Martje H.L. van der Wal

Effect of Moderate or Intensive Disease Management Program on Outcome in Patients With Heart Failure: Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure (COACH)

BACKGROUND Heart failure (HF) disease management programs are widely implemented, but data about their effect on outcome have been inconsistent. METHODS The Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure (COACH) was a multicenter, randomized, controlled trial in which 1023 patients were enrolled after hospitalization because of HF. Patients were assigned to 1 of 3 groups: a control group (follow-up by a cardiologist) and 2 intervention groups with additional basic or intensive support by a nurse specializing in management of patients with HF. Patients were studied for 18 months. Primary end points were time to death or rehospitalization because of HF and the number of days lost to death or hospitalization. RESULTS Mean patient age was 71 years; 38% were women; and 50% of patients had mild HF and 50% had moderate to severe HF. During the study, 411 patients (40%) were readmitted because of HF or died from any cause: 42% in the control group, and 41% and 38% in the basic and intensive support groups, respectively (hazard ratio, 0.96 and 0.93, respectively; P = .73 and P = .52, respectively). The number of days lost to death or hospitalization was 39 960 in the control group, 33 731 days for the basic intervention group (P = .81), and 34 268 for the intensive support group (P = .49). All-cause mortality occurred in 29% of patients in the control group, and there was a trend toward lower mortality in the intervention groups combined (hazard ratio, 0.85; 95% confidence interval, 0.66-1.08; P = .18). There were slightly more hospitalizations in the 2 intervention groups (basic intervention group, P = .89; and intensive support group, P = .60). CONCLUSIONS Neither moderate nor intensive disease management by a nurse specializing in management of patients with HF reduced the combined end points of death and hospitalization because of HF compared with standard follow-up. There was a nonsignificant, potentially relevant reduction in mortality, accompanied by a slight increase in the number of short hospitalizations in both intervention groups. Clinical Trial Registry http://trialregister.nl Identifier: NCT 98675639.

Non-compliance in patients with heart failure; how can we manage it?

Because of the improvement of the pharmacological and non‐pharmacological treatment in heart failure (HF) patients, the HF related therapeutic regimen is becoming more complicated. Non‐compliance with this regimen can result in worsening HF symptoms, sometimes leading to hospitalisation.

Design and methodology of the COACH study: a multicenter randomised Coordinating study evaluating Outcomes of Advising and Counselling in Heart failure.

While there are data to support the use of comprehensive non‐pharmacological intervention programs in patients with heart failure (HF), other studies have not confirmed these positive findings. Substantial differences in the type and intensity of disease management programs make it impossible to draw definitive conclusions about the effectiveness, optimal timing and frequency of interventions.

Development and testing of the Dutch Heart Failure Knowledge Scale.

Background: Heart failure (HF) knowledge as well as compliance are considered to be underlying mechanisms of the effects of HF management programs. However, there are no valid and reliable measurement instruments available which measures knowledge of HF patients. Aim: To develop a reliable and valid instrument, which measures the knowledge, patients have on their disease and the HF-related health care regimen. Methods: The HF knowledge scale was developed in 3 phases; (1) concept analysis and first construction, (2) revision of items and (3) testing for validity and reliability. Results: The Dutch HF knowledge scale is a 15-item, self-administered questionnaire that covers items concerning HF knowledge in general, knowledge on HF treatment (including diet and fluid restriction) and HF symptoms and symptom recognition. Face validity as well as content and construct validity was tested in HF patients in 19 hospitals in the Netherlands. The scale was able to differentiate between HF patients with high and low level of HF knowledge. Cronbachs α of the knowledge scale in this population (n = 902) was .62. Conclusion: The instrument is a valid and reliable scale that can be used in research to gain insight in the effect of education and counselling of HF patients. After additional testing, the instrument seems to be a valid and reliable scale to be used in clinical practice to measure HF knowledge.

Compliance with non-pharmacological recommendations and outcome in heart failure patients

AIMS The aim of this prospective study was to investigate the association between compliance with non-pharmacological recommendations (diet, fluid restriction, weighing, exercise) and outcome in patients with heart failure (HF). METHODS AND RESULTS In total 830 patients after an HF hospitalization participated in the study (age 70 +/- 11; left ventricular ejection fraction 34%). Compliance was measured 1 month after discharge; patients were followed for 18 months. Primary outcomes were the composite of death or HF readmission and the number of unfavourable days. Cox regression analysis was used to determine the association between primary outcome and compliance. Adjustments were made for those variables that were identified as confounders in the association between compliance and outcome. Patients who were non-compliant with at least one of the recommendations had a higher risk of mortality or HF readmission (HR 1.40; P = 0.01). Non-compliance with exercise was associated with an increased risk for mortality or HF readmission (HR 1.48; P < 0.01), while non-compliance with daily weighing was associated with an increased risk of mortality (HR 1.57; P = 0.02). Non-compliance (overall) and non-compliance with exercise were both associated with a higher risk for HF readmission [HR 1.38; P < 0.05(overall) and HR 1.55; P < 0.01(exercise)]. Patients who were overall non-compliant or with weighing and exercise had more unfavourable days than compliant patients. CONCLUSION Non-compliance with non-pharmacological recommendations in HF patients is associated with adverse outcome.

Prognostic Value of Plasma Neutrophil Gelatinase–Associated Lipocalin for Mortality in Patients With Heart Failure

Background —In patients with heart failure (HF), renal dysfunction is associated with a poor outcome. We aimed to assess the prognostic value of plasma Neutrophil Gelatinase Associated Lipocalin (NGAL), a novel marker of renal tubular damage, in HF patients with or without renal dysfunction, and compare it with two frequently used biomarkers of chronic kidney disease. Methods and Results —Plasma NGAL, estimated GFR (eGFR) and cystatin C were assessed in 562 heart failure patients. Chronic kidney disease was defined as eGFR<60 mL/min/1.73m2. Outcome was all-cause mortality at 36 months. Mean age was 71±11, 61% were men and 97% were in New York Heart Association functional class II/III. Mean baseline eGFR was 54±20 mL/min/1.73m2, mean cystatin C was 11.2 (7.7-16.2) mg/L and median plasma NGAL was 85 (60-123) ng/mL. Higher plasma NGAL levels were independently associated with an increased risk of all cause mortality, in patients with and without chronic kidney disease (HR (per SD increase in log NGAL)=1.45 [1.22-1.72], P<0.001 & HR=1.51 [1.06-2.16], P=0.023 respectively). Similarly, both in patients with high and low cystatin C (median cut-off), higher plasma NGAL levels were independently associated with an increased risk of all cause mortality. Moreover, when NGAL was entered in the multivariable risk prediction model, eGFR (P=0.616) and cystatin C (P=0.937) were no longer associated with mortality. Conclusions —Plasma NGAL predicts mortality in heart failure patients, both in patients with and without chronic kidney disease, and is a stronger predictor for mortality than the established renal function indices eGFR and cystatin C.Background— In patients with heart failure, renal dysfunction is associated with a poor outcome. We aimed to assess the prognostic value of plasma neutrophil gelatinase–associated lipocalin (NGAL), a novel marker of renal tubular damage, in patients with heart failure with or without renal dysfunction, and compare it with 2 frequently used biomarkers of chronic kidney disease. Methods and Results— Plasma NGAL, estimated glomerular filtration rate (eGFR), and cystatin C were assessed in 562 patients with heart failure. Chronic kidney disease was defined as eGFR<60 mL/min per 1.73 m2. Outcome was all-cause mortality at 36 months. Mean age was 71±11 years, 61% were men, and 97% were in New York Heart Association functional class II/III. Mean baseline eGFR was 54±20 mL/min per 1.73 m2, mean cystatin C was 11.2 (7.7–16.2) mg/L, and median plasma NGAL was 85 (60–123) ng/mL. Higher plasma NGAL levels were independently associated with an increased risk of all-cause mortality, in patients with and without chronic kidney disease (hazard ratio [per SD increase in log NGAL]=1.45 [1.22–1.72]; P<0.001 and hazard ratio=1.51 [1.06–2.16]; P=0.023, respectively). Similarly, both in patients with high and low cystatin C (median cut-off), higher plasma NGAL levels were independently associated with an increased risk of all-cause mortality. Moreover, when NGAL was entered in the multivariable risk prediction model, eGFR (P=0.616) and cystatin C (P=0.937) were no longer associated with mortality. Conclusions— Plasma NGAL predicts mortality in patients with heart failure, both in patients with and without chronic kidney disease and is a stronger predictor for mortality than the established renal function indices eGFR and cystatin C.

Prognostic Value of Plasma NGAL for Mortality in Heart Failure Patients

Background —In patients with heart failure (HF), renal dysfunction is associated with a poor outcome. We aimed to assess the prognostic value of plasma Neutrophil Gelatinase Associated Lipocalin (NGAL), a novel marker of renal tubular damage, in HF patients with or without renal dysfunction, and compare it with two frequently used biomarkers of chronic kidney disease. Methods and Results —Plasma NGAL, estimated GFR (eGFR) and cystatin C were assessed in 562 heart failure patients. Chronic kidney disease was defined as eGFR<60 mL/min/1.73m2. Outcome was all-cause mortality at 36 months. Mean age was 71±11, 61% were men and 97% were in New York Heart Association functional class II/III. Mean baseline eGFR was 54±20 mL/min/1.73m2, mean cystatin C was 11.2 (7.7-16.2) mg/L and median plasma NGAL was 85 (60-123) ng/mL. Higher plasma NGAL levels were independently associated with an increased risk of all cause mortality, in patients with and without chronic kidney disease (HR (per SD increase in log NGAL)=1.45 [1.22-1.72], P<0.001 & HR=1.51 [1.06-2.16], P=0.023 respectively). Similarly, both in patients with high and low cystatin C (median cut-off), higher plasma NGAL levels were independently associated with an increased risk of all cause mortality. Moreover, when NGAL was entered in the multivariable risk prediction model, eGFR (P=0.616) and cystatin C (P=0.937) were no longer associated with mortality. Conclusions —Plasma NGAL predicts mortality in heart failure patients, both in patients with and without chronic kidney disease, and is a stronger predictor for mortality than the established renal function indices eGFR and cystatin C.Background— In patients with heart failure, renal dysfunction is associated with a poor outcome. We aimed to assess the prognostic value of plasma neutrophil gelatinase–associated lipocalin (NGAL), a novel marker of renal tubular damage, in patients with heart failure with or without renal dysfunction, and compare it with 2 frequently used biomarkers of chronic kidney disease. Methods and Results— Plasma NGAL, estimated glomerular filtration rate (eGFR), and cystatin C were assessed in 562 patients with heart failure. Chronic kidney disease was defined as eGFR<60 mL/min per 1.73 m2. Outcome was all-cause mortality at 36 months. Mean age was 71±11 years, 61% were men, and 97% were in New York Heart Association functional class II/III. Mean baseline eGFR was 54±20 mL/min per 1.73 m2, mean cystatin C was 11.2 (7.7–16.2) mg/L, and median plasma NGAL was 85 (60–123) ng/mL. Higher plasma NGAL levels were independently associated with an increased risk of all-cause mortality, in patients with and without chronic kidney disease (hazard ratio [per SD increase in log NGAL]=1.45 [1.22–1.72]; P<0.001 and hazard ratio=1.51 [1.06–2.16]; P=0.023, respectively). Similarly, both in patients with high and low cystatin C (median cut-off), higher plasma NGAL levels were independently associated with an increased risk of all-cause mortality. Moreover, when NGAL was entered in the multivariable risk prediction model, eGFR (P=0.616) and cystatin C (P=0.937) were no longer associated with mortality. Conclusions— Plasma NGAL predicts mortality in patients with heart failure, both in patients with and without chronic kidney disease and is a stronger predictor for mortality than the established renal function indices eGFR and cystatin C.

Daily Physical Activity in Stable Heart Failure Patients

Background:Physical activity is the only nonpharmacological therapy that is proven to be effective in heart failure (HF) patients in reducing morbidity. To date, little is known about the levels of daily physical activity in HF patients and about related factors. Objective:The objectives of this study were to (a) describe performance-based daily physical activity in HF patients, (b) compare it with physical activity guidelines, and (c) identify related factors of daily physical activity. Methods:The daily physical activity of 68 HF patients was measured using an accelerometer (SenseWear) for 48 hours. Psychological characteristics (self-efficacy, motivation, and depression) were measured using questionnaires. To have an indication how to interpret daily physical activity levels of the study sample, time spent on moderate- to vigorous-intensity physical activities was compared with the 30-minute activity guideline. Steps per day was compared with the criteria for healthy adults, in the absence of HF-specific criteria. Linear regression analyses were used to identify related factors of daily physical activity. Results:Forty-four percent were active for less than 30 min/d, whereas 56% were active for more than 30 min/d. Fifty percent took fewer than 5000 steps per day, 35% took 5000 to 10 000 steps per day, and 15% took more than 10 000 steps per day. Linear regression models showed that New York Heart Association classification and self-efficacy were the most important factors explaining variance in daily physical activity. Conclusions:The variance in daily physical activity in HF patients is considerable. Approximately half of the patients had a sedentary lifestyle. Higher New York Heart Association classification and lower self-efficacy are associated with less daily physical activity. These findings contribute to the understanding of daily physical activity behavior of HF patients and can help healthcare providers to promote daily physical activity in sedentary HF patients.

Neurohormonal and clinical sex differences in heart failure

AIMS Despite disparities in pathophysiology and disease manifestation between male and female patients with heart failure, studies focusing on sex differences in biomarkers are scarce. The purpose of this study was to assess sex-specific variation in clinical characteristics and biomarker levels to gain more understanding of the potential pathophysiological mechanisms underlying sex differences in heart failure. METHODS AND RESULTS Baseline demographic and clinical characteristics, multiple biomarkers, and outcomes were compared between men and women in 567 patients. The mean age of the study group was 71 ± 11 years and 38% were female. Women were older, had a higher body mass index and left ventricular ejection fraction, more hypertension, and received more diuretic and antidepressant therapy, but less ACE-inhibitor therapy compared with men. After 3 years, all-cause mortality was lower in women than men (37.0 vs. 43.9%, multivariable hazard ratio = 0.64; 95% confidence interval 0.45-0.92, P = 0.016). Levels of biomarkers related to inflammation [C-reactive protein, pentraxin 3, growth differentiation factor 15 (GDF-15), and interleukin 6] and extracellular matrix remodelling (syndecan-1 and periostin) were significantly lower in women compared with men. N-terminal pro-brain natriuretic peptide, TNF-αR1a, and GDF-15 showed the strongest interaction between sex and mortality. CONCLUSION Female heart failure patients have a distinct clinical presentation and better outcomes compared with male patients. The lower mortality was independent of differences in clinical characteristics, but differential sex associations between several biomarkers and mortality might partly explain the survival difference.

Long-Term Compliance With Nonpharmacologic Treatment of Patients With Heart Failure

The aim of this study was to examine long-term compliance with nonpharmacologic treatment of patients with heart failure (HF) and its associated variables. Data from 648 hospitalized patients with HF (mean age 69 ± 12 years, 38% women, mean left ventricular ejection fraction 33 ± 14%) were analyzed. Compliance was assessed by means of self-report at baseline and 1, 6, 12, and 18 months after discharge. Patients completed questionnaires on depressive symptoms, HF knowledge, and physical functioning at baseline. Logistic regression analyses were performed to examine independent associations with low long-term compliance. From baseline to 18-month follow-up, long-term compliance with diet and fluid restriction ranged from 77% to 91% and from 72% to 89%, respectively. In contrast, compliance with daily weighing (34% to 85%) and exercise (48% to 64%) was lower. Patients who were in New York Heart Association functional class II were more often noncompliant with fluid restriction (odds ratio [OR] 1.97, 95% confidence interval [CI] 1.25 to 3.08). A lower level of knowledge on HF was independently associated with low compliance with fluid restriction (OR 0.78, 95% CI 0.71 to 0.86) and daily weighing (OR 0.86, 95% CI 0.79 to 0.94). Educational support improved compliance with these recommendations. Female gender (OR 1.91, 95% CI 1.26 to 2.90), left ventricular ejection fraction ≥40% (OR 1.55, 95% CI 1.03 to 2.34), a history of stroke (OR 3.55, 95% CI 1.54 to 8.16), and less physical functioning (OR 0.99, 95% CI 0.98 to 0.99) were associated with low compliance with exercise. In conclusion, long-term compliance with exercise and daily weighing was lower than long-term compliance with advice on diet and fluid restriction. Although knowledge on HF and being offered educational support positively affected compliance with weighing and fluid restriction, these variables were not related to compliance with exercise. Therefore, new approaches to help patients with HF stay physically active are needed.