| 1. |
|
|
| 2. |
- van Bragt, JJMH, et al.
(författare)
-
Characteristics and treatment regimens across ERS SHARP severe asthma registries
- 2020
-
Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:1
-
Tidskriftsartikel (refereegranskat)abstract
- Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m−2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day−1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day−1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Zaborowski, AM, et al.
(författare)
-
Microsatellite instability in young patients with rectal cancer: molecular findings and treatment response
- 2022
-
Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 109:3, s. 251-255
-
Tidskriftsartikel (refereegranskat)abstract
- In this study of 400 patients with early-onset rectal cancer, 12.5 per cent demonstrated microsatellite instability (MSI). MSI was associated with a reduced likelihood of nodal positivity, an increased rate of pathological complete response, and improved disease-specific survival.
|
|
| 8. |
- Bardella, C., et al.
(författare)
-
Expression of Idh1(R132H) in the Murine Subventricular Zone Stem Cell Niche Recapitulates Features of Early Gliomagenesis
- 2016
-
Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108. ; 30:4, s. 578-594
-
Tidskriftsartikel (refereegranskat)abstract
- Isocitrate dehydrogenase 1 mutations drive human gliomagenesis, probably through neomorphic enzyme activity that produces D-2-hydroxyglutarate. To model this disease, we conditionally expressed Idh1(R132H) in the subventricular zone (SVZ) of the adult mouse brain. The mice developed hydrocephalus and grossly dilated lateral ventricles, with accumulation of 2-hydroxyglutarate and reduced alpha-ketoglutarate. Stem and transit amplifying/progenitor cell populations were expanded,, and proliferation increased. Cells expressing SVZ markers infiltrated surrounding brain regions. SVZ cells also gate rise to proliferative subventricular nodules. DNA methylation was globally increased, while hydroxymethylation was decreased. Mutant SVZ cells overexpressed Wnt, cell-cycle and stem cell genes, and shared an expression signature with human gliomas. Idh1(R132H) mutation in the major adult neurogenic stem cell niche causes a phenotype resembling gliomagenesis.
|
|
| 9. |
- Connolly, S., et al.
(författare)
-
Rationale and design of ACTIVE: the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events
- 2006
-
Ingår i: American heart journal. - 1097-6744. ; 151:6, s. 1187-93
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 10. |
- Cowie, M. R., et al.
(författare)
-
New medicinal products for chronic heart failure: advances in clinical trial design and efficacy assessment
- 2017
-
Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 19:6, s. 718-727
-
Tidskriftsartikel (refereegranskat)abstract
- Despite the availability of a number of different classes of therapeutic agents with proven efficacy in heart failure, the clinical course of heart failure patients is characterized by a reduction in life expectancy, a progressive decline in health-related quality of life and functional status, as well as a high risk of hospitalization. New approaches are needed to address the unmet medical needs of this patient population. The European Medicines Agency (EMA) is undertaking a revision of its Guideline on Clinical Investigation of Medicinal Products for the Treatment of Chronic Heart Failure. The draft version of the Guideline was released for public consultation in January 2016. The Cardiovascular Round Table of the European Society of Cardiology (ESC), in partnership with the Heart Failure Association of the ESC, convened a dedicated two-day workshop to discuss three main topic areas of major interest in the field and addressed in this draft EMA guideline: (i) assessment of efficacy (i.e. endpoint selection and statistical analysis); (ii) clinical trial design (i.e. issues pertaining to patient population, optimal medical therapy, run-in period); and (iii) research approaches for testing novel therapeutic principles (i.e. cell therapy). This paper summarizes the key outputs from the workshop, reviews areas of expert consensus, and identifies gaps that require further research or discussion. Collaboration between regulators, industry, clinical trialists, cardiologists, health technology assessment bodies, payers, and patient organizations is critical to address the ongoing challenge of heart failure and to ensure the development and market access of new therapeutics in a scientifically robust, practical and safe way.
|
|
| 11. |
- Jackson, Alice M., et al.
(författare)
-
Sacubitril-valsartan as a treatment for apparent resistant hypertension in patients with heart failure and preserved ejection fraction
- 2021
-
Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:36, s. 3741-3752
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: Patients with heart failure and preserved ejection fraction (HFpEF) frequently have difficult-to-control hypertension. We examined the effect of neprilysin inhibition on apparent resistant hypertension in patients with HFpEF in the PARAGON-HF trial, which compared the effect of sacubitril-valsartan with valsartan.Methods and results: In this post hoc analysis, patients were categorized according to systolic blood pressure at the end of the valsartan run-in (n=4795). Apparent resistant hypertension was defined as systolic blood pressure >= 14 0mmHg (>= 135 mmHg if diabetes) despite treatment with valsartan, a calcium channel blocker, and a diuretic. Apparent mineralocorticoid receptor antagonist (MRA)-resistant hypertension was defined as systolic blood pressure >= 140 mmHg (>= 135 mmHg if diabetes) despite the above treatments and an MRA. The primary outcome in the PARAGON-HF trial was a composite of total hospitalizations for heart failure and death from cardiovascular causes. We examined clinical endpoints and the safety of sacubitril-valsartan according to the hypertension category. We also examined reductions in blood pressure from the end of valsartan run-in to Weeks 4 and 16 after randomization. Overall, 731 patients (15.2%) had apparent resistant hypertension and 135 (2.8%) had apparent MRA-resistant hypertension. The rate of the primary outcome was higher in patients with apparent resistant hypertension [17.3; 95% confidence interval (CI) 15.6-19.1 per 100 person-years] compared to those with a controlled systolic blood pressure (13.4; 12.7-14.3 per 100 person-years), with an adjusted rate ratio of 1.28 (95% CI 1.05-1.57). The reduction in systolic blood pressure at Weeks 4 and 16, respectively, was greater with sacubitril-valsartan vs. valsartan in patients with apparent resistant hypertension [-4.8 (-7.0 to -2.5) and 3.9 (-6.6 to -1.3) mmHg] and apparent MRA-resistant hypertension [-8.8 (-14.0 to -3.5) and -6.3 (-12.5 to -0.1) mmHg]. The proportion of patients with apparent resistant hypertension achieving a controlled systolic blood pressure by Week 16 was 47.9% in the sacubitril-valsartan group and 34.3% in the valsartan group [adjusted odds ratio (OR) 1.78, 95% CI 1.30-2.43]. In patients with apparent MRA-resistant hypertension, the respective proportions were 43.6% vs. 28.4% (adjusted OR 2.63, 95% CI 1.18-5.89).Conclusion: Sacubitril-valsartan may be useful in treating apparent resistant hypertension in patients with HFpEF, even in those who continue to have an elevated blood pressure despite treatment with at least four antihypertensive drug classes, including an MRA.
|
|
| 12. |
- Tromp, J., et al.
(författare)
-
Age-Related Characteristics and Outcomes of Patients With Heart Failure With Preserved Ejection Fraction
- 2019
-
Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 74:5, s. 601-612
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 13. |
- Welsh, P., et al.
(författare)
-
Prognostic importance of emerging cardiac, inflammatory, and renal biomarkers in chronic heart failure patients with reduced ejection fraction and anaemia: RED-HF study
- 2018
-
Ingår i: European journal of heart failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 20, s. 268-277
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS: To test the prognostic value of emerging biomarkers in the Reduction of Events by Darbepoetin Alfa in Heart Failure (RED-HF) trial. METHODS AND RESULTS: Circulating cardiac [N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hsTnT)], neurohumoral [mid-regional pro-adrenomedullin (MR-proADM) and copeptin], renal (cystatin C), and inflammatory [high-sensitivity C-reactive protein (hsCRP)] biomarkers were measured at randomization in 1853 participants with complete data. The relationship between these biomarkers and the primary composite endpoint of heart failure hospitalization or cardiovascular death over 28 months of follow-up (n = 834) was evaluated using Cox proportional hazards regression, the c-statistic and the net reclassification index (NRI). After adjustment, the hazard ratio (HR) for the composite outcome in the top tertile of the distribution compared to the lowest tertile for each biomarker was: NT-proBNP 3.96 (95% CI 3.16-4.98), hsTnT 3.09 (95% CI 2.47-3.88), MR-proADM 2.28 (95% CI 1.83-2.84), copeptin 1.66 (95% CI 1.35-2.04), cystatin C 1.92 (95% CI 1.55-2.37), and hsCRP 1.51 (95% CI 1.27-1.80). A basic clinical prediction model was improved on addition of each biomarker individually, most strongly by NT-proBNP (NRI +62.3%, P < 0.001), but thereafter was only improved marginally by addition of hsTnT (NRI +33.1%, P = 0.004). Further addition of biomarkers did not improve discrimination further. Findings were similar for all-cause mortality. CONCLUSION: Once NT-proBNP is included, only hsTnT moderately further improved risk stratification in this group of chronic heart failure with reduced ejection fraction patients with moderate anaemia. NT-proBNP and hsTnT far outperform other emerging biomarkers in prediction of adverse outcome.
|
|
| 14. |
- Abdul-Rahim, A. H., et al.
(författare)
-
Risk of stroke in chronic heart failure patients with preserved ejection fraction, but without atrial fibrillation: analysis of the CHARM-Preserved and I-Preserve trials
- 2017
-
Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 38:10, s. 742-750
-
Tidskriftsartikel (refereegranskat)abstract
- Aims The incidence and predictors of stroke in patients with heart failure and preserved ejection fraction (HF-PEF), but without atrial fibrillation (AF), are unknown. We described the incidence of stroke in HF-PEF patients with and without AF and predictors of stroke in those without AF. Methods and results We pooled data from the CHARM-Preserved and I-Preserve trials. Using Cox regression, we derived a model for stroke in patients without AF in this cohort and compared its performance with a published model in heart failure patients with reduced ejection fraction (HF-REF)-predictive variables: age, body mass index, New York Heart Association class, history of stroke, and insulin-treated diabetes. The two stroke models were compared and Kaplan-Meier curves for stroke estimated. The risk model was validated in a third HF-PEF trial. Of the 6701 patients, 4676 did not have AF. Stroke occurred in 124 (6.1%) with AF and in 171 (3.7%) without AF (rates 1.80 and 1.00 per 100 patient-years, respectively). There was no difference in performance of the stroke model derived in the HF-PEF cohort and the published HF-REF model (c-index 0.71, 95% confidence interval 0.57-0.84 vs. 0.73, 0.59-0.85, respectively) as the predictive variables overlapped. The model performed well in the validation cohort (0.86, 0.62-0.99). The rate of stroke in patients in the upper third of risk approximated to that in patients with AF (1.60 and 1.80 per 100 patient-years, respectively). Conclusions A small number of clinical variables identify a subset of patients with HF-PEF, but without AF, at elevated risk of stroke.
|
|
| 15. |
- Badar, A. A., et al.
(författare)
-
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
-
Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 17:2, s. 196-204
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 16. |
|
|
| 17. |
- Chang, S. M., et al.
(författare)
-
Efficacy and safety of angiotensin receptor blockade are not modified by aspirin in patients with chronic heart failure: a cohort study from the Candesartan in Heart failure--Assessment of Reduction in Mortality and morbidity (CHARM) programme
- 2010
-
Ingår i: European Journal of Heart Failure. - 1388-9842. ; 12:7, s. 738-745
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS: It is unknown whether there is an interaction between aspirin and angiotensin receptor blockers on outcomes in patients with heart failure (HF). METHODS AND RESULTS: The efficacy and safety of candesartan vs. placebo was assessed in 7599 patients with symptomatic HF and reduced or preserved left ventricular ejection fraction enrolled in the CHARM programme according to baseline aspirin use. Patients were randomized to candesartan or matching placebo and were followed for a median of 38 months. Aspirin was used in 4246 (55.9%) of patients at baseline. When compared with placebo, candesartan use was associated with lower event rates for cardiovascular (CV) death or HF hospitalization (primary outcome) in both the aspirin group (28 vs. 31.9%, HR 0.81, 95% CI 0.72-0.90) and non-aspirin group (33 vs. 38%, HR 0.81, 95% CI 0.72-0.91). Baseline aspirin use did not modify the effectiveness of candesartan in reducing the risk of CV death or HF hospitalization in CHARM overall (P = 0.64) or in the CHARM individual trials. In addition, there was no significant interaction between aspirin therapy and candesartan in terms of discontinuation of study drug due to adverse reactions (P = 0.72). CONCLUSION: There appears to be no significant modification of the benefit of candesartan on CV mortality and morbidity outcomes or safety by concomitant use of aspirin in patients with chronic HF.
|
|
| 18. |
- Cunningham, J. W., et al.
(författare)
-
Myocardial Infarction in Heart Failure With Preserved Ejection Fraction Pooled Analysis of 3 Clinical Trials
- 2020
-
Ingår i: Jacc-Heart Failure. - : Elsevier BV. - 2213-1779. ; 8:8, s. 618-626
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES The authors investigated the relationship between past or incident myocardial infarction (MI) and car-diovascular (CV) events in heart failure with preserved ejection fraction (HFpEF). BACKGROUND MI and HFpEF share some common risk factors. The prognostic significance of MI in patients with HFpEF is uncertain. METHODS The authors pooled data from 3 trials-CHARM Preserved (Candesartan Cilexietil in Heart Failure Assessment of Reduction in Mortality and Morbidity), I-Preserve (Irbesartan in Heart Failure With Preserved Systolic Function), and the Americas region of TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) (N 1/4 8,916)-and examined whether MI before or following enrollment independently predicted CV death and heart failure (HF) hospitalization. RESULTS At baseline, 2,668 patients (30%) had history of MI. Prior MI was independently associated with greater risk of CV death (4.7 vs. 3.5 events/100 patient-years [py], adjusted hazard ratio [HR]: 1.42 [95% confidence interval (CI): 1.23 to 1.64]; p < 0.001). Excess sudden death drove this difference (1.9 vs. 1.2 events/100 py, adjusted HR: 1.55 [95% CI: 1.23 to 1.97]; p < 0.001). There was no difference in HF hospitalization (5.9 vs. 5.5 events/100 py, adjusted HR: 1.05, 95% CI: 0.92 to 1.19) or HF death by prior MI. During follow-up, MI occurred in 336 patients (3.8%). Risk of CV death increased 31-fold in the first 30 days after first post-enrollment MI, and remained 58% higher beyond 1 year after MI. Risk of first or recurrent HF hospitalization increased 2.4-fold after MI. CONCLUSIONS Prior MI in HFpEF is associated with greater CV and sudden death but similar risk of HF outcomes. Patients with HFpEF who experience MI are at high risk of subsequent CV death and HF hospitalization. These data highlight the importance of primary and secondary prevention of MI in patients with HFpEF. (Candesartan Cilexietil in Heart Failure Assessment of Reduction in Mortality and Morbidity [CHARM Preserved]; NCT00634712; Irbesartan in Heart Failure With Preserved Systolic Function [I-Preserve]; NCT00095238; and Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist [TOPCAT]; NCT00094302) (J Am Coll Cardiol HF 2020;8:618-26) (c) 2020 by the American College of Cardiology Foundation.
|
|
| 19. |
- Kristensen, S. L., et al.
(författare)
-
International Geographic Variation in Event Rates in Trials of Heart Failure With Preserved and Reduced Ejection Fraction
- 2015
-
Ingår i: Circulation. - 1524-4539. ; 131, s. 43-53
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: -International geographic differences in outcomes may exist for clinical trials of heart failure and reduced ejection fraction (HF-REF), but there are few data for those with preserved ejection fraction (HF-PEF). METHODS AND RESULTS: -We analyzed outcomes by international geographic region in the Irbesartan in Heart Failure with Preserved systolic function trial (I-Preserve), the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM)-Preserved trial, the CHARM-Alternative and CHARM-Added HF-REF trials, and the Controlled Rosuvastatin Multinational Trial in HF-REF (CORONA). Crude rates of heart failure hospitalization varied by geographic region, and more so for HF-PEF than for HF-REF. Rates in patients with HF-PEF were highest in the United States/Canada (HF hospitalization rate 7.6 per 100 patient-years in I-Preserve; 8.8 in CHARM-Preserved), intermediate in Western Europe (4.8/100 and 4.7/100), and lowest in Eastern Europe/Russia (3.3/100 and 2.8/100). The difference between the United States/Canada versus Eastern Europe/Russia persisted after adjustment for key prognostic variables: adjusted hazard ratios 1.34 (95% confidence interval, 1.01-1.74; P=0.04) in I-Preserve and 1.85 (95% confidence interval, 1.17-2.91; P=0.01) in CHARM-Preserved. In HF-REF, rates of HF hospitalization were slightly lower in Western Europe compared with other regions. For both HF-REF and HF-PEF, there were few regional differences in rates of all-cause or cardiovascular mortality. CONCLUSIONS: -The differences in event rates observed suggest there is international geographic variation in 1 or more of the definition and diagnosis of HF-PEF, the risk profile of patients enrolled, and the threshold for hospitalization, which has implications for the conduct of future global trials.
|
|
| 20. |
- Mancini, G. B. J., et al.
(författare)
-
Pharmacologic Options for the Management of Systolic Heart Failure: Examining Underlying Mechanisms
- 2015
-
Ingår i: Canadian Journal of Cardiology. - : Pulsus Group Inc.. - 0828-282X. ; 31:10, s. 1282-1292
-
Forskningsöversikt (refereegranskat)abstract
- The optimal management of systolic heart failure includes combination therapy to influence myocardial remodelling favourably by affecting neurohormonal activation and underlying maladaptive pathophysiological pathways. These medications include modulators of the renin-angiotensin-aldosterone system (eg, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists) and β-adrenergic receptor blockers. In addition, an agent with a distinct and complementary mechanism of bradycardic action, the selective pacemaker-current (If) inhibitor ivabradine, provides further reduction of heart rate. Also, a new drug that incorporates neprilysin inhibition combined with angiotensin receptor blockade shows incremental effectiveness. The primary goal of this review is to provide a mechanistic explanation of the complementary role of therapeutic interventions in modulating pathways leading to progressive systolic heart failure. A secondary goal is to summarize the key findings of the pivotal clinical trials that have demonstrated the efficacy of these agents in this population. © 2015 Canadian Cardiovascular Society.
|
|
| 21. |
- Mc Causland, F. R., et al.
(författare)
-
Angiotensin-neprilysin inhibition and renal outcomes across the spectrum of ejection fraction in heart failure
- 2022
-
Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 24:9, s. 1591-8
-
Tidskriftsartikel (refereegranskat)abstract
- Aims Patients with heart failure are at higher risk of progression to end-stage renal disease (ESRD), regardless of ejection fraction (EF). We assessed the renal effects of angiotensin-neprilysin inhibition in a pooled analysis of 13 195 patients with heart failure with reduced and preserved EF. Methods and results We combined data from PARADIGM-HF (EF <= 40%; n = 8399) and PARAGON-HF (EF >= 45%; n = 4796) in a pre-specified pooled analysis. We assessed the effect of treatment (sacubitril/valsartan vs. enalapril or valsartan) on a composite of either >= 50% reduction in estimated glomerular filtration rate (eGFR), ESRD, or death from renal causes, in addition to changes in eGFR slope. We assessed whether baseline renal function or EF modified the effect of therapy on renal outcomes. At randomization, eGFR was 68 +/- 20 ml/min/1.73 m(2) in PARADIGM-HF and 63 +/- 19 ml/min/1.73 m(2) in PARAGON-HF. The composite renal outcome occurred in 70 of 6594 patients (1.1%) in the sacubitril/valsartan group and in 123 of 6601 patients (1.9%) in the valsartan or enalapril group (hazard ratio 0.56, 95% confidence interval [CI] 0.42-0.75; p < 0.001). The mean eGFR change was -1.8 (95% CI -1.9 to -1.7) ml/min/1.73 m(2)/year for the sacubitril/valsartan group, compared with -2.4 (95% CI -2.5 to -2.2) ml/min/1.73 m(2)/year for the valsartan or enalapril group. The treatment effect on the composite renal endpoint was not modified by categories of baseline eGFR (p-interaction = 0.64), but was most pronounced in those with baseline EF between 30% and 60% (p-interaction = 0.001). Conclusions In patients with heart failure, sacubitril/valsartan reduced the risk of serious adverse renal outcomes and slowed decline in eGFR, compared with valsartan or enalapril, independent of baseline renal function.
|
|
| 22. |
- Pfeffer, W. Tad, et al.
(författare)
-
The Randolph Glacier Inventory : a globally complete inventory of glaciers
- 2014
-
Ingår i: Journal of Glaciology. - 0022-1430 .- 1727-5652. ; 60:221, s. 537-552
-
Tidskriftsartikel (refereegranskat)abstract
- The Randolph Glacier Inventory (RGI) is a globally complete collection of digital outlines of glaciers, excluding the ice sheets, developed to meet the needs of the Fifth Assessment of the Intergovernmental Panel on Climate Change for estimates of past and future mass balance. The RGI was created with limited resources in a short period. Priority was given to completeness of coverage, but a limited, uniform set of attributes is attached to each of the similar to 198 000 glaciers in its latest version, 3.2. Satellite imagery from 1999-2010 provided most of the outlines. Their total extent is estimated as 726 800 +/- 34 000 km(2). The uncertainty, about +/- 5%, is derived from careful single-glacier and basin-scale uncertainty estimates and comparisons with inventories that were not sources for the RGI. The main contributors to uncertainty are probably misinterpretation of seasonal snow cover and debris cover. These errors appear not to be normally distributed, and quantifying them reliably is an unsolved problem. Combined with digital elevation models, the RGI glacier outlines yield hypsometries that can be combined with atmospheric data or model outputs for analysis of the impacts of climatic change on glaciers. The RGI has already proved its value in the generation of significantly improved aggregate estimates of glacier mass changes and total volume, and thus actual and potential contributions to sea-level rise.
|
|
| 23. |
- Ricke-Hoch, Melanie, et al.
(författare)
-
Impaired immune response mediated by prostaglandin E2 promotes severe COVID-19 disease
- 2021
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:8
-
Tidskriftsartikel (refereegranskat)abstract
- The SARS-CoV-2 coronavirus has led to a pandemic with millions of people affected. The present study finds that risk-factors for severe COVID-19 disease courses, i.e. male sex, older age and sedentary life style are associated with higher prostaglandin E2 (PGE2) serum levels in blood samples from unaffected subjects. In COVID-19 patients, PGE2 blood levels are markedly elevated and correlate positively with disease severity. SARS-CoV-2 induces PGE2 generation and secretion in infected lung epithelial cells by upregulating cyclo-oxygenase (COX)-2 and reducing the PG-degrading enzyme 15-hydroxyprostaglan-din-dehydrogenase. Also living human precision cut lung slices (PCLS) infected with SARS-CoV-2 display upregulated COX-2. Regular exercise in aged individuals lowers PGE2 serum levels, which leads to increased Paired-Box-Protein-Pax-5 (PAX5) expression, a master regulator of B-cell survival, proliferation and differentiation also towards long lived memory B-cells, in human pre-B-cell lines. Moreover, PGE2 levels in serum of COVID-19 patients lowers the expression of PAX5 in human pre-B-cell lines. The PGE2 inhibitor Taxifolin reduces SARS-CoV-2-induced PGE2 production. In conclusion, SARS-CoV-2, male sex, old age, and sedentary life style increase PGE2 levels, which may reduce the early anti-viral defense as well as the development of immunity promoting severe disease courses and multiple infections. Regular exercise and Taxifolin treatment may reduce these risks and prevent severe disease courses.
|
|
| 24. |
- Shen, L., et al.
(författare)
-
Developing and validating models to predict sudden death and pump failure death in patients with heart failure and preserved ejection fraction
- 2021
-
Ingår i: Clinical Research in Cardiology. - : Springer Science and Business Media LLC. - 1861-0684 .- 1861-0692. ; 110:8, s. 1234-1248
-
Tidskriftsartikel (refereegranskat)abstract
- Background Sudden death (SD) and pump failure death (PFD) are leading modes of death in heart failure and preserved ejection fraction (HFpEF). Risk stratification for mode-specific death may aid in patient enrichment for new device trials in HFpEF. Methods Models were derived in 4116 patients in the Irbesartan in Heart Failure with Preserved Ejection Fraction trial (I-Preserve), using competing risks regression analysis. A series of models were built in a stepwise manner, and were validated in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Preserved and Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trials. Results The clinical model for SD included older age, men, lower LVEF, higher heart rate, history of diabetes or myocardial infarction, and HF hospitalization within previous 6 months, all of which were associated with a higher SD risk. The clinical model predicting PFD included older age, men, lower LVEF or diastolic blood pressure, higher heart rate, and history of diabetes or atrial fibrillation, all for a higher PFD risk, and dyslipidaemia for a lower risk of PFD. In each model, the observed and predicted incidences were similar in each risk subgroup, suggesting good calibration. Model discrimination was good for SD and excellent for PFD with Harrell's C of 0.71 (95% CI 0.68-0.75) and 0.78 (95% CI 0.75-0.82), respectively. Both models were robust in external validation. Adding ECG and biochemical parameters, model performance improved little in the derivation cohort but decreased in validation. Including NT-proBNP substantially increased discrimination of the SD model, and simplified the PFD model with marginal increase in discrimination. Conclusions The clinical models can predict risks for SD and PFD separately with good discrimination and calibration in HFpEF and are robust in external validation. Adding NT-proBNP further improved model performance. These models may help to identify high-risk individuals for device intervention in future trials.
|
|
| 25. |
- Shen, L., et al.
(författare)
-
Incidence and Outcomes of Pneumonia in Patients With Heart Failure
- 2021
-
Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 77:16, s. 1961-1973
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The incidence of pneumonia and subsequent outcomes has not been compared in patients with heart failure and reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). Objectives: This study aimed to examine the rate and impact of pneumonia in the PARADIGM-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) and PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in Heart Failure with Preserved Ejection Fraction) trials. Methods: The authors analyzed the incidence of investigator-reported pneumonia and the rates of HF hospitalization, cardiovascular death, and all-cause death before and after the occurrence of pneumonia, and estimated risk after the first occurrence of pneumonia in unadjusted and adjusted analyses (the latter including N-terminal pro–B-type natriuretic peptide). Results: In PARADIGM-HF, 528 patients (6.3%) developed pneumonia after randomization, giving an incidence rate of 29 (95% CI: 27 to 32) per 1,000 patient-years. In PARAGON-HF, 510 patients (10.6%) developed pneumonia, giving an incidence rate of 39 (95% CI: 36 to 42) per 1,000 patient-years. The subsequent risk of all trial outcomes was elevated after the occurrence of pneumonia. In PARADIGM-HF, the adjusted hazard ratio (HR) for the risk of death from any cause was 4.34 (95% CI: 3.73 to 5.05). The corresponding adjusted HR in PARAGON-HF was 3.76 (95% CI: 3.09 to 4.58). Conclusions: The incidence of pneumonia was high in patients with HF, especially HFpEF, at around 3 times the expected rate. A first episode of pneumonia was associated with 4-fold higher mortality. (Prospective Comparison of Angiotensin Receptor–Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF], NCT01035255; Prospective Comparison of ARNI [Angiotensin Receptor–Neprilysin Inhibitor] With ARB [Angiotensin Receptor Blocker] Global Outcomes in Heart Failure With Preserved Ejection Fraction [PARAGON-HF], NCT01920711) © 2021 The Authors
|
|
