| 1. |
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| 2. |
- George, T. S., et al.
(author)
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Organic phosphorus in the terrestrial environment : a perspective on the state of the art and future priorities
- 2018
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In: Plant and Soil. - : Springer Netherlands. - 0032-079X .- 1573-5036. ; 427:1-2, s. 191-208
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Journal article (peer-reviewed)abstract
- Background: The dynamics of phosphorus (P) in the environment is important for regulating nutrient cycles in natural and managed ecosystems and an integral part in assessing biological resilience against environmental change. Organic P (P-o) compounds play key roles in biological and ecosystems function in the terrestrial environment being critical to cell function, growth and reproduction.Scope: We asked a group of experts to consider the global issues associated with P-o in the terrestrial environment, methodological strengths and weaknesses, benefits to be gained from understanding the P-o cycle, and to set priorities for P-o research.Conclusions: We identified seven key opportunities for P-o research including: the need for integrated, quality controlled and functionally based methodologies; assessment of stoichiometry with other elements in organic matter; understanding the dynamics of P-o in natural and managed systems; the role of microorganisms in controlling P-o cycles; the implications of nanoparticles in the environment and the need for better modelling and communication of the research. Each priority is discussed and a statement of intent for the P-o research community is made that highlights there are key contributions to be made toward understanding biogeochemical cycles, dynamics and function of natural ecosystems and the management of agricultural systems.
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| 3. |
- Leisawitz, David, et al.
(author)
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The origins space telescope
- 2019
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In: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 11115
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Conference paper (peer-reviewed)abstract
- The Origins Space Telescope will trace the history of our origins from the time dust and heavy elements permanently altered the cosmic landscape to present-day life. How did galaxies evolve from the earliest galactic systems to those found in the universe today? How do habitable planets form? How common are life-bearing worlds? To answer these alluring questions, Origins will operate at mid-and far-infrared wavelengths and offer powerful spectroscopic instruments and sensitivity three orders of magnitude better than that of Herschel, the largest telescope flown in space to date. After a 3 1/2 year study, the Origins Science and Technology Definition Team will recommend to the Decadal Survey a concept for Origins with a 5.9-m diameter telescope cryocooled to 4.5 K and equipped with three scientific instruments. A mid-infrared instrument (MISC-T) will measure the spectra of transiting exoplanets in the 2.8-20 μm wavelength range and offer unprecedented sensitivity, enabling definitive biosignature detections. The Far-IR Imager Polarimeter (FIP) will be able to survey thousands of square degrees with broadband imaging at 50 and 250 μm. The Origins Survey Spectrometer (OSS) will cover wavelengths from 25-588 μm, make wide-area and deep spectroscopic surveys with spectral resolving power R ∼ 300, and pointed observations at R ∼ 40,000 and 300,000 with selectable instrument modes. Origins was designed to minimize complexity. The telescope has a Spitzer-like architecture and requires very few deployments after launch. The cryo-thermal system design leverages JWST technology and experience. A combination of current-state-of-the-art cryocoolers and next-generation detector technology will enable Origins' natural backgroundlimited sensitivity.
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| 4. |
- Leisawitz, David, et al.
(author)
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Origins Space Telescope: Baseline mission concept
- 2021
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In: Journal of Astronomical Telescopes, Instruments, and Systems. - 2329-4221 .- 2329-4124. ; 7:1
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Journal article (peer-reviewed)abstract
- The Origins Space Telescope will trace the history of our origins from the time dust and heavy elements permanently altered the cosmic landscape to present-day life. How did galaxies evolve from the earliest galactic systems to those found in the Universe today? How do habitable planets form? How common are life-bearing worlds? To answer these alluring questions, Origins will operate at mid-and far-infrared (IR) wavelengths and offer powerful spectroscopic instruments and sensitivity three orders of magnitude better than that of the Herschel Space Observatory, the largest telescope flown in space to date. We describe the baseline concept for Origins recommended to the 2020 US Decadal Survey in Astronomy and Astrophysics. The baseline design includes a 5.9-m diameter telescope cryocooled to 4.5 K and equipped with three scientific instruments. A mid-infrared instrument (Mid-Infrared Spectrometer and Camera Transit spectrometer) will measure the spectra of transiting exoplanets in the 2.8 to 20 μm wavelength range and offer unprecedented spectrophotometric precision, enabling definitive exoplanet biosignature detections. The far-IR imager polarimeter will be able to survey thousands of square degrees with broadband imaging at 50 and 250 μm. The Origins Survey Spectrometer will cover wavelengths from 25 to 588 μm, making wide-area and deep spectroscopic surveys with spectral resolving power R ∼ 300, and pointed observations at R ∼ 40,000 and 300,000 with selectable instrument modes. Origins was designed to minimize complexity. The architecture is similar to that of the Spitzer Space Telescope and requires very few deployments after launch, while the cryothermal system design leverages James Webb Space Telescope technology and experience. A combination of current-state-of-the-art cryocoolers and next-generation detector technology will enable Origins' natural background-limited sensitivity.
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| 5. |
- Clark, Andrew G., et al.
(author)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Journal article (peer-reviewed)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 6. |
- Connolly, S., et al.
(author)
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Rationale and design of ACTIVE: the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events
- 2006
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In: American heart journal. - 1097-6744. ; 151:6, s. 1187-93
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Journal article (peer-reviewed)abstract
- BACKGROUND: Atrial fibrillation (AF) is the most frequently occurring cardiac arrhythmia with often serious clinical consequences. Many patients have contraindications to anticoagulation, and it is often underused in clinical practice. The addition of clopidogrel to aspirin (ASA) has been shown to reduce vascular events in a number of high-risk populations. Irbesartan is an angiotensin receptor-blocking agent that reduces blood pressure and has other vascular protective effects. METHODS AND RESULTS: ACTIVE W is a noninferiority trial of clopidogrel plus ASA versus oral anticoagulation in patients with AF and at least 1 risk factor for stroke. ACTIVE A is a double-blind, placebo-controlled trial of clopidogrel in patients with AF and with at least 1 risk factor for stroke who receive ASA because they have a contraindication for oral anticoagulation or because they are unwilling to take an oral anticoagulant. ACTIVE I is a partial factorial, double-blind, placebo-controlled trial of irbesartan in patients participating in ACTIVE A or ACTIVE W. The primary outcomes of these studies are composites of vascular events. A total of 14000 patients will be enrolled in these trials. CONCLUSIONS: ACTIVE is the largest trial yet conducted in AF. Its results will lead to a new understanding of the role of combined antiplatelet therapy and the role of blood pressure lowering with an angiotensin II receptor blocker in patients with AF.
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| 7. |
- Leisawitz, David, et al.
(author)
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The Origins Space Telescope: Mission concept overview
- 2018
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In: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 10698
-
Conference paper (peer-reviewed)abstract
- Downloading of the abstract is permitted for personal use only. The Origins Space Telescope (OST) will trace the history of our origins from the time dust and heavy elements permanently altered the cosmic landscape to present-day life. How did the universe evolve in response to its changing ingredients? How common are life-bearing planets? To accomplish its scientific objectives, OST will operate at mid- and far-infrared wavelengths and offer superlative sensitivity and new spectroscopic capabilities. The OST study team will present a scientifically compelling, executable mission concept to the 2020 Decadal Survey in Astrophysics. To understand the concept solution space, our team studied two alternative mission concepts. We report on the study approach and describe both of these concepts, give the rationale for major design decisions, and briefly describe the mission-enabling technology.
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| 8. |
- Assimes, Themistocles L., et al.
(author)
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Lack of Association Between the Trp719Arg Polymorphism in Kinesin-Like Protein-6 and Coronary Artery Disease in 19 Case-Control Studies
- 2010
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In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 56:19, s. 1552-1563
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Journal article (peer-reviewed)abstract
- Objectives We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455), and clinical coronary artery disease (CAD). Background Recent prospective studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with noncarriers. Methods The KIF6 Trp719Arg polymorphism (rs20455) was genotyped in 19 case-control studies of nonfatal CAD either as part of a genome-wide association study or in a formal attempt to replicate the initial positive reports. Results A total of 17,000 cases and 39,369 controls of European descent as well as a modest number of South Asians, African Americans, Hispanics, East Asians, and admixed cases and controls were successfully genotyped. None of the 19 studies demonstrated an increased risk of CAD in carriers of the 719Arg allele compared with noncarriers. Regression analyses and fixed-effects meta-analyses ruled out with high degree of confidence an increase of >= 2% in the risk of CAD among European 719Arg carriers. We also observed no increase in the risk of CAD among 719Arg carriers in the subset of Europeans with early-onset disease (younger than 50 years of age for men and younger than 60 years of age for women) compared with similarly aged controls as well as all non-European subgroups. Conclusions The KIF6 Trp719Arg polymorphism was not associated with the risk of clinical CAD in this large replication study. (J Am Coll Cardiol 2010;56:1552-63) (C) 2010 by the American College of Cardiology Foundation
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| 9. |
- Badar, A. A., et al.
(author)
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Clinical characteristics and outcomes of patients with angina and heart failure in the CHARM (Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity) Programme
- 2015
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In: European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 17:2, s. 196-204
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Journal article (peer-reviewed)abstract
- AimsTo investigate the relationship between angina pectoris and fatal and non-fatal clinical outcomes in heart failure with reduced and preserved ejection fraction (HF-REF and HF-PEF, respectively). Methods and resultsOf 7599 patients in the CHARM program, 5408 had ischaemic heart disease; 3855 had HF-REF (ejection fraction 45%) and 1553 had HF-PEF. These patients were separated into three groups: no history of angina, previous angina, and current angina. Three coronary outcomes were examined: fatal or non-fatal myocardial infarction (MI); MI or hospitalization for unstable angina (UA); and MI, UA or coronary revascularization. The composite heart failure outcome of cardiovascular death or heart failure hospitalization (HFH) was also analysed, along with its components and all-cause mortality. New York Heart Association functional class was worse in both HF-REF and HF-PEF patients with current angina compared with patients without angina (P<0.001 and P=0.005 respectively), despite similar clinical examination findings and ejection fraction. Patients with current angina had a higher risk of all three coronary outcomes (adjusted hazard ratios ranging from 1.8-3.1) than those without angina but did not have a higher risk of heart failure outcomes or all-cause mortality. ConclusionIn patients with heart failure current angina is associated with significantly more functional limitation and a higher risk of coronary events, across the spectrum of left ventricular ejection fraction.
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| 10. |
- Gottselig, N., et al.
(author)
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Elemental Composition of Natural Nanoparticles and Fine Colloids in European Forest Stream Waters and Their Role as Phosphorus Carriers
- 2017
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In: Global Biogeochemical Cycles. - 0886-6236 .- 1944-9224. ; 31:10, s. 1592-1607
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Journal article (peer-reviewed)abstract
- Biogeochemical cycling of elements largely occurs in dissolved state, but many elements may also be bound to natural nanoparticles (NNP, 1-100 nm) and fine colloids (100-450 nm). We examined the hypothesis that the size and composition of stream water NNP and colloids vary systematically across Europe. To test this hypothesis, 96 stream water samples were simultaneously collected in 26 forested headwater catchments along two transects across Europe. Three size fractions (~1-20 nm, >20-60 nm, and >60 nm) of NNP and fine colloids were identified with Field Flow Fractionation coupled to inductively coupled plasma mass spectrometry and an organic carbon detector. The results showed that NNP and fine colloids constituted between 2 ± 5% (Si) and 53 ± 21% (Fe; mean ± SD) of total element concentrations, indicating a substantial contribution of particles to element transport in these European streams, especially for P and Fe. The particulate contents of Fe, Al, and organic C were correlated to their total element concentrations, but those of particulate Si, Mn, P, and Ca were not. The fine colloidal fractions >60 nm were dominated by clay minerals across all sites. The resulting element patterns of NNP <60 nm changed from North to South Europe from Fe- to Ca-dominated particles, along with associated changes in acidity, forest type, and dominant lithology.
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| 11. |
- Loley, C, et al.
(author)
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No Association of Coronary Artery Disease with X-Chromosomal Variants in Comprehensive International Meta-Analysis
- 2016
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 35278-
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Journal article (peer-reviewed)abstract
- In recent years, genome-wide association studies have identified 58 independent risk loci for coronary artery disease (CAD) on the autosome. However, due to the sex-specific data structure of the X chromosome, it has been excluded from most of these analyses. While females have 2 copies of chromosome X, males have only one. Also, one of the female X chromosomes may be inactivated. Therefore, special test statistics and quality control procedures are required. Thus, little is known about the role of X-chromosomal variants in CAD. To fill this gap, we conducted a comprehensive X-chromosome-wide meta-analysis including more than 43,000 CAD cases and 58,000 controls from 35 international study cohorts. For quality control, sex-specific filters were used to adequately take the special structure of X-chromosomal data into account. For single study analyses, several logistic regression models were calculated allowing for inactivation of one female X-chromosome, adjusting for sex and investigating interactions between sex and genetic variants. Then, meta-analyses including all 35 studies were conducted using random effects models. None of the investigated models revealed genome-wide significant associations for any variant. Although we analyzed the largest-to-date sample, currently available methods were not able to detect any associations of X-chromosomal variants with CAD.
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| 12. |
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| 13. |
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| 14. |
- Jackson, C. E., et al.
(author)
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Albuminuria in chronic heart failure: prevalence and prognostic importance
- 2009
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In: Lancet. - 1474-547X. ; 374:9689, s. 543-50
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Journal article (peer-reviewed)abstract
- BACKGROUND: Increased excretion of albumin in urine might be a marker of the various pathophysiological changes that arise in patients with heart failure. Therefore our aim was to assess the prevalence and prognostic value of a spot urinary albumin to creatinine ratio (UACR) in patients with heart failure. METHODS: UACR was measured at baseline and during follow-up of 2310 patients in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) Programme. The prevalence of microalbuminuria and macroalbuminuria, and the predictive value of UACR for the primary composite outcome of each CHARM study--ie, death from cardiovascular causes or admission to hospital with worsening heart failure--and death from any cause were assessed. FINDINGS: 1349 (58%) patients had a normal UACR, 704 (30%) had microalbuminuria, and 257 (11%) had macroalbuminuria. The prevalence of increased UACR was similar in patients with reduced and preserved left ventricular ejection fractions. Patients with an increased UACR were older, had more cardiovascular comorbidity, worse renal function, and a higher prevalence of diabetes mellitus than did those with normoalbuminuria. However, a high prevalence of increased UACR was still noted among patients without diabetes, hypertension, or renal dysfunction. Elevated UACR was associated with increased risk of the composite outcome and death even after adjustment for other prognostic variables including renal function, diabetes, and haemoglobin A1c. The adjusted hazard ratio (HR) for the composite outcome in patients with microalbuminuria versus normoalbuminuria was 1.43 (95% CI 1.21-1.69; p<0.0001) and for macroalbuminuria versus normoalbuminuria was 1.75 (1.39-2.20; p<0.0001). The adjusted values for death were 1.62 (1.32-1.99; p<0.0001) for microalbuminuria versus normoalbuminuria, and 1.76 (1.32-2.35; p=0.0001) for macroalbuminuria versus normoalbuminuria. Treatment with candesartan did not reduce or prevent the development of excessive excretion of urinary albumin. INTERPRETATION: Increased UACR is a powerful and independent predictor of prognosis in heart failure. FUNDING: AstraZeneca.
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| 15. |
- Lopes, Renato D., et al.
(author)
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Highlights from the III International Symposium of Thrombosis and Anticoagulation (ISTA), October 14-16, 2010, Sao Paulo, Brazil
- 2011
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In: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 32:2, s. 242-266
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Journal article (peer-reviewed)abstract
- To discuss and share knowledge around advances in the care of patients with thrombotic disorders, the Third International Symposium of Thrombosis and Anticoagulation was held in So Paulo, Brazil, from October 14-16, 2010. This scientific program was developed by clinicians for clinicians, and was promoted by four major clinical research institutes: the Brazilian Clinical Research Institute, the Duke Clinical Research Institute of the Duke University School of Medicine, the Canadian VIGOUR Centre, and the Uppsala Clinical Research Center. Comprising 3 days of academic presentations and open discussion, the symposium had as its primary goal to educate, motivate, and inspire internists, cardiologists, hematologists, and other physicians by convening national and international visionaries, thought-leaders, and dedicated clinician-scientists. This paper summarizes the symposium proceedings.
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| 16. |
- Nikpay, Majid, et al.
(author)
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A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease
- 2015
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:10, s. 1121-1121
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Journal article (peer-reviewed)abstract
- Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of similar to 185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.
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| 17. |
- O'Meara, E., et al.
(author)
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Clinical correlates and consequences of anemia in a broad spectrum of patients with heart failure: results of the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) Program
- 2006
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In: Circulation. - 1524-4539. ; 113:7, s. 986-94
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Journal article (peer-reviewed)abstract
- BACKGROUND: We wished to determine the prevalence of, potential mechanistic associations of, and clinical outcomes related to anemia in patients with heart failure and a broad spectrum of left ventricular ejection fraction (LVEF). METHODS AND RESULTS: In multivariable analyses, we examined the associations between hemoglobin and baseline characteristics, laboratory variables, and outcomes in 2653 patients randomized in the CHARM Program in the United States and Canada. Anemia was equally common in patients with preserved (27%) and reduced (25%) LVEF but was more common in black and older patients. Anemia was associated with ethnicity, diabetes, low body mass index, higher systolic and lower diastolic blood pressure, and recent heart failure hospitalization. More than 50% of anemic patients had a glomerular filtration rate <60 mL.min(-1).1.73 m(-2) compared with <30% of nonanemic patients. Despite an inverse relationship between hemoglobin and LVEF, anemia was associated with an increased risk of death and hospitalization, a relationship observed in patients with both reduced and preserved LVEF. There were 133 versus 69 deaths and 527 versus 352 hospitalizations per 1000 patient-years of follow-up in anemic versus nonanemic patients (both P<0.001). The effect of candesartan in reducing outcomes was independent of hemoglobin. CONCLUSIONS: Anemia was common in heart failure, regardless of LVEF. Lower hemoglobin was associated with higher LVEF yet was an independent predictor of adverse mortality and morbidity outcomes. In heart failure, the causes of anemia and the associations between anemia and outcomes are probably multiple and complex.
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| 18. |
- Wong, C. M., et al.
(author)
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Clinical characteristics and outcomes of young and very young adults with heart failure: the CHARM programme
- 2013
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In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 62:20, s. 1845-1854
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To determine the characteristics and outcomes of young adults with heart failure (HF). BACKGROUND: Few studies have focused on young and very young adults with HF. METHODS: Patients were categorized into 5 age groups: 20-39, 40-49, 50-59, 60-69, and >/=70 years. RESULTS: The youngest patients with HF were more likely to be obese (youngest vs. oldest: BMI>/=35kg/m2: 23% vs. 6%), of black ethnicity (18% vs. 2%), and have idiopathic dilated cardiomyopathy (IDCM 62% vs. 9%) (all p<0.0001). They were less likely to adhere to medication (non-adherence in youngest vs. oldest: 24% vs. 7%, p=0.001), salt intake and other dietary measures (21% vs. 9%, p=0.002). The youngest patients were less likely to have clinical and radiological signs of HF during hospitalization. Quality of life was worst but all-cause mortality was lowest in the youngest age group (3 years mortality rates across the respective age categories: 12%, 13%, 13%, 19%, and 31%). Compared to the referent age group of 60-69 years, both all-cause and cardiovascular mortality were lower in the youngest group even after multivariable adjustment (respective HR 0.60 (0.36-1.00) [p=0.049] and 0.71 (0.42-1.18) [p=0.186]). Three-year HF hospitalisation rates were 24%, 15%, 15%, 22% and 28% in age categories 20-39, 40-49, 50-59, 60-69 and >/=70 years respectively (p<0.0001). Conclusion: Beyond divergent etiology and comorbidities, younger patients exhibit striking differences in presentation and outcomes compared with older counterparts. Clinical and radiological signs of HF are less common, yet quality of life more significantly impaired. Fatal and non-fatal outcomes are discordant, with better survival despite higher hospitalization rates.
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| 19. |
- Ariti, C. A., et al.
(author)
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Days alive and out of hospital and the patient journey in patients with heart failure: Insights from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program
- 2011
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In: American heart journal. - : Elsevier BV. - 1097-6744 .- 0002-8703. ; 162:5, s. 900-6
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Journal article (peer-reviewed)abstract
- BACKGROUND: Conventional composite outcomes in heart failure (HF) trials, for example, time to cardiovascular death or first HF hospitalization, have recognized limitations. We propose an alternative outcome, days alive and out of hospital (DAOH), which incorporates mortality and all hospitalizations into a single measure. A refinement, the patient journey, also uses functional status (New York Heart Association [NYHA] class) measured during follow-up. The CHARM program is used to illustrate the methodology. METHODS: CHARM randomized 7,599 patients with symptomatic HF to placebo or candesartan, with median follow-up of 38 months. We related DAOH and percent DAOH (ie, percentage of time spent alive and out of hospital) to treatment using linear regression adjusting for follow-up time. RESULTS: Mean increase in DAOH for patients on candesartan versus placebo was 24.1 days (95% CI 9.8-38.3 days, P < .001). The corresponding mean increase in percent DAOH was 2.0% (95% CI 0.8%-3.1%, P < .001). These findings were dominated by reduced mortality (23 days) but enhanced by reduced time in hospital (1 day). Percent time spent in hospital because of HF was reduced by 0.10% (95% CI 0.04%-0.14%, P < .001). The patient journey analysis showed that patients in the candesartan group spent more follow-up time in NYHA classes I and II and less in NYHA class IV. CONCLUSIONS: Days alive and out of hospital, especially percent DAOH, provide a valuable tool for summarizing the overall absolute treatment effect on mortality and morbidity. In future HF trials, percent DAOH can provide a useful alternative perspective on the effects of treatment.
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| 20. |
- Bahit, M C, et al.
(author)
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Heart failure complicating non-ST-segment elevation acute coronary syndrome: timing, predictors, and clinical outcomes
- 2013
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In: JACC. Heart failure. - : Elsevier BV. - 2213-1779 .- 2213-1787. ; 1:3, s. 223-229
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Journal article (peer-reviewed)abstract
- OBJECTIVES: This study sought to describe the occurrence and timing of heart failure (HF), associated clinical factors, and 30-day outcomes in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). BACKGROUND: Little is known about HF-complicating NSTE-ACS. METHODS: Using pooled patient-level data from 7 clinical trials from 1994 to 2008, we describe the occurrence and timing of HF, associated clinical factors, and 30-day outcomes in NSTE-ACS patients. HF at presentation was defined as Killip classes II to III; patients with Killip class IV or cardiogenic shock were excluded. New in-hospital cases of HF included new pulmonary edema. After adjusting for baseline variables, we created logistic regression models to identify clinical factors associated with HF at presentation and to determine the association between HF and 30-day mortality. RESULTS: Of 46,519 NSTE-ACS patients, 4,910 (10.6%) had HF at presentation. Of the 41,609 with no HF at presentation, 1,194 (2.9%) developed HF during hospitalization. A total of 40,415 (86.9%) had no HF at any time. Patients presenting with or developing HF during hospitalization were older, more often female, and had a higher risk of death at 30 days than patients without HF (adjusted odds ratio [OR]: 1.74; 95% confidence interval: 1.35 to 2.26). Older age, higher presenting heart rate, diabetes, prior myocardial infarction (MI), and enrolling MI were significantly associated with HF during hospitalization. CONCLUSIONS: In this large cohort of NSTE-ACS patients, presenting with or developing HF during hospitalization was associated with an increased risk of 30-day mortality. Research targeting new strategies to prevent and manage HF in this high-risk population is needed.
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| 21. |
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| 22. |
- Berry, C, et al.
(author)
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The survival of patients with heart failure with preserved or reduced left ventricular ejection fraction: an individual patient data meta-analysis.
- 2012
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In: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 33:14, s. 1750-7
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Journal article (peer-reviewed)abstract
- A substantial proportion of patients with heart failure have preserved left ventricular ejection fraction (HF-PEF). Previous studies have reported mixed results whether survival is similar to those patients with heart failure and reduced EF (HF-REF).We compared survival in patients with HF-PEF with that in patients with HF-REF in a meta-analysis using individual patient data. Preserved EF was defined as an EF ≥ 50%. The 31 studies included 41 972 patients: 10 347 with HF-PEF and 31 625 with HF-REF. Compared with patients with HF-REF, those with HF-PEF were older (mean age 71 vs. 66 years), were more often women (50 vs. 28%), and have a history of hypertension (51 vs. 41%). Ischaemic aetiology was less common (43 vs. 59%) in patients with HF-PEF. There were 121 [95% confidence interval (CI): 117, 126] deaths per 1000 patient-years in those with HF-PEF and 141 (95% CI: 138, 144) deaths per 1000 patient-years in those with HF-REF. Patients with HF-PEF had lower mortality than those with HF-REF (adjusted for age, gender, aetiology, and history of hypertension, diabetes, and atrial fibrillation); hazard ratio 0.68 (95% CI: 0.64, 0.71). The risk of death did not increase notably until EF fell below 40%.Patients with HF-PEF have a lower risk of death than patients with HF-REF, and this difference is seen regardless of age, gender, and aetiology of HF. However, absolute mortality is still high in patients with HF-PEF highlighting the need for a treatment to improve prognosis.
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| 23. |
- Bosworth, H. B., et al.
(author)
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Medication adherence: a call for action
- 2011
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In: American heart journal. - : Elsevier BV. - 1097-6744 .- 0002-8703. ; 162:3, s. 412-24
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Journal article (peer-reviewed)abstract
- Poor adherence to efficacious cardiovascular-related medications has led to considerable morbidity, mortality, and avoidable health care costs. This article provides results of a recent think-tank meeting in which various stakeholder groups representing key experts from consumers, community health providers, the academic community, decision-making government officials (Food and Drug Administration, National Institutes of Health, etc), and industry scientists met to evaluate the current status of medication adherence and provide recommendations for improving outcomes. Below, we review the magnitude of the problem of medication adherence, prevalence, impact, and cost. We then summarize proven effective approaches and conclude with a discussion of recommendations to address this growing and significant public health issue of medication nonadherence.
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| 24. |
- Bowers, Robert M., et al.
(author)
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Minimum information about a single amplified genome (MISAG) and a metagenome-assembled genome (MIMAG) of bacteria and archaea
- 2017
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In: Nature Biotechnology. - : NATURE PUBLISHING GROUP. - 1087-0156 .- 1546-1696. ; 35:8, s. 725-731
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Journal article (peer-reviewed)abstract
- We present two standards developed by the Genomic Standards Consortium (GSC) for reporting bacterial and archaeal genome sequences. Both are extensions of the Minimum Information about Any (x) Sequence (MIxS). The standards are the Minimum Information about a Single Amplified Genome (MISAG) and the Minimum Information about a Metagenome-Assembled Genome (MIMAG), including, but not limited to, assembly quality, and estimates of genome completeness and contamination. These standards can be used in combination with other GSC checklists, including the Minimum Information about a Genome Sequence (MIGS), Minimum Information about a Metagenomic Sequence (MIMS), and Minimum Information about a Marker Gene Sequence (MIMARKS). Community-wide adoption of MISAG and MIMAG will facilitate more robust comparative genomic analyses of bacterial and archaeal diversity.
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| 25. |
- Demers, C., et al.
(author)
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Impact of candesartan on nonfatal myocardial infarction and cardiovascular death in patients with heart failure
- 2005
-
In: JAMA. - 1538-3598. ; 294:14, s. 1794-8
-
Research review (peer-reviewed)abstract
- CONTEXT: Angiotensin-converting enzyme (ACE) inhibitors reduce the risk of myocardial infarction (MI), but it is not known whether angiotensin receptor blockers have the same effect. OBJECTIVE: To assess the impact of the angiotensin receptor blocker candesartan on MI and other coronary events in patients with heart failure. DESIGN, SETTING, AND PARTICIPANTS: The Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program, a randomized, placebo-controlled study enrolling patients (mean age, 66 [SD, 11] years) with New York Heart Association class II to IV symptoms who were randomly allocated to receive candesartan (target dose, 32 mg once daily) or matching placebo given in addition to optimal therapy for heart failure. Patients were enrolled from March 1999 through March 2001. Of 7599 patients allocated, 4004 (53%) had experienced a previous MI, and 1808 (24%) currently had angina. At baseline, 3125 (41%) were receiving an ACE inhibitor; 4203 (55%), a beta-blocker; 3153 (42%), a lipid-lowering drug; 4246 (56%), aspirin; and 6286 (83%), a diuretic. MAIN OUTCOME MEASURE: The primary outcome of the present analysis was the composite of cardiovascular death or nonfatal MI in patients with heart failure receiving candesartan or placebo. RESULTS: During the median follow-up of 37.7 months, the primary outcome of cardiovascular death or nonfatal MI was significantly reduced in the candesartan group (775 patients [20.4%]) vs the placebo group (868 [22.9%]) (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.79-0.96; P = .004; number needed to treat [NNT], 40). Nonfatal MI alone was also significantly reduced in the candesartan group (116 [3.1%]) vs the placebo group (148 [3.9%]) (HR, 0.77; 95% CI, 0.60-0.98; P = .03; NNT, 118). The secondary outcome of fatal MI, sudden death, or nonfatal MI was significantly reduced with candesartan (459 [12.1%]) vs placebo (522 [13.8%]) (HR, 0.86; 95% CI, 0.75-0.97; P = .02; NNT, 59). Risk reductions in cardiovascular death or nonfatal MI were similar across predetermined subgroups and the component CHARM trials. There was no impact on hospitalizations for unstable angina or coronary revascularization procedures with candesartan. CONCLUSION: In patients with heart failure, candesartan significantly reduces the risk of the composite outcome of cardiovascular death or nonfatal MI.
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| 26. |
- Granger, B. B., et al.
(author)
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Adherence to candesartan and placebo and outcomes in chronic heart failure in the CHARM programme: double-blind, randomised, controlled clinical trial
- 2005
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In: Lancet. - 1474-547X. ; 366:9502, s. 2005-11
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Chronic heart failure (CHF) is an important cause of hospital admission and death. Poor adherence to medication is common in some chronic illnesses and might reduce the population effectiveness of proven treatments. Because little is known about adherence in patients with CHF and about the consequences of non-adherence, we assessed the association between adherence and clinical outcome in the CHARM (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) programme. METHODS: CHARM was a double-blind, randomised, controlled clinical trial, comparing the effects of the angiotensin receptor blocker candesartan with placebo in 7599 patients with CHF. Median follow-up was 38 months. The proportion of time patients took more than 80% of their study medication was defined as good adherence and 80% or less as poor adherence. We used a Cox proportional hazards regression model, with adherence as a time-dependent covariate in the model, to examine the association between adherence and mortality in the candesartan and placebo groups. FINDINGS: We excluded 187 patients because of missing information on adherence. In the time-dependent Cox regression model, after adjustment for predictive factors (demographics, physiological and severity-of-illness variables, smoking history, and number of concomitant medications), good adherence was associated with lower all-cause mortality in all patients (hazard ratio [HR] 0.65, 95% CI 0.57-0.75, p<0.0001). The adjusted HR for good adherence was similar in the candesartan (0.66, 0.55-0.81, p<0.0001) and placebo (0.64, 0.53-0.78, p<0.0001) groups. INTERPRETATION: Good adherence to medication is associated with a lower risk of death than poor adherence in patients with CHF, irrespective of assigned treatment. This finding suggests that adherence is a marker for adherence to effective treatments other than study medications, or to other adherence behaviours that affect outcome. Understanding these factors could provide an opportunity for new interventions, including those aimed at improving adherence.
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| 27. |
- Granger, B. B., et al.
(author)
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Adherence to medication according to sex and age in the CHARM programme
- 2009
-
In: European Journal of Heart Failure. - 1879-0844. ; 11:11, s. 1092-8
-
Journal article (peer-reviewed)abstract
- AIMS: Although many patients with heart failure have incomplete adherence to prescribed medications, predisposing factors remain unclear. This analysis investigates factors associated with adherence, with particular emphasis on age and sex. METHODS AND RESULTS: A multivariable regression analysis of 7599 heart failure patients from the CHARM trial was done to evaluate factors associated with adherence. Adherence was measured as the proportion of time patients took more than 80% of study medication. The mean age was 66 years (SD 11) and 31.5% (n = 2400) were women. Women were slightly less adherent than men (87.3 vs. 89.8%, P = 0.002), even in adjusted, multivariable models (treatment, P = 0.006; placebo P = 0.004; and overall P < 0.001). However, all-cause mortality was lower in women (21.5%) than in men (25.3%) (adjusted hazard ratio, 0.77; 95% CI, 0.69-0.86; P < 0.001), but patients with a low adherence regardless of sex had a higher mortality. Age, severity of heart failure, number of medications, and smoking status were not associated with adherence. CONCLUSION: Women, particularly those <75 years of age, were less likely to be adherent in this large sample of patients with symptomatic heart failure. Understanding factors associated with adherence may provide opportunities for intervention.
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| 28. |
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| 29. |
- Hawkins, N. M., et al.
(author)
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Severity of renal impairment in patients with heart failure and atrial fibrillation: implications for non-vitamin K antagonist oral anticoagulant dose adjustment
- 2016
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In: European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 18:9, s. 1162-1171
-
Journal article (peer-reviewed)abstract
- Aims: The non-vitamin K antagonist oral anticoagulants (NOACs) have varying degrees of renal elimination which may be challenging in patients with heart failure (HF) and atrial fibrillation (AF). We examined the severity and variation in renal impairment, and the proportion of patients requiring NOAC cessation or dose reduction. Methods and results: A retrospective analysis of patients with HF and AF in the Candesartan in Heart failure Assessment of Reduction in Mortality and Morbidity programme was carried out. Trends in renal impairment over 26 months were defined using Cockcroft–Gault (CG), simplified Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Mean estimated glomerular filtration rate (eGFR) was worse at every time point in patients with AF compared with those without AF, the difference being ∼11 mL/min (CG), 9 mL/min (CKD-EPI), and 7 mL/min (MDRD). As renal function declined, CG classified a greater proportion of patients as having moderate or severe CKD and agreement with MDRD/CKD-EPI declined. At least moderate renal impairment was present in a quarter of patients with AF at baseline, a third by study completion, and approaching a half at least once during follow-up. The projected need for NOAC dose reduction was accordingly high, though it varied between individual NOACs due to different criteria for adjustment. Conclusions: Renal impairment in patients with HF and AF is common, fluctuates, progresses, and frequently mandates NOAC dose reduction, though the need for cessation is rare. Baseline renal function, the method of estimating GFR, and intensity of monitoring should be considered when commencing oral anticoagulation. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology
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| 30. |
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| 31. |
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| 32. |
- Lund, L. H., et al.
(author)
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Heart failure with mid-range ejection fraction in CHARM: characteristics, outcomes and effect of candesartan across the entire ejection fraction spectrum
- 2018
-
In: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 20:8, s. 1230-1239
-
Journal article (peer-reviewed)abstract
- Aims We tested the hypothesis that candesartan improves outcomes in heart failure (HF) with mid-range ejection fraction [HFmrEF; ejection fraction (EF) 40-49%]. Methods and results In 7598 patients enrolled in the CHARM Programme (HF across the spectrum of EF), we assessed characteristics, outcomes and treatment effect of candesartan according to EF. Patients with HFmrEF (n = 1322, 17%) were similar to those with HF with reduced EF (HFrEF; n = 4323, 57%) with respect to some characteristics, and intermediate between HFrEF and HF with preserved EF (HFpEF; n = 1953, 26%) with respect to others. Over a mean follow-up of 2.9 years, the incidence rates for the primary outcome of cardiovascular death or HF hospitalization were 15.9, 8.5 and 8.9 per 100 patient-years in HFrEF, HFmrEF and HFpEF. In adjusted analyses, the rates of the primary outcome declined with increasing EF up to 50%. For treatment effect, the incidence rates for the primary outcome for candesartan vs. placebo were 14.4 vs. 17.5 per 100 patient-years in HFrEF [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.75-0.91; P < 0.001], 7.4 vs. 9.7 per 100 patient-years in HFmrEF (HR 0.76, 95% CI 0.61-0.96; P = 0.02), and 8.6 vs. 9.1 per 100 patient-years in HFpEF (HR 0.95, 95% CI 0.79-1.14; P = 0.57). For recurrent HF hospitalization, the incidence rate ratios were 0.68 in HFrEF (95% CI 0.58-0.80; P < 0.001), 0.48 in HFmrEF (95% CI 0.33-0.70; P < 0.001), and 0.78 in HFpEF (95% CI 0.59-1.03; P = 0.08). With EF as a continuous spline variable, candesartan significantly reduced the primary outcome until EF well over 50% and recurrent HF hospitalizations until EF well over 60%. Conclusion Candesartan improved outcomes in HFmrEF to a similar degree as in HFrEF.
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| 33. |
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| 34. |
- McMurray, J. J., et al.
(author)
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Resource utilization and costs in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme
- 2006
-
In: European heart journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 27:12, s. 1447-58
-
Journal article (peer-reviewed)abstract
- AIMS: More treatments are needed to improve clinical outcomes in chronic heart failure (HF). It is, however, important that treatments for a condition as common as HF are affordable. We have carried out a prospective economic analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme. METHODS AND RESULTS: Patients with NYHA class II-IV HF and LVEF < or =0.40 were randomized to CHARM-Alternative if intolerant of an ACE-inhibitor or to CHARM-Added if taking an ACE-inhibitor. Patients with a LVEF >0.40 were randomized in CHARM-Preserved. Each trial compared the effect of candesartan to placebo on the primary outcome of cardiovascular death or HF hospitalization. Detailed information was prospectively collected on hospital admissions, procedures/operations and drugs. A cost-consequence analysis was performed for France, Germany and the UK for CHARM-Overall and a cost-effectiveness analysis for the low LVEF trials. The cost of candesartan was substantially offset by a reduction in hospital admissions, especially for HF. In the cost-consequence analysis, candesartan was cost-saving in most scenarios for CHARM-Alternative and Added but the marginal annual net cost per patient was upto 372 euros per year in CHARM-Preserved, in which candesartan did not reduce the primary outcome significantly. In the cost-effectiveness analysis of patients with a LVEF < or = 0.40, candesartan was cost-saving in some scenarios and in the others the maximum cost per life year gained was 3881 euros. CONCLUSION: Candesartan improves functional class, reduces the risk of hospital admission, and increases survival in patients with a HF and a LVEF < or =0.40 at an acceptable cost.
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| 35. |
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| 36. |
- Plessky, V., et al.
(author)
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Bulk Acoustic Wave Transformer employing Periodically Polled array of Piezoelectric Rods
- 2016
-
In: IEEE International Ultrasonics Symposium, IUS. - 1948-5719 .- 1948-5727. - 9781467398978 ; 2016-November, s. Art no 7728583-
-
Conference paper (peer-reviewed)abstract
- Multilayer bulk acoustic wave transformer employing a periodical array of piezoelectric rods with alternating polarization is experimentally demonstrated for the first time. Voltage transformation coefficient in excess of 6 was measured at a frequency of 150kHz, providing thus a solid experimental verification of the recently proposed principle of operation. Finite element analysis is used to reveal the underlying device physics.
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| 37. |
- Preiss, D., et al.
(author)
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Predictors of development of diabetes in patients with chronic heart failure in the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) program
- 2009
-
In: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 32:5, s. 915-20
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: The purpose of this study was to identify predictors of incident diabetes during follow-up of nondiabetic patients with chronic heart failure (CHF) in the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) program. RESEARCH DESIGN AND METHODS: A total of 1,620 nondiabetic patients had full baseline datasets. We compared baseline demographic, medication, and laboratory data for patients who did or did not develop diabetes and conducted logistic regression and receiver operator characteristic curve analyses. RESULTS: Over a median period of 2.8 years, 126 of the 1,620 patients (7.8%) developed diabetes. In multiple logistic regression analysis, the following baseline characteristics were independently associated with incident diabetes in decreasing order of significance by stepwise selection: higher A1C (odds ratio [OR] 1.78 per 1 SD increase; P < 0.0001), higher BMI (OR 1.64 per 1 SD increase; P < 0.0001), lipid-lowering therapy (OR 2.05; P = 0.0005), lower serum creatinine concentration (OR 0.68 per 1 SD increase; P = 0.0018), diuretic therapy (OR 4.81; P = 0.003), digoxin therapy (OR 1.65; P = 0.022), higher serum alanine aminotransferase concentration (OR 1.15 per 1 SD increase; P = 0.027), and lower age (OR 0.81 per 1 SD increase; P = 0.048). Using receiver operating characteristic curve analysis, A1C and BMI yielded areas under the curve of 0.723 and 0.712, respectively, increasing to 0.788 when combined. Addition of other variables independently associated with diabetes risk minimally improved prediction of diabetes. CONCLUSIONS: In nondiabetic patients with CHF in CHARM, A1C and BMI were the strongest predictors of the development of diabetes. Other minor predictors in part reflected CHF severity or drug-associated diabetes risk. Identifying patients with CHF at risk of diabetes through simple criteria appears possible and could enable targeted preventative measures.
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| 38. |
- Shen, L., et al.
(author)
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Declining Risk of Sudden Death in Heart Failure
- 2017
-
In: New England Journal of Medicine. - 0028-4793. ; 377:1, s. 41-51
-
Journal article (peer-reviewed)abstract
- BACKGROUND The risk of sudden death has changed over time among patients with symptomatic heart failure and reduced ejection fraction with the sequential introduction of medications including angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, and mineralocorticoid-receptor antagonists. We sought to examine this trend in detail. We analyzed data from 40,195 patients who had heart failure with reduced ejection fraction and were enrolled in any of 12 clinical trials spanning the period from 1995 through 2014. Patients who had an implantable cardioverter-defibrillator at the time of trial enrollment were excluded. Weighted multivariable regression was used to examine trends in rates of sudden death over time. Adjusted hazard ratios for sudden death in each trial group were calculated with the use of Cox regression models. The cumulative incidence rates of sudden death were assessed at different time points after randomization and according to the length of time between the diagnosis of heart failure and randomization. Sudden death was reported in 3583 patients. Such patients were older and were more often male, with an ischemic cause of heart failure and worse cardiac function, than those in whom sudden death did not occur. There was a 44% decline in the rate of sudden death across the trials (P = 0.03). The cumulative incidence of sudden death at 90 days after randomization was 2.4% in the earliest trial and 1.0% in the most recent trial. The rate of sudden death was not higher among patients with a recent diagnosis of heart failure than among those with a longer-standing diagnosis. Rates of sudden death declined substantially over time among ambulatory patients with heart failure with reduced ejection fraction who were enrolled in clinical trials, a finding that is consistent with a cumulative benefit of evidence-based medications on this cause of death. (Funded by the China Scholarship Council and the University of Glasgow.)
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| 39. |
- Shen, L., et al.
(author)
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Insulin treatment and clinical outcomes in patients with diabetes and heart failure with preserved ejection fraction
- 2019
-
In: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 21:8, s. 974-984
-
Journal article (peer-reviewed)abstract
- Aims Insulin causes sodium retention and hypoglycaemia and its use is associated with worse outcomes in heart failure (HF) with reduced ejection fraction. We have investigated whether this is also the case in HF with preserved ejection fraction (HFpEF). Methods and results We examined the association between diabetes/diabetes treatments and the risk of the primary composite of cardiovascular death or HF hospitalization, as well as other outcomes in adjusted analyses in CHARM-Preserved (left ventricular ejection fraction >= 45%), I-Preserve and TOPCAT (Americas) pooled. Of 8466 patients, 2653 (31%) had diabetes, including 979 (37%) receiving insulin. Patients receiving insulin were younger, had a higher body mass index, prevalence of ischaemic aetiology, N-terminal pro-B-type natriuretic peptide and use of diuretics, worse New York Heart Association class and signs and symptoms, and worse quality of life and renal function, compared to patients with diabetes not on insulin. Among the 1398 patients with echocardiographic data, insulin use was associated with higher left ventricular end-diastolic pressure and more diastolic dysfunction than in other participants. The primary outcome occurred at a rate of 6.3 per 100 patient-years in patients without diabetes, and 10.2 and 17.1 per 100 patient-years in diabetes patients without and with insulin use, respectively [fully adjusted hazard ratio (aHR) insulin-treated diabetes vs. other diabetes: 1.41, 95% confidence interval (CI) 1.23-1.63, P < 0.001]. The adjusted HR is 1.67 (95% CI 1.20-2.32, p = 0.002) for sudden death (insulin-treated diabetes vs. other diabetes). Conclusions Insulin use is associated with poor outcomes in HFpEF. Although we cannot conclude a causal association, the safety of insulin and alternative glucose-lowering treatments in HF needs to be evaluated in clinical trials.
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| 40. |
- Shen, L., et al.
(author)
-
Prior Pacemaker Implantation and Clinical Outcomes in Patients With Heart Failure and Preserved Ejection Fraction
- 2019
-
In: Jacc-Heart Failure. - : Elsevier BV. - 2213-1779. ; 7:5, s. 418-427
-
Journal article (peer-reviewed)abstract
- OBJECTIVES This study examined the relationship between prior pacemaker implantation and clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF). BACKGROUND Conventional right ventricular pacing causes electrical and mechanical left ventricular dyssynchrony and may worsen left ventricular systolic dysfunction and HF. Whether conventional pacing is also associated with worse outcomes in HFpEF is unknown. METHODS Patient data were pooled from the CHARM-Preserved (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity), I-PRESERVE (Irbesartan in Heart Failure with Preserved Ejection Fraction), and TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial) studies and were examined for the association between having a pacemaker and the risk of the primary composite of cardiovascular death or HF hospitalization, the individual components of the composite, the 2 main modes of cardiovascular death (i.e., sudden death and pump failure death), and all-cause death in unadjusted and adjusted analyses. RESULTS Of the 8,466 patients included, 682 patients (8%) had a pacemaker. Pacemaker patients were older and more often men and had lower body mass indexes, estimated glomerular filtration rates, and blood pressures but higher concentrations of N-terminal pro-B-type natriuretic peptide than those without a pacemaker. The rate of the primary composite outcome in pacemaker patients was almost twice that in patients without a pacemaker (13.6 vs. 7.6 per 100 patient-years of follow up, respectively), with a similar finding for HF hospitalizations (10.8 vs. 5.1 per 100 patient-years, respectively). This risk rate persisted after adjusting for other prognostic variables (hazard ratio [HR] for the composite outcome: 1.17; 95% confidence interval [CI]: 1.02 to 1.33; p = 0.026), driven mainly by HF hospitalization (HR: 1.37; 95% CI: 1.17 to 1.60; p < 0.001). The risk of death was not significantly higher in pacemaker patients in the adjusted analyses. CONCLUSIONS These findings raise the possibility that right ventricular pacing-induced left ventricular dyssynchrony may be detrimental in HFpEF patients. (C) 2019 by the American College of Cardiology Foundation.
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| 41. |
- Tromp, J., et al.
(author)
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Age-Related Characteristics and Outcomes of Patients With Heart Failure With Preserved Ejection Fraction
- 2019
-
In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 74:5, s. 601-612
-
Journal article (peer-reviewed)abstract
- BACKGROUND Although heart failure with preserved ejection fraction (HFpEF) is considered a disease of the elderly, younger patients are not spared from this syndrome. OBJECTIVES This study therefore investigated the associations among age, clinical characteristics, and outcomes in patients with HFpEF. METHODS Using data on patients with left ventricular ejection fraction >= 45% from 3 large HFpEF trials (TOPCAT [Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function], I-PRESERVE [Irbesartan in Heart Failure With Preserved Systolic Function], and CHARM Preserved [Candesartan Cilexetil in Heart Failure Assessment of Reduction in Mortality and Morbidity]), patients were categorized according to age: <= 55 years (n = 522), 56 to 64 years (n = 1,679), 65 to 74 years (n = 3,405), 75 to 84 years (n = 2,464), and >= 85 years (n = 398). This study compared clinical and echocardiographic characteristics, as well as mortality and hospitalization rates, mode of death, and quality of life across age categories. RESULTS Younger patients (age <= 55 years) with HFpEF were more often obese, nonwhite men, whereas older patients with HFpEF were more often white women with a higher prevalence of atrial fibrillation, hypertension, and chronic kidney disease (eGFR <60 ml/min/1.73 m(2)). Despite fewer comorbidities, younger patients had worse quality of life compared with older patients (age >= 85 years). Compared with patients age <= 55 years, patients age >= 85 years had higher mortality (hazard ratio: 6.9; 95% confidence interval: 4.2 to 11.4). However, among patients who died, sudden death was, proportionally, the most common mode of death (p < 0.001) in patients age <= 55 years. In contrast, older patients (age >= 85 years) died more often from noncardiovascular causes (34% vs. 20% in patients age <= 55 years; p < 0.001). CONCLUSIONS Compared with the elderly, younger patients with HFpEF were less likely to be white, were more frequently obese men, and died more often of cardiovascular causes, particularly sudden death. In contrast, elderly patients with HFpEF had more comorbidities and died more often from noncardiovascular causes. (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function [TOPCAT]; NCT00094302; Irbesartan in Heart Failure With Preserved Systolic Function [I-PRESERVE]; NCT00095238; Candesartan Cilexetil in Heart Failure Assessment of Reduction in Mortality and Morbidity [CHARM Preserved]; NCT00634712) (C) 2019 by the American College of Cardiology Foundation.
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| 42. |
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| 43. |
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| 44. |
- Welsh, R C, et al.
(author)
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Time to treatment and the impact of a physician on prehospital management of acute ST elevation myocardial infarction : insights from the ASSENT-3 PLUS trial
- 2005
-
In: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 91:11, s. 1400-1406
-
Journal article (peer-reviewed)abstract
- OBJECTIVES:To assess the impact of variation in prehospital care across distinct health care environments in ASSENT (assessment of the safety and efficacy of a new thrombolytic) -3 PLUS, a large (n = 1639) contemporary multicentred international trial of prehospital fibrinolysis. Specifically, the objectives were to assess predictors of time to treatment, whether components of time to treatment vary across countries, and the impact of physician presence before hospitalisation on time to treatment, adherence to protocol, and clinical events.METHODS:Patient characteristics associated with early treatment (< or = 2 hours), comparison of international variation in time to treatment, and components of delay were assessed. Trial specific patient data were linked with site specific survey responses.RESULTS:Younger age, slower heart rate, lower systolic blood pressure, and prior percutaneous coronary intervention were associated with early treatment. Country of origin accounted for the largest proportion of variation in time. Intercountry heterogeneity was shown in components of elapsed time to treatment. Physicians in the prehospital setting enrolled 63.8% of patients. The presence of a physician was associated with greater adherence to protocol mandated treatments and procedures but with delay in time to treatment (120 v 108 minutes, p < 0.001).CONCLUSION:Country of enrollment accounted for the largest proportion of variation in time to treatment and intercountry heterogeneity modulated components of delay. The effectiveness and safety of prehospital fibrinolysis was not influenced by the presence of a physician. These data, acquired in diverse health care environments, provide new understanding into the components of prehospital treatment delay and the opportunities to further reduce time to fibrinolysis for patients with ST elevation myocardial infarction.
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| 45. |
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| 46. |
- Yusuf, S., et al.
(author)
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Effects of candesartan on the development of a new diagnosis of diabetes mellitus in patients with heart failure
- 2005
-
In: Circulation. - 1524-4539. ; 112:1, s. 48-53
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Diabetes is a risk factor for heart failure, and both conditions are increasing. Identifying treatments that prevent both conditions will be clinically important. We previously reported that candesartan (an angiotensin receptor blocker) reduces cardiovascular mortality and heart failure hospitalizations in heart failure patients (CHARM: Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity Program). METHODS AND RESULTS: We assessed the impact of candesartan versus placebo on the development of diabetes, a predefined secondary outcome in a randomized, controlled, double-blind study involving 5436 of the 7601 patients with heart failure, irrespective of ejection fraction, who did not have a diagnosis of diabetes at entry into the trial. Patients received candesartan (target of 32 mg once daily) or matching placebo for 2 to 4 years. One hundred sixty-three (6.0%) individuals in the candesartan group developed diabetes, as compared with 202 (7.4%) in the placebo group (hazard ratio [HR], 0.78 with a 95% confidence interval [CI] of 0.64 to 0.96; P=0.020). The composite end point of death or diabetes occurred in 692 (25.2%) and 779 (28.6%), respectively, in the candesartan and placebo groups (HR, 0.86; 95% CI, 0.78 to 0.95; P=0.004). The results were not statistically heterogeneous in the various subgroups examined, although the apparent magnitude of benefit appeared to be smaller among those treated concomitantly with angiotensin-converting enzyme inhibitors at trial entry (HR, 0.88; 95% CI, 0.65 to 1.20) compared with those not receiving these drugs (HR, 0.71; 95% CI, 0.53 to 0.93; P for heterogeneity, 0.28). CONCLUSIONS: The angiotensin receptor blocker candesartan appears to prevent diabetes in heart failure patients, suggesting that the renin-angiotensin axis is implicated in glucose regulation.
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| 47. |
- Abrahamsson, Putte, 1965, et al.
(author)
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Impact of hospitalization for acute coronary events on subsequent mortality in patients with chronic heart failure
- 2009
-
In: Eur Heart J. - 1522-9645. ; 30:3, s. 338-45
-
Journal article (peer-reviewed)abstract
- AIMS: We explored the impact of having a hospital admission for an acute coronary syndrome (ACS) on the subsequent prognosis among patients with chronic heart failure (CHF). METHODS AND RESULTS: A total of 7599 patients with CHF, New York Heart Association Classes II-IV, were randomly assigned to candesartan or placebo. We assessed the risk of death after a first ACS using time-updated Cox proportional hazard models adjusted for baseline predictors. During a mean follow-up of 3.3 years, 1174 patients experienced at least one ACS. Myocardial infarction (MI) was the first ACS in 442 subjects and unstable angina (UA) in 732. After these events, 219 (49.5%) and 167 (22.8%) patients died during follow-up. The early risk of death was more pronounced after MI: 30.2% died within 30 days compared with 3.6% after UA. After an ACS event, the risk of death declined steadily over time, although 18 months after an MI the risk was still twice that of patients without an ACS. CONCLUSION: Patients with CHF, who develop an ACS, have markedly increased subsequent mortality, particularly in the early phase after an MI.
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| 48. |
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| 49. |
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| 50. |
- Allen, L. A., et al.
(author)
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Liver function abnormalities and outcome in patients with chronic heart failure: data from the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program
- 2009
-
In: Eur J Heart Fail. - : Wiley. - 1388-9842. ; 11:2, s. 170-7
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Journal article (peer-reviewed)abstract
- AIMS: The prevalence and importance of liver function test (LFT) abnormalities in a large contemporary cohort of heart failure patients have not been systematically evaluated. METHODS AND RESULTS: We characterized the LFTs of 2679 patients with symptomatic chronic heart failure from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity program (CHARM). We used multivariable modelling to assess the relationships between baseline LFT values and long-term outcomes. Liver function test abnormalities were common in patients with chronic heart failure, ranging from alanine aminotransferase elevation in 3.1% of patients to low albumin in 18.3% of patients; total bilirubin was elevated in 13.0% of patients. In multivariable analysis, elevated total bilirubin was the strongest LFT predictor of adverse outcome for both the composite outcome of cardiovascular death or heart failure hospitalization (HR 1.21 per 1 SD increase, P<0.0001) and all-cause mortality (HR 1.19 per 1 SD increase, P<0.0001). Even after adjustment for other variables, elevated total bilirubin was one of the strongest independent predictors of poor prognosis (by global chi-square). CONCLUSION: Bilirubin is independently associated with morbidity and mortality. Changes in total bilirubin may offer insight into the underlying pathophysiology of chronic heart failure.
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