Jane A. Cannon

Dementia-related adverse events in PARADIGM-HF and other trials in heart failure with reduced ejection fraction.

Inhibition of neprilysin, an enzyme degrading natriuretic and other vasoactive peptides, is beneficial in heart failure with reduced ejection fraction (HFrEF), as shown in PARADIGM‐HF which compared the angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan with enalapril. As neprilysin is also one of many enzymes clearing amyloid‐β peptides from the brain, there is a theoretical concern about the long‐term effects of sacubitril/valsartan on cognition. Therefore, we have examined dementia‐related adverse effects (AEs) in PARADIGM‐HF and placed these findings in the context of other recently conducted HFrEF trials.

‘Hearts and minds’: association, causation and implication of cognitive impairment in heart failure

The clinical syndrome of heart failure is one of the leading causes of hospitalisation and mortality in older adults. An association between cognitive impairment and heart failure is well described but our understanding of the relationship between the two conditions remains limited. In this review we provide a synthesis of available evidence, focussing on epidemiology, the potential pathogenesis, and treatment implications of cognitive decline in heart failure. Most evidence available relates to heart failure with reduced ejection fraction and the syndromes of chronic cognitive decline or dementia. These conditions are only part of a complex heart failure-cognition paradigm. Associations between cognition and heart failure with preserved ejection fraction and between acute delirium and heart failure also seem evident and where data are available we will discuss these syndromes. Many questions remain unanswered regarding heart failure and cognition. Much of the observational evidence on the association is confounded by study design, comorbidity and insensitive cognitive assessment tools. If a causal link exists, there are several potential pathophysiological explanations. Plausible underlying mechanisms relating to cerebral hypoperfusion or occult cerebrovascular disease have been described and it seems likely that these may coexist and exert synergistic effects. Despite the prevalence of the two conditions, when cognitive impairment coexists with heart failure there is no specific guidance on treatment. Institution of evidence-based heart failure therapies that reduce mortality and hospitalisations seems intuitive and there is no signal that these interventions have an adverse effect on cognition. However, cognitive impairment will present a further barrier to the often complex medication self-management that is required in contemporary heart failure treatment.

Cognitive impairment and heart failure: systematic review and meta-analysis

BACKGROUND Cognitive impairment and dementia are associated with a range of cardiovascular conditions, including hypertension, coronary artery disease, and atrial fibrillation. We aimed to describe the association with heart failure, summarizing published data to give estimates of prevalence, incidence, and relative risk of cognitive impairment/dementia in heart failure. METHODS We searched multidisciplinary databases including MEDLINE (OVID), EMBASE (OVID), CINAHL (EBSCO), PsychINFO (EBSCO), Web of Science (Thomson Reuters), and CENTRAL (Cochrane Library) from inception until May 31, 2015. All relevant studies looking at cognitive impairment/dementia in heart failure were included. Studies were selected by 2 independent reviewers using prespecified inclusion/exclusion criteria. Where data allowed, we performed meta-analysis and pooled results using random effects models. RESULTS From 18,000 titles, 37 studies were eligible (n = 8411 participants). Data from 4 prospective cohorts (n = 2513 participants) suggest greater cognitive decline in heart failure compared with non-heart failure over the longer term. These data were not suitable for meta-analysis. In case control studies describing those with and without heart failure (n = 4 papers, 1414 participants) the odds ratio for cognitive impairment in the heart failure population was 1.67 (95% confidence interval 1.15-2.42). Prevalence of cognitive impairment in heart failure cohorts (n = 26 studies, 4176 participants) was 43% (95% confidence interval 30-55). CONCLUSIONS This review suggests a substantial proportion of patients with heart failure have concomitant cognitive problems. This has implications for planning treatment and services. These data do not allow us to comment on causation, and further work is needed to describe the underlying pathophysiology.

Clinical outcomes according to QRS duration and morphology in the Eplerenone in Mild Patients: Hospitalization and SurvIval Study in Heart Failure (EMPHASIS-HF).

We examined the relationship between different degrees of QRS prolongation and different QRS morphologies and clinical outcomes in patients with heart failure, reduced ejection fraction (HF‐REF), and mild symptoms in the Eplerenone in Mild Patients Hospitalization and SurvIval Study in Heart Failure trial (EMPHASIS‐HF). We also evaluated the effect of eplerenone in these patients according to QRS duration/morphology.

What can we learn from RELAX-AHF compared to previous AHF trials and what does the future hold?

Each year in the USA there are over 1 million hospital admissions directly related to heart failure (HF). With similar rates across Europe, this places a huge economic burden on healthcare systems globally. Hospitalisation for HF is associated with poor clinical outcomes with 25% of patients being readmitted with signs and symptoms of HF within 1 month of discharge and 10–20% dying in the 6 months after discharge. Although hospital admission could be a sign of disease progression, it is also possible that some of the treatments given acutely for example, inotropic therapy, may result in neurohormonal, haemodynamic and other effects accelerating end-organ damage and contributing to these poor outcomes after discharge. In contrast to the treatment of chronic heart failure (CHF), clinical trials conducted over the past decade in patients with acute HF (AHF) have failed to show significant reductions in morbidity or mortality despite some agents causing beneficial changes in symptoms. As such, the current treatment of patients hospitalised with HF is mainly based on consensus rather than clinical evidence and has changed little over time. We review RELAX-AHF in the context of the other key, large-scale AHF trials conducted over the past 15 years and compare and contrast study design and outcomes in an attempt to determine which factors might be associated with a successful trial in the future.

Gut Feelings About Heart Failure

There are few if any conditions that involve as many organs as heart failure (HF). Clinicians see lung, kidney, liver, brain, and skeletal muscle involvement on a day-to-day basis when managing patients with HF. For some years, the gut has also been implicated in HF. Specifically, it has been

Clinical outcomes according to QRS duration and morphology in the irbesartan in patients with heart failure and preserved systolic function (I-PRESERVE) trial

The aims of this study were to describe the prevalence of QRS prolongation and abnormal QRS morphology in patients with heart failure and preserved ejection fraction (HF‐PEF) and to examine the relationship between these QRS abnormalities and clinical outcomes.

Emerging biomarkers for heart failure: an update

A growing array of biological pathways underpins the syndrome we recognize as heart failure. These include both deleterious pathways promoting its development and progression, as well as compensatory cardioprotective pathways. Components of these pathways can be utilized as biomarkers of this condition to aid diagnosis, prognostication and potentially guide management. As our understanding of the pathophysiology of heart failure deepens further candidate biomarkers are being identified. We provide an overview of the more recently emerging biomarkers displaying potential promise for future clinical use.

Uncertainties about medical treatment of acute heart failure

Dworzynski and colleagues’ summary of latest guidelines on the management of acute heart failure from the National Institute for Health and Care Excellence failed to mention one important point.1 To date, …

Improving outcomes in peripartum cardiomyopathy

Peripartum cardiomyopathy (PPCM) is a rare condition with a diverse spectrum of potential outcomes, ranging from frequent complete recovery to fulminant heart failure and death. The pathogenesis of PPCM is not well understood, and relatively little is known about its incidence and prevalence. PPCM is often under-recognised in the clinical setting. Early investigation and diagnosis with subsequent expert management may improve outcomes. The development of registries will allow this condition to be better characterised and may help answer crucial questions regarding its optimal medical and surgical management. This paper reviews the potential approaches to improve outcomes in patients with PPCM.