Safety of continuing mineralocorticoid receptor antagonist treatment in patients with heart failure with reduced ejection fraction and severe kidney disease: Data from Swedish Heart Failure Registry

AIMS Mineralocorticoid receptor antagonists (MRAs) improve outcomes in heart failure with reduced ejection fraction (HFrEF) but remain underused and are often discontinued especially in patients with chronic kidney disease (CKD) due to concerns on renal safety. Therefore, in a real-world HFrEF population we investigated the safety of MRA use, in terms of risk of renal events, any mortality and any hospitalization, across the estimated glomerular filtration rate (eGFR) spectrum including severe CKD. METHODS AND RESULTS We analysed patients with HFrEF (ejection fraction <40%), not on dialysis, from the Swedish Heart Failure Registry. We performed multivariable logistic regression models to investigate patient characteristics independently associated with MRA use, and univariable and multivariable Cox regression models to assess the associations between MRA use and outcomes. Of 33 942 patients, 17 489 (51%) received MRA, 32%, 45%, 54%, 54% with eGFR <30, 30-44, 45-59 or ≥60 ml/min/1.73 m$^{2}$ , respectively. An eGFR ≥60 ml/min/1.73 m$^{2}$ and patient characteristics linked with more severe HF were independently associated with more likely MRA use. In multivariable analyses, MRA use was consistently not associated with a higher risk of renal events (i.e. composite of dialysis/renal death/hospitalization for renal failure or hyperkalaemia) (hazard ratio [HR] 1.04, 95% confidence interval [CI] 0.98-1.10), all-cause death (HR 1.02, 95% CI 0.97-1.08) as well as of all-cause hospitalization (HR 0.99, 95% CI 0.95-1.02) across the eGFR spectrum including also severe CKD. CONCLUSIONS The use of MRAs in patients with HFrEF decreased with worse renal function; however their safety profile was demonstrated to be consistent across the entire eGFR spectrum

Post-discharge prognosis of patients admitted to hospital for heart failure by world region, and national level of income and income disparity (REPORT-HF): a cohort study

Background: Heart failure is a global public health problem, affecting a large number of individuals from low-income and middle-income countries. REPORT-HF is, to our knowledge, the first prospective global registry collecting information on patient characteristics, management, and prognosis of acute heart failure using a single protocol. The aim of this study was to investigate differences in 1-year post-discharge mortality according to region, country income, and income inequality. Methods: Patients were enrolled during hospitalisation for acute heart failure from 358 centres in 44 countries on six continents. We stratified countries according to a modified WHO regional classification (Latin America, North America, western Europe, eastern Europe, eastern Mediterranean and Africa, southeast Asia, and western Pacific), country income (low, middle, high) and income inequality (according to tertiles of Gini index). Risk factors were identified on the basis of expert opinion and knowledge of the literature. Findings: Of 18 102 patients discharged, 3461 (20%) died within 1 year. Important predictors of 1-year mortality were old age, anaemia, chronic kidney disease, presence of valvular heart disease, left ventricular ejection fraction phenotype (heart failure with reduced ejection fraction [HFrEF] vs preserved ejection fraction [HFpEF]), and being on guideline-directed medical treatment (GDMT) at discharge (p&lt;0·0001 for all). Patients from eastern Europe had the lowest 1-year mortality (16%) and patients from eastern Mediterranean and Africa (22%) and Latin America (22%) the highest. Patients from lower-income countries (ie, ≤US$3955 per capita; hazard ratio 1·58, 95$12 235 per capita) or lower income inequality (ie, from the lowest Gini tertile). Compared with patients with HFrEF, patients with HFpEF had a lower 1-year mortality with little variation by income level (pinteraction for HFrEF vs HFpEF &lt;0·0001). Interpretation: Acute heart failure is associated with a high post-discharge mortality, particularly in patients with HFrEF from low-income regions with high income inequality. Regional differences exist in the proportion of eligible patients discharged on GDMT, which was strongly associated with mortality and might reflect lack of access to post-discharge care and prescribing of GDMT. Funding: Novartis Pharma

Multimorbidity in patients with acute heart failure across world regions and country income levels (REPORT-HF): a prospective, multicentre, global cohort study

Background Multimorbidity (two or more comorbidities) is common among patients with acute heart failure, but comprehensive global information on its prevalence and clinical consequences across different world regions and income levels is scarce. This study aimed to investigate the prevalence of multimorbidity and its effect on pharmacotherapy and prognosis in participants of the REPORT-HF study. Methods REPORT-HF was a prospective, multicentre, global cohort study that enrolled adults (aged ≥18 years) admitted to hospital with a primary diagnosis of acute heart failure from 358 hospitals in 44 countries on six continents. Patients who currently or recently participated in a clinical treatment trial were excluded. Follow-up data were collected at 1-year post-discharge. The primary outcome was 1-year post-discharge mortality. All patients in the REPORT-HF cohort with full data on comorbidities were eligible for the present study. We stratified patients according to the number of comorbidities, and countries by world region and country income level. We used one-way ANOVA, χ2 test, or Mann-Whitney U test for comparisons between groups, as applicable, and Cox regression to analyse the association between multimorbidity and 1-year mortality. Findings Between July 23, 2014, and March 24, 2017, 18 553 patients were included in the REPORT-HF study. Of these, 18 528 patients had full data on comorbidities, of whom 11 360 (61%) were men and 7168 (39%) were women. Prevalence rates of multimorbidity were lowest in southeast Asia (72%) and highest in North America (92%). Fewer patients from lower-middle-income countries had multimorbidity than patients from high-income countries (73% vs 85%, p<0·0001). With increasing comorbidity burden, patients received fewer guideline-directed heart failure medications, yet more drugs potentially causing or worsening heart failure. Having more comorbidities was associated with worse outcomes: 1-year mortality increased from 13% (no comorbidities) to 26% (five or more comorbidities). This finding was independent of common baseline risk factors, including age and sex. The population-attributable fraction of multimorbidity for mortality was higher in high-income countries than in upper-middle-income or lower-middle-income countries (for patients with five or more comorbidities: 61% vs 27% and 31%, respectively). Interpretation Multimorbidity is highly prevalent among patients with acute heart failure across world regions, especially in high-income countries, and is associated with higher mortality, less prescription of guideline-directed heart failure pharmacotherapy, and increased use of potentially harmful medications.publishedVersio

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

Background: The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. Methods: We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. Results: During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P=0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro–B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. Conclusions: Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329. opens in new tab; EudraCT number, 2016-002299-28. opens in new tab.

Computer-based education for patients with chronic heart failure - A randomised, controlled, multicentre trial of the effects on knowledge, compliance and quality of life

Objective: To evaluate the effects of a single-session, interactive computer-based educational program on knowledge, compliance and quality of life in heart failure patients with special emphasis on gender differences. Methods: One hundred and fifty-four patients, mean age 70 years, from five heart failure clinics were randomised to either receiving only standard education (n = 72) or standard education and additional computer-based education (n = 82). Results: Knowledge was increased in both groups after I month with a trend towards higher knowledge (P = 0.07) in the computer-based group. The increase in knowledge was significantly higher in the computer-based group after 6 months (P = 0.03). No differences were found between the groups with regard to compliance with treatment and self-care or quality of life. The women had significantly lower quality of life and did not improve after 6 months as the men did (P = 0.0001). Conclusion: Computer-based education gave increased knowledge about heart failure. Practice implications: Computers can be a useful too] in heart failure education, but to improve compliance a single-session educational intervention is not sufficient. Gender differences in learning and quality of life should be further evaluated. (c) 2005 Elsevier Ireland Ltd. All rights reserved

Nurse-led heart failure follow-up in primary care in Sweden

Background: Little or no knowledge is available about which service is offered to patients with heart failure in primary care. Aims: To describe nurse-led follow-up of patients with heart failure in primary care in Sweden. Methods and results: A questionnaire was sent to all primary health care centres in Sweden and 6 10 of 939 centres returned the questionnaire. Special nurses had designated time for follow-up of heart failure patients at 18% (n = 111) of the centres, compared to 93% and 78% for diabetes and obstructive lung disease. Centres with nurse-led follow-up of heart failure patients more frequently provided heart failure information (p<0.001), had more doctors interested in heart failure (p<0.001), more often had special care programmes (P<0.001) and had more co-operation with the hospitals around patients with heart failure (p<0.01), compared to centres without such follow-up (n = 499). Conclusion: In primary care in Sweden, nurse-led follow-up is uncommon for patients with heart failure, despite being common for patients with diabetes and obstructive pulmonary disease. To improve this situation in primary care, an increased number of specially trained nurses is needed, together with further research to ensure a high quality follow-up in primary care. (C) 2008 European Society of Cardiology. Published by Elsevier B.V. All rights reserved

Sleep disordered breathing, hypoxia and inflammation : Associations with sickness behaviour in community dwelling elderly with and without cardiovascular disease

Background: Inflammation can induce a cluster of symptoms, referred to as sickness behaviour (e.g., depressive symptoms, sleep disturbances, pain and fatigue). Cardiovascular disease (CVD) and sleep disordered breathing (SDB) are common in older adults. CVD is associated with an increased inflammatory activity and in SDB, hypoxia can also increase inflammation. The purpose of this study is to explore if SDB-related hypoxia is associated differently with inflammation and the presence of sickness behaviour in older adults with and without CVD. Methods: Three hundred and thirty-one older adults, whose mean age is 78 years, underwent one-night polygraphic recording to measure SDB and hypoxia. CVD was established by a clinical investigation. Questionnaires were used to measure sickness behaviour and depressive symptoms. High sensitivity C-reactive protein was used as a marker of inflammation. Results: Structural Equation Modelling showed that SDB-related hypoxia was associated with inflammation (β > 0.40) which mediated indirect associations with sickness behaviour (β=0.19) and depressive symptoms (β=0.11), but only in those with CVD (n=119). In this model, inflammation had a direct effect on sickness behaviour (β=0.43) and an indirect effect on depressive symptoms (β=0.24). Hypoxia had the strongest effect (i.e., β=0.41; significant) on inflammation, whereas the AHI or ODI had weak and non-significant effects (β=0.03 and β=0.15). Conclusions: Older adults with CVD and SDB are at a particular risk of developing sickness behaviour and depressive symptoms. The effect of SDB was mainly caused by hypoxia, suggesting that hypoxia is an important marker of SDB severity in older adults with CVD

Sickness behavior in community-dwelling elderly : Associations with impaired cardiac function and inflammation

Sickness behavior is a cluster of symptoms that occur as a response to an infection and alterations in the inflammatory response. Under normal circumstances, sickness behavior is fully reversible once the pathogen has been cleared. Aging and chronic illness such as heart failure are associated with enhanced inflammatory activity that lasts for a long duration and no longer represents an adaptive response. The aim of this study was to explore whether inflammation mediates the relationship between impaired cardiac function and a symptom cluster including anhedonia, fatigue, and sleepiness, which might represent sickness behavior in community-dwelling elders. Structural equation modeling (SEM) showed that the factor impaired cardiac function (i.e., N-terminal fragment of pro-brain natriuretic peptide, left ventricular ejection fraction, and the heart failure medications angiotensin converting enzyme inhibitor, angiotensin receptor blockade, β-blocker, and diuretics) was associated with both inflammation (i.e., C-reactive protein; β = .26) and the symptom cluster (β = .31). Inflammation had a significant direct, but smaller, association with the symptom cluster (β = .21). By this pathway, inflammation also mediated an indirect association between impaired cardiac function and the symptom cluster (β = .05). Including creatinine, blood glucose, ischemic heart disease, previous and current tumor, respiratory disease, age, and body mass index in the SEM model did not change these associations. Our results imply that some aspects of the symptom panorama in elderly individuals with impaired cardiac function or heart failure could represent sickness behavior