The clinical epidemiology of fatigue in newly diagnosed heart failure

BackgroundFatigue is a common and distressing but poorly understood symptom among patients with heart failure (HF). This study sought to evaluate the prevalence, predictors, and prognostic value of clinically documented fatigue in newly diagnosed HF patients from the community.MethodsThis retrospective cohort study consisted of 12,285 newly diagnosed HF patients receiving health care services through the Geisinger Health System, with passive data collection through electronic medical records (EMR). Incident HF, fatigue, and other study variables were derived from coded data within EMRs. A collection of 87 candidate predictors were evaluated to ascertain the strongest independent predictors of fatigue using logistic regression. Patients were followed for all-cause mortality for an average of 4.8 years. The associations between fatigue and 6-month, 12-month, and overall mortality were evaluated via Cox proportional hazards regression models.ResultsClinically documented fatigue was found in 4827 (39%) newly diagnosed HF patients. Depression demonstrated the strongest association with fatigue. Fatigue was often part of a symptom cluster, as other HF symptoms including dyspnea, chest pain, edema, syncope, and palpitations were significant predictors of fatigue. Volume depletion, lower body mass index, and abnormal weight loss were also strong predictors of fatigue. Fatigue was not significantly associated with either 6-month (HR = 1.12, p = 0.16) or overall mortality (HR = 1.00, p = 0.89) in adjusted models.ConclusionsFatigue is a commonly documented symptom among newly diagnosed HF patients, and its origins may lie in both psychologic and physiologic factors. Though fatigue did provide a prognostic signal in the short-term, this was largely explained by physiologic confounders. Proper therapeutic remediation of fatigue in HF relies on identifying underlying factors.

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title: End points for comparative effectiveness research in heart failure.
abstract: CER for heart failure continues to evolve, including its assessment of end points. Reliance on surrogate end points is unacceptable as a means of definitively establishing comparisons of clinical effectiveness. CER needs to focus on measures that clearly reflect clinical effectiveness and safety, not just survival but also standardized assessments of health status and detailed resource utilization, and it must do so in a standardized way to allow for comparison. This strategy almost certainly requires increased reliance on prospective studies with proactive end-point capture, preferably in the setting of randomized allocation of the interventions being compared.

title: Patterns of symptom recognition, interpretation, and response in heart failure patients: an integrative review.
abstract: Heart failure (HF) is a chronic illness affecting more than 5 million Americans, and it continues to lead healthcare-related expenditures in the United States. Hospitalization rates remain high and are caused by many factors, including poor self-care behaviors. Self-care research is growing, and a situation-specific theory for the HF population is now published. Self-care management, which is part of self-care, includes a series of responses and actions that the individual living with HF assumes in response to a change in baseline health. A critical aspect of enacting a self-care management plan is the ability to recognize changes in baseline health as being related to HF.



This integrative review examined research to date on self-reported patterns of symptom recognition, an antecedent to self-care management, and treatment-seeking behaviors in HF patients.



Descriptive research strategies were predominantly used to examine symptom recognition, interpretation, and response in HF patients. Seven studies used retrospective approaches, such as chart review or patient recall, to collect data, and 7 studies collected data from the patient prospectively. The quantitative portion of 2 mixed-methods study was also analyzed. Dyspnea was the most frequently reported symptom across all studies reviewed. Dyspnea was characterized in terms of duration and was defined inconsistently across studies. In some studies, duration of dyspnea was associated with treatment-seeking delays. Elderly patients and newly diagnosed HF patients are more likely to delay treatment seeking for onset of symptoms.



Research is limited on symptom recognition and treatment-seeking behaviors in HF patients. Evidence suggests that symptom recognition may be impaired in the elderly population. Research studies to date on symptom recognition have largely been descriptive; no studies in this review followed patients' ability to recognize and respond to symptoms prospectively in their home environment. Symptoms may vary and their pattern may influence patients' recognition and/or response patterns.

title: A Patient’s Guide to Living Confidently With Chronic Heart Failure
abstract: Chronic heart failure (CHF) refers to the ongoing condition of your heart’s inability to pump sufficient blood to meet your body’s demands. The name of any medical condition that includes the word failure can be intimidating, particularly when it concerns your heart. After all, failure implies there is no hope, right? Wrong! The medical term “failure” can be demoralizing, but patients can identify ways to increase the chances of living longer and living well with CHF. To live successfully with CHF, it is important to develop confidence. For heart patients, confidence can refer to self-assurance, positive and healthy actions, and expectations that desirable health outcomes can be achieved. CHF is challenging because it requires patients and families to understand and monitor CHF symptoms, manage distress, accept the value of the implantable cardioverter-defibrillator (ICD), and pursue quality of life (QoL). For CHF patients, these ambitious goals involve developing confidence in each aspect of the treatment plan, spanning disease confidence, device confidence, and QoL confidence.

Disease confidence is a way of thinking and feeling about your disease that results in a greater sense of personal security and empowerment. Disease confidence can be developed by taking appropriate self-care in managing your CHF. Self-care involves a level of understanding about your medical condition, as well as making informed decisions about your care to minimize symptoms and/or to respond effectively to symptoms that may occur.1

 The first and most important step in becoming disease confident is being knowledgeable about CHF and how it affects you. Similar to mastering subjects in school, a patient with heart failure can and should learn …

title: The experience of fatigue as a distressing symptom of heart failure.
abstract: We explored the perceptions, experience, and meaning of fatigue as a distressing symptom of chronic heart failure (HF).



Fatigue, a common symptom of HF, may indicate worsening condition. Patients interpret their symptoms to determine the need for assistance. The meaning of fatigue in everyday life for HF patients in the United States is not well understood.



We performed an interpretive study of in-depth interviews with HF patients (n = 26) who reported fatigue as a symptom, using a thematic analysis of transcripts within an iterative group framework.



Fatigue is characterized by patient values related to their self-identity, their body, their experience of time, their environment, and their relationships with others, including the healthcare system.



Fatigue influences perceived proximity to death and how patients try to preserve what they can do. A patient's HF management plan should be tailored and responsive to that patient's experience of fatigue as communicated by the patient.

title: Fatigue With Systolic Heart Failure
abstract: Fatigue is one of the most prevalent symptoms in persons with systolic heart failure (HF). There remains insufficient information about the physiological and psychosocial underpinnings of fatigue in HF. The specific aims of this study were to (1) determine the psychometric properties of 2 fatigue questionnaires in patients with HF, (2) compare fatigue in patients with HF to published scores of healthy adults and patients with cancer undergoing treatment, and (3) identify the physiological (eg, hemoglobin, B-type natriuretic peptide, body mass index, and ejection fraction) and psychosocial (eg, depressed mood) correlates of fatigue in HF. A convenience sample of 87 HF outpatients was recruited from 2 urban medical centers. Patients completed the Fatigue Symptom Inventory, Profile of Mood States, and Short Form-36 Health Survey. Patients with HF and patients with cancer reported similar levels of fatigue, and both patient groups reported significantly more fatigue than did healthy adults. Physical functioning and hemoglobin categories explained 30% of the variance in Fatigue Symptom Inventory-Interference Scale scores, whereas depressed mood and physical functioning explained 47% of the variance in Profile of Mood States Fatigue subscale scores. Patients with HF experienced substantial fatigue that is comparable with cancer-related fatigue. Low physical functioning, depressed mood, and low hemoglobin level were associated with HF-related fatigue.

title: Patient's View of Heart Failure: From the Understanding to the Quality of Life
abstract: Non-pharmacological management is one of heart failure treatment cornerstones. Despite its importance several studies showed lack of clinical advising by medical staff as well as poor patient compliance to education and pharmacological treatment. Hospitalizations and symptoms of heart failure negatively influence patients’ quality of life. In Slovenia there is a scarcity of non-pharmacological management and quality of life data in heart failure patients.  We wanted to obtain data on heart failure patient's quality of life and their satisfaction with management of the condition in Slovenia.  During 6 weeks, patients from one university and two community Slovenian hospitals were prospectively enrolled to the EuroHeart survey. We invited 415 patients (mean age 70.6±11.4 years, 53% men) to attend an interview 12 weeks after the discharge.  Out of 415 eligible patients 25 (6%) died during follow up period and 187 (45%) attended the interview. Twenty-three percent of them were re-hospitalized. Vast majority (89%) of interviewed patients were aware of their heart condition but only 61% were satisfied with the explanation of their clinical condition given by medical staff. On average they were taking 6.3±2.3 drugs. General clinical advice (salt intake 65%, cholesterol or fat intake 63%) was more common than specific (daily weighing 35%, avoidance of non-steroidal anti-inflammatory drugs 17%). Patients reported high adherence as only 3% of given advice were neglected. Symptoms of heart failure were much less common at rest than during daily activity (breathlessness in 20% and 78%, fatigue in 18% and 81%, respectively). Psychological symptoms as anxiety (70%), depression (50%) and stress (48%) were common, as well as cognitive and sleep disturbances, both present in more than half of the patients.  Patients with heart failure experienced restrictions in quality of life and psychological status. Non-pharmacological and pharmacological management and patient's satisfaction with medical care were below optimal. Educational strategies for medical staff and patients as well as organization of an out-patient setting in community hospitals are needed.

title: Explaining fatigue in congestive heart failure.
abstract: Fatigue is a prominent symptom in patients with chronic heart failure, limiting physical activity and impairing quality of life. Although the underlying mechanisms are not clearly identified, alterations associated with peripheral adaptation in heart failure appear to play an important role, including a variably impaired peripheral perfusion during exercise, reduced oxidative capacity of skeletal muscle, impaired muscle strength, and possibly reflex mechanisms associated with alterations in the metabolism of skeletal muscle. Exercise training can, in part, reverse these peripheral alterations, improve exercise capacity, and alleviate fatigue.

title: Fatigue as a predictor of outcome in patients with heart failure: analysis of CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure).
abstract: The purpose of this study was to examine the relationship between fatigue and clinical outcomes, using dyspnea as a comparator, in patients with left ventricular ejection fraction (LVEF) ≤35% enrolled in the CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure) study.



Although fatigue is a common symptom in heart failure (HF), little is known about its association with prognosis.



At baseline in CORONA, fatigue "during the past few days" was measured using a 5-point exertion scale (0 = none, 1 = heavy exertion, 2 = moderate exertion, 3 = slight exertion, 4 = rest); a 4-point scale was used for dyspnea (1 to 4 as for fatigue). Patients were grouped into 3 categories: a fatigue score 0 to 1 (n = 535), fatigue score 2 (n = 1,632), and fatigue score 3 to 4 (n = 1,663); and a dyspnea score of 1 (n = 292), dyspnea score of 2 (n = 1,695), and dyspnea score of 3 to 4 (n = 1,843). The association between fatigue and dyspnea and the composite outcome of cardiovascular (CV) death or HF hospital stay and each component separately was examined using Kaplan-Meier analysis and Cox proportional-hazard models. We also examined all-cause mortality.



In univariate analyses, symptom severity was associated with a higher risk of CV death or HF hospital stay (fatigue: group 3, 49% [n = 810], vs. group 1, 30% [n = 160]; dyspnea: group 3, 50% [n = 918], vs. group 1, 28% [n = 82]) and all-cause mortality (fatigue: group 3, 38% [n = 623], vs. group 1, 24% [n = 130]; dyspnea: group 3, 38% [n = 697], vs. group 1, 23% [n = 66], log-rank p < 0.0001 for all). After adjusting for other prognostic variables, including LVEF, New York Heart Association class, and N-terminal pro-B-type natriuretic peptide level, worse fatigue remained associated with higher risk of HF hospital stay but not mortality (worse dyspnea remained associated with a higher risk of both). An increase in fatigue (or dyspnea) between baseline and 6 months was also associated with worse outcomes.



In HF, greater fatigue is associated with worse clinical outcomes. Closer attention should be paid to this symptom in clinical practice, with more done to standardize its measurement and understand its origins, with a view to improving treatment.

title: Symptom Clusters Predict Event-Free Survival in Patients With Heart Failure
abstract: Physical symptoms are likely to occur in clusters that may be associated with adverse outcome in patients with heart failure (HF). Despite the importance of early recognition of worsening symptoms in HF management, the impact of physical symptoms on adverse outcome has not been explored in the context of symptom clusters. The purposes of this study were to explore which physical symptom clusters occur in HF patients and to determine the impact of symptom clusters on event-free survival. A total of 421 patients (60% male; 62 [SD, 14] years; 72% New York Heart Association class II/III) completed the modified Memorial Symptom Assessment Scale-Heart Failure to measure physical symptoms during an index hospitalization in Seoul, Korea. Times to first event of cardiac rehospitalization and cardiac death were collected for 12 months after discharge and confirmed by review of hospital records. An agglomerative hierarchical clustering approach with Ward's method was used to identify symptom clusters. Hierarchical Cox hazard regression was used to determine the impact of symptom clusters on cardiac rehospitalization and cardiac mortality. Two distinct symptom clusters, the dyspneic and the weary symptom clusters, occurred in patients with HF. Shortness of breath, difficulty breathing when lying flat, and waking up breathless at night comprised the dyspneic symptom cluster. Lack of energy, lack of appetite, and difficulty sleeping comprised the weary symptom cluster. In hierarchical Cox hazard regression, elevated distress from the weary symptom cluster independently predicted cardiac rehospitalization (hazard ratio, 1.45; 95% confidence interval, 1.09-1.93), and increased distress from the dyspneic symptom cluster independently predicted cardiac mortality (hazard ratio, 2.00; 95% confidence interval, 1.16-3.34). The weary and the dyspneic symptom clusters predicted cardiac rehospitalization and cardiac mortality, respectively. Patient education for self-monitoring of symptoms should focus on symptom clusters rather than single symptom.

title: Fatigue is a Prevalent and Severe Symptom Associated with Uncertainty and Sense of Coherence in Patients with Chronic Heart Failure
abstract: Fatigue is a common symptom in patients with chronic heart failure (CHF) and has a major impact on their daily life activities. The purpose of this study was to examine the prevalence and severity of fatigue, conceptualized as a multiple dimensional symptom, and to determine the influence of sense of coherence and uncertainty on the fatigue experience in patients with CHF.  Ninety-three consecutive patients, hospitalized with a diagnosis of CHF, completed the Multidimensional Fatigue Inventory Scale (MFI-20), Cardiovascular Population Scale (CPS), and Sense of Coherence Scale (SOC) and were classified according to the New York Heart Association (NYHA) functional classification criteria. Associations between selected variables were explored with multiple regression analysis.  The patients reported high prevalence and severity in the physical dimensions of fatigue. Uncertainty was associated positively with tiredness and reduced functional status. High age predicted reduced motivation and the ability to concentrate were affected by low SOC.  Fatigue is a prevalent and distressing experience in patients with CHF, where a variety of factors influence different dimensions of the fatigue experience. Recognising this, symptom management must be directed towards comprehensive assessment and a broad approach in interventions aimed at alleviating fatigue.

title: Pro-A-type natriuretic peptide, proadrenomedullin, and N-terminal pro-B-type natriuretic peptide used in a multimarker strategy in primary health care in risk assessment of patients with symptoms of heart failure.
abstract: Use of new biomarkers in the handling of heart failure patients has been advocated in the literature, but most often in hospital-based populations. Therefore, we wanted to evaluate whether plasma measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP), midregional pro-A-type natriuretic peptide (MR-proANP), and midregional proadrenomedullin (MR-proADM), individually or combined, gives prognostic information regarding cardiovascular and all-cause mortality that could motivate use in elderly patients presenting with symptoms suggestive of heart failure in primary health care.



The study included 470 elderly patients (mean age 73 years) with symptoms of heart failure in primary health care. All participants underwent clinical examination, 2-dimenstional echocardiography, and plasma measurement of the 3 propeptides and were followed for 13 years. All mortality was registered during the follow-up period. The 4th quartiles of the biomarkers were applied as cutoff values. NT-proBNP exhibited the strongest prognostic information with >4-fold increased risk for cardiovascular mortality within 5 years. For all-cause mortality MR-proADM exhibited almost 2-fold and NT-proBNP 3-fold increased risk within 5 years. In the 5-13-year perspective, NT-proBNP and MR-proANP showed significant and independent cardiovascular prognostic information. NT-proBNP and MR-proADM showed significant prognostic information regarding all-cause mortality during the same time. In those with ejection fraction (EF) <40%, MR-proADM exhibited almost 5-fold increased risk of cardiovascular mortality with 5 years, whereas in those with EF >50% NT-proBNP exhibited >3-fold increased risk if analyzed as the only biomarker in the model. If instead the biomarkers were all below the cutoff value, the patients had a highly reduced mortality risk, which also could influence the handling of patients.



The 3 biomarkers could be integrated in a multimarker strategy for use in primary health care.

title: Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-DHF randomized controlled trial.
abstract: Diastolic heart failure (ie, heart failure with preserved ejection fraction) is a common condition without established therapy, and aldosterone stimulation may contribute to its progression.



To assess the efficacy and safety of long-term aldosterone receptor blockade in heart failure with preserved ejection fraction. The primary objective was to determine whether spironolactone is superior to placebo in improving diastolic function and maximal exercise capacity in patients with heart failure with preserved ejection fraction.



The Aldo-DHF trial, a multicenter, prospective, randomized, double-blind, placebo-controlled trial conducted between March 2007 and April 2012 at 10 sites in Germany and Austria that included 422 ambulatory patients (mean age, 67 [SD, 8] years; 52% female) with chronic New York Heart Association class II or III heart failure, preserved left ventricular ejection fraction of 50% or greater, and evidence of diastolic dysfunction.



Patients were randomly assigned to receive 25 mg of spironolactone once daily (n=213) or matching placebo (n=209) with 12 months of follow-up.



The equally ranked co-primary end points were changes in diastolic function (E/e') on echocardiography and maximal exercise capacity (peak VO2) on cardiopulmonary exercise testing, both measured at 12 months.



Diastolic function (E/e') decreased from 12.7 (SD, 3.6) to 12.1 (SD, 3.7) with spironolactone and increased from 12.8 (SD, 4.4) to 13.6 (SD, 4.3) with placebo (adjusted mean difference, -1.5; 95% CI, -2.0 to -0.9; P < .001). Peak VO2 did not significantly change with spironolactone vs placebo (from 16.3 [SD, 3.6] mL/min/kg to 16.8 [SD, 4.6] mL/min/kg and from 16.4 [SD, 3.5] mL/min/kg to 16.9 [SD, 4.4] mL/min/kg, respectively; adjusted mean difference, +0.1 mL/min/kg; 95% CI, -0.6 to +0.8 mL/min/kg; P = .81). Spironolactone induced reverse remodeling (left ventricular mass index declined; difference, -6 g/m2; 95% CI, -10 to-1 g/m2; P = .009) and improved neuroendocrine activation (N-terminal pro-brain-type natriuretic peptide geometric mean ratio, 0.86; 95% CI, 0.75-0.99; P = .03) but did not improve heart failure symptoms or quality of life and slightly reduced 6-minute walking distance (-15 m; 95% CI, -27 to -2 m; P = .03). Spironolactone also modestly increased serum potassium levels (+0.2 mmol/L; 95% CI, +0.1 to +0.3; P < .001) and decreased estimated glomerular filtration rate (-5 mL/min/1.73 m2; 95% CI, -8 to -3 mL/min/1.73 m2; P < .001) without affecting hospitalizations.



In this randomized controlled trial, long-term aldosterone receptor blockade improved left ventricular diastolic function but did not affect maximal exercise capacity, patient symptoms, or quality of life in patients with heart failure with preserved ejection fraction. Whether the improved left ventricular function observed in the Aldo-DHF trial is of clinical significance requires further investigation in larger populations.

title: Prognostic value of the 6 min walk test and self-perceived symptom severity in older patients with chronic heart failure.
abstract: The 6 min walk test (6-MWT) is a simple and popular test for evaluating functional status in patients with chronic heart failure (CHF). However, the prognostic value of the 6-MWT in a large, representative sample of CHF patients, and in patients with different degrees of left ventricular systolic dysfunction (LVSD) remains unclear.



Of an initial population of 1592 patients, 212 died representing a crude death rate of 13.3%. In surviving patients, the median time to follow-up period was 36.6 months [inter-quartile range (IQR) 28-45 months]. Five variables remained independent predictors of all-cause mortality; decreasing 6-MWT distance, self-perceived signs of breathlessness at night (SOBAN), beta-blocker usage, elevated log NT-proBNP, and reduced haemoglobin concentration. We also dichotomized our analysis by LVSD status (<or=mild LVSD or >mild LVSD). For patients with >mild LVSD, 6-MWT remained an important prognostic indicator but not in patients with <or=mild LVSD.



The 6-MWT is an important independent predictor of mortality in CHF patients, and this was especially evident in patients with >mild LVSD. The 6-MWT provides little prognostic utility in patients with <or=mild LVSD. While log NT-proBNP was the most potent independent predictor, an additive prognostic effect was evident with the additional selection of 6-MWT. Patients' self-perceived symptoms, especially SOBAN was an independent predictor of mortality in our patients.

title: Prevalence of symptoms in a community-based sample of heart failure patients.
abstract: This study explored the prevalence and burden of symptoms in a community-based sample of patients aged >60 with symptomatic heart failure. Five hundred forty-two patients were recruited from UK general practices. Participants completed the Kansas City Cardiomyopathy Questionnaire every 3 months for 2 years. Data are presented at baseline alongside findings from in-depth interviews with patients and focus groups with primary care professionals. Over half the participants experienced breathlessness and/or fatigue daily. Factors identified as predictive of symptom prevalence and burden were as follows: being female; being staged at New York Heart Association Class III or IV; having symptoms of depression; and having two or more comorbidities. Interviews identified other symptoms, including chest pain, nausea, sleep disruption, and confusion. Participants felt that symptoms restricted activities of daily living. Health professionals reported symptom control as being a concern of patients and identified their own educational needs in this area. Findings suggest that symptom prevalence and burden for this population is high. Primary care professionals should offer comprehensive assessment and treatment of symptoms.

title: Symptoms in patients with heart failure are prognostic predictors: insights from COMET.
abstract: Although functional status, as assessed by the New York Heart Association classification, is known to be a powerful prognostic marker in chronic heart failure (CHF), the significance of individual symptoms such as breathlessness and fatigue are unknown.



To assess the relative importance of self-reported severity of symptoms as predictors of outcomes in CHF.



All 3029 patients randomized in the Carvedilol or Metoprolol European Trial (ie, COMET) study were included in the analysis. Mean follow-up was 58 months. Symptoms were assessed by 5-point scales. In a univariate analysis, worse scores for breathlessness, orthopnea and fatigue were all significantly related to increased mortality (all P < .0001) and development of worsening heart failure. In a multivariate Cox regression analysis including 16 baseline covariates, only the symptom of breathlessness remained significantly related to mortality (risk ratio [RR] 1.14 per unit: 95% CI 1.04-1.26; P = .01). Fatigue, but not breathlessness, remained a significant predictor for developing worsening heart failure (RR 1.09 per unit; 95% CI 1.02-1.18; P = .02).



Fatigue and breathlessness, common symptoms in CHF, have important and independent long-term prognostic implications. Accordingly, symptoms need to be effectively evaluated not only because symptom alleviation is a target for treatment, but also because they guide prognosis in patients with CHF.

title: Depression in heart failure
abstract: This review aims to provide a general overview of the recent advances in understanding of depression as it pertains to heart failure. The focus is to impart an up to date knowledge in this field. Recent findings The mortality associated with heart failure remains high despite recent pharmacologic interventions that have improved survival. The situation is complicated by recent recognition of depression being widespread in this population. Depression is a hard diagnosis, as some of the features coincide with the symptoms of heart failure. Recently the psychological sequelae of depression have been under major scrutiny, as it has been associated with increased morbidity. In addition, current data are quite compelling on prevalence of depression in heart failure patients. Therefore, it is imperative to highlight the recent challenges and to recognize areas requiring future research.  Despite the prevalence of depression in heart failure, we remain abysmal in detecting, diagnosing and treating depression, which remains an independent predictor of mortality. Therefore, more research and more awareness are required in this arena.

title: Symptoms of fatigue in chronic heart failure patients: Clinical and psychological predictors
abstract: To examine the role of clinical and psychological characteristics as predictors of fatigue in CHF.

title: Symptom clusters and quality of life among patients with advanced heart failure
abstract: To identify symptom clusters among patients with advanced heart failure (HF) and the independent relationships with their quality of life (QoL).  This is the secondary data analysis of a cross-sectional study which interviewed 119 patients with advanced HF in the geriatric unit of a regional hospital in Hong Kong. The symptom profile and QoL were assessed by using the Edmonton Symptom Assessment Scale (ESAS) and the McGill QoL Questionnaire. Exploratory factor analysis was used to identify the symptom clusters. Hierarchical regression analysis was used to examine the independent relationships with their QoL, after adjusting the effects of age, gender, and comorbidities.  The patients were at an advanced age (82.9 ± 6.5 years). Three distinct symptom clusters were identified: they were the distress cluster (including shortness of breath, anxiety, and depression), the decondition cluster (fatigue, drowsiness, nausea, and reduced appetite), and the discomfort cluster (pain, and sense of generalized discomfort). These three symptom clusters accounted for 63.25% of variance of the patients' symptom experience. The small to moderate correlations between these symptom clusters indicated that they were rather independent of one another. After adjusting the age, gender and comorbidities, the distress (β = −0.635, P < 0.001), the decondition (β = −0.148, P = 0.01), and the discomfort (β = −0.258, P < 0.001) symptom clusters independently predicted their QoL.  This study identified the distinctive symptom clusters among patients with advanced HF. The results shed light on the need to develop palliative care interventions for optimizing the symptom control for this life-limiting disease.

title: A Cross-Cultural Comparison of Symptom Reporting and Symptom Clusters in Heart Failure
abstract: An understanding of symptoms in heart failure (HF) among different cultural groups has become increasingly important. The purpose of this study was to compare symptom reporting and symptom clusters in HF patients between a Western (the United States) and an Eastern Asian sample (China and Taiwan). A secondary analysis of a cross-sectional observational study was conducted. The data were obtained from a matched HF patient sample from the United States and China/Taiwan (N = 240 in each). Eight selective items related to HF symptoms from the Minnesota Living with Heart Failure Questionnaire were analyzed. Compared with the U.S. sample, HF patients from China/Taiwan reported a lower level of symptom distress. Analysis of two different regional groups did not result in the same number of clusters using latent class approach: the United States (four classes) and China/Taiwan (three classes). The study demonstrated that symptom reporting and identification of symptom clusters might be influenced by cultural factors.

title: Heart failure symptom clusters and functional status - a cross-sectional study.
abstract: To identify symptom clusters in individuals with heart failure and evaluate the relationship of the identified clusters to functional status.



Heart Failure is a global health problem affecting approximately 1-2% of the adult population in developed countries worldwide. Individuals with heart failure may experience as many as nine symptoms and may limit activities that worsen their symptoms or adjust the way they engage in activities.



Cross-sectional.



A convenience sample of individuals (n = 117) with a confirmed diagnosis of heart failure was recruited from an academic medical centre during 2011-2012. Prevalent heart failure symptoms and functional status outcomes (functional limitations and mobility) were evaluated. Factor analysis using the principal components method was used to extract symptom clusters. Regression analysis using a backwards stepwise model-building approach was used to examine the effects of the symptom clusters, age and co-morbidity on functional limitations and mobility.



Three symptom clusters, sickness behaviour, discomforts of illness and gastrointestinal distress were extracted. When sickness behaviours and discomforts of illness were both present, functional limitations were more sensitive to sickness behaviours. Sickness behaviour and co-morbidity were related to limited mobility.



Individuals with heart failure may be helped to improve their functional status by managing sickness behaviour and discomforts of illness symptoms. Identification of symptom clusters may lead to the development of interventions focusing on a cluster of heart failure symptoms.

title: Cluster dyads of risk factors and symptoms are associated with major adverse cardiac events in patients with acute myocardial infarction.
abstract: The purpose of this study was to examine the cluster dyads of risk factors and symptoms and their impact on the incidence of 12 month major adverse cardiac events (MACEs) among patients with first-time myocardial infarction (MI). In a descriptive study, a total of 522 patients completed semi-structured interviews for data on risk factors and symptoms. Patients were followed for 12 months to determine MACEs. Latent class cluster analysis was performed to identify risk factor clusters and symptom clusters. Logistic regression analysis was performed to determine the impact of cluster dyads on 12 month MACEs. There were 436 event-free survivors and 86 patients with MACEs for 12 months. Ten risk factors and 14 symptoms were clustered into two (dyslipidemia/smoking, hypertension/diabetes dominant) and three (typical, multiple, atypical) memberships, respectively. Six cluster dyads which were generated based on the association between risk factors and symptom clusters were a significant predictor of 12 month MACEs, with the incidence occurring three times higher in a dyad of hypertension/diabetes-and-atypical symptoms than a dyad of dyslipidemia/smoking-and-typical symptoms (odds ratio = 3.10, P = 0.01), after adjustment for age, gender and a type of MI diagnosis. The information on cluster dyads suggests that health-care providers need to consider both risk factors and symptoms at hospital presentation for risk stratification to prevent adverse outcomes.

title: Heart failure symptom monitoring and response training.
abstract: The purpose of this study was to test the efficacy of a heart failure (HF) training program on patients' ability to recognize and respond to changes in HF symptoms. The primary aim was to compare event-free survival at 90 days.



A total of 99 HF patients randomized to the HF symptom training intervention or usual care completed instruments about self-care (Self-Care of HF Index) and at baseline and 3 months. Demographic, clinical, and comorbidity data were collected by interview and chart review. Time to first event (death or a HF-related hospitalization) was tracked by electronic records and patient interview.



The sample was predominately male (67.7%), elderly (67.7 yrs ± 12.1) and Caucasian (88.9%). The intervention group reported more events but the difference was not significantly different (χ(2) = 1.18, p = 0.26). There was no difference in survival time between groups (χ(2) = 1.53, p = 0.216). In paired t-tests, the intervention group had significantly improved self-care maintenance, management and confidence scores (all p < 0.01). The usual care group had significantly improved self-care maintenance and management (both p < 0.01). Improvements in self-care maintenance and confidence were higher in the intervention group compared with usual care (18.0 vs. 12.9 points).



HF symptom awareness training appeared to have an early but not sustained benefit resulting in no difference in 90-day event-free survival. However, larger improvement in self-care maintenance and confidence scores in the intervention group compared to usual care is promising. Embedding meaningful symptom monitoring strategies in self-care maintenance interventions requires further investigation.

title: Making the Case for Skeletal Myopathy as the Major Limitation of Exercise Capacity in Heart Failure
abstract: In chronic heart failure (HF) from systolic cardiac dysfunction, the degree of exercise intolerance is not directly related to the degree of cardiac weakness.1–5 Somewhat surprisingly symptoms that typify HF, including shortness of breath and fatigue, are often directly related to the abnormalities of the skeletal musculature in HF. Our understanding of the features of skeletal myopathy is evolving as therapy for HF is changing and improving. Understanding the skeletal myopathy of HF is important for 2 reasons: (1) therapies, including heart transplantation, only directed at improving cardiac function, will not immediately and may never improve exercise capacity in HF, and (2) with greater understanding of the mechanisms underlying the skeletal myopathy of HF, specific therapies targeting these abnormalities can be developed.

I will review the features of the skeletal myopathy of HF, as currently understood, based on state-of-the-art research in humans and animal models. I will then examine the mechanisms underlying the skeletal myopathy, which appears not to be unique to HF but are shared by other chronic diseases such as chronic obstructive pulmonary disease(COPD) and chronic renal disease.3 Specifically, the role of “coordinated adaptation,” an energy-conserving strategy to maximize efficiency in a damaged system, will be examined in the development of the skeletal myopathy in all of these chronic diseases.6 Further, I will present evidence supporting the concept that sympathetic nerve activation (SNA) initiates and maintains this systemic, coordinated adaptation. Finally, the impact of current and future pharmacological and nonpharmacological therapies will be related to the above pathophysiology of the skeletal myopathy of HF.

There are several features of the skeletal myopathy that have been described and confirmed by many different investigative groups. Patients with chronic HF on stable medical therapy have decreased muscle bulk compared with healthy humans.7,8 The …

title: The Effects of Exercise Training on Fatigue and Dyspnea in Heart Failure
abstract: Physiological benefits of exercise training for heart failure (HF) patients have been demonstrated, however little is known about the effects of training on the symptoms of fatigue and dyspnea.  The purpose of this study was to examine HF symptoms of fatigue and dyspnea in response to a 24-week exercise training intervention.  This pilot study was a randomized, two-group repeated measures design. Fifteen subjects in the intervention group completed a combination of aerobic and resistance training three times per week in a standard cardiac rehabilitation setting. The control group consisted of 6 subjects who were instructed not to begin any formal exercise program during the 24-week intervention.  Subjects (19 males and 2 females) had a mean age of 66.2 ± 10.2 years and mean ejection fraction (EF) of 28.4 ± 7.4%. Non-parametric Friedman Analysis of Variance by Ranks showed the exercise group significantly decreased sensory fatigue (Piper Fatigue Scale) over time (χ 2 = 6.49, p = .04) while the control group did not change (χ 2 = 0.93, p = .63). Dyspnea showed a non-significant decrease over time for the exercise group (χ 2 = 4.16, p = .13) while the control group showed a decrease from baseline to 12 weeks but an increase to above baseline values by week 24 (χ 2 = 0.18, p = .91).  These results provide support for the beneficial effects of exercise training on symptoms of fatigue and dyspnea in HF patients. Larger studies to evaluate symptom response to exercise are needed.

title: Erythropoiesis-stimulating agents for anaemia in chronic heart failure patients.
abstract: Chronic heart failure (CHF) is a leading cause of morbidity and mortality worldwide. Anaemia is a common (12-55%) co-morbid condition and is associated with worsening symptoms and increased mortality. Anaemia is treatable and can be targeted in the treatment of patients with CHF. Erythropoiesis-stimulating agents (ESA), supplemented by iron therapy, are used to treat anaemia in chronic kidney disease and cancer, however safety concerns have been raised in these patients. The clinical benefit and safety of these agents in CHF remains unclear.



To assess the benefits and risks of ESA for CHF patients with anaemia.


SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2008, Issue 3), MEDLINE (1950 to October 2008), EMBASE (1980 to October 2008) and reference lists of articles. No language restrictions were applied.



Randomised controlled trials of any ESA, with or without iron therapy, in CHF patients were eligible for inclusion.



Three reviewers independently assessed study quality and extracted data. Original authors were contacted for additional information. The outcomes of interest were: exercise tolerance, haemoglobin level, New York Heart Association (NYHA) functional class, quality of life, left-ventricular ejection fraction, B-type natriuretic peptide, CHF-related hospitalisations, all-cause mortality and adverse effects. Risk ratios (RR) were calculated for dichotomous data and weighted mean difference (WMD) for continuous data.



Eleven studies (794 participants) were included. Overall quality of studies was moderate with nine studies being placebo-controlled but only five double-blinded. Compared to control, ESA treatment significantly improved exercise duration by 96.8 seconds (95% CI 5.2 to 188.4, p=0.04) and 6-minute walk distance by 69.3 metres (95% CI 17.0 to 121.7, p=0.009). Benefit was also noted in terms of peak VO2 (+2.29 mL/kg/min, p=0.007), NYHA class (-0.73, p<0.001), ejection fraction (+5.8%, p<0.001), B-type natriuretic peptide (-226.99 pg/mL, p<0.001) and quality-of-life indicators, with a mean increase in haemoglobin of 1.98 g/dL (p<0.0001). There was also a significantly lower rate of heart failure related hospitalisations (RR 0.62, 95% CI 0.44 to 0.87) and lower all-cause mortality (RR 0.61, 95% CI 0.37 to 0.99). No increase in adverse events with ESA therapy was observed, however studies were of small sample sizes and limited duration.



Meta-analysis of small RCTs suggests that ESA treatment in patients with symptomatic CHF and mild anaemia (haemoglobin more than 10g/dL) can improve anaemia and exercise tolerance, reduce symptoms and have benefits on clinical outcomes. Confirmation requires well-designed studies with careful attention to dose, haemoglobin treatment target and associated iron therapy.

title: Prognosis of all-cause heart failure and borderline left ventricular systolic dysfunction: 5 year mortality follow-up of the Echocardiographic Heart of England Screening Study (ECHOES).
abstract: Heart failure (HF) is reported to have an essentially malignant prognosis that can be modified by several interventions. Most outcome data on HF are available from randomized controlled treatment trials and longitudinal epidemiological studies. However, for a number of reasons, neither type of study have, to date, provided generalizable data on HF mortality. Furthermore, data on the prognosis of borderline left ventricular systolic dysfunction (LVSD) are even more limited.



ECHOES (Echocardiographic Heart of England Screening Study) screened a total of 6,162 patients from a total of 10,161 invited (61% response rate). Patients were randomly selected from four pre-specified cohorts: the general population, diuretic users, those with a prior clinical label of HF, and a population with risk factors for HF, to identify the prevalence of HF and LVSD based on clinical assessment, ECG, and echocardiography. Causes of death during a 5-9 year follow-up period were recorded from routine mortality statistics. The 5-year survival rate of the general population was 93%, compared with 69% of those with LVSD without HF, 62% with HF and no LVSD, and 53% with HF plus LVSD. Survival improved significantly with increasing ejection fraction (EF) (log rank test for trend, chi(2) = 534.5, 1, P < 0.0001).



The ECHOES mortality data confirm the poor prognosis of patients suffering prevalent HF across the community with a mortality risk estimate of 9% per year. Borderline systolic dysfunction (EF 40-50%) on echocardiography carries a poor prognosis.