Browsing by Author "Inkrot, Simone (35784615000)"

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.

ᅟ: The interaction between the heart and the arterial system (ventricular-arterial coupling - VA) is an important determinant of cardiovascular performance. Vascular stiffness (Ea) and left ventricular (LV) endsystolic stiffness (Elv) augment with age and in heart failure (HF). Beta blockers (BB) are recommended therapy for patients with HF. However, data about the effects of BB on VA coupling are scarce. Aims of the Study: To assess: 1) changes in VA after BB therapy; 2) interactions between VA and LV functions, 3) predictive factors influencing VA change. Methods: Eight hundred seventy-seven elderly patients with HF (aged ≥ 65, NYHA ≥ II, LV ejection fraction (LVEF) ≤ 45 %), treated with BB according to the CIBIS-ELD protocol of up-titration, underwent Doppler echocardiography with clinical and laboratory assessment before and after 12 weeks of BB. VA coupling was calculated as Ea/Elv ratio. Results: Ventriculo-arterial interaction improved after 12 weeks of BB in elderly patients with HF. Values of Ea significantly decreased from 2.73 ± 1.16 to 2.40 ± 1.01, p < 0.001, resulting in a VA level close to the optimal range i.e. from 1.70 ± 1.05 (1.46) to 1.50 ± 0.94 (1.29), p < 0.001. A similar degree of VA change was found in the patients with ischemic and non-ischemic HF after the treatment. Improvement in the clinical stage of HF closely correlated with VA coupling change after BB (p = 0.006). The strongest predictor of VA coupling alteration during BB was the improvement in global LVEF (p < 0.001) followed by the age of patients (p = 0.014). Conclusions: The beneficial effect of BB in elderly patients with HF was achieved by optimizing VA coupling close to recommended range, associated with an improvement in LVEF and contractility. © 2015, Springer Science+Business Media New York.

ᅟ: The interaction between the heart and the arterial system (ventricular-arterial coupling - VA) is an important determinant of cardiovascular performance. Vascular stiffness (Ea) and left ventricular (LV) endsystolic stiffness (Elv) augment with age and in heart failure (HF). Beta blockers (BB) are recommended therapy for patients with HF. However, data about the effects of BB on VA coupling are scarce. Aims of the Study: To assess: 1) changes in VA after BB therapy; 2) interactions between VA and LV functions, 3) predictive factors influencing VA change. Methods: Eight hundred seventy-seven elderly patients with HF (aged ≥ 65, NYHA ≥ II, LV ejection fraction (LVEF) ≤ 45 %), treated with BB according to the CIBIS-ELD protocol of up-titration, underwent Doppler echocardiography with clinical and laboratory assessment before and after 12 weeks of BB. VA coupling was calculated as Ea/Elv ratio. Results: Ventriculo-arterial interaction improved after 12 weeks of BB in elderly patients with HF. Values of Ea significantly decreased from 2.73 ± 1.16 to 2.40 ± 1.01, p < 0.001, resulting in a VA level close to the optimal range i.e. from 1.70 ± 1.05 (1.46) to 1.50 ± 0.94 (1.29), p < 0.001. A similar degree of VA change was found in the patients with ischemic and non-ischemic HF after the treatment. Improvement in the clinical stage of HF closely correlated with VA coupling change after BB (p = 0.006). The strongest predictor of VA coupling alteration during BB was the improvement in global LVEF (p < 0.001) followed by the age of patients (p = 0.014). Conclusions: The beneficial effect of BB in elderly patients with HF was achieved by optimizing VA coupling close to recommended range, associated with an improvement in LVEF and contractility. © 2015, Springer Science+Business Media New York.

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.

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.

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.

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.

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.

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.