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Browsing by Author "Düngen, Hans-Dirk (16024171900)"

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    Association of adiponectin with peripheral muscle status in elderly patients with heart failure
    (2013)
    Loncar, Goran (55427750700)
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    Bozic, Biljana (57203497573)
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    Von Haehling, Stephan (6602981479)
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    Düngen, Hans-Dirk (16024171900)
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    Prodanovic, Nenad (24477604800)
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    Lainscak, Mitja (9739432000)
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    Arandjelovic, Aleksandra (8603366600)
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    Dimkovic, Sinisa (25642588400)
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    Radojicic, Zoran (6507427734)
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    Popovic, Vera (35451450900)
    Background Reduced peripheral muscle mass was demonstrated in patients with chronic heart failure (HF). Adipokines may have potent metabolic effects on skeletal muscle. The associations between adipokines, peripheral muscle mass, and muscle function have been poorly investigated in patients with HF. Methods We measured markers of fat and bone metabolism (adiponectin, leptin, 25-hydroxy vitamin D, parathyroid hormone, osteoprotegerin, RANKL), N-terminal pro B-type natriuretic peptide (NT-pro-BNP) in 73 non-cachectic, non-diabetic, male patients with chronic HF (age: 68 ± 7 years, New York Heart Association class II/III: 76/26%, left ventricular ejection fraction 29 ± 8%) and 20 healthy controls of similar age. Lean mass as a measure of skeletal muscle mass was measured by dual energy X-ray absorptiometry (DEXA), while muscle strength was assessed by hand grip strength measured by Jamar dynamometer. Results Serum levels of adiponectin, parathyroid hormone, osteoprotegerin, RANKL, and NT-pro-BNP were elevated in patients with chronic HF compared to healthy controls (all p < 0.0001), while no difference in serum levels of leptin, testosterone or SHBG was noted. Levels of 25-hydroxy vitamin D were reduced (p = 0.002) in HF group. Peripheral lean mass and hand grip strength were reduced in patients with HF compared to healthy subjects (p = 0.006 and p < 0.0001, respectively). Using backward selection multivariable regression, serum levels of increased adiponectin remained significantly associated with reduced arm lean mass and muscle strength. Conclusions Our findings may indicate a cross-sectional metabolic association of increased serum adiponectin with reduced peripheral muscle mass and muscle strength in non-cachectic, non-diabetic, elderly HF patients. © 2013 European Federation of Internal Medicine.
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    Beta blockers therapy is associated with improved left ventricular systolic function and sustained exercise capacity in elderly patients with heart failure. CIBIS-ELD sub-study
    (2012)
    Dekleva, Milica (56194369000)
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    Düngen, Hans-Dirk (16024171900)
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    Gelbrich, Götz (14119833600)
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    Incrot, Simone (55671234100)
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    Lazic, Jelena Suzic (37023567700)
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    Kleut, Milena Pavlovic (55902138300)
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    Tahirovic, Elvis (24339336300)
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    Waagstein, Finn (56216780700)
    Background: Exercise capacity is critical for therapy and prognosis in patients with heart failure (HF). Effect of beta-blockers (BB) on exercise capacity in elderly patients with HF remains unclear. Objectives: To assess contribution of BB to functional capacity and left ventricular (LV) function in the elderly with HF. Design: According to the protocol of CIBIS-ELD study group, elderly patients were treated with BB during 12 weeks. In CPET subgroup, an integral part of the CIBIS ELD study group, patients were performed Doppler echocardiography and cardiopulmonary exercise testing (CPET) before BB therapy and after 12 weeks. Setting: Randomized patients with HF beta blockers naïve. Participants: thirty patients with HF aged over 65 years were included in CPET subgroup, while 847 were incorporated in CIBIS ELD study group. Results: Heart rate (HR) and systolic blood pressure (SBP) after BB significantly decreased at rest (p<0.001) and during exercise (p<0.05), with sustained level of peak VO2. Observed changes of resting HR and peak HR were closely correlated (p<0.001). Significant improvement of LV ejection fraction after BB was obtained (p=0.003) and symptoms of breathlessness were reduced (p=0.001). Left ventricular diastolic dysfunction at rest significantly contributed to exercise capacity (p=0.019). Conclusions: Beta-blockers in elderly patients with HF are related to a significant decrease of HR and SBP, improvement of systolic LV function and sustained exercise tolerance. Resting LV diastolic dysfunction is strongly associated with lower exercise capacity. ©2012, Editrice Kurtis.
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    Beta blockers therapy is associated with improved left ventricular systolic function and sustained exercise capacity in elderly patients with heart failure. CIBIS-ELD sub-study
    (2012)
    Dekleva, Milica (56194369000)
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    Düngen, Hans-Dirk (16024171900)
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    Gelbrich, Götz (14119833600)
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    Incrot, Simone (55671234100)
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    Lazic, Jelena Suzic (37023567700)
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    Kleut, Milena Pavlovic (55902138300)
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    Tahirovic, Elvis (24339336300)
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    Waagstein, Finn (56216780700)
    Background: Exercise capacity is critical for therapy and prognosis in patients with heart failure (HF). Effect of beta-blockers (BB) on exercise capacity in elderly patients with HF remains unclear. Objectives: To assess contribution of BB to functional capacity and left ventricular (LV) function in the elderly with HF. Design: According to the protocol of CIBIS-ELD study group, elderly patients were treated with BB during 12 weeks. In CPET subgroup, an integral part of the CIBIS ELD study group, patients were performed Doppler echocardiography and cardiopulmonary exercise testing (CPET) before BB therapy and after 12 weeks. Setting: Randomized patients with HF beta blockers naïve. Participants: thirty patients with HF aged over 65 years were included in CPET subgroup, while 847 were incorporated in CIBIS ELD study group. Results: Heart rate (HR) and systolic blood pressure (SBP) after BB significantly decreased at rest (p<0.001) and during exercise (p<0.05), with sustained level of peak VO2. Observed changes of resting HR and peak HR were closely correlated (p<0.001). Significant improvement of LV ejection fraction after BB was obtained (p=0.003) and symptoms of breathlessness were reduced (p=0.001). Left ventricular diastolic dysfunction at rest significantly contributed to exercise capacity (p=0.019). Conclusions: Beta-blockers in elderly patients with HF are related to a significant decrease of HR and SBP, improvement of systolic LV function and sustained exercise tolerance. Resting LV diastolic dysfunction is strongly associated with lower exercise capacity. ©2012, Editrice Kurtis.
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    Depression, anxiety, and quality of life as predictors of rehospitalization in patients with chronic heart failure
    (2023)
    Veskovic, Jovan (56951285600)
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    Cvetkovic, Mina (59571521900)
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    Tahirovic, Elvis (24339336300)
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    Zdravkovic, Marija (24924016800)
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    Apostolovic, Svetlana (13610076800)
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    Kosevic, Dragana (15071017200)
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    Loncar, Goran (55427750700)
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    Obradovic, Danilo (35731962400)
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    Matic, Dragan (25959220100)
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    Ignjatovic, Aleksandra (54395417600)
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    Cvetkovic, Tatjana (57211064383)
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    Posch, Maximilian G. (35307873000)
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    Radenovic, Sara (57000170900)
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    Ristić, Arsen D. (7003835406)
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    Dokic, Danilo (58670130200)
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    Milošević, Nenad (58669174900)
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    Panic, Natasa (58670130300)
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    Düngen, Hans-Dirk (16024171900)
    Background: Chronic heart failure (CHF) is a severe condition, often co-occurring with depression and anxiety, that strongly affects the quality of life (QoL) in some patients. Conversely, depressive and anxiety symptoms are associated with a 2–3 fold increase in mortality risk and were shown to act independently of typical risk factors in CHF progression. The aim of this study was to examine the impact of depression, anxiety, and QoL on the occurrence of rehospitalization within one year after discharge in CHF patients. Methods: 148 CHF patients were enrolled in a 10-center, prospective, observational study. All patients completed two questionnaires, the Hospital Anxiety and Depression Scale (HADS) and the Questionnaire Short Form Health Survey 36 (SF-36) at discharge timepoint. Results: It was found that demographic and clinical characteristics are not associated with rehospitalization. Still, the levels of depression correlated with gender (p ≤ 0.027) and marital status (p ≤ 0.001), while the anxiety values ​​were dependent on the occurrence of chronic obstructive pulmonary disease (COPD). However, levels of depression (HADS-Depression) and anxiety (HADS-Anxiety) did not correlate with the risk of rehospitalization. Univariate logistic regression analysis results showed that rehospitalized patients had significantly lower levels of Bodily pain (BP, p = 0.014), Vitality (VT, p = 0.005), Social Functioning (SF, p = 0.007), and General Health (GH, p = 0.002). In the multivariate model, poor GH (OR 0.966, p = 0.005) remained a significant risk factor for rehospitalization, and poor General Health is singled out as the most reliable prognostic parameter for rehospitalization (AUC = 0.665, P = 0.002). Conclusion: Taken together, our results suggest that QoL assessment complements clinical prognostic markers to identify CHF patients at high risk for adverse events. Clinical Trial Registration: The study is registered under http://clinicaltrials.gov (NCT01501981, first posted on 30/12/2011), sponsored by Charité – Universitätsmedizin Berlin. © 2023, The Author(s).
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    Determinants of Change in Quality of Life in the Cardiac Insufficiency Bisoprolol Study in Elderly (CIBIS-ELD)
    (2013)
    Scherer, Martin (12805380800)
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    Düngen, Hans-Dirk (16024171900)
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    Inkrot, Simone (35784615000)
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    Tahirović, Elvis (24339336300)
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    Lashki, Diana Jahandar (53863775800)
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    Apostolović, Svetlana (13610076800)
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    Edelmann, Frank (35366308700)
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    Wachter, Rolf (12775831800)
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    Loncar, Goran (55427750700)
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    Haverkamp, Wilhelm (7005423154)
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    Neskovic, Aleksandar (35597744900)
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    Herrmann-Lingen, Christoph (6603417225)
    Objective Little is known about parameters that lead to improvement in QoL in individual patients. We analysed the data of the Cardiac Insufficiency Bisoprolol Study in Elderly (CIBIS-ELD) in order to answer the question of how and to what extent change in health-related QoL during up-titration with bisoprolol vs. carvedilol is influenced by clinical and psychosocial factors in elderly patients with heart failure. Methods This is a QoL analysis of CIBIS-ELD, an investigator-initiated multi-center randomised phase III trial in elderly patients (65 years or older) with moderate to severe heart failure. Clinical parameters such as New York Heart Association functional class, heart rate, left ventricular ejection fraction (LVEF), 6-min walk distance, as well as the physical and psychosocial component scores on the short-form QoL health survey (SF36) and depression were recorded at baseline and at the final study visit. Results Full baseline and follow-up QoL data were available for 589 patients (292 in the bisoprolol and 297 in the carvedilol group). Mean physical and psychosocial QoL improved significantly during treatment. In regression analyses, changes in both SF36 component scores from baseline to follow-up were mainly predicted by baseline QoL and depression as well as change in depression over time. Changes in cardiac severity markers were significantly weaker predictors. Conclusion Mean QoL increased during up-titration of bisoprolol and carvedilol. Both baseline depression and improvement in depression over time are associated with greater improvement in QoL more strongly than changes in cardiac severity measures. © 2013 European Federation of Internal Medicine.
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    Early NT-proBNP and MR-proANP associated with QoL 1 year after acutely decompensated heart failure: secondary analysis from the MOLITOR trial
    (2019)
    Zelenak, Christine (36873788500)
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    Chavanon, Mira-Lynn (14048024000)
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    Tahirovic, Elvis (24339336300)
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    Trippel, Tobias Daniel (16834210300)
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    Tscholl, Verena (54982696400)
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    Stroux, Andrea (10139008600)
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    Veskovic, Jovan (56951285600)
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    Apostolovic, Svetlana (13610076800)
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    Obradovic, Danilo (35731962400)
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    Zdravkovic, Marija (24924016800)
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    Loncar, Goran (55427750700)
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    Störk, Stefan (6603842450)
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    Herrmann-Lingen, Christoph (6603417225)
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    Düngen, Hans-Dirk (16024171900)
    Aim: Heart failure negatively impacts quality of life (QoL), which in turn contributes to an adverse long-term prognosis. We aimed at identifying biomarker trajectories after an episode of acutely decompensated heart failure (ADHF) that differ between patients showing average versus impaired QoL 1 year later, thus allowing to predict impaired QoL. Methods: Biomarkers were repeatedly measured throughout the year in 104 ADHF patients. QoL was assessed at discharge and 1 year after ADHF. Logistic regression and receiver operating characteristic analyses were used to identify predictors of impaired QoL while controlling psychosocial confounders. Results: MR-proANP predicted impaired physical and mental QoL. NT-proBNP measurements were important predictors for poor physical QoL. Conclusion: MR-proANP and NT-proBNP predict poor QoL after an epidode of ADHF. The trial is registered at http://clinicaltrials.gov as MOLITOR (IMpact of therapy optimisation On the Level of biomarkers in paTients with Acute and Decompensated ChrOnic HeaRt Failure) with unique identifier: NCT01501981. © 2019 Future Medicine Ltd.
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    Early NT-proBNP and MR-proANP associated with QoL 1 year after acutely decompensated heart failure: secondary analysis from the MOLITOR trial
    (2019)
    Zelenak, Christine (36873788500)
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    Chavanon, Mira-Lynn (14048024000)
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    Tahirovic, Elvis (24339336300)
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    Trippel, Tobias Daniel (16834210300)
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    Tscholl, Verena (54982696400)
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    Stroux, Andrea (10139008600)
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    Veskovic, Jovan (56951285600)
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    Apostolovic, Svetlana (13610076800)
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    Obradovic, Danilo (35731962400)
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    Zdravkovic, Marija (24924016800)
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    Loncar, Goran (55427750700)
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    Störk, Stefan (6603842450)
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    Herrmann-Lingen, Christoph (6603417225)
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    Düngen, Hans-Dirk (16024171900)
    Aim: Heart failure negatively impacts quality of life (QoL), which in turn contributes to an adverse long-term prognosis. We aimed at identifying biomarker trajectories after an episode of acutely decompensated heart failure (ADHF) that differ between patients showing average versus impaired QoL 1 year later, thus allowing to predict impaired QoL. Methods: Biomarkers were repeatedly measured throughout the year in 104 ADHF patients. QoL was assessed at discharge and 1 year after ADHF. Logistic regression and receiver operating characteristic analyses were used to identify predictors of impaired QoL while controlling psychosocial confounders. Results: MR-proANP predicted impaired physical and mental QoL. NT-proBNP measurements were important predictors for poor physical QoL. Conclusion: MR-proANP and NT-proBNP predict poor QoL after an epidode of ADHF. The trial is registered at http://clinicaltrials.gov as MOLITOR (IMpact of therapy optimisation On the Level of biomarkers in paTients with Acute and Decompensated ChrOnic HeaRt Failure) with unique identifier: NCT01501981. © 2019 Future Medicine Ltd.
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    Incremental prognostic value of a novel metabolite-based biomarker score in congestive heart failure patients
    (2020)
    McGranaghan, Peter (57204009675)
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    Düngen, Hans-Dirk (16024171900)
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    Saxena, Anshul (56050611500)
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    Rubens, Muni (37061927200)
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    Salami, Joseph (57188720738)
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    Radenkovic, Jasmin (57214457696)
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    Bach, Doris (57201795994)
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    Apostolovic, Svetlana (13610076800)
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    Loncar, Goran (55427750700)
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    Zdravkovic, Marija (24924016800)
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    Tahirovic, Elvis (24339336300)
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    Veskovic, Jovan (56951285600)
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    Störk, Stefan (6603842450)
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    Veledar, Emir (6602398313)
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    Pieske, Burkert (35499467500)
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    Edelmann, Frank (35366308700)
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    Trippel, Tobias Daniel (16834210300)
    Aims: The Cardiac Lipid Panel (CLP) is a newly discovered panel of metabolite-based biomarkers that has shown to improve the diagnostic value of N terminal pro B type natriuretic peptide (NT-proBNP). However, little is known about its usefulness in predicting outcomes. In this study, we developed a risk score for 4-year cardiovascular death in elderly chronic heart failure (CHF) patients using the CLP. Methods and results: From the Cardiac Insufficiency Bisoprolol Study in Elderly trial, we included 280 patients with CHF aged >65 years. A targeted metabolomic analysis of the CLP biomarkers was performed on baseline serum samples. Cox regression was used to determine the association of the biomarkers with the outcome after accounting for established risk factors. A risk score ranging from 0 to 4 was calculated by counting the number of biomarkers above the cut-offs, using Youden index. During the mean (standard deviation) follow-up period of 50 (8) months, 35 (18%) subjects met the primary endpoint of cardiovascular death. The area under the receiver operating curve for the model based on clinical variables was 0.84, the second model with NT-proBNP was 0.86, and the final model with the CLP was 0.90. The categorical net reclassification index was 0.25 using three risk categories: 0–60% (low), 60–85% (intermediate), and >85% (high). The continuous net reclassification index was 0.772, and the integrated discrimination index was 0.104. Conclusions: In patients with CHF, incorporating a panel of three metabolite-based biomarkers into a risk score improved the prognostic utility of NT-proBNP by predicting long-term cardiovascular death more precisely. This novel approach holds promise to improve clinical risk assessment in CHF patients. © 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology
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    Poor self-rated health predicts mortality in patients with stable chronic heart failure
    (2016)
    Inkrot, Simone (35784615000)
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    Lainscak, Mitja (9739432000)
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    Edelmann, Frank (35366308700)
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    Loncar, Goran (55427750700)
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    Stankovic, Ivan (57197589922)
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    Celic, Vera (57132602400)
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    Apostolovic, Svetlana (13610076800)
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    Tahirovic, Elvis (24339336300)
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    Trippel, Tobias (16834210300)
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    Herrmann-Lingen, Christoph (6603417225)
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    Gelbrich, Götz (14119833600)
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    Düngen, Hans-Dirk (16024171900)
    Aims: In heart failure, a holistic approach incorporating the patient's perspective is vital for prognosis and treatment. Self-rated health has strong associations with adverse events and short-term mortality risk, but long-term data are limited. We investigated the predictive value of two consecutive self-rated health assessments with regard to long-term mortality in a large, well characterised sample of elderly patients with stable chronic heart failure. Methods and results: We measured self-rated health by asking 'In general, would you say your health is: 1, excellent; 2, very good; 3, good; 4, fair; 5, poor?' twice: at baseline and the end of a 12-week beta-blocker up-titration period in the CIBIS-ELD trial. Mortality was assessed in an observational follow-up after 2-4 years. A total of 720 patients (mean left ventricular ejection fraction 45±12%, mean age 73±5 years, 36% women) rated their health at both time points. During long-term follow-up, 144 patients died (all-cause mortality 20%). Fair/poor self-rated health in at least one of the two reports was associated with increased mortality (hazard ratio 1.42 per level; 95% confidence interval 1.16-1.75; P<0.001). It remained independently significant in multiple Cox regression analysis, adjusted for N-terminal pro B-type natriuretic peptide (NTproBNP), heart rate and other risk prediction covariates. Self-rated health by one level worse was as predictive for mortality as a 1.9-fold increase in NTproBNP. Conclusion: Poor self-rated health predicts mortality in our long-term follow-up of patients with stable chronic heart failure, even after adjustment for established risk predictors. We encourage clinicians to capture patient-reported self-rated health routinely as an easy to assess, clinically meaningful measure and pay extra attention when self-rated health is poor. © The European Society of Cardiology 2015.
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    Poor self-rated health predicts mortality in patients with stable chronic heart failure
    (2016)
    Inkrot, Simone (35784615000)
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    Lainscak, Mitja (9739432000)
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    Edelmann, Frank (35366308700)
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    Loncar, Goran (55427750700)
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    Stankovic, Ivan (57197589922)
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    Celic, Vera (57132602400)
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    Apostolovic, Svetlana (13610076800)
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    Tahirovic, Elvis (24339336300)
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    Trippel, Tobias (16834210300)
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    Herrmann-Lingen, Christoph (6603417225)
    ;
    Gelbrich, Götz (14119833600)
    ;
    Düngen, Hans-Dirk (16024171900)
    Aims: In heart failure, a holistic approach incorporating the patient's perspective is vital for prognosis and treatment. Self-rated health has strong associations with adverse events and short-term mortality risk, but long-term data are limited. We investigated the predictive value of two consecutive self-rated health assessments with regard to long-term mortality in a large, well characterised sample of elderly patients with stable chronic heart failure. Methods and results: We measured self-rated health by asking 'In general, would you say your health is: 1, excellent; 2, very good; 3, good; 4, fair; 5, poor?' twice: at baseline and the end of a 12-week beta-blocker up-titration period in the CIBIS-ELD trial. Mortality was assessed in an observational follow-up after 2-4 years. A total of 720 patients (mean left ventricular ejection fraction 45±12%, mean age 73±5 years, 36% women) rated their health at both time points. During long-term follow-up, 144 patients died (all-cause mortality 20%). Fair/poor self-rated health in at least one of the two reports was associated with increased mortality (hazard ratio 1.42 per level; 95% confidence interval 1.16-1.75; P<0.001). It remained independently significant in multiple Cox regression analysis, adjusted for N-terminal pro B-type natriuretic peptide (NTproBNP), heart rate and other risk prediction covariates. Self-rated health by one level worse was as predictive for mortality as a 1.9-fold increase in NTproBNP. Conclusion: Poor self-rated health predicts mortality in our long-term follow-up of patients with stable chronic heart failure, even after adjustment for established risk predictors. We encourage clinicians to capture patient-reported self-rated health routinely as an easy to assess, clinically meaningful measure and pay extra attention when self-rated health is poor. © The European Society of Cardiology 2015.
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    Prognostic performance of serial in-hospital measurements of copeptin and multiple novel biomarkers among patients with worsening heart failure: results from the MOLITOR study
    (2018)
    Düngen, Hans-Dirk (16024171900)
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    Tscholl, Verena (54982696400)
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    Obradovic, Danilo (35731962400)
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    Radenovic, Sara (57000170900)
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    Matic, Dragan (25959220100)
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    Musial Bright, Lindy (25642935600)
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    Tahirovic, Elvis (24339336300)
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    Marx, Almuth (57034878400)
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    Inkrot, Simone (35784615000)
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    Hashemi, Djawid (57195309402)
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    Veskovic, Jovan (56951285600)
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    Apostolovic, Svetlana (13610076800)
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    von Haehling, Stephan (6602981479)
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    Doehner, Wolfram (6701581524)
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    Cvetinovic, Natasa (55340266600)
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    Lainscak, Mitja (9739432000)
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    Pieske, Burkert (35499467500)
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    Edelmann, Frank (35366308700)
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    Trippel, Tobias (16834210300)
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    Loncar, Goran (55427750700)
    Aims: In heart failure, various biomarkers are established for diagnosis and risk stratification; however, little is known about the relevance of serial measurements during an episode worsening heart failure (WHF). This study sought to investigate the trajectory of natriuretic peptides and multiple novel biomarkers during hospitalization for WHF and to determine the best time point to predict outcome. Methods and results: MOLITOR (Impact of Therapy Optimisation on the Level of Biomarkers in Patients with Acute and Decompensated Chronic Heart Failure) was an eight-centre prospective study of 164 patients hospitalized with a primary diagnosis of WHF. C-terminal fragment of pre-pro-vasopressin (copeptin), N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional pro-atrial natriuretic peptide (MR-proANP), mid-regional pro-adrenomedullin (MR-proADM), and C-terminal pro-endothelin-1 (CT-proET1) were measured on admission, after 24, 48, and 72 h, and every 72 h thereafter, at discharge and follow-up visits. Their performance to predict all-cause mortality and rehospitalization at 90 days was compared. All biomarkers decreased during recompensation (P < 0.05) except MR-proADM. Copeptin at admission was the best predictor of 90 day mortality or rehospitalization (χ2 = 16.63, C-index = 0.724, P < 0.001), followed by NT-proBNP (χ2 = 10.53, C-index = 0.646, P = 0.001), MR-proADM (χ2 = 9.29, C-index = 0.686, P = 0.002), MR-proANP (χ2 = 8.75, C-index = 0.631, P = 0.003), and CT-proET1 (χ2 = 6.60, C-index = 0.64, P = 0.010). Re-measurement of copeptin at 72 h and of NT-proBNP at 48 h increased prognostic value (χ2 = 23.48, C-index = 0.718, P = 0.00001; χ2 = 14.23, C-index = 0.650, P = 0.00081, respectively). Conclusions: This largest sample of serial measurements of multiple biomarkers in WHF found copeptin at admission with re-measurement at 72 h to be the best predictor of 90 day mortality and rehospitalization. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.
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    Regional differences in health-related quality of life in elderly heart failure patients: results from the CIBIS-ELD trial
    (2017)
    Chavanon, Mira-Lynn (14048024000)
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    Inkrot, Simone (35784615000)
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    Zelenak, Christine (36873788500)
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    Tahirovic, Elvis (24339336300)
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    Stanojevic, Dragana (58530775100)
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    Apostolovic, Svetlana (13610076800)
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    Sljivic, Aleksandra (55848628200)
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    Ristic, Arsen D. (7003835406)
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    Matic, Dragan (25959220100)
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    Loncar, Goran (55427750700)
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    Veskovic, Jovan (56951285600)
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    Zdravkovic, Marija (24924016800)
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    Lainscak, Mitja (9739432000)
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    Pieske, Burkert (35499467500)
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    Herrmann-Lingen, Christoph (6603417225)
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    Düngen, Hans-Dirk (16024171900)
    Aim: Patient-reported outcomes such as health-related quality of life (HRQoL) are main treatment goals for heart failure (HF) and therefore endpoints in multinational therapy trials. However, little is known about country-specific differences in HRQoL and in treatment-associated HRQoL improvement. The present work sought to examine those questions. Methods and results: We analysed data from the Cardiac Insufficiency Bisoprolol Study in Elderly (CIBIS-ELD) trial, in which patients from central and south-eastern Europe completed the HRQoL questionnaire SF-36 at baseline and the end of a 12-week beta-blocker up-titration (follow-up). 416 patients from Serbia (mean age 72.21 years, 69% NYHA-class I–II, 27.4% women) and 114 from Germany (mean age 73.64 years, 78.9% NYHA-class I–II, 47.4% women) were included. Controlling for clinical variables, the change in mental HRQoL from baseline to follow-up was modulated by Country: Serbian patients, Mbaseline = 37.85 vs. Mfollow−up = 40.99, t(526) = 5.34, p <.001, reported a stronger increase than Germans, Mbaseline = 37.66 vs. Mfollow−up = 38.23, t(526) = 0.68, ns. For physical HRQoL, we observed a main effect of Country, MSerbia = 39.28 vs. MGermany = 35.29, t(526) = 4.24, p <.001. Conclusion: We observed significant differences in HF patients from Germany and Serbia and country-specific differences between Serbian and German patients in mean physical HRQoL. Changes in mental HRQoL were modulated by country. Those results may reflect psychological, sociocultural, aetiological differences or regional differences in phenotype prevalence. More importantly, they suggest that future multinational trials should consider such aspects when designing a trial in order to avoid uncertainties aligned to data interpretation and to improve subsequent treatment optimisation. © 2017, Springer-Verlag Berlin Heidelberg.
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    Self-rated health predicts adverse events during beta-blocker treatment: The CIBIS-ELD randomised trial analysis
    (2013)
    Lainscak, Mitja (9739432000)
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    Farkas, Jerneja (25225081600)
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    Inkrot, Simone (35784615000)
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    Gelbrich, Götz (14119833600)
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    Neskovic, Aleksandar N. (35597744900)
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    Rau, Thomas (57214509568)
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    Tahirovic, Elvis (24339336300)
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    Töpper, Agnieszka (38863078500)
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    Apostolovic, Svetlana (13610076800)
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    Haverkamp, Wilhelm (7005423154)
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    Herrmann-Lingen, Christoph (6603417225)
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    Anker, Stefan D. (56223993400)
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    Düngen, Hans-Dirk (16024171900)
    Background: Self-rated health (SRH) predicts outcome in patients with heart failure. Beta-blockers are known to improve health-related quality of life and reduce mortality in such patients. We aimed to evaluate the relation between SRH and adverse events during titration of beta-blockers in elderly patients with heart failure. Methods: The cardiac insufficiency bisoprolol study in the elderly (CIBIS-ELD) is a multicentre, double-blind trial, in which 883 patients aged ≥ 65 years with chronic heart failure (73 ± 6 years, 38% women, left ventricular ejection fraction [LVEF] 42% ± 14%) were randomised to bisoprolol or carvedilol. SRH was assessed at baseline and after 12 weeks, using a 5-grade descriptive scale: excellent, very good, good, fair, and poor. Results: Median SRH at baseline and follow-up was good, but more patients reported fair/poor SRH at baseline (36% vs. 30%, p = 0.012). Women, beta-blocker-naïve patients, patients in NYHA class III/IV and those with PHQ-9 score ≥ 12 were more likely to report fair/poor baseline SRH (p < 0.001 for all). During follow-up, SRH improved in 34% of patients and worsened in 8% (p < 0.001). Adverse events were experienced by 64% patients and 38% experienced > 1 adverse event or serious adverse event, with higher prevalence in lower SRH categories. In a multivariate logistic regression model, SRH, age, distance achieved on the 6-min walk test and LVEF > 45% predicted adverse events (p < 0.05 for all). Conclusions: SRH is an independent predictor of adverse events during titration of beta-blockers and correlates with the proportion and number of adverse events per patient. © 2011 Elsevier Ireland Ltd. All rights reserved.
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    Systemic inflammation and functional capacity in elderly heart failure patients
    (2018)
    Radenovic, Sara (57000170900)
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    Loncar, Goran (55427750700)
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    Busjahn, Andreas (7004503495)
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    Apostolovic, Svetlana (13610076800)
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    Zdravkovic, Marija (24924016800)
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    Karlicic, Valentina (57201378162)
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    Veskovic, Jovan (56951285600)
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    Tahirovic, Elvis (24339336300)
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    Butler, Javed (57203521637)
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    Düngen, Hans-Dirk (16024171900)
    Background: Elevated C-reactive protein (CRP) is associated with adverse outcomes in heart failure (HF) patients. Beta-blocker therapy may lower CRP levels. Methods and results: To assess if the changes of high-sensitivity (hs) CRP levels in HF patients over 12-week titration with beta-blockers correlate with functional capacity, plasma hs-CRP levels were measured in 488 HF patients [72.1 ± 5.31 years, LVEF 40% (33/50)]. Hs-CRP, NT-proBNP and 6-min-walk-test (6MWT) were assessed at baseline and at week 12. Patients were divided based on hs-CRP changes (cut-off > 0.3 mg/dl) into low–low (N = 225), high–high (N = 132), low–high (N = 54), high–low (N = 77) groups. At baseline, median hs-CRP concentration was 0.25 (0.12/0.53) mg/dl, NT-proBNP 551 (235/1455) pg/ml and average 6MWT distance 334 ± 105 m. NT-proBNP changes were significantly different between the four hs-CRP groups (P = 0.011). NT-proBNP increased in the low–high group by 30 (− 14/88) pg/ml and decreased in the high–low group by − 8 (− 42/32) pg/ml. 6MWT changes significantly differed between groups [P = 0.002; decrease in the low–high group (− 18 ± 90 m) and improvement in the low–low group (24 ± 62 m)]. Conclusion: After beta-blocker treatment, hs-CRP levels are associated with functional capacity in HF patients. Whether this represents a potential target for intervention needs further study. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.
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    The β-blocker uptitration in elderly with heart failure regarding biomarker levels: CIBIS-ELD substudy
    (2018)
    Cvetinovic, Natasa (55340266600)
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    Sekularac, Nikola (23981224200)
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    Haehling, Stephan Von (6602981479)
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    Tahirovic, Elvis (24339336300)
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    Inkrot, Simona (35784615000)
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    Lainscak, Mitja (9739432000)
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    Apostolovic, Svetlana (13610076800)
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    Putnikovic, Biljana (6602601858)
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    Waagstein, Finn (56216780700)
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    Gelbrich, Goetz (14119833600)
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    Aleksic, Andja (57206730766)
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    Loncar, Goran (55427750700)
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    Düngen, Hans-Dirk (16024171900)
    Aim: We investigated if the baseline value of mid-regional pro-atrial natriuretic peptide (NP), N-terminal pro-B-type NP and copeptin may be helpful in optimizing β-blocker uptitration in elderly patients with heart failure. Patients & methods: According to the biomarkers’ levels, 457 patients were divided into three subgroups and compared with each other at baseline and 3 months after. Results: All mid-regional pro-atrial NP and N-terminal pro-B-type NP subgroups had significant amelioration of left ventricle ejection fraction and New York Heart Association (NYHA) class after 3 months of β-blocker uptitration (p < 0.001). More prominent improvement of left ventricle ejection fraction and New York Heart Association class was observed in subgroups with lower versus higher NPs levels. Conclusion: NPs levels, unlike copeptin levels, might be useful tool for objective selection of elderly heart failure patients who could have the greatest benefit of forced uptitration. C 2018 Future Medicine Ltd
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    The β-blocker uptitration in elderly with heart failure regarding biomarker levels: CIBIS-ELD substudy
    (2018)
    Cvetinovic, Natasa (55340266600)
    ;
    Sekularac, Nikola (23981224200)
    ;
    Haehling, Stephan Von (6602981479)
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    Tahirovic, Elvis (24339336300)
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    Inkrot, Simona (35784615000)
    ;
    Lainscak, Mitja (9739432000)
    ;
    Apostolovic, Svetlana (13610076800)
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    Putnikovic, Biljana (6602601858)
    ;
    Waagstein, Finn (56216780700)
    ;
    Gelbrich, Goetz (14119833600)
    ;
    Aleksic, Andja (57206730766)
    ;
    Loncar, Goran (55427750700)
    ;
    Düngen, Hans-Dirk (16024171900)
    Aim: We investigated if the baseline value of mid-regional pro-atrial natriuretic peptide (NP), N-terminal pro-B-type NP and copeptin may be helpful in optimizing β-blocker uptitration in elderly patients with heart failure. Patients & methods: According to the biomarkers’ levels, 457 patients were divided into three subgroups and compared with each other at baseline and 3 months after. Results: All mid-regional pro-atrial NP and N-terminal pro-B-type NP subgroups had significant amelioration of left ventricle ejection fraction and New York Heart Association (NYHA) class after 3 months of β-blocker uptitration (p < 0.001). More prominent improvement of left ventricle ejection fraction and New York Heart Association class was observed in subgroups with lower versus higher NPs levels. Conclusion: NPs levels, unlike copeptin levels, might be useful tool for objective selection of elderly heart failure patients who could have the greatest benefit of forced uptitration. C 2018 Future Medicine Ltd
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    Tolerability and Feasibility of Beta-Blocker Titration in HFpEF Versus HFrEF: Insights From the CIBIS-ELD Trial
    (2016)
    Edelmann, Frank (35366308700)
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    Musial-Bright, Lindy (25642935600)
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    Gelbrich, Goetz (14119833600)
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    Trippel, Tobias (16834210300)
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    Radenovic, Sara (57000170900)
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    Wachter, Rolf (12775831800)
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    Inkrot, Simone (35784615000)
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    Loncar, Goran (55427750700)
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    Tahirovic, Elvis (24339336300)
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    Celic, Vera (57132602400)
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    Veskovic, Jovan (56951285600)
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    Zdravkovic, Marija (24924016800)
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    Lainscak, Mitja (9739432000)
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    Apostolović, Svetlana (13610076800)
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    Neskovic, Aleksandar N. (35597744900)
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    Pieske, Burkert (35499467500)
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    Düngen, Hans-Dirk (16024171900)
    Objectives: This study evaluated the tolerability and feasibility of titration of 2 distinctly acting beta-blockers (BB) in elderly heart failure patients with preserved (HFpEF) and reduced (HFrEF) left ventricular ejection fraction. Background: Broad evidence supports the use of BB in HFrEF, whereas the evidence for beta blockade in HFpEF is uncertain. Methods: In the CIBIS-ELD (Cardiac Insufficiency Bisoprolol Study in Elderly) trial, patients >65 years of age with HFrEF (n = 626) or HFpEF (n = 250) were randomized to bisoprolol or carvedilol. Both BB were up-titrated to the target or maximum tolerated dose. Follow-up was performed after 12 weeks. HFrEF and HFpEF patients were compared regarding tolerability and clinical effects (heart rate, blood pressure, systolic and diastolic functions, New York Heart Association functional class, 6-minute-walk distance, quality of life, and N-terminal pro-B-type natriuretic peptide). Results: For both of the BBs, tolerability and daily dose at 12 weeks were similar. HFpEF patients demonstrated higher rates of dose escalation delays and treatment-related side effects. Similar HR reductions were observed in both groups (HFpEF: 6.6 beats/min; HFrEF: 6.9 beats/min, p = NS), whereas greater improvement in NYHA functional class was observed in HFrEF (HFpEF: 23% vs. HFrEF: 34%, p < 0.001). Mean E/e' and left atrial volume index did not change in either group, although E/A increased in HFpEF. Conclusions: BB tolerability was comparable between HFrEF and HFpEF. Relevant reductions of HR and blood pressure occurred in both groups. However, only HFrEF patients experienced considerable improvements in clinical parameters and left ventricular function. Interestingly, beta-blockade had no effect on established and prognostic markers of diastolic function in either group. Long-term studies using modern diagnostic criteria for HFpEF are urgently needed to establish whether BB therapy exerts significant clinical benefit in HFpEF. (Comparison of Bisoprolol and Carvedilol in Elderly Heart Failure [HF] Patients: A Randomised, Double-Blind Multicentre Study [CIBIS-ELD]; ISRCTN34827306). © 2016 American College of Cardiology Foundation.

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