Multimarker Analysis of Serially Measured GDF-15, NT-proBNP, ST2, GAL-3, cTnI, Creatinine, and Prognosis in Acute Heart Failure.

BACKGROUND: Studies on serially measured GDF-15 (growth differentiation factor 15) in acute heart failure (HF) are limited. Moreover, several pathophysiological pathways contribute to HF. Therefore, we aimed to explore the (additional) prognostic value of serially measured GDF-15 using a multi-marker approach to more accurately predict HF risk. METHODS: TRIUMPH (Translational Initiative on Unique and Novel Strategies for Management of Patients With Heart Failure) is a prospective cohort of 496 patients with acute HF who were enrolled in 14 hospitals in the Netherlands between 2009 and 2014. Blood sampling was scheduled at 7 moments during 1-year follow-up. GDF-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), ST2 (suppression of tumorigenicity 2), galectin-3, troponin I, and creatinine were measured in a central laboratory. We associated repeated measurements of these biomarkers with the composite primary end point of all-cause mortality and HF rehospitalization, using multivariable joint modeling. RESULTS: Median age was 74 years, and 37% were women. Median baseline GDF-15 was 4632 pg/mL. The primary end point was reached in 188 (40%) patients. The average estimated GDF-15 level increased weeks before the primary end point was reached. The hazard ratio per 1 SD difference in log-GDF-15 was 2.14 (95% CI, 1.78-2.57) unadjusted, 1.96 (1.49-2.53) after adjustment for clinical confounders and 1.44 (1.05-1.91) when jointly modeled with all biomarkers. The adjusted HRs for NT-proBNP were 2.38 (1.78-3.33) and 1.52 (1.15-2.08), respectively. The multimarker model combining GDF-15, NT-proBNP, and troponin I provided a favorable risk discrimination (area under the curve=0.785). CONCLUSIONS: Sequentially measured GDF-15 independently and dynamically predicts risk of adverse outcomes during 1-year follow-up after index admission for acute HF. NT-proBNP remains a robust predictor among potential candidates. Multiple biomarkers should be considered for stratification in clinical practice. REGISTRATION: URL: https://www.trialregister.nl/trial/1783; Unique Identifier: NTR1893. (The trial can be found temporarily at https://trialsearch.who.int/Trial2.aspx?TrialID=NTR1893.).

Family caregivers' perspectives on their interaction and relationship with people living with dementia in a nursing home: a qualitative study.

BACKGROUND: Social interactions are important for people living with dementia in a nursing home. However, not much is known about interactions and relationships between residents and family caregivers and related experiences of family caregivers. We aim to advance the knowledge on how family caregivers interact with people living with dementia in a nursing home and how they maintain or redesign a meaningful connection. METHODS: Qualitative research using interviews with family caregivers (n = 31) to explore perspectives on their interaction and relationship with the person living with dementia. Interviews were held during the reopening of nursing homes after the first COVID-19 lockdown in the Netherlands. In this situation, family caregivers became more aware of their interaction and relationship with the resident, which provided a unique opportunity to reflect on this. The interviews explored the interaction and relationship in a broad sense, not specifically for the COVID-19 situation. Thematic analysis was performed to analyze the data. RESULTS: We were able to identify three key themes reflecting the experiences of family caregivers: (1) changes in the interaction and relationship, (2) strategies to promote connection, and (3) appreciation of the interaction and relationship. From the viewpoint of family caregivers, the interaction and relationship are important for both the resident living with dementia and for themselves, and family caregivers have different strategies for establishing a meaningful connection. Nevertheless, some appear to experience difficulties with constructing such a connection with the resident. CONCLUSIONS: Our results provide a basis for supporting family caregivers in perceiving and establishing mutuality and reciprocity so that they can experience togetherness.

Reopening the doors of Dutch nursing homes during the COVID-19 crisis: results of an in-depth monitoring.

OBJECTIVES: On May 11, the Dutch Government allowed 26 nursing homes to welcome 1 visitor per resident, after 2 months of lockdown. The study aimed to monitor in-depth the feasibility of the regulations and their impact on the well-being of residents, their visitors, and healthcare staff. DESIGN: Mixed-methods study in 5 of the 26 facilities; the facilities were affiliated to an academic network of nursing homes. PARTICIPANTS: Visitors and healthcare professionals. INTERVENTION: Allowing visitors using local regulations based on national guidelines. MEASUREMENTS: Digital questionnaire, analyzing documentation such as infection prevention control protocols, attending meetings of COVID-19 crisis teams, in-depth telephone or in-person interviews with visitors and healthcare professionals, and on-site observations. RESULTS: National guidelines were translated with great variety into local care practice. Healthcare professionals agreed that reopening would increase the well-being of the residents and their loved ones. However, there were also great worries for increasing workload, increasing the risk of emotional exhaustion, and the risk of COVID-19 infections. Compliance with local regulations was generally satisfactory, but maintaining social distance and correctly wearing face masks appeared to be difficult. Care staff remained ambivalent for fear of infections. In general, allowing visitors was experienced as having a positive impact on the well-being of all stakeholders. Nevertheless, some residents with dementia showed negative effects. CONCLUSION: The complete lockdown of Dutch nursing homes had a substantial impact on the well-being of the residents. The reopening was welcomed by all stakeholders, but provided a high organizational workload as well as feelings of ambivalence among care staff. In the second wave, a more tailored approach is being implemented. However, facilities are sometimes still struggling to find the right balance between infection control and well-being.

Determinants of quality of life in acute heart failure patients with and without comorbidities: a prospective, observational study.

AIMS: The relation between non-cardiac comorbidities and health-related quality of life (HRQoL) in patients with heart failure (HF) has been studied to a limited extent. To investigate the HRQoL and their determinants among HF patients with and without comorbidities. METHODS AND RESULTS: TRIUMPH (TRanslational Initiative on Unique and novel strategies for Management of Patients with Heart failure) is a Dutch prospective, multicentre study enrolling 496 acute HF patients between 2009 and 2014. We included 334 patients who had completed the HRQoL questionnaires at baseline. The HRQoL was measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) en EuroQuality-of-life five Dimensions (EQ-5D). Comorbidity was defined as having a history of at least one of the following comorbidities: chronic kidney disease, diabetes mellitus, chronic obstructive pulmonary disease (COPD), and/or cerebrovascular accident. Patients with comorbidity (n = 205, 61%) had lower scores on the physical limitation scale and clinical summary score of the KCCQ (P = 0.03 and P = 0.01, respectively). Female sex, COPD, previous HF, increasing body mass index (BMI), elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP), high systolic blood pressure, and the presence of anxiety and/or depression negatively influenced the HRQoL among HF patients with comorbidity. Besides anxiety and depression, we hardly found any other determinant of HRQoL in patients without comorbidity. CONCLUSION: Heart failure patients without comorbidity had better HRQoL than patients with comorbidity. Sex, previous HF, BMI, COPD, systolic blood pressure, NT-proBNP levels, and also anxiety and depression were determinants of HRQoL in patients with comorbidity. In those without comorbidity, apart from anxiety and depression, no further determinants of HRQoL were found.

Vibration threshold in non-diabetic subjects.

Measuring vibration perception threshold (VPT) accurately classifies and quantifies the severity of loss of vibration perception. A biothesiometer (Bio-thesiometer®; Bio Medical Instrument Co, Ohio, USA) appears to be the most suitable tool to determine VPT due to its low inter-rater variability and low occurence of adaption to the sensation. Different VPT values for a biothesiometer have been described, however, specification on age, height and different measurement locations is currently lacking. The objective of our study was to identify determinants of vibration perception in non-diabetic subjects, in order to provide individualized normal values of VPTs for clinical practice. Measurements of the vibration perception were performed on the big toes, insteps, lateral malleoli, and wrists. A total of 205 healthy subjects were included (108 (52.7%) males) with a median [interquartile range] age of 59 [51;64] (range 21-80) years. Mean height was 174.45 ± 9.20 cm and mean weight was 82.94 ± 14.84 kg, resulting in a mean BMI of 27.19 ± 4.00 kg/m2. In stepwise forward linear regression analyses, age (st. ß = 0.51, p < 0.001) and height (st. ß = 0.43, p < 0.001) were found to be the independent unmodifiable determinants of the VPT at the big toe. Regression coefficients for quantiles of the determinants age and height were incorporated in the corresponding regression equations. This study provides equations to calculate age- and height-specific normal values for VPT that can be used in clinical practice and in large research studies.

Patients with heart failure with and without a history of stroke in the Netherlands: a secondary analysis of psychosocial, behavioural and clinical outcomes up to three years from the COACH trial.

OBJECTIVE: To identify differences in psychosocial, behavioural and clinical outcomes between patients with heart failure (HF) with and without stroke. DESIGN AND PARTICIPANTS: A secondary analysis of 1023 patients with heart failure enrolled in the Coordinating study evaluating Outcomes of Advising and Counselling in Heart failure. SETTING: Seventeen hospitals located across the Netherlands. OUTCOMES MEASURES: Depressive symptoms (Centre for Epidemiological Studies Depression Scale), quality of life (Minnesota Living with Heart Failure Questionnaire, Ladder of Life Scale), self-care (European Heart Failure Self-Care Behaviour Scale), adherence to HF management (modified version of the Heart Failure Compliance Questionnaire) and readmission for HF, cardiovascular-cause and all-cause hospitalisations at 18 months, and all-cause mortality at 18 months and 3 years. RESULTS: Compared with those without stroke, patients with HF with a stroke (10.3%; n=105) had twice the likelihood of severe depressive symptoms (OR 2.83, 95% CI 1.27 to 6.28, p=0.011; OR 2.24, 95% CI 1.03 to 4.88, p=0.043) at 12 and 18 months, poorer disease-specific and generic quality of life (OR 2.80, 95% CI 1.61 to 4.84, p<0.001; OR 2.00, 95% CI 1.09 to 3.50, p=0.019) at 12 months, poorer self-care (OR 1.80, 95% CI 1.05 to 3.11, p=0.034; OR 2.87, 95% CI 1.61 to 5.11, p<0.0011) and HF management adherence (OR 0.39, 95% CI 0.18 to 0.81, p=0.012; OR 0.35, 95% CI 0.17 to 0.72, p=0.004) at 12 and 18 months, higher rates of hospitalisations and mortality at 18 months and higher all-cause mortality (HR 1.43, 95% CI 1.07 to 1.91, p=0.016) at 3 years. CONCLUSIONS: Patients with HF and stroke have worse psychosocial, behavioural and clinical outcomes, notably from 12 months, than those without stroke. To ameliorate these poor outcomes long-term, integrated disease management pathways are warranted.

Research Costs Investigated: A Study Into the Budgets of Dutch Publicly Funded Drug-Related Research.

BACKGROUND: The costs of performing research are an important input in value of information (VOI) analyses but are difficult to assess. OBJECTIVE: The aim of this study was to investigate the costs of research, serving two purposes: (1) estimating research costs for use in VOI analyses; and (2) developing a costing tool to support reviewers of grant proposals in assessing whether the proposed budget is realistic. METHODS: For granted study proposals from the Netherlands Organization for Health Research and Development (ZonMw), type of study, potential cost drivers, proposed budget, and general characteristics were extracted. Regression analysis was conducted in an attempt to generate a 'predicted budget' for certain combinations of cost drivers, for implementation in the costing tool. RESULTS: Of 133 drug-related research grant proposals, 74 were included for complete data extraction. Because an association between cost drivers and budgets was not confirmed, we could not generate a predicted budget based on regression analysis, but only historic reference budgets given certain study characteristics. The costing tool was designed accordingly, i.e. with given selection criteria the tool returns the range of budgets in comparable studies. This range can be used in VOI analysis to estimate whether the expected net benefit of sampling will be positive to decide upon the net value of future research. CONCLUSION: The absence of association between study characteristics and budgets may indicate inconsistencies in the budgeting or granting process. Nonetheless, the tool generates useful information on historical budgets, and the option to formally relate VOI to budgets. To our knowledge, this is the first attempt at creating such a tool, which can be complemented with new studies being granted, enlarging the underlying database and keeping estimates up to date.

Prognostic Value of Serial Galectin-3 Measurements in Patients With Acute Heart Failure.

BACKGROUND: Several clinical studies have evaluated the association between galectin-3 levels and outcome in patients with heart failure (HF). However, little is known about the predictive value of repeated galectin-3 measurements. This study evaluates the prognostic value of repeated time-dependent galectin-3 measurements in acute HF patients. METHODS AND RESULTS: In the TRIUMPH (Translational Initiative on Unique and Novel Strategies for Management of Patients with Heart Failure) clinical cohort study, 496 acute HF patients were enrolled in 14 hospitals in The Netherlands, between 2009 and 2014. Repeated blood samples (7) were drawn during 1-year follow-up. Associations between repeated biomarker measurements and the primary end point were assessed using a joint model. Median age was 74 years and 37% were women. The primary end point, composite of all-cause mortality and HF rehospitalization, was reached in 188 patients (40%), during a median follow-up of 325 days (interquartile range 85-401). The median baseline galectin-3 level was 24 ng/mL (interquartile range 18-34). The mean number of galectin-3 measurements available per patient was 4.3. After adjustment for clinical factors and N-terminal pro-brain natriuretic peptide, there was a weak association between baseline galectin-3 and risk of the primary end point. When repeated measurements were taken into account, the adjusted hazard ratio per 1 SD increase of the galectin-3 level (on the log2 scale) at any time point increased to 1.67 (95% confidence interval, 1.24-2.23, P<0.001). After additional adjustment for repeated N-terminal pro-brain natriuretic peptide measurements, the association remained statistically significant. CONCLUSIONS: Repeated galectin-3 measurements appeared to be a strong predictor of outcome in acute HF patients, independent of N-terminal pro-brain natriuretic peptide. Hence, galectin-3 may be helpful in clinical practice for prognostication and treatment monitoring.

Prognostic Value of Serial ST2 Measurements in Patients With Acute Heart Failure.

BACKGROUND: Several clinical studies have evaluated the association between ST2 and outcome in patients with heart failure (HF). However, little is known about the predictive value of frequently measured ST2 levels in patients with acute HF. OBJECTIVES: This study sought to describe the prognostic value of baseline and repeated ST2 measurements in patients with acute HF. METHODS: In the TRIUMPH (Translational Initiative on Unique and novel strategies for Management of Patients with Heart failure) clinical cohort study, 496 patients with acute HF were enrolled in 14 hospitals in the Netherlands between 2009 and 2014. Repeated blood samples (7) were drawn during 1-year follow-up. ST2 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured in a central laboratory. The primary endpoint was the composite of all-cause mortality and HF rehospitalization. Associations between repeated biomarker measurements and the primary endpoint were assessed using a joint model. RESULTS: Median age was 74 years, and 37% of patients were women. The primary endpoint was reached in 188 patients (40%) during a median follow-up of 325 days (interquartile range: 85 to 401). The median baseline ST2 level was 71 ng/ml (interquartile range: 46 to 102). After adjustment for clinical factors and NT-proBNP, baseline ST2 was associated with an increased risk of the primary endpoint, and the hazard ratio per 1 SD increase of the baseline ST2 level (on the log2 scale) was 1.30 (95% confidence interval: 1.08 to 1.56; p = 0.005). When repeated measurements were taken into account, the adjusted hazard ratio per 1 SD increase of the ST2 level (on the log2 scale) during follow-up increased to 1.85 (95% confidence interval: 1.02 to 3.33; p = 0.044), adjusted for clinical factors and repeated measurements of NT-proBNP. Furthermore, ST2 levels appeared to elevate several weeks before the time of the primary endpoint. CONCLUSIONS: Repeated ST2 measurements appeared to be a strong predictor of outcome in patients with acute HF, independent of repeatedly measured NT-proBNP. Hence ST2 may be helpful in clinical practice for prognostication and treatment monitoring. (TRanslational Initiative on Unique and novel strategies for Management of Patients with Heart failure [TRIUMPH]; NTR1893).

Time-course of depressive symptoms in patients with heart failure.

BACKGROUND: It is unclear how depressive symptoms in patients with heart failure develop over time and whether this trajectory of depressive symptoms is associated with hospital admission and prognosis. AIM: To describe the time-course of depressive symptoms and determine the relationship with hospitalisation and mortality. METHOD: Data was analysed using 611 patients with completed CES-D questionnaires at baseline and at 18 months. Data on hospitalisation was collected 18 months after discharge and data on mortality was collected 18 and 36 months post-discharge. RESULTS: A total of 140 (61%) of the 229 patients with depressive symptoms at discharge had recovered from depressive symptoms after 18 months whereas 71 (18%) of the 382 non-depressed developed depressive symptoms and 89 (39%) of the 229 depressed remained depressed. Patients with recently (i.e. during the last 18 months) developed depressive symptoms showed a significantly higher risk for cardiovascular hospitalisation (HR 1.7, 95% CI 1.1-2.6, P=.016). After 36 months, patients with developed depressive symptoms after discharge were at a higher risk of all-cause mortality (HR 2.0, 95% CI 1.2-3.5, P=.012) and there was a trend towards a higher risk of all-cause mortality in patients with ongoing depressive symptoms (HR 1.7, 95% CI 0.98-3.1, P=.056). CONCLUSION: A significant proportion of patients with HF, who were reported depressive symptoms at discharge recovered from depressive symptoms during the following 18 months. However, patients who remained having depressive symptoms or patients who developed depressive symptoms had a worse prognosis.

Quality of life and survival in patients with heart failure.

AIMS: To examine whether self-rated disease-specific and generic quality of life predicts long-term mortality, independent of brain natriuretic peptide (BNP) levels, and to explore factors related to low quality of life in a well-defined heart failure (HF) population. METHODS AND RESULTS: A cohort of 661 patients (62% male; age 71 years; left ventricular ejection fraction 34%) was followed prospectively for 3 years. Quality of life questionnaires (Ladder of Life, RAND36, and Minnesota Living with Heart Failure Questionnaire) and BNP levels were assessed at discharge after a hospital admission for HF. Three-year mortality was 42%. After adjustment for demographic variables, clinical variables, and BNP levels, poor quality of life scores predicted higher mortality; per 10 units on the physical functioning [hazard ratio (HR) 1.08, 95% confidence interval (CI) 1.02-1.14] and general health (HR 1.08, 95% CI 1.01-1.16) dimensions of the RAND36. Patients with low scores on these dimensions were more likely to be in New York Heart Association class III-IV, diagnosed with co-morbidities, have suffered longer from HF, have lower estimated glomerular filtration rates, and have fewer beta-blocker prescriptions. CONCLUSION: Quality of life was independently related to survival in a cohort of hospitalized patients with HF. TRIAL REGISTRATION: NCT 98675639.

Sexual problems in elderly male and female patients with heart failure.

OBJECTIVES: To investigate perceived sexual problems in a large group of younger and older patients with heart failure (HF), with and without a partner, focusing on a broad range of perceived sexual problems, and compare this with a sample of healthy community-dwelling elderly people. DESIGN: Cross-sectional study. SETTING: 17 HF clinics and general practices in The Netherlands. PARTICIPANTS: 438 patients with HF and 459 healthy community-dwelling elderly people. MAIN OUTCOME MEASURES: Differences in sexual functioning, related factors and perceived causes of sexual problems between patients with HF and healthy community controls. RESULTS: In total, 59% of HF patients reported sexual problems, mostly problems with erectile function. HF patients with a partner (67%) and younger patients (65%) reported significantly more sexual problems than healthy community controls (58%, p=0.011 and 53%, p=0.011, respectively). Multivariate analyses show that sexual problems in HF patients with a partner were more common in men (OR 2.73, 95% CI 1.572 to 4.753) and in those with a prescription of ß-blockers (OR 2.00, 95% CI 1.10 to 3.586). In younger patients, sexual problems were independently associated with male gender (OR 3.21, 95% CI 2.099 to 4.908) and having a partner (OR 2.00, 95% CI 1.283 to 3.110). HF patients mainly attribute their sexual problems to symptoms of HF. CONCLUSION: Sexual problems are common in patients with HF, particularly in younger patients and those with a partner. As patients attribute their sexual problems mostly to HF symptoms, adequate treatment and education of HF patients is needed.

What keeps nurses from the sexual counseling of patients with heart failure?

OBJECTIVES: We sought to examine the current practice of discussing sexual health by heart failure (HF) nurses, and to explore which barriers prevent nurses from discussing sexuality. METHODS: The Nurses' Survey of Sexual Counseling of Myocardial Infarction Patients and a list of barriers were used to form a questionnaire, which was sent to all HF clinics (n = 122) in the Netherlands. RESULTS: The majority (75%) of nurses (n = 146) felt a certain responsibility to discuss patients' sexual health. However, in practice, 61% of the nurses rarely or never addressed sexuality. Barriers that prevented nurses from addressing sexuality and that differed between nurses who do (n = 58) and do not (n = 88) discuss sexuality include a lack of organizational policy (49% vs. 79%, respectively; P < .001) and lack of training (43% vs. 80%, respectively; P < .001), and not knowing how to initiate the subject (24% vs. 72%, respectively; P < .001). Nurses preferred to address sexuality during a follow-up visit or when discussing medication. CONCLUSIONS: Although HF nurses feel responsible for discussing sexuality, this topic is rarely addressed in clinics. Several barriers were identified, relating to personal, patient, and organizational factors.

Perceived sexual difficulties and associated factors in patients with heart failure.

BACKGROUND: Sexual dysfunction is a common problem of increasing incidence in patients with heart failure (HF). However, there is no knowledge on which demographic, clinical, and quality of life (QoL) aspects are related to difficulties in sexual activity nor on the course of sexual difficulties in patients with HF. METHODS: Data on sexual difficulties were collected at 1 and 18 months after an HF hospitalization (n = 792, mean age 69 ± 12 years, 35% female, mean left ventricular ejection fraction 33% ± 14%) by the question on sexuality of the Minnesota living with HF questionnaire. Demographic and clinical factors were assessed from medical records and QoL by Minnesota living with HF questionnaire, Medical Outcome Study 36-item General Health Survey, and Ladder of Life. RESULTS: In total, 48% (n = 380) of the patients perceive difficulties in sexual activity at 1 month after discharge, and 70% continued to perceive this at 18 months. Furthermore, 27% of the patients without difficulties at 1 month developed them during follow-up. Living with a partner (OR 3.76, 95% CI 2.58-5.48), younger age (OR 0.96, 95% CI 0.94-0.97)), male gender (OR 3.08, 95% CI 2.10-4.43), overall well-being (OR 1.13, 95% CI 1.00-1.27), and physical (OR 1.06, 95% CI 1.06-1.08) and emotional (OR 1.07, 95% CI 1.03-1.10) QoL were independently associated with perceived difficulties in sexual activity. CONCLUSIONS: Perceived difficulties in sexual activity are common in patients with HF, particularly in younger and male patients and continue over time. Patients who perceive difficulties in sexual activity report a significant lower QoL and overall well-being than those who do not.

Quality of life is impaired similarly in heart failure patients with preserved and reduced ejection fraction.

AIMS: To compare quality of life (QoL) in heart failure (HF) patients with preserved ejection fraction (HF-PEF) and HF patients with reduced ejection fraction (HF-REF) in a well-defined HF population. METHODS AND RESULTS: Patients with HF-PEF [left ventricular ejection fraction (LVEF) ≥40%] were matched by age and gender to patients with HF-REF (LVEF <40%). In the current study, we only included HF patients with a B-type natriuretic peptide level (BNP) >100 pg/mL. Quality of life was assessed by Cantril's Ladder of Life, RAND-36, and the Minnesota Living with Heart Failure questionnaire, and impairment of QoL was adjusted for by BNP as a marker for severity of HF. We examined a total of 290 HF patients, of whom 145 had HF-PEF (41% female; age 72 ± 10; LVEF 51 ± 8%) and 145 had HF-REF (41% female; age 73 ± 10, LVEF 26 ± 7%). All HF patients reported markedly low scores of QoL, both on the general and disease-specific QoL questionnaires. Quality of life between patients with HF-PEF and HF-REF did not differ significantly. When adjusting the QoL scores for BNP, an association between QoL and LVEF was not found, i.e. patients with HF-PEF and HF-REF with similar BNP levels had the same impairment in QoL. CONCLUSION: Quality of life is similarly impaired in patients with HF-PEF as in HF-REF. These findings further support the need for more pharmacological and non-pharmacological studies in patients with HF-PEF. TRIAL REGISTRATION NUMBER: NCT 98675639.

Depressive symptoms and inflammation in patients hospitalized for heart failure.

BACKGROUND: Depressive symptoms in patients with heart failure (HF) are common and might be associated with inflammation. No studies have examined both the cross-sectional and prospective association between inflammation and depressive symptoms in patients with HF with adequate correction for disease severity. The aim of this study was to describe if the cytokines interleukin-6 (IL-6) and C-reactive protein (CRP) are associated with depressive symptoms in hospitalized HF patients. METHODS: Data from 517 patients hospitalized for HF from the COACH study were analyzed on inflammation markers (IL-6 and CRP) and depressive symptoms (Center for Epidemiological Studies Depression-Scale). RESULTS: Heart failure patients with depressive symptoms (n = 208, 40%) had significantly higher plasma values of IL-6 (median 12.8 pg/mL vs median 11.0 pg/mL, P = .018) and CRP (median 2.4 mg/mL vs median 2.1 mg/mL, P = .03) compared with the nondepressed patients. Structural equation modelling showed that the factor inflammation (including IL-6 and CRP) was associated with depressive symptoms (ß = 0.18, P < .05) when left ventricular ejection fraction and plasma values brain natriuretic peptides were included in the model. A small negative (ß = -0.18, P < .05) effect was found between inflammation at baseline and the change in depressive symptoms during the 18 months of follow-up. CONCLUSIONS: Higher levels of inflammatory markers are independently associated with depressive symptoms in HF patients, even after correcting for disease severity. There is no clear relationship between inflammation at baseline and depressive symptoms during the 18 months of follow-up.

Depression and the delay between symptom onset and hospitalization in heart failure patients.

AIMS: Heart failure (HF) patients frequently suffer from episodes of deterioration and may need medical treatment. An adequate reaction from the patient is needed to decrease the delay between the onset of deterioration and consulting a medical professional (i.e. consulting behaviour). The aim of the present study was to evaluate whether depressive symptoms are associated with the duration of the delay between the onset of symptoms of worsening HF and hospitalization, and to examine how consulting behaviour correlates to depressive symptoms and delay in HF patients. METHODS AND RESULTS: Data on the time between the onset of symptoms of worsening HF and hospitalization, depressive symptoms, and self-care behaviour were collected in 958 HF patients (37% female; age 71 ± 11 years; New York Heart Association functional class II-IV), using validated questionnaires. The median delay time of the total sample was 72 h (ranging from 0 to 243 days). Patients with depressive symptoms delayed longer compared with those without depressive symptoms (120 vs. 54 h, P= 0.001). Patients with depressive symptoms had a 1.5 times higher risk for a delay of ≥ 72 h, independent of demographic and clinical variables (P= 0.008). Consulting behaviour did not correlate with depressive symptoms but was weakly associated with delay (r= -0.07, P= 0.03). CONCLUSIONS: Heart failure patients with depressive symptoms have a significantly longer delay between HF deterioration and hospital admission. Interventions designed to improve the consulting behaviour in HF patients with depressive symptoms may have a limited effect on delay. Further research is needed to obtain more insight into the mechanisms underlying the relationship between delay and depression.

Depression and the usefulness of a disease management program in heart failure: insights from the COACH (Coordinating study evaluating Outcomes of Advising and Counseling in Heart failure) study.

OBJECTIVES: Our aim was to study the possible role of depressive symptoms in the effectiveness of a disease management program (DMP) in heart failure (HF) patients. BACKGROUND: Disease management programs are recommended in current HF guidelines, but certain patient groups, such as those with depression, might be less responsive to such programs. METHODS: From the data of a large multicenter study, in which we examined the effect of a DMP in HF patients, we investigated a potential interaction between depressive symptoms at baseline and the effect of such a program. RESULTS: Of the 958 HF patients (37% female; age 71 +/- 11 years; New York Heart Association functional class II to IV), 377 (39%) reported depressive symptoms at baseline. During 18 months of follow-up, the primary end point (composite of all-cause mortality and HF readmission) occurred in 39% of the nondepressed patients and 42% of depressed patients. In the overall sample, there was no significant effect of DMP on the composite primary end point. The effect of the DMP was significantly different in nondepressed than in depressed HF patients. A significant effect modification by depressive symptoms was observed in evaluating the effect of the DMP on all-cause mortality and HF readmission (p = 0.03). In patients without depressive symptoms, DMP resulted in a trend for lower incidence of the primary end point (hazard ratio: 0.8, 95% confidence interval: 0.61 to 1.04), whereas the reverse was observed in patients with depressive symptoms (hazard ratio: 1.3, 95% confidence interval: 0.95 to 1.98). CONCLUSIONS: Depressive symptoms in patients with HF have a major effect on the usefulness of DMP. Identification of depressive symptoms before enrollment in a DMP might lead to more accurate use of a DMP, because depressive patients might not benefit from a general program. (Netherlands Heart Foundation Coordinating study evaluating Outcomes of Advising and Counselling in Heart Failure; ISRCTN98675639).

Nurse-led interventions in heart failure care: patient and nurse perspectives.

BACKGROUND: Perspectives of nurses and patients on the intensity and content of disease management programmes (DMPs) in heart failure are seldom addressed but are important in optimizing these programmes. AIM: To describe the perspectives of patients and nurses on delivered care in two DMPs. METHODS: In total 442 patients (62% male; age 68±12years; LVEF 33%±14), assigned to the intervention groups of the Coordinating Study Evaluating Outcomes of Advising and Counselling in HF (COACH), and 32 registered nurses, completed questionnaires on satisfaction with the intensity and components of the DMPs. RESULTS: In spite of large differences in intensity and components, patients were satisfied with the content of both DMPs. In patients (NYHA III-IV), treatment and educational goals were more often achieved in those who received intensive support, compared to patients who received basic support (85% vs. 70%). Patients and nurses perceived that most home visits were adding significant value to the HF care, while 12% of the home visits were perceived as unnecessary by the nurses. CONCLUSION: Patients and nurses did not perceive the intense DMP as an emotional and physical burden for themselves. Patients with severe HF might be in need of more support to achieve optimal treatment and educational goals.