| 1. |
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| 2. |
- Lumbers, R. T., et al.
(författare)
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The genomics of heart failure: design and rationale of the HERMES consortium
- 2021
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Ingår i: Esc Heart Failure. - : Wiley. - 2055-5822. ; 8:6, s. 5531-5541
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Tidskriftsartikel (refereegranskat)abstract
- Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 x 10(-8) under an additive genetic model. Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.
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| 3. |
- Shah, S, et al.
(författare)
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Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 163-
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Tidskriftsartikel (refereegranskat)abstract
- Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.
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| 4. |
- Zannad, F., et al.
(författare)
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Clinical outcome endpoints in heart failure trials: a European Society of Cardiology Heart Failure Association consensus document
- 2013
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 15:10, s. 1082-1094
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Tidskriftsartikel (refereegranskat)abstract
- Endpoint selection is a critically important step in clinical trial design. It poses major challenges for investigators, regulators, and study sponsors, and it also has important clinical and practical implications for physicians and patients. Clinical outcomes of interest in heart failure trials include all-cause mortality, cause-specific mortality, relevant non-fatal morbidity (e.g. all-cause and cause-specific hospitalization), composites capturing both morbidity and mortality, safety, symptoms, functional capacity, and patient-reported outcomes. Each of these endpoints has strengths and weaknesses that create controversies regarding which is most appropriate in terms of clinical importance, sensitivity, reliability, and consistency. Not surprisingly, a lack of consensus exists within the scientific community regarding the optimal endpoint(s) for both acute and chronic heart failure trials. In an effort to address these issues, the Heart Failure Association of the European Society of Cardiology (HFA-ESC) convened a group of expert heart failure clinical investigators, biostatisticians, regulators, and pharmaceutical industry scientists (Nice, France, 12-13 February 2012) to evaluate the challenges of defining heart failure endpoints in clinical trials and to develop a consensus framework. This report summarizes the group's recommendations for achieving common views on heart failure endpoints in clinical trials.
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| 5. |
- Zannad, F., et al.
(författare)
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Mineralocorticoid receptor antagonists for heart failure with reduced ejection fraction: integrating evidence into clinical practice
- 2012
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Ingår i: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 33:22, s. 2782-2795
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Tidskriftsartikel (refereegranskat)abstract
- Mineralocorticoid receptor antagonists (MRAs) improve survival and reduce morbidity in patients with heart failure, reduced ejection fraction (HF-REF), and mild-to-severe symptoms, and in patients with left ventricular systolic dysfunction and heart failure after acute myocardial infarction. These clinical benefits are observed in addition to those of angiotensin converting enzyme inhibitors or angiotensin receptor blockers and beta-blockers. The morbidity and mortality benefits of MRAs may be mediated by several proposed actions, including antifibrotic mechanisms that slow heart failure progression, prevent or reverse cardiac remodelling, or reduce arrhythmogenesis. Both eplerenone and spironolactone have demonstrated survival benefits in individual clinical trials. Pharmacologic differences exist between the drugs, which may be relevant for therapeutic decision making in individual patients. Although serious hyperkalaemia events were reported in the major MRA clinical trials, these risks can be mitigated through appropriate patient selection, dose selection, patient education, monitoring, and follow-up. When used appropriately, MRAs significantly improve outcomes across the spectrum of patients with HF-REF.
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| 6. |
- O'Connor, C. M., et al.
(författare)
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Effect of nesiritide in patients with acute decompensated heart failure
- 2011
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Ingår i: The New England journal of medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 365:1, s. 32-43
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. METHODS: We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. RESULTS: Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but the prespecified level for significance (P
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| 7. |
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| 8. |
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| 9. |
- Povinec, Pavel, et al.
(författare)
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Reference material for radionuclides in sediment. IAEA-384 (Fangataufa lagoon sediment).
- 2007
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Ingår i: Journal of Radioanalytical and Nuclear Chemistry. - Dordrecht : Springer. - 0236-5731 .- 1588-2780. ; 273:2, s. 383-393
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Tidskriftsartikel (refereegranskat)abstract
- A reference material designed for the determination of anthropogenic and natural radionuclides in sediment, IAEA-384 (Fangataufa Lagoon sediment), is described and the results of certification are presented. The material has been certified for 8 radionuclides (40K, 60Co, 155Eu, 230Th, 238U, 238Pu, 239+240Pu and 241Am). Information values are given for 12 radionuclides (90Sr, 137Cs, 210Pb (210Po), 226Ra, 228Ra, 232Th, 234U, 235U, 239Pu, 240Pu and 241Pu). Less reported radionuclides include 228Th, 236U, 239Np and 242Pu. The reference material may be used for quality management of radioanalytical laboratories engaged in the analysis of radionuclides in the environment, as well as for the development and validation of analytical methods and for training purposes. The material is available from IAEA in 100 g units.
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| 10. |
- Wellens, H. J., et al.
(författare)
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Risk stratification for sudden cardiac death: current status and challenges for the future
- 2014
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 35:25, s. 1642-1651
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Tidskriftsartikel (refereegranskat)abstract
- Sudden cardiac death (SCD) remains a daunting problem. It is a major public health issue for several reasons: from its prevalence (20% of total mortality in the industrialized world) to the devastating psycho-social impact on society and on the families of victims often still in their prime, and it represents a challenge for medicine, and especially for cardiology. This text summarizes the discussions and opinions of a group of investigators with a long-standing interest in this field. We addressed the occurrence of SCD in individuals apparently healthy, in patients with heart disease and mild or severe cardiac dysfunction, and in those with genetically based arrhythmic diseases. Recognizing the need for more accurate registries of the global and regional distribution of SCD in these different categories, we focused on the assessment of risk for SCD in these four groups, looking at the significance of alterations in cardiac function, of signs of electrical instability identified by ECG abnormalities or by autonomic tests, and of the progressive impact of genetic screening. Special attention was given to the identification of areas of research more or less likely to provide useful information, and thereby more or less suitable for the investment of time and of research funds.
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| 11. |
- Metra, M., et al.
(författare)
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Geographic Differences in Patients in a Global Acute Heart Failure Clinical Trial (from the ASCEND-HF Trial)
- 2016
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149. ; 117:11, s. 1771-1778
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Tidskriftsartikel (refereegranskat)abstract
- A growing number of countries and geographical regions are involved in major clinical trials. Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure is the largest trial in acutely decompensated heart failure (HF) with patients from 5 geographical regions: North America (NA), Latin America (LA), Western Europe (WE), Central Europe (CE), and Asia-Pacific (AP). Data from the 5 geographical, areas were compared including baseline characteristics, medications, 30-day outcomes (mortality and mortality or HF hospitalization), and 180-day mortality. Of the 7,141 study patients, 3,243 (45.4%) were from NA (average of 15.2 patients/site), 1,762 (24.7%) from AP (28.4 patients/site), 967 (13.5%) from CE (20.2 patients/site), 665 (9.3%) from LA (17.1 patients/site), and 504 (7.1%) from WE (14.4 patients/site). There were marked differences in co-morbidities, clinical profile, medication use, length of stay, 30-day event rates, and 180-day mortality by region. Compared with NA, the adjusted risk for death or HF hospitalization at 30 days was significantly lower in CE (odds ratio [OR] 0.46, 95% CI 0.33 to 0.64), WE (OR 0.52 95% CI 0.35 to 0.75), and AP (OR 0.62 95% CI 0.48 to 0:79) and numerically lower in LA (OR 0.77, 95% CI 0.57 to 1.04) with similar results for 180-day mortality. In conclusion, in patients with acutely decompensated HF, major differences in baseline characteristics, treatments, length of the hospital stay, and 30-day HF rehospitalization rates, and 180-day mortality were found in patients enrolled from different, geographical areas. (C) 2016 Elsevier Inc. All rights reserved.
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| 12. |
- Müller, M, et al.
(författare)
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Central sleep apnoea syndrome in chronic heart failure : an underestimated and treatable comorbidity.
- 2010
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Ingår i: Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation. - 1568-5888. ; 18:5, s. 260-3
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Tidskriftsartikel (refereegranskat)abstract
- Chronic heart failure is a clinical syndrome with a high mortality and morbidity. Despite optimal therapy, five-year survival is still only 50%. Central sleep apnoea syndrome is seen in approximately 40% of patients with congestive heart failure. Sleep apnoea syndrome can be divided into two forms in these patients: obstructive sleep apnoea syndrome (OSAS) and central sleep apnoea syndrome (CSAS, Cheyne-Stokes respiration), of which CSAS is the most common. CSAS is a form of sleep apnoea in congestive heart failure which is driven by changes in pCO(2). As a consequence of apnoea-hypopnoea an imbalance in myocardial oxygen delivery/consumption ratio will develop, sympathetic and other neurohormonal systems will be activated and right and left ventricular afterload will be increased. Sleep apnoea is associated with an increased mortality in patients with systolic heart failure. Treatment of sleep apnoea increases left ventricular ejection fraction and transplant-free survival. Because of its high prevalence, poor quality of life, poor outcome, and the beneficial effects of treatment, physicians treating patients with heart failure should be aware of central sleep apnoea. There are different treatment options, but the exact effects and indications of each option have not yet been fully determined. Further studies should be done to further investigate its prevalence, and to establish the most adequate therapy for the individual patient. (Neth Heart J 2010;18:260-3.).
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| 13. |
- Nunez, Julio, et al.
(författare)
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Congestion in heart failure: a circulating biomarker-based perspective. A review from the Biomarkers Working Group of the Heart Failure Association, European Society of Cardiology
- 2022
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Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 24:10, s. 1751-1766
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Forskningsöversikt (refereegranskat)abstract
- Congestion is a cardinal sign of heart failure (HF). In the past, it was seen as a homogeneous epiphenomenon that identified patients with advanced HF. However, current evidence shows that congestion in HF varies in quantity and distribution. This updated view advocates for a congestive-driven classification of HF according to onset (acute vs. chronic), regional distribution (systemic vs. pulmonary), compartment of distribution (intravascular vs. extravascular), and clinical vs. subclinical. Thus, this review will focus on the utility of circulating biomarkers for assessing and managing the different fluid overload phenotypes. This discussion focused on the clinical utility of the natriuretic peptides, carbohydrate antigen 125 (also called mucin 16), bio-adrenomedullin and mid-regional pro-adrenomedullin, ST2 (also known as interleukin-1 receptor-like 1), cluster of differentiation 146, troponin, C-terminal pro-endothelin-1, and parameters of haemoconcentration. The utility of circulation biomarkers on top of clinical evaluation, haemodynamics, and imaging needs to be better determined by dedicated studies. Some multiparametric frameworks in which these tools contribute to management are proposed.
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| 14. |
- Voors, A. A., et al.
(författare)
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The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial
- 2022
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 28, s. 568-574
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Tidskriftsartikel (refereegranskat)abstract
- The sodium–glucose cotransporter 2 inhibitor empagliflozin reduces the risk of cardiovascular death or heart failure hospitalization in patients with chronic heart failure, but whether empagliflozin also improves clinical outcomes when initiated in patients who are hospitalized for acute heart failure is unknown. In this double-blind trial (EMPULSE; NCT04157751), 530 patients with a primary diagnosis of acute de novo or decompensated chronic heart failure regardless of left ventricular ejection fraction were randomly assigned to receive empagliflozin 10 mg once daily or placebo. Patients were randomized in-hospital when clinically stable (median time from hospital admission to randomization, 3 days) and were treated for up to 90 days. The primary outcome of the trial was clinical benefit, defined as a hierarchical composite of death from any cause, number of heart failure events and time to first heart failure event, or a 5 point or greater difference in change from baseline in the Kansas City Cardiomyopathy Questionnaire Total Symptom Score at 90 days, as assessed using a win ratio. More patients treated with empagliflozin had clinical benefit compared with placebo (stratified win ratio, 1.36; 95% confidence interval, 1.09–1.68; P = 0.0054), meeting the primary endpoint. Clinical benefit was observed for both acute de novo and decompensated chronic heart failure and was observed regardless of ejection fraction or the presence or absence of diabetes. Empagliflozin was well tolerated; serious adverse events were reported in 32.3% and 43.6% of the empagliflozin- and placebo-treated patients, respectively. These findings indicate that initiation of empagliflozin in patients hospitalized for acute heart failure is well tolerated and results in significant clinical benefit in the 90 days after starting treatment. © 2022, The Author(s).
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| 15. |
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| 16. |
- de Boer, Rudolf A, et al.
(författare)
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Predictive value of plasma galectin-3 levels in heart failure with reduced and preserved ejection fraction
- 2011
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Ingår i: Annals of Medicine. - : Informa UK Limited. - 0785-3890 .- 1365-2060. ; 43:1, s. 60-68
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: galectin-3 is an emerging biomarker which has been studied in relatively small heart failure (HF) cohorts with predominantly systolic HF. We studied the prognostic value of base-line galectin-3 in a large HF cohort, with preserved and reduced left ventricular ejection fraction (LVEF), and compared this to other biomarkers. METHODS: we studied 592 HF patients who had been hospitalized for HF and were followed for 18 months. The primary end-point was a composite of all-cause mortality and HF hospitalization. RESULTS: a doubling of galectin-3 levels was associated with a hazard ratio (HR) of 1.97 (1.62-2.42) for the primary outcome (P < 0.001). After correction for age, gender, BNP, eGFR, and diabetes the HR was 1.38 (1.07-1.78; P = 0.015). Galectin-3 levels were correlated with higher IL-6 and CRP levels (P < 0.002). Changes of galectin-3 levels after 6 months did not add prognostic information to the base-line value (n = 291); however, combining plasma galectin-3 and BNP levels increased prognostic value over either biomarker alone (ROC analysis, P < 0.05). The predictive value of galectin-3 was stronger in patients with preserved LVEF (n = 114) compared to patients with reduced LVEF (P < 0.001). CONCLUSIONS: galectin-3 is an independent marker for outcome in HF and appears to be particularly useful in HF patients with preserved LVEF.
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| 17. |
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| 18. |
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| 19. |
- Metra, Marco, et al.
(författare)
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y Effects of Serelaxin in Patients with Acute Heart Failure
- 2019
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 381:8, s. 716-726
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSerelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. MethodsIn this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 mu g per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days.ResultsA total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P=0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P=0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups.ConclusionsIn this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778.) In a randomized trial, 6545 patients with acute heart failure were assigned to either serelaxin or placebo in addition to standard care. There were no significant differences between the two groups in the incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days.
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| 20. |
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| 21. |
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| 22. |
- Seferovic, Petar M., et al.
(författare)
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Clinical practice update on heart failure 2019: pharmacotherapy, procedures, devices and patient management. An expert consensus meeting report of the Heart Failure Association of the European Society of Cardiology
- 2019
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Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 21:10, s. 1169-1186
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Tidskriftsartikel (refereegranskat)abstract
- The European Society of Cardiology (ESC) has published a series of guidelines on heart failure (HF) over the last 25 years, most recently in 2016. Given the amount of new information that has become available since then, the Heart Failure Association (HFA) of the ESC recognized the need to review and summarise recent developments in a consensus document. Here we report from the HFA workshop that was held in January 2019 in Frankfurt, Germany. This expert consensus report is neither a guideline update nor a position statement, but rather a summary and consensus view in the form of consensus recommendations. The report describes how these guidance statements are supported by evidence, it makes some practical comments, and it highlights new research areas and how progress might change the clinical management of HF. We have avoided re-interpretation of information already considered in the 2016 ESC/HFA guidelines. Specific new recommendations have been made based on the evidence from major trials published since 2016, including sodium-glucose co-transporter 2 inhibitors in type 2 diabetes mellitus, MitraClip for functional mitral regurgitation, atrial fibrillation ablation in HF, tafamidis in cardiac transthyretin amyloidosis, rivaroxaban in HF, implantable cardioverter-defibrillators in non-ischaemic HF, and telemedicine for HF. In addition, new trial evidence from smaller trials and updated meta-analyses have given us the chance to provide refined recommendations in selected other areas. Further, new trial evidence is due in many of these areas and others over the next 2 years, in time for the planned 2021 ESC guidelines on the diagnosis and treatment of acute and chronic heart failure.
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| 23. |
- Teerlink, John R., et al.
(författare)
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Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure
- 2021
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Ingår i: New England Journal of Medicine. - Waltham, MA, United States : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 384:2, s. 105-116
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Tidskriftsartikel (refereegranskat)abstract
- Among patients with heart failure and a reduced ejection fraction, those who received the cardiac myosin activator omecamtiv mecarbil had a lower incidence of a composite of heart-failure events or cardiovascular death at a median of 22 months than those who received placebo. 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, ; EudraCT number, 2016-002299-28.)
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| 24. |
- Teerlink, John R., et al.
(författare)
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Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction: GALACTIC-HF baseline characteristics and comparison with contemporary clinical trials
- 2020
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Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 22:11, s. 2160-2171
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Tidskriftsartikel (refereegranskat)abstract
- Aims The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is being tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) trial. Here we describe the baseline characteristics of participants in GALACTIC-HF and how these compare with other contemporary trials. Methods and results Adults with established HFrEF, New York Heart Association (NYHA) functional class >= II, ejection fraction <= 35%, elevated natriuretic peptides and either current hospitalization for heart failure or history of hospitalization/emergency department visit for heart failure within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic-guided dosing: 25, 37.5, or 50 mg bid). A total of 8256 patients [male (79%), non-white (22%), mean age 65 years] were enrolled with a mean ejection fraction 27%, ischaemic aetiology in 54%, NYHA class II 53% and III/IV 47%, and median N-terminal pro-B-type natriuretic peptide 1971 pg/mL. Heart failure therapies at baseline were among the most effectively employed in contemporary heart failure trials. GALACTIC-HF randomized patients representative of recent heart failure registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure <100 mmHg (n = 1127), estimated glomerular filtration rate <30 mL/min/1.73 m(2) (n = 528), and treated with sacubitril/valsartan at baseline (n = 1594). Conclusions GALACTIC-HF enrolled a well-treated, high-risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation.
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| 25. |
- Tromp, Jasper, et al.
(författare)
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Biomarker Profiles in Heart Failure Patients With Preserved and Reduced Ejection Fraction
- 2017
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Ingår i: Journal of the American Heart Association. - : WILEY. - 2047-9980. ; 6:4
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Tidskriftsartikel (refereegranskat)abstract
- Background-Biomarkers may help us to unravel differences in the underlying pathophysiology between heart failure (HF) patients with a reduced ejection fraction (HFrEF) and a preserved ejection fraction (HFpEF). Therefore, we compared biomarker profiles to characterize pathophysiological differences between patients with HFrEF and HFpEF. Methods and Results-We retrospectively analyzed 33 biomarkers from different pathophysiological domains (inflammation, oxidative stress, remodeling, cardiac stretch, angiogenesis, arteriosclerosis, and renal function) in 460 HF patients (21% HFpEF, left ventricular ejection fraction amp;gt;= 45%) measured at discharge after hospitalization for acute HF. The association between these markers and the occurrence of all-cause mortality and/or HF-related rehospitalizations at 18 months was compared between patients with HFrEF and HFpEF. Patients were 70.6 +/- 11.4 years old and 37.4% were female. Patients with HFpEF were older, more often female, and had a higher systolic blood pressure. Levels of high-sensitive C-reactive protein were significantly higher in HFpEF, while levels of pro-atrial-type natriuretic peptide and N-terminal pro-brain natriuretic peptide were higher in HFrEF. Linear regression followed by network analyses revealed prominent inflammation and angiogenesis-associated interactions in HFpEF and mainly cardiac stretch-associated interactions in HrEF. The angiogenesis-specific marker, neuropilin and the remodeling-specific marker, osteopontin were predictive for all-cause mortality and/or HF-related rehospitalizations at 18 months in HFpEF, but not in HFrEF (P for interaction amp;lt;0.05). Conclusions-In HFpEF, inflammation and angiogenesis- mediated interactions are predominantly observed, while stretch-mediated interactions are found in HFrEF. The remodeling marker osteopontin and the angiogenesis marker neuropilin predicted outcome in HFpEF, but not in HFrEF.
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| 26. |
- Adler, Eric D., et al.
(författare)
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Improving risk prediction in heart failure using machine learning
- 2020
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 22:1, s. 139-147
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Tidskriftsartikel (refereegranskat)abstract
- Background: Predicting mortality is important in patients with heart failure (HF). However, current strategies for predicting risk are only modestly successful, likely because they are derived from statistical analysis methods that fail to capture prognostic information in large data sets containing multi-dimensional interactions. Methods and results: We used a machine learning algorithm to capture correlations between patient characteristics and mortality. A model was built by training a boosted decision tree algorithm to relate a subset of the patient data with a very high or very low mortality risk in a cohort of 5822 hospitalized and ambulatory patients with HF. From this model we derived a risk score that accurately discriminated between low and high-risk of death by identifying eight variables (diastolic blood pressure, creatinine, blood urea nitrogen, haemoglobin, white blood cell count, platelets, albumin, and red blood cell distribution width). This risk score had an area under the curve (AUC) of 0.88 and was predictive across the full spectrum of risk. External validation in two separate HF populations gave AUCs of 0.84 and 0.81, which were superior to those obtained with two available risk scores in these same populations. Conclusions: Using machine learning and readily available variables, we generated and validated a mortality risk score in patients with HF that was more accurate than other risk scores to which it was compared. These results support the use of this machine learning approach for the evaluation of patients with HF and in other settings where predicting risk has been challenging.
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| 27. |
- de Boer, Rudolf A, et al.
(författare)
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The WAP four-disulfide core domain protein HE4 : a novel biomarker for heart failure.
- 2013
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Ingår i: JACC. Heart failure. - : Elsevier BV. - 2213-1787 .- 2213-1779. ; 1:2, s. 164-169
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This study investigated clinical determinants and added prognostic value of HE4 as a biomarker not previously described in heart failure (HF).BACKGROUND: Identification of plasma biomarkers that help to risk stratify HF patients may help to improve treatment.METHODS: Plasma HE4 levels were determined in 567 participants of the COACH (Coordinating study evaluating outcomes of Advising and Counseling in Heart failure). Patients had been hospitalized for HF and were followed for 18 months. The primary endpoint of this study was a composite of all-cause mortality and HF hospitalization.RESULTS: HE4 showed a strong correlation with HF severity, according to New York Heart Association functional class and brain natriuretic peptide (BNP) levels (p < 0.001). HE4 also showed a positive correlation with GDF15 (p < 0.001) and, in addition, correlated with kidney function (estimated glomerular filtration rate [eGFR]; p < 0.001). Cox regression analysis revealed that a doubling of HE4 levels was associated with a hazard ratio (HR) of 1.73 (95% confidence interval [CI]: 1.53 to 1.95) for the primary outcome (p < 0.001). After correction for age, gender, BNP, and eGFR, the HR was 1.46 (95% CI: 1.23 to 1.72; p < 0.001), and after additional adjustment for GDF15, the HR lowered to 1.30 (95% CI: 1.07 to 1.59; p = 0.009). The area under the curve in the receiver-operating characteristic curve analysis increased from 0.727 to 0.752 when HE4 was included in the clinical evaluation (p = 0.051). The integrated discrimination improvement and net reclassification index for reclassification showed significant improvements when HE4 was added to the clinical model, and this remained significant after BNP inclusion in the model.CONCLUSIONS: HE4 plasma levels are correlated with markers of HF severity, show prognostic value, and can improve risk assessment in HF.
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| 28. |
- Hogenhuis, Jochem, et al.
(författare)
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Anaemia and renal dysfunction are independently associated with BNP and NT-proBNP levels in patients with heart failure.
- 2007
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 9:8, s. 787-94
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Anaemia may affect B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) levels, but this has not been well described in heart failure (HF) patients without the exclusion of patients with renal dysfunction. AIMS: To study the influence of both anaemia and renal function on BNP and NT-proBNP levels in a large group of hospitalised HF patients. METHODS AND RESULTS: We studied 541 patients hospitalised for HF (mean age 71+/-11 years, 62% male, and left ventricular ejection fraction 0.33+/-0.14). Of these patients, 30% (n=159) were anaemic (women: Hb<7.5 mmol/l, men: Hb<8.1 mmol/l). Of the 159 anaemic patients, 73% had renal dysfunction (eGFR<60 ml/min/1.73 m2) and of the non-anaemic patients, 57% had renal dysfunction. BNP and NT-proBNP levels were measured in all patients before discharge. In multivariable analyses both plasma haemoglobin and eGFR were independently related to the levels of BNP and NT-proBNP (standardised beta's of -0.16, -0.14 [BNP] and -0.19, -0.26 [NT-proBNP] respectively, P-values<0.01). CONCLUSION: Anaemia and renal dysfunction are related to increased BNP and NT-proBNP levels, independent of the severity of HF. These results indicate that both anaemia and renal dysfunction should be taken into consideration during the interpretation of BNP and NT-proBNP levels in HF patients.
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| 29. |
- Huzen, Jardi, et al.
(författare)
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Telomere length and psychological well-being in patients with chronic heart failure.
- 2010
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Ingår i: Age and Ageing. - : Oxford University Press (OUP). - 0002-0729 .- 1468-2834. ; 39:2, s. 223-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: psychological stress and depressive symptoms have been implicated with accelerated ageing and increased progression of diseases. Shorter telomere length indicates a more advanced biological age. It is unknown whether psychological well-being is associated with telomere length in patients with the somatic condition of chronic heart failure (CHF). DESIGN: a cross-sectional analysis was used. SETTING: patients were admitted to the hospital with signs and symptoms of CHF. OBJECTIVE: the study aimed to assess the association between telomere length and psychological well-being in patients with CHF. METHODS: telomere length was determined by quantitative polymerase chain reaction in 890 patients with New York Heart Association functional class II to IV CHF. We evaluated the perceived mental health by the validated RAND-36 questionnaire. Depressive symptoms were assessed by the Centre for Epidemiologic Studies Depression scale (CES-D), and the presence of type D personality was evaluated by the DS14. RESULTS: a lower perceived mental health on the RAND-36 score was associated with shorter telomere length. Adjustment for age and gender did not change our findings (standardised beta, 0.11; P-value, 0.002). Telomere length was not associated with the CES-D or DS14 score. CONCLUSION: decreased perceived mental health is associated with shorter leukocyte telomere length in patients with CHF. Future work should determine whether psychological stress accelerates biological ageing.
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| 30. |
- Kleijn, Lennaert, et al.
(författare)
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Inflammation and anaemia in a broad spectrum of patients with heart failure
- 2012
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Ingår i: Heart. - : BMJ Publishing Group. - 1355-6037 .- 1468-201X. ; 98:16, s. 1237-1241
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Anaemia in heart failure (HF) is associated with a poor prognosis. Although inflammation is assumed to be an important cause of anaemia, the association between anaemia and inflammatory markers in patients with HF has not been well established.METHODS: Data from a multicentre randomised clinical trial, in which patients were eligible if they were >18 years of age and admitted for HF (New York Heart Association II-IV), were used. In a subset of 326 patients, haemoglobin (Hb), haematocrit, high sensitivity C-reactive protein (hsCRP), interleukin-(IL) 6, soluble tumour necrosis factor receptor (sTNFR)-1 and erythropoietin (Epo) were measured at discharge and the primary endpoint was all-cause mortality. Follow-up was 18 months.RESULTS: Anaemia (Hb <13 g/dl (men) and <12 g/dl (women)) was present in 40% (130/326) of the study population. Median levels of IL-6, hsCRP and sTNFR-1 were significantly higher in anaemic patients than in non-anaemic patients. Logistic regression demonstrated that each increase in hsCRP values (OR 1.58 per SD log hsCRP; 95% CI 1.09 to 2.29; p=0.016) and each increase in sTNFR-1 values (OR 1.62 per SD log sTNFR-1; 95% CI 1.24 to 2.11; p<0.001) were independently associated with anaemia. Epo (HR 1.31 per log Epo; 95% CI 1.01 to 1.69; p=0.041) and sTNFR-1 (HR 1.47 per log sTNFR-1; 95% CI 1.16 to 1.86; p=0.001) levels were independently associated with outcome.CONCLUSION: Anaemia is present in 40% of patients hospitalised for HF and is independently associated with inflammation.
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| 31. |
- Linssen, G. C. M., et al.
(författare)
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A comparison of the prognostic value of BNP versus NT-proBNP after hospitalisation for heart failure
- 2018
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Ingår i: Netherlands Heart Journal. - : BOHN STAFLEU VAN LOGHUM BV. - 1568-5888 .- 1876-6250. ; 26:10, s. 486-492
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Tidskriftsartikel (refereegranskat)abstract
- Aims Concentrations of circulating B-type natriuretic peptides provide important prognostic information in heart failure (HF) patients. We directly compared the prognostic performance of brain natriuretic peptide (BNP) versus N-terminal-proBNP (NT-proBNP) measurements in a large population of HF patients at hospital discharge after an admission for decompensated HF. Methods and results BNP and NT-proBNP were measured in 563 stable HF patients before discharge. All patients were followed for a fixed period of 18 months. The primary endpoint was time to first major event (HF hospitalisation or death). Patients were in NYHA class II (47%) or III/IV (53%) at discharge and the mean age of the patients was 71 +/- 11 years, 217 (39%) females, mean left ventricular ejection fraction was 0.32 +/- 0.14 and 234 (42%) had an ischaemic aetiology of HF. During the study, 236 patients (42%) reached the primary endpoint. Multivariate odds ratios of the primary endpoint for doubling of baseline levels of BNP and NT-proBNP were 1.46 (95% CI 1.19-1.80, p amp;lt; 0.001) and 1.45 (95% CI 1.18-1.78, p amp;lt; 0.001), respectively. The multivariable adjusted areas under the receiver-operating characteristic curve for prediction of the primary endpoint for doubling of BNP and NT-proBNP were 0.69 and 0.68, respectively. Direct comparison of the prognostic value of BNP and NT-proBNP did not reveal significant differences. Conclusions BNP and NT-proBNP at discharge for hospitalisation for HF are powerful, and equally strong and independent predictors of all-cause death and HF rehospitalisation.
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| 32. |
- Liu, Licette C Y, et al.
(författare)
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Vitamin D status and outcomes in heart failure patients
- 2011
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 13:6, s. 619-625
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Vitamin D status has been implicated in the pathophysiology of heart failure (HF). The aims of this study were to determine whether a low vitamin D status is associated with prognosis in HF and whether activation of the renin-angiotensin system (RAS) and inflammatory markers could explain this potential association. METHODS AND RESULTS: We measured 25-hydroxy-vitamin D (25(OH)D), plasma renin activity (PRA), interleukin-6 (IL-6), C-reactive protein (CRP), and the incidence of death or HF rehospitalization in 548 patients with HF. Median age was 74 (64-80) years, left ventricular ejection fraction was 30% (23-42), and mean follow-up was 18 months. Low 25(OH)D levels were associated with female gender (P< 0.001), higher age (P= 0.002), and higher N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (P< 0.001). Multivariable linear regression analysis showed that PRA (P= 0.048), and CRP levels (P= 0.006) were independent predictors of 25(OH)D levels. During follow-up, 155 patients died and 142 patients were rehospitalized. Kaplan-Meier analysis showed that lower 25(OH)D concentration was associated with an increased risk for the combined endpoint (all-cause mortality and HF rehospitalization; log rank test P= 0.045) and increased risk for all-cause mortality (log rank test P= 0.014). After adjustment in a multivariable Cox regression analysis, low 25(OH)D concentration remained independently associated with an increased risk for the combined endpoint [hazard ratio (HR) 1.09 per 10 nmol/L decrease; 95% confidence interval (CI) 1.00-1.16; P= 0.040] and all-cause mortality (HR 1.10 per 10 nmol/L decrease; 95% CI 1.00-1.22; P= 0.049). CONCLUSION: A low 25(OH)D concentration is associated with a poor prognosis in HF patients. Activation of the RAS and inflammation may confer the adverse effects of low vitamin D levels.
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| 33. |
- Maisel, Alan, et al.
(författare)
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Effect of Spironolactone on 30-Day Death and Heart Failure Rehospitalization (from the COACH Study)
- 2014
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Ingår i: American Journal of Cardiology. - : Elsevier. - 0002-9149 .- 1879-1913. ; 114:5, s. 737-742
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Tidskriftsartikel (refereegranskat)abstract
- The aim of our study is to investigate the effect of spironolactone on 30-day outcomes in patients with acute heart failure (AHF) and the association between treatment and outcomes stratified by biomarkers. We conducted a secondary analysis of the biomarker substudy of the multicenter COACH (Co-ordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure) trial involving 534 AHF patients for 30-day mortality and HF rehospitalizations. Spironolactone therapy was initiated and terminated at the discretion of the treating physician; 30-day outcomes were compared between patients who were treated with spironolactone and those who were not. Outcomes with spironolactone therapy. were explored based on N-terminal pro-B-type natriuretic peptide, ST2, galectin-3, and creatinine levels. Spironolactone was prescribed to 297 (55.6%) patients at discharge (158 new and 139 continued). There were 19 deaths and 30 HF rehospitalizations among 46 patients by 30 days. Patients discharged on spironolactone had significantly less 30-day event (hazard ratio 0.538, p = 0.039) after adjustment for multiple risk factors. Initiation of spironolactone in patients who were not on spironolactone before admission was associated with a significant reduction in event rate (hazard ratio 0.362, p = 0.027). The survival benefit of spironolactone was more prominent in patient groups with elevations of creatinine, N-terminal pro B-type natriuretic peptide, ST2, or galectin-3. In conclusion, AHF patients who received spironolactone during hospitalization had significantly fewer 30-day mortality and HF rehospitalizations, especially in high-risk patients.
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| 34. |
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| 35. |
- Meijers, Wouter C., et al.
(författare)
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Biomarkers and low risk in heart failure. Data from COACH and TRIUMPH
- 2015
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Ingår i: European Journal of Heart Failure. - : WILEY-BLACKWELL. - 1388-9842 .- 1879-0844. ; 17:12, s. 1271-1282
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Tidskriftsartikel (refereegranskat)abstract
- AimTraditionally, risk stratification in heart failure (HF) emphasizes assessment of high risk. We aimed to determine if biomarkers could identify patients with HF at low risk for death or HF rehospitalization. Methods and resultsThis analysis was a substudy of The Coordinating Study Evaluating Outcomes of Advising and Counselling in Heart Failure (COACH) trial. Enrolment of HF patients occurred before discharge. We defined low risk as the absence of death and/or HF rehospitalizations at 180days. We tested a diverse group of 29 biomarkers on top of a clinical risk model, with and without N-terminal pro-B-type natriuretic peptide (NT-proBNP), and defined the low risk biomarker cut-off at the 10th percentile associated with high positive predictive value. The best performing biomarkers together with NT-proBNP and cardiac troponin I (cTnI) were re-evaluated in a validation cohort of 285 HF patients. Of 592 eligible COACH patients, the mean (SD) age was 71 (+/- 11) years and median (IQR) NT-proBNP was 2521 (1301-5634) pg/mL. Logistic regression analysis showed that only galectin-3, fully adjusted, was significantly associated with the absence of events at 180days (OR 8.1, 95% confidence interval 1.06-50.0, P=0.039). Galectin-3, showed incremental value when added to the clinical risk model without NT-proBNP (increase in area under the curve from 0.712 to 0.745, P=0.04). However, no biomarker showed significant improvement by net reclassification improvement on top of the clinical risk model, with or without NT-proBNP. We confirmed our results regarding galectin-3, NT-proBNP, and cTnI in the independent validation cohort. Conclusion We describe the value of various biomarkers to define low risk, and demonstrate that galectin-3 identifies HF patients at (very) low risk for 30-day and 180-day mortality and HF rehospitalizations after an episode of acute HF. Such patients might be safely discharged.
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| 36. |
- Michaëlsson, Erik, et al.
(författare)
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Myeloperoxidase Inhibition Reverses Biomarker Profiles Associated With Clinical Outcomes in HFpEF.
- 2023
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Ingår i: JACC. Heart failure. - 2213-1787. ; 11:7, s. 775-87
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Tidskriftsartikel (refereegranskat)abstract
- Systemic microvascular dysfunction and inflammation are postulated to play a pathophysiologic role in heart failure with preserved ejection fraction (HFpEF).This study aimed to identify biomarker profiles associated with clinical outcomes in HFpEF and investigate how inhibition of the neutrophil-derived reactive oxygen species-producing enzyme, myeloperoxidase, affects these biomarkers.Using supervised principal component analyses, the investigators assessed the associations between baseline plasma proteomic Olink biomarkers and clinical outcomes in 3 independent observational HFpEF cohorts (n=86, n=216, and n=242). These profiles were then compared with the biomarker profiles discriminating patients treated with active drug vs placebo in SATELLITE (Safety and Tolerability Study of AZD4831 in Patients With HeartFailure), a double-blind randomized 3-month trial evaluating safety and tolerability of the myeloperoxidase inhibitor AZD4831 in HFpEF (n=41). Pathophysiological pathways were inferred from the biomarker profiles by interrogation of the Ingenuity Knowledge database.TNF-R1, TRAIL-R2, GDF15, U-PAR, and ADM were the top individual biomarkers associated with heart failure hospitalization or death, and FABP4, HGF, RARRES2, CSTB, and FGF23 were associated with lower functional capacity and poorer quality of life. AZD4831 downregulated many markers (most significantly CDCP1, PRELP, CX3CL1, LIFR, VSIG2). There was remarkable consistency among pathways associated with clinical outcomes in the observational HFpEF cohorts, the top canonical pathways being associated with tumor microenvironments, wound healing signaling, and cardiac hypertrophy signaling. These pathways were predicted to be downregulated in AZD4831 relative to placebo-treated patients.Biomarker pathways that were most strongly associated with clinical outcomes were also the ones reduced by AZD4831. These results support the further investigation of myeloperoxidase inhibition in HFpEF.
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| 37. |
- Tromp, Jasper, et al.
(författare)
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Fibrosis Marker Syndecan-1 and Outcome in Patients With Heart Failure With Reduced and Preserved Ejection Fraction
- 2014
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Ingår i: Circulation Heart Failure. - : American Heart Association. - 1941-3289 .- 1941-3297. ; 7:3, s. 457-U119
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Tidskriftsartikel (refereegranskat)abstract
- Background-Syndecan-1 is a member of the proteoglycan family involved in cell-matrix interactions. Experimental studies showed that syndecan-1 is associated with inflammation in acute myocardial infarction and remodeling. The goal of this study was to explore the role of syndecan-1 in human heart failure (HF). Methods and Results-We analyzed plasma syndecan-1 levels in 567 patients with chronic HF. Primary end point was a composite of all-cause mortality and rehospitalization for HF at 18 months. Mean age was 71.0 +/- 11.0 years, 38% was women, and mean left ventricular ejection fraction was 32.5 +/- 14.0%. Median syndecan-1 levels were 20.1 ng/mL (interquartile range, 13.9-27.7 ng/mL). Patients with higher syndecan-1 levels were more often men, had higher N-terminal probrain-type natriuretic peptide levels, and worse renal function. Multivariable regression analyses showed a positive correlation between syndecan-1 levels and markers of fibrosis and remodeling but no correlation with inflammation markers. Interaction analysis revealed an interaction between left ventricular ejection fraction and syndecan-1 (P=0.047). A doubling of syndecan-1 was associated with an increased risk of the primary outcome in patients with HF with preserved ejection fraction (hazard ratio, 2.10; 95% confidence interval, 1.14-3.86; P=0.017) but not in patients with HF with reduced ejection fraction (hazard ratio, 0.95; 95% confidence interval, 0.71-1.27; P=0.729). Finally, syndecan-1 enhanced risk classification in patients with HF with preserved ejection fraction when added to a prediction model with established risk factors. Conclusions-In patients with HF, syndecan-1 levels correlate with fibrosis biomarkers pointing toward a role in cardiac remodeling. Syndecan-1 was associated with clinical outcome in patients with HF with preserved ejection fraction but not in patients with HF with reduced ejection fraction.
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| 38. |
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| 39. |
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| 40. |
- van der Harst, Pim, et al.
(författare)
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Telomere length and outcome in heart failure.
- 2010
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Ingår i: Annals of Medicine. - : Informa UK Limited. - 0785-3890 .- 1365-2060. ; 42:1, s. 36-44
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Telomeres are causally involved in senescence. Senescence is a potential factor in the pathogenesis and progression of heart failure. In heart failure telomeres are shorter, but the prognostic value associated with telomere length has not been defined. METHODS: Telomere length was prospectively determined by quantitative polymerase chain reaction in 890 patients with New York Heart Association (NYHA) functional class II to IV heart failure. After 18 months, we examined the association between telomere length and the predefined primary end-point: time to death or hospitalization for heart failure. RESULTS: Mean age of the patients was 71 years, 39% were women, 51% were in NYHA class II, and 49% were in class III/IV. A total of 344 patients reached the primary end-point (130 deaths and 214 hospitalizations). Patients with shorter telomeres were at an increased risk of reaching the primary end-point (hazard ratio 1.79; 95% confidence interval (CI) 1.21-2.63). In multivariate analysis shorter telomere length remained associated with a higher risk for death or hospitalization (hazard ratio, 1.74; 95% CI 1.07-2.95) after adjustment for age of heart failure onset, gender, hemoglobin, renal function, and N-terminal pro-B-type natriuretic peptide level, a history of stroke, atrial fibrillation, and diabetes. CONCLUSIONS: Shorter length of telomeres predicts the occurrence of death or hospitalization in patients with chronic heart failure.
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| 41. |
- Voors, A. A., et al.
(författare)
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The effect of heart rate reduction with ivabradine on renal function in patients with chronic heart failure: an analysis from SHIFT
- 2014
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 16:4, s. 426-434
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: We studied the relationship between heart rate and renal function and the effects of heart rate reduction with ivabradine in heart failure patients with and without renal dysfunction. METHODS AND RESULTS: From the 6505 patients who were randomized in SHIFT, baseline creatinine and at least one follow-up measurement were available in 6160 patients. Median follow-up was 22.9 months. Worsening renal function (WRF) was defined as a creatinine increase of >/=0.3 mg/dL and >/=25% from the baseline value. WRF developed in 1029 (17%) patients and was directly related to baseline heart rate, with an incremental risk of 5% for every 5 b.p.m. heart rate increment (P = 0.003). WRF was associated with an increased risk of the primary composite endpoint of hospitalization for worsening heart failure or cardiovascular death [hazard ratio (HR) 1.38, P < 0.001] and of all-cause mortality (HR 1.42, P < 0.001). Ivabradine use was associated with a reduction of the primary composite endpoint in patients both with (HR 0.82, P = 0.023) and without renal dysfunction (HR 0.81, P < 0.001) at baseline (P for interaction = 0.89), and tolerability of ivabradine was comparable in the two groups. No differences were found in changes in renal function over time between ivabradine- and placebo-treated patients. CONCLUSION: In chronic stable systolic heart failure patients, heart rate is directly and independently associated with the risk of WRF, but reduction in heart rate by ivabradine had a neutral effect on renal function during 2 years of follow-up. The beneficial cardiovascular effects and safety of ivabradine were similar in patients with and without renal dysfunction.
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| 42. |
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| 43. |
- Wong, Liza S M, et al.
(författare)
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Anaemia is associated with shorter leucocyte telomere length in patients with chronic heart failure.
- 2010
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 12:4, s. 348-53
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Anaemia is highly prevalent and associated with poor prognosis in patients with chronic heart failure (CHF). Reduced erythroid proliferation capacity of haematopoietic progenitor cells is associated with reduced telomere length, a marker of cellular ageing. We hypothesize that short telomere length contributes to the susceptibility to develop anaemia in patients with CHF. METHODS AND RESULTS: We studied 875 CHF patients, of whom 254 (29%) fulfilled the WHO criteria of anaemia. Telomere length in DNA from peripheral leucocytes was measured with real-time quantitative polymerase chain reaction. Age, gender, and baseline differences adjusted telomere length was correlated with haemoglobin levels (partial r = 0.130; P = 0.011). One standard deviation shorter telomere length was associated with an increased risk of having anaemia [odds ratio (OR), 1.31; 95% confidence interval (CI), 1.12-1.53; P = 0.001]. This observation was not affected by adjustment for potential confounders (OR, 1.38; 95% CI, 1.05-1.81; P = 0.021 after adjustment for age, gender, erythropoietin levels, renal function, left ventricular ejection fraction, age of CHF onset, blood pressure, history of stroke, diabetes, and B-type natriuretic peptide levels). CONCLUSION: Shorter telomere length increases the odds of having anaemia in CHF patients. This finding supports the hypothesis that cellular ageing in CHF contributes to the susceptibility to develop anaemia.
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| 44. |
- Wong, Liza S M, et al.
(författare)
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Renal dysfunction is associated with shorter telomere length in heart failure.
- 2009
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Ingår i: Clinical research in cardiology : official journal of the German Cardiac Society. - : Springer Science and Business Media LLC. - 1861-0692. ; 98:10, s. 629-34
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Renal dysfunction is a frequent comorbidity associated with high mortality in patients with chronic heart failure (CHF). The intrinsic biological age might affect the ability of the kidney to cope with the challenging environment caused by CHF. We explored the association between leukocyte telomere length, a marker for biological age, and renal function in patients with CHF. METHODS AND RESULTS: Telomere length was determined by a real-time quantitative polymerase chain reaction in 866 CHF patients. Renal function was estimated with the simplified Modification of Diet in Renal Disease equation. The median age was 74 (interquartile range 64-79) years, 61% male, left ventricular ejection fraction of 30 (23-44)%, and the estimated glomerular filtration rate was 53 (40-68) ml/min/1.73 m(2). Telomere length was associated with renal function (correlation coefficient 0.123, P < 0.001). This relationship remained significant after adjustment for age, gender, age of CHF onset (standardized-beta 0.091, P = 0.007). Also additionally adjusting for the severity of CHF and baseline differences did not change our findings. CONCLUSION: The association between shorter leukocyte telomere length and reduced renal function in heart failure suggests that intrinsic biological aging affects the ability of the kidney to cope with the systemic changes evoked by heart failure.
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| 45. |
- Armstrong, Paul W, et al.
(författare)
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Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction.
- 2020
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 382:20, s. 1883-1893
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The effect of vericiguat, a novel oral soluble guanylate cyclase stimulator, in patients with heart failure and reduced ejection fraction who had recently been hospitalized or had received intravenous diuretic therapy is unclear.METHODS: In this phase 3, randomized, double-blind, placebo-controlled trial, we assigned 5050 patients with chronic heart failure (New York Heart Association class II, III, or IV) and an ejection fraction of less than 45% to receive vericiguat (target dose, 10 mg once daily) or placebo, in addition to guideline-based medical therapy. The primary outcome was a composite of death from cardiovascular causes or first hospitalization for heart failure.RESULTS: Over a median of 10.8 months, a primary-outcome event occurred in 897 of 2526 patients (35.5%) in the vericiguat group and in 972 of 2524 patients (38.5%) in the placebo group (hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P = 0.02). A total of 691 patients (27.4%) in the vericiguat group and 747 patients (29.6%) in the placebo group were hospitalized for heart failure (hazard ratio, 0.90; 95% CI, 0.81 to 1.00). Death from cardiovascular causes occurred in 414 patients (16.4%) in the vericiguat group and in 441 patients (17.5%) in the placebo group (hazard ratio, 0.93; 95% CI, 0.81 to 1.06). The composite of death from any cause or hospitalization for heart failure occurred in 957 patients (37.9%) in the vericiguat group and in 1032 patients (40.9%) in the placebo group (hazard ratio, 0.90; 95% CI, 0.83 to 0.98; P = 0.02). Symptomatic hypotension occurred in 9.1% of the patients in the vericiguat group and in 7.9% of the patients in the placebo group (P = 0.12), and syncope occurred in 4.0% of the patients in the vericiguat group and in 3.5% of the patients in the placebo group (P = 0.30).CONCLUSIONS: Among patients with high-risk heart failure, the incidence of death from cardiovascular causes or hospitalization for heart failure was lower among those who received vericiguat than among those who received placebo. (Funded by Merck Sharp & Dohme [a subsidiary of Merck] and Bayer; VICTORIA ClinicalTrials.gov number, NCT02861534.).
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| 46. |
- Belonje, Anne M S, et al.
(författare)
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Endogenous erythropoietin and outcome in heart failure.
- 2010
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 121:2, s. 245-51
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Endogenous erythropoietin is increased in patients with heart failure (HF). Previous small-scale data suggest that these erythropoietin levels are related to prognosis. This study aims to analyze the clinical and prognostic value of erythropoietin levels in relation to hemoglobin in a large cohort of HF patients. METHODS AND RESULTS: In patients hospitalized for HF, endogenous erythropoietin levels were measured at discharge and after 6 months. In anemic patients, the relation between erythropoietin and hemoglobin levels was determined by calculating the observed/predicted ratio of erythropoietin levels. We studied data from 605 patients with HF. Mean age was 71+/-11 years; 62% were male; and mean left ventricular ejection fraction was 0.33+/-0.14. Median erythropoietin levels were 9.6 U/L at baseline and 10.5 U/L at 6 months. Higher erythropoietin levels at baseline were independently related to an increased mortality at 18 months (hazard ratio, 2.06; 95% confidence interval, 1.40 to 3.04; P<0.01). In addition, persistently elevated erythropoietin levels (higher than median at baseline and at 6 months) were related to an increased mortality risk (hazard ratio, 2.24; 95% confidence interval, 1.02 to 4.90; P=0.044). The observed/predicted ratio was determined in a subset of anemic patients, 79% of whom had erythropoietin levels lower than expected and 9% had levels higher than expected on the basis of their hemoglobin. Multivariate Cox regression analysis revealed that a higher observed/predicted ratio was related to an increased mortality risk (hazard ratio, 3.52; 95% confidence interval, 1.53 to 8.12; P=0.003). CONCLUSIONS: Erythropoietin levels predict mortality in HF patients, and persistently elevated levels have an independent prognostic value. In anemic HF patients, the majority had a low observed/predicted ratio. However, a higher observed/predicted ratio may be related to an independent increased mortality risk.
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| 47. |
- Callen, Michael, et al.
(författare)
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COVID-19 vaccine acceptance and hesitancy in low- and middle-income countries
- 2021
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Ingår i: Nature Medicine. - : Springer Nature. - 1546-170X .- 1078-8956. ; 27:8, s. 1385-1394
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Tidskriftsartikel (refereegranskat)abstract
- Widespread acceptance of COVID-19 vaccines is crucial for achieving sufficient immunization coverage to end the global pandemic, yet few studies have investigated COVID-19 vaccination attitudes in lower-income countries, where large-scale vaccination is just beginning. We analyze COVID-19 vaccine acceptance across 15 survey samples covering 10 low- and middle-income countries (LMICs) in Asia, Africa and South America, Russia (an upper-middle-income country) and the United States, including a total of 44,260 individuals. We find considerably higher willingness to take a COVID-19 vaccine in our LMIC samples (mean 80.3%; median 78%; range 30.1 percentage points) compared with the United States (mean 64.6%) and Russia (mean 30.4%). Vaccine acceptance in LMICs is primarily explained by an interest in personal protection against COVID-19, while concern about side effects is the most common reason for hesitancy. Health workers are the most trusted sources of guidance about COVID-19 vaccines. Evidence from this sample of LMICs suggests that prioritizing vaccine distribution to the Global South should yield high returns in advancing global immunization coverage. Vaccination campaigns should focus on translating the high levels of stated acceptance into actual uptake. Messages highlighting vaccine efficacy and safety, delivered by healthcare workers, could be effective for addressing any remaining hesitancy in the analyzed LMICs. © 2021, The Author(s).
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| 48. |
- Chen, Yuntao, et al.
(författare)
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A heart failure phenotype stratified model for predicting 1-year mortality in patients admitted with acute heart failure: results from an individual participant data meta-analysis of four prospective European cohorts
- 2021
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Ingår i: BMC Medicine. - : BMC. - 1741-7015. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Prognostic models developed in general cohorts with a mixture of heart failure (HF) phenotypes, though more widely applicable, are also likely to yield larger prediction errors in settings where the HF phenotypes have substantially different baseline mortality rates or different predictor-outcome associations. This study sought to use individual participant data meta-analysis to develop an HF phenotype stratified model for predicting 1-year mortality in patients admitted with acute HF. Methods Four prospective European cohorts were used to develop an HF phenotype stratified model. Cox model with two rounds of backward elimination was used to derive the prognostic index. Weibull model was used to obtain the baseline hazard functions. The internal-external cross-validation (IECV) approach was used to evaluate the generalizability of the developed model in terms of discrimination and calibration. Results 3577 acute HF patients were included, of which 2368 were classified as having HF with reduced ejection fraction (EF) (HFrEF; EF < 40%), 588 as having HF with midrange EF (HFmrEF; EF 40-49%), and 621 as having HF with preserved EF (HFpEF; EF >= 50%). A total of 11 readily available variables built up the prognostic index. For four of these predictor variables, namely systolic blood pressure, serum creatinine, myocardial infarction, and diabetes, the effect differed across the three HF phenotypes. With a weighted IECV-adjusted AUC of 0.79 (0.74-0.83) for HFrEF, 0.74 (0.70-0.79) for HFmrEF, and 0.74 (0.71-0.77) for HFpEF, the model showed excellent discrimination. Moreover, there was a good agreement between the average observed and predicted 1-year mortality risks, especially after recalibration of the baseline mortality risks. Conclusions Our HF phenotype stratified model showed excellent generalizability across four European cohorts and may provide a useful tool in HF phenotype-specific clinical decision-making.
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| 49. |
- Damman, Kevin, et al.
(författare)
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Both in- and out-hospital worsening of renal function predict outcome in patients with heart failure : results from the Coordinating Study Evaluating Outcome of Advising and Counseling in Heart Failure (COACH).
- 2009
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 11:9, s. 847-54
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The effect of worsening renal function (WRF) after discharge on outcome in patients with heart failure is unknown. METHODS AND RESULTS: We assessed estimated glomerular filtration rate (eGFR) and serum creatinine at admission, discharge, and 6 and 12 months after discharge, in 1023 heart failure patients. Worsening renal function was defined as an increase in serum creatinine of >26.5 micromol/L and >25%. The primary endpoint was a composite of all-cause mortality and heart failure admissions. The mean age of patients was 71 +/- 11 years, and 62% was male. Mean eGFR at admission was 55 +/- 21 mL/min/1.73 m(2). In-hospital WRF occurred in 11% of patients, while 16 and 9% experienced WRF from 0 to 6, and 6 to 12 months after discharge, respectively. In multivariate landmark analysis, WRF at any point in time was associated with a higher incidence of the primary endpoint: hazard ratio (HR) 1.63 (1.10-2.40), P = 0.014 for in-hospital WRF, HR 2.06 (1.13-3.74), P = 0.018 for WRF between 0-6 months, and HR 5.03 (2.13-11.88), P < 0.001 for WRF between 6-12 months. CONCLUSION: Both in- and out-hospital worsening of renal function are independently related to poor prognosis in patients with heart failure, suggesting that renal function in heart failure patients should be monitored long after discharge.
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| 50. |
- Egger, Dennis, et al.
(författare)
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Falling living standards during the COVID-19 crisis : Quantitative evidence from nine developing countries
- 2021
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Despite numerous journalistic accounts, systematic quantitative evidence on economic conditions during the ongoing COVID-19 pandemic remains scarce for most low- and middle-income countries, partly due to limitations of official economic statistics in environments with large informal sectors and subsistence agriculture. We assemble evidence from over 30,000 respondents in 16 original household surveys from nine countries in Africa (Burkina Faso, Ghana, Kenya, Rwanda, Sierra Leone), Asia (Bangladesh, Nepal, Philippines), and Latin America (Colombia). We document declines in employment and income in all settings beginning March 2020. The share of households experiencing an income drop ranges from 8 to 87% (median, 68%). Household coping strategies and government assistance were insufficient to sustain precrisis living standards, resulting in widespread food insecurity and dire economic conditions even 3 months into the crisis. We discuss promising policy responses and speculate about the risk of persistent adverse effects, especially among children and other vulnerable groups.
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