Expanded nursing competencies to improve person-centred care for nursing home residents with complex health needs (Expand-Care): study protocol for an exploratory cluster-randomised trial.

INTRODUCTION: Older age is associated with multimorbidity, chronic diseases and acute deteriorations and leads to complex care needs. Nursing home residents are more often unnecessarily transferred to emergency departments or hospitals than community dwellers-largely due to a lack of qualified staff and diffusion of responsibility in the institutions. In Germany, only few academically trained nurses work in nursing homes, and their potential roles are unclear. Therefore, we aim to explore feasibility and potential effects of a newly defined role profile for nurses with bachelors' degree or equivalent qualification in nursing homes. METHODS AND ANALYSIS: A pilot study (Expand-Care) with a cluster-randomised controlled design will be conducted in 11 nursing homes (cluster) in Germany, with an allocation ratio of 5:6 to the intervention or control group, aiming to include 15 residents per cluster (165 participants in total). Nurses in the intervention group will receive training to perform role-related tasks such as case reviews and complex geriatric assessments. We will collect data at three time points (t0 baseline, t1 3 months and t2 6 months after randomisation). We will measure on residents' level: hospital admissions, further health services use and quality of life; clinical outcomes (eg, symptom burden), physical functioning and delivery of care; mortality, adverse clinical incidents and changes in care level. On nurses' level, we will measure perception of the new role profile, competencies and implementation of role-related tasks as part of the process evaluation (mixed methods). An economic evaluation will explore resource use on residents' (healthcare utilisation) and on nurses' level (costs and time expenditure). ETHICS AND DISSEMINATION: The ethics committees of the University of Lübeck (Nr. 22-162) and the University Clinic Hamburg-Eppendorf (Nr. 2022-200452-BO-bet) approved the Expand-Care study. Informed consent is a prerequisite for participation. Study results will be published in open-access, peer-reviewed journals and reported at conferences and in local healthcare providers' networks. TRIAL REGISTRATION NUMBER: DRKS00028708.

[Role understanding of expert nurses in primary and acute care in Germany: A descriptive cross-sectional study]. / Rollenverständnis von Pflegeexpert_innen in der Primär- und Akutversorgung in Deutschland.

Role understanding of expert nurses in primary and acute care in Germany: A descriptive cross-sectional study Abstract. Background: Innovative care concepts are necessary to cope with the increase in complex care situations due to a rising number of older people with chronic diseases and a simultaneous shortage of nursing and medical staff. In the context of the implementation and development of new, innovative nursing roles, an unclear role understanding is considered a barrier. Aim: Description of expert nurses' (EN) role understanding in primary and acute care in Germany. Method: Using questionnaires, EN are asked cross-sectionally about role clarity, competencies and performance as well as perceived autonomy and interprofessional collaboration. Results are analysed descriptively. Results: A total of eight (primary care) and 14 (acute care) EN completed the questionnaires. The majority of EN often/very often perform both the clinical (77.5% and 85.7%, respectively) and the expert role (75% and 78.6%, respectively) and indicate that they can explain their role to patients (75% and 92.9%, respectively) and physicians (87.5% and 90.9%, respectively). Having a high degree of autonomy is more likely to be perceived by EN working in acute care. Conclusion: Although there are similarities in terms of role understanding, EN working in acute care can apparently benefit from already established structures, which is reflected, among other things, in their perceived autonomy.

Process evaluation of a multi-disciplinary complex intervention to improve care for older patients with chronic conditions in rural areas (the HandinHand Study): study protocol.

BACKGROUND: To improve health care in rural areas, especially for increasing numbers of people with chronic diseases, academically qualified nurses could take over expanded roles to meet the challenges of an ageing society and a decreasing number of General Practitioners (GPs). In the project "HandinHand" (HiH), qualified nurses (Expert nurses, ENs) will carry out home visits to older people with chronic diseases over a period of six months. ENs will prepare a care plan in cooperation with GPs to stabilise the care situation and avoid unplanned hospital admissions and GP visits. The process evaluation aims to provide an in-depth analysis of the implementation process and gather important information on barriers and facilitators to the implementation of ENs as a complementary health care structure in primary care, taking into account several context factors. METHODS: Based on the Medical Research Council (MRC) Framework for complex interventions, a logic model was developed and applied as the basis for data collection. Qualitative and quantitative data will be collected during the study. A mixed methods approach should allow to gain important insights from participants (e.g. ENs, GPs, patients) involved in the study as well as relevant stakeholders. Semi-structured interviews and surveys will be conducted. Data analysis will be based on the logical model, combining qualitative and quantitative data. Qualitative data will be analysed inductively-deductively using qualitative thematic framework analysis. DISCUSSION: The process evaluation will provide guidance and conclusions on further development and transferability. Of particular interest is the expanded role of ENs in primary care, which has barely been implemented in Germany and can be seen as a precursor to the development of an Advanced Practice Nursing (APN) role in primary care.

Translation and Psychometric Evaluation of the German Version of the Thirst Distress Scale for Patients With Heart Failure.

BACKGROUND: In patients with chronic heart failure, thirst can be perceived as an intensive and burdensome symptom, which may have a negative impact on patients' quality of life. To initiate thirst-relieving interventions, assessment of thirst and its related distress is essential. At the time of this study, no instrument was available to evaluate thirst distress in patients with heart failure in Germany. OBJECTIVE: The aims of this study were to translate the "Thirst Distress Scale for patients with Heart Failure" (TDS-HF) from English into German and to test validity and reliability of the scale. METHODS: The English version of the TDS-HF was translated into German. A linguistically and culturally sensitive forward-and-backward translation was performed. Psychometric evaluation included confirmatory factor analysis, reliability in terms of internal consistency, and concurrent validity. RESULTS: Eighty-four hospitalized patients (mean age, 72 ± 10 years; 29% female; mean left ventricular ejection fraction, 36% ± 12%; 62% New York Heart Association functional classes III-IV, 45% on fluid restriction) from an acute care hospital were involved in the study. The item-total correlation ranged from 0.58 to 0.78. Interitem correlations varied between 0.37 and 0.79. Internal consistency was high, with a Cronbach α of 0.89. There was a high correlation between the total score of the TDS-HF and the visual analog scale to assess thirst intensity ( r = 0.72, P ≤ .001), and a low correlation with fluid restriction ( r = 0.35, P = .002). CONCLUSIONS: The evaluation of the German TDS-HF showed satisfactory psychometric properties in this sample. The instrument is usable for further research and additional psychometric testing.

Prognostic performance of serial in-hospital measurements of copeptin and multiple novel biomarkers among patients with worsening heart failure: results from the MOLITOR study.

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.

Heart failure awareness survey in Germany: general knowledge on heart failure remains poor.

AIMS: Previous studies demonstrated poor public awareness of heart failure (HF) compared with myocardial infarction and stroke. With respect to several activities to improve HF awareness in recent years, we present data on the development of HF awareness and information sources in Germany over 8 years. METHODS AND RESULTS: In 2007, 2012, and 2015, respectively, 2531, 359, and 171 respondents answered questions about causes, presentation, prognosis, and treatment of HF from a survey developed by the German Competence Network HF. Relationships between respondents' sociodemographic data and their HF knowledge were explored and changes in knowledge and use of information sources analysed. Sixty-eight per cent of respondents knew HF as 'weakness of the heart'. Seventy-nine per cent knew shortness of breath, 74% reduced exercise tolerance, and 52% knew leg edema as symptoms. Only 40% knew all three symptoms. Although up to 34% of the respondents were directly or indirectly affected by HF, they demonstrated poor knowledge about severity and prognosis. Between 2007 and 2015, overall HF awareness has not changed; awareness about treatment has dropped significantly. Younger respondents used all media, especially internet, for information about health; older respondents preferred printed/verbal media and their physician. CONCLUSIONS: We found rather insufficient public knowledge on HF etiology and symptoms but especially about management, severity, and prognosis, which is essential for good self-care and adherence of patients. Heart failure awareness has not improved even though awareness campaigns were held over the years. It seems that especially older patients should be much more approached by their family physicians.

Regional differences in health-related quality of life in elderly heart failure patients: results from the CIBIS-ELD trial.

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, M baseline = 37.85 vs. M follow-up = 40.99, t(526) = 5.34, p < .001, reported a stronger increase than Germans, M baseline = 37.66 vs. M follow-up = 38.23, t(526) = 0.68, ns. For physical HRQoL, we observed a main effect of Country, M Serbia = 39.28 vs. M Germany = 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.

Tolerability and Feasibility of Beta-Blocker Titration in HFpEF Versus HFrEF: Insights From the CIBIS-ELD Trial.

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).

Poor self-rated health predicts mortality in patients with stable chronic heart failure.

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.

Improvement of Ventricular-Arterial Coupling in Elderly Patients with Heart Failure After Beta Blocker Therapy: Results from the CIBIS-ELD Trial.

UNLABELLED: 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.

Heart rate following short-term beta-blocker titration predicts all-cause mortality in elderly chronic heart failure patients: insights from the CIBIS-ELD trial.

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 ± 9 months, 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.

Regional differences among female patients with heart failure from the Cardiac Insufficiency BIsoprolol Study in ELDerly (CIBIS-ELD).

BACKGROUND: The aim of our study was to examine regional differences in the demographics, etiology, risk factors, comorbidities and treatment of female patients with heart failure (HF) in the Cardiac Insufficiency BIsoprolol Study in ELDerly (CIBIS-ELD) clinical trial. METHODS AND RESULTS: One hundred and fifty-nine female patients from Germany and 169 from Southeastern (SE) Europe (Serbia, Slovenia and Montenegro) were included in this subanalysis of the CIBIS-ELD trial. Women comprised 54% of the study population in Germany and 29% in SE Europe. German patients were significantly older. The leading cause of HF was arterial hypertension in German patients, 71.7% of whom had a preserved ejection fraction. The leading etiology in SE Europe was the coronary artery disease; 67.6% of these patients had a reduced left ventricular ejection fraction (34.64 ± 7.75%). No significant differences were found in the prevalence of traditional cardiovascular risk factors between the two regions (hypertension, diabetes, hypercholesterolemia, smoking and family history of myocardial infarction). Depression, chronic obstructive pulmonary disease and malignancies were the comorbidities that were noted more frequently in the German patients, while the patients from SE Europe had a lower glomerular filtration rate. Compared with the German HF patients, the females in SE Europe received significantly more angiotensin converting enzyme inhibitors, loop diuretics and less frequently angiotensin receptor blockers and mineralocorticoid receptor antagonists. CONCLUSIONS: Significant regional differences were noted in the etiology, comorbidities and treatment of female patients with HF despite similar risk factors. Such differences should be considered in the design and implementation of future clinical trials, especially as women remain underrepresented in large trial populations.

Comparison of self-care behaviors of heart failure patients in 15 countries worldwide.

OBJECTIVE: Clinicians worldwide seek to educate and support heart failure patients to engage in self-care. We aimed to describe self-care behaviors of patients from 15 countries across three continents. METHODS: Data on self-care were pooled from 5964 heart failure patients from the United States, Europe, Australasia and South America. Data on self-care were collected with the Self-care of Heart Failure Index or the European Heart Failure Self-care Behavior Scale. RESULTS: In all the samples, most patients reported taking their medications as prescribed but exercise and weight monitoring were low. In 14 of the 22 samples, more than 50% of the patients reported low exercise levels. In 16 samples, less than half of the patients weighed themselves regularly, with large differences among the countries. Self-care with regard to receiving an annual flu shot and following a low sodium diet varied most across the countries. CONCLUSION: Self-care behaviors are sub-optimal in heart failure patients and need to be improved worldwide. PRACTICE IMPLICATIONS: Interventions that focus on specific self-care behaviors may be more effective than general educational programs. Changes in some health care systems and national policies are needed to support patients with heart failure to increase their self-care behavior.

Determinants of change in quality of life in the Cardiac Insufficiency Bisoprolol Study in Elderly (CIBIS-ELD).

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.

Self-rated health predicts adverse events during ß-blocker treatment: the CIBIS-ELD randomised trial analysis.

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.

Sinus rhythm versus atrial fibrillation in elderly patients with chronic heart failure--insight from the Cardiac Insufficiency Bisoprolol Study in Elderly.

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-blockers were 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 from beta-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.

Effect of beta blockade on natriuretic peptides and copeptin in elderly patients with heart failure and preserved or reduced ejection fraction: results from the CIBIS-ELD trial.

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.

Is target dose the treatment target? Uptitrating beta-blockers for heart failure in the elderly.

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 naïve 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.

N-terminal pro-B-type natriuretic peptide and long-term mortality in non-ischaemic cardiomyopathy.

AIM: The inactive N-terminal fragment of B-type natriuretic peptide is a strong predictor of mortality among patients with acute and chronic heart failure secondary to ischaemic heart disease. Its prognostic utility in patients with non-ischaemic heart disease is not well established. We therefore assessed the relationship of N-terminal proBNP levels and long-term mortality in patients with non-ischaemic cardiomyopathy. METHODS: N-terminal proBNP was measured in serum samples of 156 patients who presented to a single academic centre with worsening heart failure secondary to non-ischaemic cardiomyopathy. The rate of death from all causes was determined after a mean follow-up of 8.9 years. RESULTS: Multivariate analyses, using Cox proportional hazards models, established NT-proBNP and left ventricular diastolic diameter as predictors for cardiac mortality with estimated hazard ratios of 2.76 (95% confidence interval: 1.53, 4.98) and 1.06 (95% confidence interval: 1.02, 1.10), respectively. CONCLUSION: This to date longest-term analysis of N-terminal proBNP and mortality in patients with proven non-ischaemic cardiomyopathy confirms this cardiac-specific biomarker as powerful, independent risk predictor. It is a superior prognostic determinant to New York Heart Association functional class and left ventricular ejection fraction.

Titration to target dose of bisoprolol vs. carvedilol in elderly patients with heart failure: the CIBIS-ELD trial.

AIMS: Various beta-blockers with distinct pharmacological profiles are approved in heart failure, yet they remain underused and underdosed. Although potentially of major public health importance, whether one agent is superior in terms of tolerability and optimal dosing has not been investigated. The aim of this study was therefore to compare the tolerability and clinical effects of two proven beta-blockers in elderly patients with heart failure. METHODS AND RESULTS: We performed a double-blind superiority trial of bisoprolol vs. carvedilol in 883 elderly heart failure patients with reduced or preserved left ventricular ejection fraction in 41 European centres. The primary endpoint was tolerability, defined as reaching and maintaining guideline-recommended target doses after 12 weeks treatment. Adverse events and clinical parameters of patient status were secondary endpoints. None of the beta-blockers was superior with regards to tolerability: 24% [95% confidence interval (CI) 20-28] of patients in the bisoprolol arm and 25% (95% CI 21-29) of patients in the carvedilol arm achieved the primary endpoint (P= 0.64). The use of bisoprolol resulted in greater reduction of heart rate (adjusted mean difference 2.1 b.p.m., 95% CI 0.5-3.6, P= 0.008) and more, dose-limiting, bradycardic adverse events (16 vs. 11%; P= 0.02). The use of carvedilol led to a reduction of forced expiratory volume (adjusted mean difference 50 mL, 95% CI 4-95, P= 0.03) and more, non-dose-limiting, pulmonary adverse events (10 vs. 4%; P < 0.001). CONCLUSION: Overall tolerability to target doses was comparable. The pattern of intolerance, however, was different: bradycardia occurred more often in the bisoprolol group, whereas pulmonary adverse events occurred more often in the carvedilol group. This study is registered with controlled-trials.com, number ISRCTN34827306.