Search

Aims Cognitive dysfunction occurs frequently in patients with heart failure (HF), but early detection remains challenging. Serum glial fibrillary acidic protein (GFAP) is an emerging biomarker of cognitive decline in disorders of primary neurodegeneration such as Alzheimer's disease. We evaluated the utility of serum GFAP as a biomarker for cognitive dysfunction and structural brain damage in patients with stable chronic HF. Methods and results Using bead-based single molecule immunoassays, we quantified serum levels of GFAP in patients with HF participating in the prospective Cognition.Matters-HF study. Participants were extensively phenotyped, including cognitive testing of five separate domains and magnetic resonance imaging (MRI) of the brain. Univariable and multivariable models, also accounting for multiple testing, were run. One hundred and forty-six chronic HF patients with a mean age of 63.8 ± 10.8 years were included (15.1% women). Serum GFAP levels (median 246 pg/mL, quartiles 165, 384 pg/mL; range 66 to 1512 pg/mL) did not differ between sexes. In the multivariable adjusted model, independent predictors of GFAP levels were age (T = 5.5; P < 0.001), smoking (T = 3.2; P = 0.002), estimated glomerular filtration rate (T = −4.7; P < 0.001), alanine aminotransferase (T = −2.1; P = 0.036), and the left atrial end-systolic volume index (T = 3.4; P = 0.004). NT-proBNP but not serum GFAP explained global cerebral atrophy beyond ageing. However, serum GFAP levels were associated with the cognitive domain visual/verbal memory (T = −3.0; P = 0.003) along with focal hippocampal atrophy (T = 2.3; P = 0.025). Conclusions Serum GFAP levels are affected by age, smoking, and surrogates of the severity of HF. The association of GFAP with memory dysfunction suggests that astroglial pathologies, which evade detection by conventional MRI, may contribute to memory loss beyond ageing in patients with chronic HF.

Aims We quantified the concurring dynamics affecting total and hippocampal brain volume and cognitive function in patients with chronic heart failure (HF) over a period of three years. Methods and results A total of 148 patients with mild stable HF entered this monocentric prospective cohort study: mean age 64.5 (10.8) years; 16.2% female; 77% in New York Heart Association functional classes I–II; 128 and 105 patients attended follow-up visits after 1 and 3 years, respectively. The assessment included cardiological, neurological, psychological work-up, and brain magnetic resonance imaging. Total and regional brain volumes were quantified using an operator-independent fully automated approach and reported normalized to the mean estimated intracranial volume. At baseline, the mean hippocampal volume was ∼13% lower than expected. However, the 3-year progressive hippocampal volume loss was small: −62 mm3 [95% confidence interval (CI) −81 to −42, P Conclusion In patients with predominantly mild HF, the markedly reduced hippocampal volume observed at baseline was associated with impaired cognitive function, but no accelerated deterioration in cognition and brain atrophy became evident over a mid-term period of three years.

This study sought to determine the spectrum of brain lesions seen in heart failure (HF) patients and the extent to which lesion type contributes to cognitive impairment.Cognitive deficits have been reported in patients with HF.A total of 148 systolic and diastolic HF patients (mean age 64 ± 11 years; 16% female; mean left ventricular ejection fraction 43 ± 8%) were extensively evaluated within 2 days by cardiological, neurological, and neuropsychological testing and brain magnetic resonance imaging (MRI). A total of 288 healthy, sex- and age-matched subjects sampled from the Austrian Stroke Prevention Study served as MRI controls.Deficits in reaction times were apparent in 41% of patients and deficits in verbal memory in 46%. On brain MRI, patients showed more advanced medial temporal lobe atrophy (MTA) (Scheltens score) compared to controls (2.1 ± 0.9 vs. 1.0 ± 0.6; p 0.001). The degree of MTA was strongly associated with the severity of cognitive impairment, whereas the extent of white matter hyperintensities was similar in patients and controls. Moreover, patients had a 2.7-fold increased risk for presence of clinically silent lacunes.HF patients exhibit cognitive deficits in the domains of attention and memory. MTA but not white matter lesion load seems to be related to cognitive impairment.

Aims To investigate in detail the correlates of dysnatremia, and to estimate its differential prognostic relevance in patients with heart failure with reduced or preserved LVEF. Background Hyponatraemia has been shown to carry important prognostic information in patients with heart failure with reduced left ventricular ejection fraction (LVEF). However, exact serum sodium cut-off levels are not defined and the implications for heart failure with preserved ejection fraction (HF-pEF) are unclear. The prognostic value of hypernatraemia has not been investigated systematically. Therefore, the aim of this study was to investigate in detail the correlates of dysnatraemia, and to estimate its differential prognostic relevance in patients with heart failure with reduced or preserved LVEF. Methods and results One thousand consecutive patients with heart failure of any cause and severity from the Wurzburg Interdisciplinary Network for Heart Failure registry were included. Non-linear models for the association between serum sodium and mortality risk were calculated using restricted cubic splines and Cox proportional hazard regression. Median follow-up time for survivors was 5.1 years. Results Independent correlates of dysnatraemia included guideline-recommended medication for chronic heart failure, indicators of renal function, and reverse associations with established cardiac risk factors. Overall mortality was 56%. Both hyponatraemia (n = 72) and hypernatraemia (n = 98) were associated with a significantly increased mortality risk: hazard ratio (HR) 2.10, 95% confidence interval (CI) 1.60–2.77; and HR 1.91, 95% CI 1.49–2.45, respectively. A U-shaped association of serum sodium with mortality risk was found. Prognosis was best for patients with high normal sodium levels, i.e. 140–145 mmol/L. Conclusions Both hypo- and hypernatraemia indicate a markedly compromised prognosis in heart failure regardless of LVEF. Sodium levels within the reference range carry differential information on survival, with serum levels of 135–139 mmol/L indicating an increased mortality risk.

In our Cognition Matters HF study [(1)][1], we recruited patients between August 2011 and May 2014; thus, it was before sacubitril/valsartan had been approved for clinical use in Europe in 2015 [(2)][2]. Therefore, our baseline data provided in this paper are not influenced by sacubitril/valsartan

This editorial refers to ‘Cognitive and brain changes associated with ischaemic heart disease and heart failure’†, by O.P. Almeida et al. , on page 1769 and ‘Cognitive impairment and risk of cardiovascular events and mortality’‡, by M. O'Donell et al. , on page 1777 ARTICLE In 1977 the term ‘cardiogenic dementia’ was coined, suggesting that this disorder might at least in some instances be secondary to cardiovascular disease (CVD).1 To date, various smaller studies have sought to clarify this issue, but results have not always been consistent. Since in the elderly, cognitive impairment (CI), CVD, and heart failure (HF) frequently co-occur, the precise mechanisms underlying CI have remained difficult to disentangle. Neurobiology of important disorders such as depression and dementia has proposed exciting hypotheses,2 but has so far not thoroughly clarified the biological links with CVD. In experimental animals post-myocardial infarction, neurohumoral ‘remodelling’ was observed in multiple brain areas, and reduction of hypothalamic inflammation appeared to prevent heart failure.3,4 In humans, an association between the total burden of CVD and cognitive deterioration was reported.5,6 Further, the degree of CI correlated with the severity of left ventricular systolic dysfunction in HF patients.7 Reduced brain perfusion as a consequence of hypotension or low cardiac output was found to be implicated in cerebral dysfunction,8,9 and patients with impaired cerebrovascular reactivity due to old age, recent stroke, or carotid occlusive disease appeared at particular risk for brain ischaemia and atrophy due to hypoperfusion.10 Atrial fibrillation as a frequent complication of CVD and HF was found associated with both Alzheimer's disease and vascular dementia.11 Vice versa, cortical and autonomic nerve dysfunction and the brainstem appear also to affect cardiac electrophysiology and arrhythmias.12 Close associations between CI and other neuropsychological or functional perturbations, …

Background: Depression and anxiety are common and independent outcome predictors in patients with chronic heart failure (CHF). However, it is unclear whether CHF causes depression. Thus, we investigated whether mice develop anxiety- and depression-like behavior after induction of ischemic CHF by myocardial infarction (MI). Methods and Results: In order to assess depression-like behavior, anhedonia was investigated by repeatedly testing sucrose preference for 8 weeks after coronary artery ligation or sham operation. Mice with large MI and increased left ventricular dimensions on echocardiography (termed CHF mice) showed reduced preference for sucrose, indicating depression-like behavior. 6 weeks after MI, mice were tested for exploratory activity, anxiety-like behavior and cognitive function using the elevated plus maze (EPM), light-dark box (LDB), open field (OF), and object recognition (OR) tests. In the EPM and OF, CHF mice exhibited diminished exploratory behavior and motivation despite similar movement capability. In the OR, CHF mice had reduced preference for novelty and impaired short-term memory. On histology, CHF mice had unaltered overall cerebral morphology. However, analysis of gene expression by RNA-sequencing in prefrontal cortical, hippocampal, and left ventricular tissue revealed changes in genes related to inflammation and cofactors of neuronal signal transduction in CHF mice, with Nr4a1 being dysregulated both in prefrontal cortex and myocardium after MI. Conclusions: After induction of ischemic CHF, mice exhibited anhedonic behavior, decreased exploratory activity and interest in novelty, and cognitive impairment. Thus, ischemic CHF leads to distinct behavioral changes in mice analogous to symptoms observed in humans with CHF and comorbid depression.

Background Therapeutic and prognostic implications of subclinical thyroid dysfunction in patients with heart failure (HF) are unclear. We compared the prognostic impact of euthyroidism, subclinical thyroid dysfunction, and euthyroid sick syndrome (ESS) in systolic HF. Methods We included 1032 patients hospitalized for systolic HF (left ventricular ejection fraction [LVEF] ≤40%) who participated in a randomized trial assessing the effects of a HF disease management program. Patients with incomplete thyroid function tests or thyrotropic medication were excluded. In the remaining 758 subjects, the risk of all-cause death was estimated based on TSH only, or full thyroid function profile. Changes of thyroid function after six months were assessed in 451 subjects. Results Subclinical thyroid dysfunction was present in 103 patients at baseline (14%). No differences were found between groups regarding NYHA class (P=0.29), and LVEF (P=0.60). After a median follow-up of three years patients with ESS (n=13) had a 3-fold age-adjusted increased risk of death compared to euthyroid patients (P=0.001). However, neither subclinical hyperthyroidism (HR 1.18, 95%CI:0.82–1.70) nor hypothyroidism (HR 1.07, 95%CI:0.58–1.98) were associated with increased age-adjusted mortality risk. Subclinical thyroid dysfunction had normalized spontaneously at follow-up in 77% of patients. However, persistent subclinical thyroid dysfunction was also not associated with worse outcome. Conclusions In this large well-characterized HF cohort, subclinical thyroid dysfunction did not predict an increased mortality risk. Thus, in patients with moderate to severe HF, further diagnostic and therapeutic procedures for subclinical thyroid dysfunction appear dispensable. ESS was an infrequent but important indicator of a poor prognosis in HF. Clinical trial registration URL: http://www.controlled-trials.com. Unique identifier: ISRCTN23325295.