential to improve outcomes for patients with heart failure and ultimately to save lives. Compliance with clinical practice guidelines is also associated with improved outcomes for patients with heart failure. However, in many countries, there is considerable variation in how closely physicians follow guideline recommendations. To promote equity of care, improvements should be encouraged through the use of hospital performance measures and incentives appropriate to the locality. To this end, policies should promote the research required to establish an evidence base for performance measures that reflect improved outcomes for patients. Continuing research is essential if we are to address unmet needs in caring for patients with heart failure. New therapies are required for patients with types of heart failure for which current treatments relieve symptoms but do not address the disease. More affordable therapies are desperately needed in the economically developing world. International collaborative research focusing on the causes and treatment of heart failure worldwide has the potential to benefit tens of millions of people. Change at the policy level has the power to drive improvements in prevention and care that will save lives. It is time to make a difference across the globe by confronting the problem of heart failure. A call to action: policy recommendations We urge policymakers at local, national and international levels to collaborate and act on the following recommendations. Promote heart failure prevention Support the development and implementation of public awareness programmes about heart failure. These should define heart failure in simple and accessible language, explain how to recognize the symptoms and emphasize that most types of heart failure are preventable.Highlight the need for healthcare professionals across all clinical disciplines to identify patients with illnesses that increase the risk of heart failure and to prescribe preventive medications.Prioritize the elimination of infectious diseases in parts of the world where they still cause heart failure. Improve heart failure awareness amongst healthcare professionals Encourage the development and use of heart failure education programmes for all appropriate healthcare professionals. These should aim to improve the prevention, diagnosis, treatment and long‐term management of heart failure and raise awareness of clinical practice guidelines. Ensure equity of care for all patients with heart failure Provide a healthcare system that delivers timely access to diagnostic services and treatment of heart failure, as well as a seamless transition to long‐term management.Ensure that the best available and most appropriate care is consistently provided to all patients with heart failure through efficient use of resources. Support and empower patients and their caregivers Provide resources for the education and practical support of patients with heart failure and their families or other caregivers, empowering them to engage proactively in long‐term care. Promote heart failure research Fund and encourage international collaborative research to improve understanding of the patterns, causes and effects of modern day heart failure and how the disease can be prevented across the globe.Fund and encourage research into new and more affordable therapies and medical devices for all types of heart failure.Fund and encourage research into evidence‐based healthcare performance measures that reflect improved clinical outcomes for patients with heart failure.

Heart failure is appropriately described as an epidemic, with 1–2% of health care expenditure being directed at its management. In England, the National Institute for Health and Care Excellence (NICE) has issued guidance on the best practice for the diagnosis and treatment of acute and chronic heart failure. Echocardiography is key to the diagnosis of the underlying cardiac abnormalities, and access to this (with our without biochemical testing using natriuretic peptides) is key to high-quality and speedy diagnosis. New models of care aim to speed up access to echocardiography, but a shortage of technically trained staff remains a limiting factor in improving standards of care. The NHS audits the quality of care and outcome for patients admitted to hospital with heart failure, and this continues to show wide variation in practice, particularly, where patients are not reviewed by the local heart failure multidisciplinary team. Recently, the All Party Parliamentary Group on Cardiac Disease issued 10 suggestions for improvement in care for patients with heart failure – access to echocardiography being one of the key suggestions. Time will tell as to whether this support from law makers will assist in the implementation of NICE-recommended standards of care consistently across the country.

Abstract Aims Improving quality of life (QoL) in heart failure patients is a key management objective. Validated health-related QoL (HR-QoL) measurement tools have been incorporated into clinical trials but not routinely into daily practice. The aims of this study were to investigate the acceptability and feasibility of implementing validated HR-QoL instruments into heart failure clinics and to examine the impact of patient characteristics on HR-QoL. Methods and results One hundred and sixty-three patients attending heart failure clinics at a UK tertiary centre were invited to complete three HR-QoL assessments: the Minnesota Living with Heart Failure Questionnaire (MLHFQ); the EuroQoL 5D-3L (EQ-5D-3L); and the Kansas City Cardiomyopathy Questionnaire (KCCQ) in that order. Data on patient demographics, co-morbidities, New York Heart Association (NYHA) class, plasma B-type natriuretic peptide (BNP), renal function, and left ventricular ejection fraction were recorded. 94% of patients attending clinic were willing to participate. The EQ-5D-3L had all questions answered by 92% of patients, compared with 86% and 51% for the MLHFQ and KCCQ, respectively. HR-QoL significantly correlated with NYHA class using each tool (MLHFQ, r = 0.59; KCCQ, r = −0.61; EQ-5D-3L, r = −0.44, all P < 0.01). However, within each NYHA class, there was a widespread of HR-QoL scores. There was no association between patient demographics, left ventricular ejection fraction, plasma B-type natriuretic peptide, or renal function with HR-QoL using any tool. Conclusions Health-related QoL assessment by validated questionnaire was acceptable to patients and feasible to perform in routine practice. Although NYHA class correlated significantly with HR-QoL scores, there was high variability in HR-QoL within each NYHA class, highlighting its limitation as the sole assessment of HR-QoL. Clinicians should encourage the assessment of HR-QoL to facilitate patient-centred care and make more specific use of HR-QoL measurement tools.

Background Comorbidity is common and has a substantial negative impact on the prognosis of patients with acute myocardial infarction (AMI). Whilst receipt of guideline-indicated treatment for AMI is associated with improved prognosis, the extent to which comorbidities influence treatment provision its efficacy is unknown. Therefore, we investigated the association between treatment provision for AMI and survival for seven common comorbidities. Methods We used data of 693,388 AMI patients recorded in the Myocardial Ischaemia National Audit Project (MINAP), 2003–2013. We investigated the association between comorbidities and receipt of optimal care for AMI (receipt of all eligible guideline-indicated treatments), and the effect of receipt of optimal care for comorbid AMI patients on long-term survival using flexible parametric survival models. Results A total of 412,809 [59.5%] patients with AMI had at least one comorbidity, including hypertension (302,388 [48.7%]), diabetes (122,228 [19.4%]), chronic obstructive pulmonary disease (COPD, 89,221 [14.9%]), cerebrovascular disease (51,883 [8.6%]), chronic heart failure (33,813 [5.6%]), chronic renal failure (31,029 [5.0%]) and peripheral vascular disease (27,627 [4.6%]). Receipt of optimal care was associated with greatest survival benefit for patients without comorbidities (HR 0.53, 95% CI 0.51–0.56) followed by patients with hypertension (HR 0.60, 95% CI 0.58–0.62), diabetes (HR 0.83, 95% CI 0.80–0.87), peripheral vascular disease (HR 0.85, 95% CI 0.79–0.91), renal failure (HR 0.89, 95% CI 0.84–0.94) and COPD (HR 0.90, 95% CI 0.87–0.94). For patients with heart failure and cerebrovascular disease, optimal care for AMI was not associated with improved survival. Conclusions Overall, guideline-indicated care was associated with improved long-term survival. However, this was not the case in AMI patients with concomitant heart failure or cerebrovascular disease. There is therefore a need for novel treatments to improve outcomes for AMI patients with pre-existing heart failure or cerebrovascular disease.

ObjectivesStroke is a major cause of morbidity and mortality. This study aimed to investigate secular trends in stroke across the UK.DesignThis study aimed to investigate recent trends in the epidemiology of stroke in the UK. The study was a time-trend analysis from 1999 to 2008 within the UK General Practice Research Database. Outcome measures were incidence and prevalence of stroke, stroke mortality, rate of secondary cardiovascular events, and prescribing of pharmacological therapy for primary and secondary prevention of cardiovascular disease.ResultsThe study cohort included 32 151 patients with a first stroke. Stroke incidence fell by 30%, from 1.48/1000 person-years in 1999 to 1.04/1000 person-years in 2008 (p<0.001). Stroke prevalence increased by 12.5%, from 6.40/1000 in 1999 to 7.20/1000 in 2008 (p<0.001). 56-day mortality after first stroke reduced from 21% in 1999 to 12% in 2008 (p<0.0001). Prescribing of drugs to control cardiovascular risk factors increased consistently over the study period, particularly for lipid lowering agents and antihypertensive agents. In patients with atrial fibrillation, use of anticoagulants prior to first stroke did not increase with increasing stroke risk.ConclusionStroke incidence in the UK has decreased and survival after stroke has improved in the past 10 years. Improved drug treatment in primary care is likely to be a major contributor to this, with better control of risk factors both before and after incident stroke. There is, however, scope for further improvement in risk factor reduction in high-risk patients with atrial fibrillation.