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Sökning: (WFRF:(Cleland John G)) > (2010-2014)

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1.
  • Broch, Kaspar, et al. (författare)
  • Soluble ST2 is associated with adverse outcome in patients with heart failure of ischaemic aetiology
  • 2012
  • Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 14:3, s. 268-277
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: In patients with ischaemic heart failure (HF), myocardial dysfunction often progresses. Elevated levels of soluble ST2 (sST2) are associated with a poor prognosis, but an association between sST2 and worsening heart failure per se has not been established. We assessed the association between sST2 and cause-specific outcome in 1449 patients enrolled in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA study). Methods and results: Soluble ST2 was measured with a highly sensitive immunoassay in 1449 patients ≥60 years of age with left ventricular ejection fraction (LVEF) ≤40% due to ischaemic heart disease. By Cox regression analyses, we found sST2 to be associated with the primary endpoint, i.e. a composite of cadiovascular (CV) death, non-fatal myocardial infarction, or stroke, as well as all pre-defined secondary endpoints in the CORONA study, even after adjustment for baseline clinical variables. After adjustment for N-terminal pro brain natriuretic peptide and C-reactive protein, the association between sST2 and the primary endpoint was attenuated and no longer statistically significant. However, sST2 remained associated with death due to worsening HF, hospitalization due to worsening HF, and hospitalization due to any CV cause, even after full adjustment. Conclusions: Soluble ST2 is associated with adverse outcomes in older patients with systolic, ischaemic HF. In particular, sST2 is independently associated with worsening HF. © The Author 2012.
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3.
  • Weinstein, John N., et al. (författare)
  • The cancer genome atlas pan-cancer analysis project
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
  • Forskningsöversikt (refereegranskat)abstract
    • The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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4.
  • Gheorghiade, Mihai, et al. (författare)
  • Assessing and grading congestion in acute heart failure : a scientific statement from the acute heart failure committee of the heart failure association of the European Society of Cardiology and endorsed by the European Society of Intensive Care Medicine.
  • 2010
  • Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 12:5, s. 423-33
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients with acute heart failure (AHF) require urgent in-hospital treatment for relief of symptoms. The main reason for hospitalization is congestion, rather than low cardiac output. Although congestion is associated with a poor prognosis, many patients are discharged with persistent signs and symptoms of congestion and/or a high left ventricular filling pressure. Available data suggest that a pre-discharge clinical assessment of congestion is often not performed, and even when it is performed, it is not done systematically because no method to assess congestion prior to discharge has been validated. Grading congestion would be helpful for initiating and following response to therapy. We have reviewed a variety of strategies to assess congestion which should be considered in the care of patients admitted with HF. We propose a combination of available measurements of congestion. Key elements in the measurement of congestion include bedside assessment, laboratory analysis, and dynamic manoeuvres. These strategies expand by suggesting a routine assessment of congestion and a pre-discharge scoring system. A point system is used to quantify the degree of congestion. This score offers a new instrument to direct both current and investigational therapies designed to optimize volume status during and after hospitalization. In conclusion, this document reviews the available methods of evaluating congestion, provides suggestions on how to properly perform these measurements, and proposes a method to quantify the amount of congestion present.
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5.
  • Massie, Barry M, et al. (författare)
  • Rolofylline, an adenosine A1-receptor antagonist, in acute heart failure.
  • 2010
  • Ingår i: The New England journal of medicine. - 1533-4406. ; 363:15, s. 1419-28
  • Tidskriftsartikel (refereegranskat)abstract
    • Worsening renal function, which is associated with adverse outcomes, often develops in patients with acute heart failure. Experimental and clinical studies suggest that counterregulatory responses mediated by adenosine may be involved. We tested the hypothesis that the use of rolofylline, an adenosine A1-receptor antagonist, would improve dyspnea, reduce the risk of worsening renal function, and lead to a more favorable clinical course in patients with acute heart failure.
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6.
  • Badar, A. A., et al. (författare)
  • Relationship between angina pectoris and outcomes in patients with heart failure and reduced ejection fraction: an analysis of the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA)
  • 2014
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 35:48, s. 3426-3433
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim Angina pectoris is common in patients with heart failure and reduced ejection fraction (HF-REF) but its relationship with outcomes has not been well defined. This relationship was investigated further in a retrospective analysis of the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA). Methods and results Four thousand, eight hundred and seventy-eight patients were divided into three categories: no history of angina and no chest pain at baseline (Group A; n = 1240), past history of angina but no chest pain at baseline (Group B; n = 1353) and both a history of angina and chest pain at baseline (Group C; n = 2285). Outcomes were examined using Kaplan-Meier and Cox regression survival analysis. Compared with Group A, Group C had a higher risk of non-fatal myocardial infarction or unstable angina (HR: 2.36, 1.54-3.61; P<0.001), this composite plus coronary revascularization (HR: 2.54, 1.76-3.68; P<0.001), as well as HF hospitalization (HR: 1.35, 1.13-1.63; P = 0.001), over a median follow-up period of 33 months. There was no difference in cardiovascular or all-cause mortality. Group B had a smaller increase in risk of coronary events but not of heart failure hospitalization. Conclusion Patients with HF-REF and ongoing angina are at an increased risk of acute coronary syndrome and HF hospitalization. Whether these patients would benefit from more aggressive medical therapy or percutaneous revascularization is not known and merits further investigation.
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7.
  • Boman, Kurt, et al. (författare)
  • Effects of carvedilol or metoprolol on PAI-1, tPA-mass concentration or Von Willebrand factor in chronic heart failure--a COMET substudy.
  • 2010
  • Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 125:2, s. e46-50
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: In COMET (Carvedilol or Metoprolol European Trial), carvedilol reduced mortality compared with metoprolol in patients with chronic heart failure. We hypothesized that carvedilol might have greater effects on endothelial derived haemostatic factors than metoprolol. We aimed to study the effects of carvedilol or metoprolol on tissue plasminogen activator (tPA), its inhibitor PAI-1 and Von Willebrand factor (VWF) in patients with heart failure. MATERIAL AND METHODS: We recruited 260 patients (134 on carvedilol, 126 on metoprolol), mean age 66 years and 84% of them men. Plasma mass concentrations of tPA and PAI-1and percent of VWF were measured at baseline and after one and two years of treatment. RESULTS: Plasma tPA, PAI-1 and VWF were similar between treatment groups at baseline and no significant differences between groups emerged after one or two years of treatment. In paired analyses in patients assigned to carvedilol, median PAI-1 level decreased from 37.2 to 32.1 microg/l at two years (p=0.034) and of VWF decreased from baseline to one year (240 vs. 218%, p=0.023) in patients assigned to carvedilol but were not reduced at any time in patients assigned to metoprolol. Plasma tPA increased over time in both treatment groups (p=0.013 and 0.027 respectively). CONCLUSION: We found no significant difference in the effects of carvedilol or metoprolol on tPA, PAI-1 and VWF. Comparison over time within treatment groups suggested that PAI-1 and VWF might have declined on carvedilol but not on metoprolol. Our hypothesis is not proved but this may reflect an inadequate sample size rather than lack of an effect.
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8.
  • Gullestad, L., et al. (författare)
  • Galectin-3 predicts response to statin therapy in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA)
  • 2012
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 33:18, s. 2290-2296
  • Tidskriftsartikel (refereegranskat)abstract
    • To investigate whether plasma galectin-3, a mediator of fibrogenesis, can identify patients with chronic heart failure (HF) for whom statins are effective. Patients with ischaemic systolic HF enrolled in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) were randomly assigned to 10 mg/day of rosuvastatin or placebo. Galectin-3 was measured in plasma. The primary outcome was cardiovascular death, myocardial infarction, or stroke. Of 1492 patients, 411 had a primary event during a median follow-up of 32.8 months. There was an interaction between baseline galectin-3 and rosuvastatin on the primary endpoint (P-value for interaction 0.036). Among patients with below the median plasma concentrations of galectin-3 (19.0 ng/mL), those assigned to rosuvastatin had a lower primary event rate [hazard ratio (HR) 0.65; 95 confidence interval (CI), 0.460.92; P 0.014], lower total mortality (HR 0.70; 95 CI, 0.500.98; P 0.038), and lower event rate of all-cause mortality and HF hospitalizations (HR 0.72; 95 CI, 0.540.98; P 0.017) compared with placebo, but no benefit was observed in patients with higher levels of galectin-3. The combination of concurrently low concentrations of galectin-3 and N-terminal pro-B-type natriuretic peptide (102.7 pmol/L) identified patients with a large benefit with rosuvastatin (HR 0.33; 95 CI, 0.160.67; P 0.002). Patients with systolic HF of ischaemic aetiology who have galectin-3 values 19.0 ng/mL may benefit from rosuvastatin treatment. However, the data from this post hoc analysis should be interpreted with caution since the overall results of the CORONA study did not show a significant effect on the primary endpoint.
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9.
  • Perez, A. C., et al. (författare)
  • Thyroid-Stimulating Hormone and Clinical Outcomes: The CORONA Trial (Controlled Rosuvastatin Multinational Study in Heart Failure)
  • 2014
  • Ingår i: JACC: Heart Failure. - : Elsevier BV. - 2213-1779. ; 2:1, s. 35-40
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: This study sought to examine the association between thyroid status and clinical outcomes in patients in the CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure) study. Background: Hypo- and hyperthyroidism were associated with worse clinical outcomes in the SCD-HeFT (Sudden Cardiac DeathinHeart Failure Trial). Methods: In CORONA, 4,987 patients underwent baseline thyroid-stimulating hormone (TSH) measurement, 237 of which(4.8%) were receiving thyroid replacement therapy (TRT). Patients were classified as euthyroid (TSH: 0.3 to 5.0μU/ml,and no TRT), hyperthyroid (<0.3 μU/ml and no TRT), or hypothyroid (>5.0 μU/ml and no TRT). The outcome composites of cardiovascular (CV) death or hospitalization for heart failure (HF), the components of this composite, and all-cause death were compared among hyperthyroid, hypothyroid, and euthyroid states, using multivariable models adjusting for previously reported prognostic variables. Results: A total of 91.3% of patients were euthyroid, 5.0% were hypothyroid, and 3.7% were hyperthyroid. Compared with euthyroid patients, hypothyroid patients were more likely to have a history of stroke, had worse renal function andhigher N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, were more likely to be treated with an antiarrhythmic drug (or have an implantable cardioverter defibrillator), and were less likely to smoke or be treated with a beta-blocker or angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. In univariate analyses, hypothyroidism was associated with an increased risk of the composite outcome of CV death or HF hospitalization (hazard ratio: 1.29; 95% confidence interval: 1.07 to 1.57; p= 0.008), as well as all-cause death (HR: 1.36; 95% confidence interval: 1.03 to 1.76; p= 0.004). However, after adjustment for other known predictors of outcome, the associations were weakened, and when NT-proBNP was added to the models, the association between hypothyroidism and all outcomes was eliminated. Conclusions: Thyroid status is not an independent predictor of outcome in heart failure with reduced ejection fraction. (Controlled Rosuvastatin Multinational Study in Heart Failure [CORONA]; NCT00206310). © 2014 American College of Cardiology Foundation.
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10.
  • Perez-Moreno, A. C., et al. (författare)
  • Fatigue as a predictor of outcome in patients with heart failure. Analysis of CORONA (Controlled rosuvastatin multinational trial in heart failure)
  • 2014
  • Ingår i: JACC: Heart Failure. - : Elsevier BV. - 2213-1779. ; 2:2, s. 187-197
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The purpose of this study was to examine the relationship between fatigue and clinical outcomes, using dyspnea as a comparator, in patients with left ventricular ejection fraction (LVEF)≤35% enrolled in the CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure) study. Background: Although fatigue is a common symptom in heart failure (HF), little is known about its association with prognosis. Methods: At baseline in CORONA, fatigue "during the past few days" was measured using a 5-point exertion scale (0= none, 1= heavy exertion, 2= moderate exertion, 3= slight exertion, 4= rest); a 4-point scale was used for dyspnea (1to4 as for fatigue). Patients were grouped into 3 categories: a fatigue score 0 to 1 (n= 535), fatigue score 2(n=1,632), and fatigue score 3 to 4 (n= 1,663); and a dyspnea score of 1 (n= 292), dyspnea score of 2(n=1,695), and dyspnea score of 3 to 4 (n= 1,843). The association between fatigue and dyspnea and the composite outcome of cardiovascular (CV) death or HF hospital stay and each component separately was examined using Kaplan-Meier analysis and Cox proportional-hazard models. We also examined all-cause mortality. Results: In univariate analyses, symptom severity was associated with a higher risk of CV death or HF hospital stay (fatigue: group 3, 49% [n= 810], vs. group 1, 30% [n= 160]; dyspnea: group 3, 50% [n= 918], vs. group 1, 28% [n= 82]) and all-cause mortality (fatigue: group 3, 38% [n= 623], vs. group 1, 24% [n= 130]; dyspnea: group 3, 38% [n=697], vs. group 1, 23% [n= 66], log-rank p< 0.0001 for all). After adjusting for other prognostic variables, including LVEF, New York Heart Association class, and N-terminal pro-B-type natriuretic peptide level, worse fatigue remained associated with higher risk of HF hospital stay but not mortality (worse dyspnea remained associated with a higher risk of both). An increase in fatigue (or dyspnea) between baseline and 6 months was also associated with worse outcomes. Conclusions: In HF, greater fatigue is associated with worse clinical outcomes. Closer attention should be paid to this symptom in clinical practice, with more done to standardize its measurement and understand its origins, with a view to improving treatment. © 2014 American College of Cardiology Foundation.
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