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Background: Previous systematic reviews have indicated that exercise-based cardiac rehabilitation (ExCR) for patients with heart failure (HF) has a beneficial effect on health-related quality-of-life (HRQoL) and exercise capacity. However, there is uncertainty regarding potential differential effects of ExCR across HF patient subgroups., Objectives: The authors sought to undertake an individual participant data (IPD) meta-analysis to: 1) assess the impact of ExCR on HRQoL and exercise capacity in patients with HF; and 2) investigate differential effects of ExCR according to a range of patient characteristics: age, sex, ethnicity, New York Heart Association functional class, ischemic etiology, ejection fraction, and exercise capacity., Methods: A single dataset was produced, comprising randomized trials where ExCR (delivered for 3 weeks or more) was compared with a no exercise control group. Each trial provided IPD on HRQoL or exercise capacity (or both), with follow-up of 6 months or more. One- and 2-stage meta-analysis models were used to investigate the effect of ExCR overall and the interactions between ExCR and participant characteristics., Results: IPD was obtained from 13 trials for 3,990 patients, predominantly (97%) with reduced ejection fraction HF. Compared with the control group, there was a statistically significant difference in favor of ExCR for HRQoL and exercise capacity. At 12-month follow-up, improvements were seen in 6-min walk test (mean 21.0 m; 95% confidence interval: 1.57 to 40.4 m; p = 0.034) and Minnesota Living With HF score (mean improvement 5.9; 95% confidence interval: 1.0 to 10.9; p = 0.018). No consistent evidence was found of differential intervention effects across patient subgroups., Conclusions: These results, based on an IPD meta-analysis of randomized trials, confirm the benefit of ExCR on HRQoL and exercise capacity and support the Class I recommendation of current international clinical guidelines that ExCR should be offered to all HF patients. (Exercise Training for Chronic Heart Failure [ExTraMATCH II]: protocol for an individual participant data meta-analysis; PROSPERO: international database of systematic reviews CRD42014007170)., (Copyright © 2019. Published by Elsevier Inc.)

Aims: To undertake an individual patient data (IPD) meta-analysis to assess the impact of exercise-based cardiac rehabilitation (ExCR) in patients with heart failure (HF) on mortality and hospitalisation, and differential effects of ExCR according to patient characteristics: age, sex, ethnicity, New York Heart Association functional class, ischaemic aetiology, ejection fraction, and exercise capacity., Methods and Results: Randomised trials of exercise training for at least 3 weeks compared with no exercise control with 6-month follow-up or longer, providing IPD time to event on mortality or hospitalisation (all-cause or HF-specific). IPD were combined into a single dataset. We used Cox proportional hazards models to investigate the effect of ExCR and the interactions between ExCR and participant characteristics. We used both two-stage random effects and one-stage fixed effect models. IPD were obtained from 18 trials including 3912 patients with HF with reduced ejection fraction. Compared to control, there was no statistically significant difference in pooled time to event estimates in favour of ExCR although confidence intervals (CIs) were wide [all-cause mortality: hazard ratio (HR) 0.83, 95% CI 0.67-1.04; HF-specific mortality: HR 0.84, 95% CI 0.49-1.46; all-cause hospitalisation: HR 0.90, 95% CI 0.76-1.06; and HF-specific hospitalisation: HR 0.98, 95% CI 0.72-1.35]. No strong evidence was found of differential intervention effects across patient characteristics., Conclusion: Exercise-based cardiac rehabilitation did not have a significant effect on the risk of mortality and hospitalisation in HF with reduced ejection fraction. However, uncertainty around effect estimates precludes drawing definitive conclusions., (© 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.)

Background: Little is known about the optimum way to deliver exercise to older, functionally impaired patients with heart failure. We tested whether an exercise program tailored to the needs of these patients could improve exercise capacity and quality of life or reduce costs to the National Health Service., Methods and Results: The study design was a parallel-group, single-blind, randomized controlled trial. Patients aged ≥70 years with symptomatic heart failure and left ventricular systolic dysfunction were randomized to either 24 weeks of exercise training or usual care. Six-minute walk distance was the primary outcome; markers of physical function, quality of life, health status, and daily activity were measured at baseline and 8 and 24 weeks. Carer strain and healthcare costs were also recorded. A total of 107 participants were randomized (mean age, 80 years; men, 72 [67%]). Six-minute walk distance did not improve compared to that of the control group at 8 weeks (-16.9 m; 95% CI, -41.8 to 7.9 m; P=0.18) or at 24 weeks (-5.3 m; 95% CI, -32.6 to 22.0 m; P=0.70). For secondary outcomes, only the sit-to-stand test improved significantly at 24 weeks (-6.4 s; 95% CI, -12.2 to 0.6 s; P=0.03); there was no difference in change for the Minnesota Living With Heart Failure score (0.1 points; 95% CI, -0.9 to 1.1 points; P=0.83) at 24 weeks. Carer strain did not decrease at 24 weeks (difference, -0.5 points; 95% CI, -8.3 to 7.3 points; P=0.80), and there was no difference in overall healthcare costs., Conclusions: This exercise intervention did not improve exercise capacity or quality of life in older patients with heart failure and was not cost saving to the National Health Service. Clinical Trial Registration- URL: http://www.controlled-trials.com. Unique identifier: ISRCTN51615566.

Recent evidence suggests a number of mechanisms whereby vitamin D may positively influence the pathophysiology of heart failure. These include actions on the renin-angiotensin system, calcium handling, reduction of proinflammatory cytokines, and improvements in endothelial function and blood pressure. Observational data suggest that low vitamin D levels are common in patients with heart failure and are associated with worse exercise capacity and natriuretic peptide levels. Little interventional data are currently available, but evidence to date does not support vitamin D supplementation, even in patients with low vitamin D levels. Further studies are needed to establish whether larger doses of vitamin D given over a longer period of time can reduce symptoms, hospitalization, and mortality in heart failure.

Background: Low 25-hydroxyvitamin D levels, commonly found in older patients with heart failure, may contribute to the chronic inflammation and skeletal myopathy that lead to poor exercise tolerance. We tested whether vitamin D supplementation of patients with heart failure and vitamin D insufficiency can improve physical function and quality of life., Methods and Results: In a randomized, parallel group, double-blind, placebo-controlled trial, patients with systolic heart failure aged >or=70 years with 25-hydroxyvitamin D levels <50 nmol/L (20 ng/mL) received 100,000 U of oral vitamin D2 or placebo at baseline and 10 weeks. Outcomes measured at baseline, 10 weeks, and 20 weeks were 6-minute walk distance, quality of life (Minnesota score), daily activity measured by accelerometry, Functional Limitations Profile, B-type natriuretic peptide, and tumor necrosis factor-alpha. Participants in the vitamin D group had an increase in their 25-hydroxyvitamin D levels compared with placebo at 10 weeks (22.9 versus 2.3 nmol/L [9.2 versus 0.9 ng/mL]; P<0.001) and maintained this increase at 20 weeks. The 6-minute walk did not improve in the treatment group relative to placebo. No significant benefit was seen on timed up and go testing, subjective measures of function, daily activity, or tumor necrosis factor. Quality of life worsened by a small, but significant amount in the treatment group relative to placebo. B-type natriuretic peptide decreased in the treatment group relative to placebo (-22 versus +78 pg/mL at 10 weeks; P=0.04)., Conclusions: Vitamin D supplementation did not improve functional capacity or quality of life in older patients with heart failure with vitamin D insufficiency. Clinical Trial Registration- www.controlled-trials.com. Identifier: ISRCTN51372896.

Aims: Patient beliefs about heart failure (HF) may be important determinants of adherence. This study assessed levels of adherence to angiotensin-converting-enzyme inhibitors (ACEI) and examined whether beliefs about HF were associated with adherence to ACEI., Methods and Results: Fifty-eight patients with chronic stable HF (mean age 80.2 years SD +/- 4.6, 43% female) were recruited from two outpatient clinics in Dundee, UK. The Illness Perception Questionnaire-Revised was used to assess beliefs about HF. Adherence to ACEI was assessed by measuring serum levels of angiotensin-converting enzyme (sACE). Adherence to ACEI (defined as sACE <5 U/L) was 72%. Beliefs about the time-line of HF and the consequences of HF accounted for 19% of the variability in adherence to ACEI in this sample. Heart failure patients who believed that their illness had a more chronic (longer term) time frame and had beliefs about the greater consequences of HF on their lives were less likely to adhere to ACEI., Conclusion: Adherence to ACEI is sub-optimal. Beliefs about HF appear to be associated with objectively measured adherence to ACEI. Future studies should attempt to identify beliefs that consistently predict adherence and examine whether modifying these beliefs can increase adherence to HF medications.

Background: Most studies of exercise training for heart failure have been conducted on relatively young patients with little comorbidity. Such programmes are unsuitable for the majority of older frail heart failure patients., Aims: To test the acceptability and tolerability of an outpatient exercise programme in older heart failure patients with comorbid disease., Methods: 17 patients aged 70 years and over with left ventricular systolic dysfunction attended twice weekly group exercise classes for 12 weeks, focussing on endurance exercise and everyday functional tasks. Outcome measures were proportion of sessions attended; adverse events and reasons for non-attendance; six-minute walk, accelerometry, hospital depression and anxiety score, Guyatt quality of life scale, carer strain and satisfaction scores., Results: 83% of sessions were attended; 80% of subjects attended at least 80% of allocated sessions. One adverse incident occurred in 324 person-sessions. Encouraging improvements were seen in six minute walk test (+19 m, p=0.14) and in Functional Limitation Profile score (-82 points, p=0.02). 50% of informal carers attended at least one session. No increase in carer strain was noted., Conclusions: Twice-weekly group exercise focussing on aerobic endurance and everyday functional tasks was acceptable and well-tolerated in this patient group.

Objectives: The demand-control (D-C) model of job strain has generated a considerable body of empirical support in predicting psychological health outcomes in the context of work. This study aimed to extend previous work using the D-C model of job strain to predict caregiver burden and satisfaction in the informal caregivers of patients with heart failure., Design and Method: Data were gathered from 60 caregiver/patient dyads in a cross-sectional design. Patients with chronic stable heart failure were recruited from out-patient clinics. The dependent variables were caregiver burden and satisfaction. Demand and control were measured using both patient- and caregiver-derived measures., Results: The D-C model accounted for 15 and 19% of the variance in caregiver burden, after controlling for age, gender and relationship to the patient. Lower control was associated with higher burden. The D-C model did not predict caregiver satisfaction., Conclusion: The D-C model was associated with caregiver burden, but not satisfaction in caregivers, with control being the dominant predictor. Research linking the theory and findings from job strain and informal caregiving studies may elucidate both fields of research. Using the demand-control model of job strain to predict caregiver burden and caregiver satisfaction in the informal caregivers of heart failure patients.

Background: Little information exists about diet in the management of heart failure., Aims: To describe the nutritional and biochemical status, and the dietary intake of older heart failure patients., Methods: Stable outpatients and patients with recent hospitalisation for decompensated heart failure were recruited. Anthropometric measurements, handgrip strength, biochemical values and echocardiography were recorded. Patients kept 7-day food diaries and completed questionnaires concerning food provision., Results: Forty-five patients with a mean (S.D.) age of 80.8 (6.8) years were studied and classed according to the New York Heart Association (NYHA) (11% Class I, 27% Class II and 62% Class III). Mean (S.D.) body mass index (BMI) was 27.1 (5.4) kg/m(2) with 7% of patients having a BMI<20 kg/m(2) and 56% with a BMI above 25 kg/m(2). 64% of participants failed to achieve the estimated average requirements for energy intake; 82% took more than 2 mg of sodium daily; and 18% had a potassium intake above 3500 mg/day. Only 29% of individuals did not need assistance with food shopping, whilst 58% required assistance with meal preparation., Conclusion: Possible targets for dietary intervention in older heart failure patients have been identified but whether such changes would be beneficial to patients is unknown.

Little is known about how physical and psychological status changes with time in older heart failure patients. The authors followed up a cohort of 82 patients (mean age, 80.5 years) enrolled in a randomized controlled trial of exercise training in heart failure. Six-minute walk test, accelerometry, functional status, quality of life, anxiety, and depression were measured at baseline, 3 months, 6 months, and a mean of 19 months post-enrollment. There were no significant differences between the exercise and control groups at long-term follow-up. Six-minute walk distance declined by only 0.2 m/month in those attending final follow-up (vs 4.6 m/month in nonattenders; P=.03). Similar results were seen for other outcomes. Only a small proportion of the variance in change of any of the outcomes was explained by differences in baseline variables.

Background: Existing tools purporting to measure quality of life in heart failure do not allow expression of individual needs and preferences. The Patient Generated Index is a recently introduced tool that allows individualised assessment of quality of life., Methods: 59 patients aged 65 years and over with a clinical diagnosis of chronic heart failure were administered the Patient Generated Index at baseline, 1 week and 12 weeks, along with the Guyatt chronic heart failure questionnaire, Minnesota Living with Heart failure questionnaire and Short Form-12 tool. Changes in questionnaire scores were used to calculate reproducibility and responsiveness to change. Comparison of Patient Generated Index scores with the other questionnaires and with New York Heart Association class was used to determine construct validity., Results: All four questionnaires were completed by >90% of participants. Intraclass correlation coefficients denoting reproducibility were high for the Guyatt (0.93) and Minnesota questionnaires (0.89), moderate for the Patient Generated Index (0.65) and Short Form-12 (0.59). Responsiveness to change was similar for all questionnaires, but lower than in previous studies. The Patient Generated Index correlated with New York Heart association class and correlated moderately with the other questionnaires. The most important domains nominated on the Patient Generated Index were walking, performing daily activities, feeling tired and climbing stairs., Conclusions: The Patient Generated Index can be administered successfully to older heart failure patients; usefulness is limited by suboptimal reproducibility and responsiveness. Impairment of physical function is the factor most cited by older heart failure patients affecting their quality of life.

Background: The impact of exercise programmes for heart failure on those close to the patient is largely unknown. We examined the effect of a hospital and home-based exercise intervention on burden, anxiety and depression of informal caregivers., Design: The study was a randomized, controlled trial. Heart failure patients were randomized to a seated 12-week hospital-based exercise programme. Caregiver measures were gathered at baseline, 3 months later and 6 months following baseline., Methods: Sixty caregivers (mean age 63.4 years, 65% female) of heart failure patients (n = 82, mean age 80.5 years, 44% female) participating in a trial of an exercise intervention were recruited. Caregiver burden, anxiety and depression were assessed., Results: There were no differences in caregiver burden, depression or anxiety between the two groups of caregivers at baseline (caregiver burden, patient control 33.1 versus patient exercise 34.1; anxiety 4.1 versus 5.5; depression 2.8 versus 3.8). At 3 months there were no differences between caregivers in the two groups on outcomes. At 6-month follow-up caregivers of heart failure patients in the exercise group had burden scores that were significantly worse than the control group. There were no differences between the carers of exercise and control groups in anxiety and depression. Levels of anxiety and depression in the entire carer sample were marginally higher than reference values in a healthy non-clinical sample., Conclusion: The present exercise interventions for frail older patients did not benefit caregivers and was associated with an increase in caregiver burden. We suggest that future exercise interventions for heart failure patients should actively incorporate informal caregivers into research designs.

Background: Exercise capacity and daily activity are key outcomes for older, frail heart failure patients. Little is known about the determinants of these outcomes in this patient group., Aims: To explore predictors of exercise capacity and daily activity in older, frail heart failure patients., Methods: Analysis of prospectively collected data from a cohort of 82 patients aged 70 years and over, enrolled in a randomised controlled trial of exercise in heart failure patients. Pathophysiological, demographic, psychological and social factors were analysed by multivariate regression to determine predictors of exercise capacity (6-min walk distance) and daily activity (daily accelerometer counts)., Results: Between 49% and 55% of the variance in 6-min walk distance was explained by variables including New York Heart Association class, depression score, attitude to ageing and use of walking aids. Only 11% to 26% of the variance in accelerometer scores was explained by the model; 6-min walk distance was the only consistent predictor of daily activity., Conclusions: Physical, psychological and attitudinal variables contribute to variance of the 6-min walk. Six-minute walk distance predicts a small amount of the variance in daily activity, but the majority of variance in daily activity remains unexplained and requires further investigation.

Background: There is increasing evidence that discharge planning and post-discharge support for CHF patients can contribute greatly to the medical management of heart failure (CHF) in the community and that the quality of the CHF patient's close personal relationships can influence outcome in CHF. However, there has been little research on the impact of CHF on the family or the role of the family in the management of the condition. In this paper, we provide a review and analysis of studies that have explicitly investigated these issues in the informal carers of CHF patients., Results of the Review: Sixteen papers were identified that examined the role and/or impact of informal caregiving for CHF patients. Our main findings were: demands specific to CHF caregiving were identified, e.g., monitoring complex medical and self-care regimen, disturbed sleep and frequent hospitalisation of patients. Relatively high levels of emotional distress were identified in CHF caregivers. Few studies explicitly investigated the role of informal carers in the management of CHF. Studies were limited in number, scope and quality., Conclusion: Caring for a family member with CHF can affect the well-being of those responsible for care, which may have consequences for the CHF patient's health. Further studies are needed to clarify these issues and to examine the role of informal caregivers in the management of CHF in the community.

Eighty-two patients aged > or = 70 years with heart failure were randomized to a gentle, seated exercise program or to usual care. Six-minute walk distance and quality of life did not change between groups, but daily activity as measured by accelerometry increased in the exercise group relative to the control group.

Neurohormonal dysfunction is an important and potentially modifiable part of the disease process of heart failure. In this review we will discuss the ways in which the autonomic system is deranged in congestive cardiac failure and the different ways we have of monitoring these abnormalities i.e.: heart rate variability, plasma norephinephrine activity, MIBG scanning, heart rate turbulence, baroreceptor function and briefly, microneurographic techniques and QT interval analysis. We will then discuss the direct effects of aldosterone and of aldosterone blockade on some of these parameters. We conclude that neurohormonal dysfunction is an important component of chronic heart failure, which is affected by aldosterone and can be modified by the use of aldosterone receptor blockade.

Aim: To assess how well heart failure patients tolerate spironolactone in routine clinical practice., Design: Retrospective analysis of 226 patients attending a specialist heart failure clinic., Results: One hundred and thirty of 226 (57.5%) patients tried spironolactone at least once. Forty-four of 130 (33.8%) discontinued spironolactone due to side-effects after a mean of 11.1 months; 59/141 (41.8%) trials of spironolactone resulted in at least one side-effect; therapy was stopped in 30/141 (21.3%) trials due to raised potassium or creatinine. Significant risk factors for raised potassium/creatinine were age and baseline potassium level., Conclusions: Potentially serious side-effects are common despite appropriate use of spironolactone.

Objectives: To evaluate how well older heart failure patients tolerate beta-blockers in everyday clinical practice., Design: Retrospective casenote analysis., Setting: Specialist heart failure clinic in a large teaching hospital., Participants: 226 patients with a clinical diagnosis of heart failure and evidence of left ventricular systolic dysfunction., Measurements: Data on age, sex, comorbid illness, other medications, duration of beta-blocker therapy, side-effects and reasons for discontinuation., Results: Patients aged 75 years and over had a higher level of comorbid disease and worse New York Heart Association status. Despite this, 60.4% of those aged 75 or over had been tried on a beta-blocker (versus 69% of those aged <75), and of those tried, 80% of those aged 75 or over were still taking a beta-blocker at the time of survey (versus 86% of those aged <75). Forty-seven percent of those aged 75 or over had at least one side-effect recorded (versus 48% of those aged <75). Significant risk factors for failing a trial of beta-blocker therapy were worse New York Heart Association status and worse left ventricular function, but importantly not age., Conclusions: A high proportion of older heart failure patients tolerate beta-blockers. Side-effects and failure rates are comparable to younger patients. Left ventricular function and worse New York Heart Association class, rather than age, predict low tolerability of therapy. Further studies are warranted to evaluate whether frail patients with heart failure can improve their quality of life by taking beta-blockers.

Despite recent advances in pharmacological therapy, chronic heart failure remains a major cause of morbidity and mortality in older people. Studies of exercise training in younger, carefully selected patients with heart failure have shown improvements in symptoms and exercise capacity and in many pathophysiological aspects of heart failure, including skeletal myopathy, ergoreceptor function, heart rate variability, endothelial function, and cytokine expression. Data on mortality and hospitalization are lacking, and effects on everyday activity, depression, and quality of life are unclear. Exercise therapy for patients with heart failure appears to be safe and has the potential to improve function and quality of life in older people with heart failure. To realize these potential benefits, exercise programs that are suitable for older, frail people need to be established and tested in an older, frail, unselected population with comorbidities.

Vitamin D has a wide range of biological effects beyond calcium and bone metabolism, and low 25-hydroxyvitamin D levels have been associated with many disease states in recent years, including cardiovascular disease, diabetes, infections and cancer. Association studies of vitamin D are notoriously prone to confounding and to reverse causality, however, and current intervention trial data for non-skeletal indications have been disappointing. Vitamin D is indicated for treatment of osteomalacia in older people, falls prevention in institutionalized older people, and as adjunctive therapy for osteoporosis. Large trials currently underway will ascertain whether potentially beneficial effects of vitamin D supplementation on all-cause mortality in older people are borne out. [ABSTRACT FROM PUBLISHER]

Background: Physical function and exercise capacity decline with age and are a major source of disability in older people. Recent evidence suggests a potential role for the reninangiotensin system in modulating muscle function. We sought to examine the effect of the angiotensin-convertingenzyme (ACE) inhibitor perindopril on physical function in elderly people with functional impairment who had no heart failure or left ventricular systolic dysfunction. Methods: In this double-blind randomized controlled trial, participants aged 65 years and older who had problems with mobility or functional impairment were randomly assigned to receive either perindopril or placebo for 20 weeks. The primary outcome was the change in the 6-minute walking distance over the 20 weeks. Secondary outcomes were changes in muscle function, daily activity levels, self-reported function and health-related quality of life. Results: A total of 130 participants were enrolled in the study (mean age 78.7, standard deviation 7.7 years); 95 completed the trial. At 20 weeks, the mean 6-minute walking distance was significantly improved in the perindopril group relative to the placebo group (mean between-group difference 31.4 m, 95% confidence interval [CI] 10.8 to 51.9 m; p = 0.003). There was a significant impact on health-related quality of life: although the mean score for part 1 of the EQ-5D questionnaire deteriorated over time in the placebo group, quality of life was maintained in the perindopril group, for a betweengroup difference of 0.09 (p = 0.046). There were no significant differences between the 2 groups in the other outcomes. Interpretation: Use of the ACE inhibitor perindopril improved exercise capacity in functionally impaired elderly people who had no heart failure and maintained healthrelated quality of life. The degree of improvement was equivalent to that reported after 6 months of exercise training. (International Standard Randomised Controlled Trial Register no. ISRCTN67679521). [ABSTRACT FROM AUTHOR]