Browsing by Author "Inkrot, Simone"

Chronic heart failure (CHF) is a widespread disease with severe quality of life impairment and a poor prognosis. Beta-blockers are the mainstay of CHF therapy; yet they are under-prescribed and under-dosed in clinical practice. This is particularly evident in elderly patients, which may be due to a fear of side-effects or intolerance. Beta-blockers have further not been adequately tested in patients with diastolic CHF, which is particularly common in elderly patients. Finally, comparative data on the use of different beta-blockers in patients with CHF is scarce. To compare the tolerance of bisoprolol and carvedilol in elderly patients with CHF. CIBIS-ELD is an investigator-initiated, multi-centre, 1:1 randomised, double-blind, phase III trial comparing bisoprolol and carvedilol in patients >= 65 years with systolic or diastolic CHF. Recruitment started in April 2005 and is anticipated to be completed by April 2008 with at least 800 patients enrolled. This is the first large scale head to head beta-blockers trial in an elderly population with CHF. Besides determining which of two standard beta-blockers is best tolerated in elderly patients with systolic or diastolic CHF, we expect to gain further insight into the treatment of the particular population of patients with diastolic CHF.

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. (C) 2013 European Federation of Internal Medicine. Published by Elsevier B. V. All rights reserved.

Background: We sought to investigate the effect of beta-blocker (BB) up-titration on serum levels of NT-proBNP and copeptin in patients with heart failure (HF) with reduced (HFREF) or preserved ejection fraction (HFPEF). Methods: Serial measurements of NT-proBNP and copeptin were obtained after initiation of BB up-titration in 219 elderly patients with HFREF or HFPEF. Results: After initial increasing trend of NT-proBNP at 6 weeks in HFREF patients, there was a subsequent decrease at 12 weeks of BB treatment up-titration (p = 0.003), while no difference was found compared to baseline levels. In contrast to NT-proBNP, there was a continuous decreasing trend of copeptin in HFREF patients (at 12 weeks: p = 0.026). In HFPEF patients, NT-proBNP significantly decreased (p = 0.043) compared to copeptin after 12 weeks of BB up-titration. Conclusions: After 12 weeks of BB optimization copeptin might reflect successful up-titration faster than NT-proBNP in HFREF, while the opposite was found in patients with HFPEF. (C) 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Aims Beta-blockers (BBs) improve outcomes in heart failure. Results from the Cardiac Insufficiency Bisoprolol Study in Elderly (CIBIS-ELD) trial previously demonstrated the feasibility of heart rate, not maximum dose, as a treatment goal. In this pre-specified analysis, we investigated the prognostic value of achieved heart rate after BB optimization on long-term mortality. Methods and results Elderly heart failure patients from the CIBIS-ELD trial were invited to participate in a follow-up examination 4 years after the initial 12-week BB up-titration period. The relationship between all-cause mortality, BB dose, and heart rate after titration and potentially confounding clinical variables was analysed by multivariable Cox regression. In total, 728 patients (38% women; mean age 72.9 +/- 5.4 years) were included. During a mean follow-up period of 45 +/- 9months, 134 patients (19%) died, thus accumulating 2268 patient-years at risk. There was no significant difference in baseline heart rate for survivors and non-survivors (P = 0.19). In models adjusting for age, sex, BB pre-treatment, ventricular function, heart rate, and NYHA class at baseline, a heart rate increase by 10 b. p. m. following up-titration was associated with a subsequent mortality hazard ratio of 1.19 (95% confidence interval 1.02-1.38, P = 0.023). The heart rate range with the lowest mortality and the fewest treatment-related adverse events was 55-64 b.p.m. The achieved BB dose was not associated with mortality risk. Conclusion The heart rate after up-titration, but not BB dose, predicted all-cause mortality risk in elderly patients with chronic heart failure. These patients should be titrated to resting heart rates between 55 and 64 b.p.m.

Background: Guideline-recommended beta-blocker (BB) target doses for patients with chronic heart failure can often not be reached. This secondary analysis of the CIBIS-ELD trial was carried out to better understand reasons for not achieving target doses. Methods: Changes in heart rate (HR) and other parameters during a 12-week up-titration period in 302 BB nave patients were evaluated in the subgroups achieving 12.5, 25, 50, and 100% of the target dose (groups 1, 2, 3, and 4, respectively). Results: Achieved doses predominantly depended on baseline HR (means 68, 74, 76, and 84 bpm in groups 1-4, respectively, P<0.001). HR was consistently reduced with each dose level to 65, 63, and 62 bpm in groups 1-3 and to 71 bpm in group 4 (P<0.001). When adjusted for baseline, HR reduction achieved in group 3 was better than in group 4 (difference -5.4 bpm, P<0.05). More patients in groups 3/4 than in groups 1/2 improved in NYHA class (P=0.01). NTproBNP increased by 38% in group 4 (P<0.01) but not in the others (P<0.05 between groups). Changes in blood pressure, six-minute walk distance and self-rated health were comparable in all groups. Conclusions: The desired effect of HR reduction appears to be a predominant limitation for BB up-titration. Vice versa, achieving the target dose may be a sign of insufficient response rather than successful treatment. In view of these results and the well-known importance of HR for survival, not target doses, but HR control should be given priority in BB treatment for heart failure. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

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 4512%, 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.

Abstract 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 ( χ 2  = 16.63, C ‐index = 0.724, P  < 0.001), followed by NT‐proBNP ( χ 2  = 10.53, C ‐index = 0.646, P  = 0.001), MR‐proADM ( χ 2  = 9.29, C ‐index = 0.686, P  = 0.002), MR‐proANP ( χ 2  = 8.75, C ‐index = 0.631, P  = 0.003), and CT‐proET1 ( χ 2  = 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 ( χ 2  = 23.48, C ‐index = 0.718, P  = 0.00001; χ 2  = 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.

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-naive 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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Background: It has been suggested that patients with chronic HF and atrial fibrillation (AF) may respond differently to beta-blockers than those in sinus rhythm (SR). Methods: In this predefined analysis of the CIBIS-ELD trial, a total of 876 chronic HF patients (164 patients with AF) were randomized to bisoprolol or carvedilol. During the 12-week-treatment phase, beta-blockerswere doubled fortnightly up to the target dose or maximally tolerated dose, which was maintained for 4 weeks. Results: Patients with AF had lower left ventricular ejection fraction (LVEF), exercise capacity, self-rated health, quality of life (QoL) scores for both SF36 physical and psychosocial component, and higher NYHA class than those in SR. Beta-blocker titration was associated with clinical improvement in both AF and SR patients: LVEF, 6-minute walk distance, physical and psychosocial components of QoL scores, self-rated health and NYHA class (p<0.05, for all). The extent of improvement did not differ between patients with AF and in SR and did not differ between bisoprolol and carvedilol. Heart rate (HR) at baseline was higher in the AF group, and remained higher until the end of the trial. Patients with higher baseline HR had larger reductions in HR, regardless of rhythm. AF patients more frequently reached target beta-blocker dose compared to those in SR (p<0.005). Conclusions: Elderly patients with chronic HF and AF derive comparable clinical benefits frombeta-blocker titration as those in SR. Patients with AF tolerate higher beta-blocker doses than those in SR, which appears to be related to higher baseline HR. (C) 2012 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) (C) 2016 by the American College of Cardiology Foundation.