Nutritional Support Reduces Circulating Cytokines in Patients with Heart Failure.

Increased inflammation is associated with the pathogenesis of heart failure (HF). Increased circulating levels of cytokines have been previously reported and generally associated with worse clinical outcomes. In this context, the modulation of inflammation-related parameters seems to be a reasonable therapeutic option for improving the clinical course of the disease. Based on this, we aimed to compare changes in circulating cytokines when Mediterranean diet alone or in combination with hypercaloric, hyperproteic oral nutritional supplements (ONS), enriched with omega-3 (n-3) polyunsaturated fatty acids were administered to patients with HF. Briefly, patients were randomly assigned to receive Mediterranean Diet (control group) vs. Mediterranean Diet plus ONS (intervention group). We observed increased circulating levels of IL-6, IL-8, MCP-1 and IP-10. MCP-1 and IL-6 were associated with overweight and obesity (p = 0.01-0.01-0.04, respectively); IL-6 and IL-8 were positively correlated with fat mass and CRP serum levels (p = 0.02-0.04, respectively). Circulating levels of IL-8 significantly decreased in all patients treated with the Mediterranean diet, while IL-6 and IP-10 only significantly decreased in patients that received plus ONS. In the univariate analysis, MCP-1 and its combination with IL-6 were associated with increased mortality (p = 0.02), while the multivariate analysis confirmed that MCP-1 was an independent factor for mortality (OR 1.01, 95%ci 1.01-1.02). In conclusion, nutritional support using hypercaloric, hyperproteic, n-3 enriched ONS in combination with Mediterranean Diet was associated with decreased circulating levels of some cytokines and could represent an interesting step for improving heart functionality of patients with HF.

Cut-Point for Satisfactory Adherence of the Dietary Sodium Restriction Questionnaire for Patients with Heart Failure / Ponto de Corte para Adesão Satisfatória do Questionário de Restrição de Sódio na Dieta em Pacientes com Insuficiência Cardíaca

Abstract Background: The low or non-adherence to reduction of sodium intake has been identified as one of the main precipitating factors of heart failure (HF). The Dietary Sodium Restriction Questionnaire (DSRQ) identifies factors that can interfere with adherence to this recommendation. However, there is still no cut-point to define adherence for this questionnaire. Objectives: To identify the cut-point for satisfactory adherence to the Brazilian version of the DSRQ, (the Questionário de Restrição de Sódio na Dieta, QRSD). Methods: Multicenter study. Patients with HF in outpatient treatment (compensated) and those treated in emergency departments due to acute HF (decompensated) were included. For the cut-point definition, the DSRQ scores were compared between groups. A ROC curve was constructed for each subscale to determine the best point of sensitivity and specificity regarding adherence. A 5% significance level was adopted. Results: A total of 206 compensated patients and 225 decompensated were included. Compensated patients exhibited scores that showed higher adhesion in all subscales (all p <0.05). Scores ≥ 40 points of a total of 45 for the subscale of Attitude and Subjective Norm; scores ≤ eight of a total of 20 for Perceived Behavioral Control; and ≤ three of a total of 15 for Dependent Behavior Control were indicative of satisfactory adherence. Conclusions: Based on the evaluation of patients in these two scenarios, it was possible to determine the cut-point for satisfactory adherence to the reduction of sodium in the diet of patients with HF. Countries with similar culture could use this cut-point, as other researchers could also use the results as a reference for further studies.

Resumo Fundamento: A baixa ou a não adesão à redução de sódio na dieta foi identificada como um dos principais fatores causais da insuficiência cardíaca (IC). O Questionário de Restrição de Sódio na Dieta (QRSD) do inglês Dietary Sodium Restriction Questionnaire (DSRQ) identifica fatores que possam interferir na adesão a essa recomendação. No entanto, anda não existe um ponto de corte que estabelece adesão segundo o QRSD. Objetivos: Identificar o ponto de corte para adesão satisfatória ao QRSD, versão brasileira do DSRQ. Métodos: Estudo multicêntrico. Foram incluídos pacientes com IC em tratamento ambulatorial (compensados) e aqueles tratados em serviços de emergência por IC aguda (descompensados). Para a definição do ponto de corte, os escores do QRSD foram comparados entre os grupos. A curva ROC foi construída para cada subescala para determinar o melhor ponto de sensibilidade e especificidade em relação à adesão. Adotou-se um nível de significância de 5%. Resultados: Foram incluídos 206 pacientes compensados e 225 pacientes descompensados. Os pacientes compensados apresentaram escores que indicaram maior adesão em todas as subescalas (p < 0,05). Escores ≥ 40 pontos de um total de 45 para a subescala "atitude e norma subjetiva"; escores ≤ 8 de um total de 20 para a subescala "controle comportamental percebido"; e escores 3 de um total de 15 para "comportamento dependente" foram indicativos de adesão satisfatória. Conclusões: A avaliação de pacientes com IC atendidos no ambulatório ou na emergência permitiu a determinação dos pontos de corte para adesão satisfatória à restrição dietética de sódio. Países de culturas similares poderiam usar esse mesmo ponto de corte, bem como outros pesquisadores poderiam utilizá-lo como referência para outros estudos.

Vitamin D Dietary Supplementation: Relationship with Chronic Heart Failure.

It is estimated that over 1 billion people worldwide have a deficiency of vitamin D, also known as hypovitaminosis D, which the World Health Organization has defined as a public health problem. Beyond its historical homeostasis regulatory function of calcium and phosphorus, in relation to the preservation of the skeletal system, several studies show today a close connection between hypovitaminosis D and the genesis of rheumatic, autoimmune, neoplastic, and cardiovascular diseases. With exclusive reference to cardiovascular aspects, multiple heart diseases such as hypertension, myocardial ischemia, and heart failures might have deficiency in vitamin D as an important causative factor. Because of the influence of concomitant pathologies caused by antibiotic-resistant agents, the function of this vitamin should be critically evaluated. However, the role of vitamin D remains to be established; only a few studies have tested the effects of its supplementation in patients with chronic heart failure diseases, and reported results are unclear. It is important to implement studies in this field in order to assess the real benefits induced by vitamin D supplementation in cardiovascular patients and, in particular, in patients with heart failure. Should the research confirm actual clinical improvement after treatment with vitamin D, such a supplementation might represent a new low-cost therapeutic approach to improving quality of life.

Effects of vitamin D supplementation on inflammatory markers in heart failure: a systematic review and meta-analysis of randomized controlled trials.

Vitamin D is reported to have anti-inflammatory properties; however the effects of vitamin D supplementation on inflammation in patients with heart failure (HF) have not been established. We performed a systematic review and meta-analysis examining effects of vitamin D supplementation on inflammatory markers in patients with HF. MEDLINE, CINAHL, EMBASE, All EBM, and Clinical Trials registries were systematically searched for RCTs from inception to 25 January 2017. Two independent reviewers screened all full text articles (no date or language limits) for RCTs reporting effects of vitamin D supplementation (any form, route, duration, and co-supplementation) compared with placebo or usual care on inflammatory markers in patients with heart failure. Two reviewers assessed risk of bias and quality using the grading of recommendations, assessment, development, and evaluation approach. Seven studies met inclusion criteria and six had data available for pooling (n = 1012). In meta-analyses, vitamin D-supplemented groups had lower concentrations of tumor necrosis factor-alpha (TNF-α) at follow-up compared with controls (n = 380; p = 0.04). There were no differences in C-reactive protein (n = 231), interleukin (IL)-10 (n = 247) or IL-6 (n = 154) between vitamin D and control groups (all p > 0.05). Our findings suggest that vitamin D supplementation may have specific, but modest effects on inflammatory markers in HF.

Dietary nitrate supplementation opposes the elevated diaphragm blood flow in chronic heart failure during submaximal exercise.

Chronic heart failure (CHF) results in a greater cost of breathing and necessitates an elevated diaphragm blood flow (BF). Dietary nitrate (NO3‾) supplementation lowers the cost of exercise. We hypothesized that dietary NO3‾ supplementation would attenuate the CHF-induced greater cost of breathing and thus the heightened diaphragm BF during exercise. CHF rats received either 5days of NO3‾-rich beetroot (BR) juice (CHF+BR, n=10) or a placebo (CHF, n=10). Respiratory muscle BFs (radiolabeled microspheres) were measured at rest and during submaximal exercise (20m/min, 5% grade). Infarcted left ventricular area and normalized lung weight were not significantly different between groups. During submaximal exercise, diaphragm BF was markedly lower for CHF+BR than CHF (CHF+BR: 195±28; CHF: 309±71mL/min/100g, p=0.04). The change in diaphragm BF from rest to exercise was less (p=0.047) for CHF+BR than CHF. These findings demonstrate that dietary NO3‾ supplementation reduces the elevated diaphragm BF during exercise in CHF rats thus providing additional support for this therapeutic intervention in CHF.

Cultural factors influencing dietary and fluid restriction behaviour: perceptions of older Chinese patients with heart failure.

AIMS AND OBJECTIVES: To explore the cultural factors related to dietary and fluid restriction behaviours among older Chinese patients. BACKGROUND: Excess dietary sodium and fluid intake are risk factors contributing to the worsening and rehospitalisation for heart failure in older patients. Managing the complex fluid and diet requirements of heart failure patients is challenging and is made more complicated by cultural variations in self-management behaviours in response to a health threat. DESIGN: Qualitative study using semi-structured in interviews and framework analysis. METHODS: The design of this study is qualitative descriptive. Semi-structured in-depth interviews were conducted with 15 heart failure patients. Data were analysed through content analysis. RESULTS: Seven cultural themes emerged from the qualitative data: the values placed on health and illness, customary way of life, preference for folk care and the Chinese healthcare system, and factors related to kinship and social ties, religion, economics and education. CONCLUSIONS: Dietary change and management in response to illness, including heart failure, is closely related to individuals' cultural background. Healthcare providers should have a good understanding of cultural aspects that can influence patients' conformity to medical recommendations. RELEVANCE TO CLINICAL PRACTICE: Heart failure patients need support that considers their cultural needs. Healthcare providers must have a good understanding of the experiences of people from diverse cultural backgrounds.

Nutritional leucine supplementation attenuates cardiac failure in tumour-bearing cachectic animals.

BACKGROUND: The condition known as cachexia presents in most patients with malignant tumours, leading to a poor quality of life and premature death. Although the cancer-cachexia state primarily affects skeletal muscle, possible damage in the cardiac muscle remains to be better characterized and elucidated. Leucine, which is a branched chain amino acid, is very useful for preserving lean body mass. Thus, this amino acid has been studied as a coadjuvant therapy in cachectic cancer patients, but whether this treatment attenuates the effects of cachexia and improves cardiac function remains poorly understood. Therefore, using an experimental cancer-cachexia model, we evaluated whether leucine supplementation ameliorates cachexia in the heart. METHODS: Male Wistar rats were fed either a leucine-rich or a normoprotein diet and implanted or not with subcutaneous Walker-256 carcinoma. During the cachectic stage (approximately 21 days after tumour implantation), when the tumour mass was greater than 10% of body weight, the rats were subjected to an electrocardiogram analysis to evaluate the heart rate, QT-c, and T wave amplitude. The myocardial tissues were assayed for proteolytic enzymes (chymotrypsin, alkaline phosphatase, cathepsin, and calpain), cardiomyopathy biomarkers (myeloperoxidase, tissue inhibitor of metalloproteinases, and total plasminogen activator inhibitor 1), and caspase-8, -9, -3, and -7 activity. RESULTS: Both groups of tumour-bearing rats, especially the untreated group, had electrocardiography alterations that were suggestive of ischemia, dilated cardiomyopathy, and sudden death risk. Additionally, the rats in the untreated tumour-bearing group but not their leucine-supplemented littermates exhibited remarkable increases in chymotrypsin activity and all three heart failure biomarkers analysed, including an increase in caspase-3 and -7 activity. CONCLUSIONS: Our data suggest that a leucine-rich diet could modulate heart damage, cardiomyocyte proteolysis, and apoptosis driven by cancer-cachexia. Further studies must be conducted to elucidate leucine's mechanisms of action, which potentially includes the modulation of the heart's inflammatory process.

Dietary management of heart failure: room for improvement?

There is growing awareness of the role of diet in both health and disease management. Much data are available on the cardioprotective diet in the primary and secondary prevention of CVD. However, there is limited information on the role of diet in the management of heart failure (HF). Animal models of HF have provided interesting insight and potential mechanisms by which dietary manipulation may improve cardiac performance and delay the progression of the disease, and small-scale human studies have highlighted beneficial diet patterns. The aim of this review is to summarise the current data available on the role of diet in the management of human HF and to demonstrate that dietary manipulation needs to progress further than the simple recommendation of salt and fluid restriction.

Nutritional Interventions in Heart Failure: A Systematic Review of the Literature.

BACKGROUND: Heart failure (HF) is a major health care burden and there is a growing need to develop strategies to maintain health and sustain quality of life in persons with HF. The purpose of this review is to critically appraise the components of nutrition interventions and to establish an evidence base for future advances in HF nutrition research and practice. METHODS AND RESULTS: Cinahl, Pubmed, and Embase were searched to identify articles published from 2005 to 2015. A total of 17 randomized controlled trials were included in this review. Results were divided into 2 categories of nutrition-related interventions: (1) educational and (2) prescriptive. Educational interventions improved patient outcomes such as adherence to dietary restriction in urine sodium levels and self-reported diet recall. Educational and prescriptive interventions resulted in decreased readmission rates and patient deterioration. Adherence measurement was subjective in many studies. Evidence showed that a normal-sodium diet and 1-liter fluid restriction along with high diuretic dosing enhanced B-type natriuretic peptide, aldosterone, tumor necrosis factor α, and interleukin-6 markers. CONCLUSIONS: Educational nutrition interventions positively affect patient clinical outcomes. Although clinical practice guidelines support a low-sodium diet and fluid restriction, research findings have revealed that a low-sodium diet may be harmful. Future research should examine the role of macronutrients, food quality, and energy balance in HF nutrition.

Iron supplementation effectively suppresses gastrocnemius muscle lesions to improve exercise capacity in chronic heart failure rats with anemia.

OBJECTIVE: For patients with chronic heart failure (CHF), exertional fatigue is one of the most common and debilitating symptoms. However, the poor relationship between heart dysfunction and exercise capacity has been ascribed to peripheral abnormalities. Several previous studies confirmed that iron supplementation could significantly improve the exercise capacity of patients with CHF, although they did not analyze effects in the musculoskeletal system. The aim of this study was to investigate the effect of iron treatment on gastrocnemius muscles of CHF rats with anemia. METHODS: Male Sprague-Dawley rats were subjected to coronary ligation to induce heart failure. At the same time, blood (1-1.5 mL) was withdrawn from the retro-orbital plexus once every week to induce anemia. After 6 wk of this process, iron dextran was administered to the CHF rats with anemia (CHFa rats) at the dose of 8, 16, 32, or 64 mg/kg every 2 d for 2 wk. RESULTS: Iron dextran (8 mg/kg every 2 d) effectively improved hemodynamic parameters (P < 0.05) compared with CHFa rats. Similarly, this dose of iron dextran significantly reduced the ratio of heart weight to body weight (P < 0.01), whereas it significantly increased the distance run (m) to exhaustion (P < 0.01). Iron dextran effectively inhibited sarcoplasmic vacuolation and muscle atrophy of gastrocnemius muscles in CHFa rats, as evaluated by pathologic examinations. Other iron treatments, however, were found to be ineffective on the same parameters, so particular focus was placed on the iron dextran (8 mg/kg every 2 d) group in subsequent analyses. Consistently, phospho-p38 in gastrocnemius muscles of CHFa rats was markedly suppressed by iron dextran. Additionally, iron dextran significantly decreased c-fos and c-jun and up-regulated cellular FLICE-inhibitory protein expression levels.

Association of nutritional risk index with metabolic biomarkers, appetite-regulatory hormones and inflammatory biomarkers and outcome in patients with chronic heart failure.

AIMS: We aimed to evaluate the association of the nutritional status by using the nutritional risk index (NRI) with metabolic and inflammatory biomarkers, and appetite-regulatory hormones in a cohort of stable patients with heart failure (HF), and to analyse its prognostic value. METHODS AND RESULTS: In this prospective observational cohort study, we included 137 stable chronic HF patients (median age, 60 years; median body mass index, 27 kg/m(2) ) with optimised medical treatment. Baseline NRI of < 113 (n = 45) was associated with a significant increase in the levels of ghrelin (p < 0.001), peptide YY (p = 0.007), pentraxin-3 (p = 0.001), tumour necrosis factor-alpha (p = 0.018), adiponectin (p < 0.0001) and the N-terminal prohormone of brain natriuretic peptide (NT-proBNP; p < 0.0001) compared with those in patients with NRI of ≥ 113. The NRI was found to be correlated with the homoeostasis model assessment of insulin resistance index (r = 0.444; p < 0.0001) and inversely correlated with the NT-proBNP level (r = -0.410; p < 0.0001). The overall mortality rate was 20%. A baseline NRI of < 113 was associated with a higher risk of all-cause mortality (log rank = 0.031). CONCLUSION: We propose that the NRI is a useful and easily applicable tool for the early identification of nutritional depletion in patients with chronic HF as it discriminates metabolic changes prior to the clinical manifestation of body wasting. Furthermore, poor nutritional status, represented as a low NRI, is associated with an increased incidence of death in such cases.

The effect of multiple micronutrient supplementation on left ventricular ejection fraction in patients with chronic stable heart failure: a randomized, placebo-controlled trial.

OBJECTIVES: This study sought to investigate the effect of a multiple micronutrient supplement on left ventricular ejection fraction (LVEF) in patients with heart failure. BACKGROUND: Observational studies suggest that patients with heart failure have reduced intake and lower concentrations of a number of micronutrients. However, there have been very few intervention studies investigating the effect of micronutrient supplementation in patients with heart failure. METHODS: This was a randomized, double-blind, placebo-controlled, parallel-group study involving 74 patients with chronic stable heart failure that compared multiple micronutrient supplementation taken once daily versus placebo for 12 months. The primary endpoint was LVEF assessed by cardiovascular magnetic resonance imaging or 3-dimensional echocardiography. Secondary endpoints were Minnesota Living With Heart Failure Questionnaire score, 6-min walk test distance, blood concentrations of N-terminal prohormone of brain natriuretic peptide, C-reactive protein, tumor necrosis factor alpha, interleukin-6, interleukin-10, and urinary levels of 8-iso-prostaglandin F2 alpha. RESULTS: Blood concentrations of a number of micronutrients increased significantly in the micronutrient supplement group, indicating excellent compliance with the intervention. There was no significant difference in mean LVEF at 12 months between treatment groups after adjusting for baseline (mean difference: 1.6%, 95% confidence interval: -2.6 to 5.8, p = 0.441). There was also no significant difference in any of the secondary endpoints at 12 months between treatment groups. CONCLUSIONS: This study provides no evidence to support the routine treatment of patients with chronic stable heart failure with a multiple micronutrient supplement. (Micronutrient Supplementation in Patients With Heart Failure [MINT-HF]; NCT01005303).

Cardiac metabolism and its interactions with contraction, growth, and survival of cardiomyocytes.

The network for cardiac fuel metabolism contains intricate sets of interacting pathways that result in both ATP-producing and non-ATP-producing end points for each class of energy substrates. The most salient feature of the network is the metabolic flexibility demonstrated in response to various stimuli, including developmental changes and nutritional status. The heart is also capable of remodeling the metabolic pathways in chronic pathophysiological conditions, which results in modulations of myocardial energetics and contractile function. In a quest to understand the complexity of the cardiac metabolic network, pharmacological and genetic tools have been engaged to manipulate cardiac metabolism in a variety of research models. In concert, a host of therapeutic interventions have been tested clinically to target substrate preference, insulin sensitivity, and mitochondrial function. In addition, the contribution of cellular metabolism to growth, survival, and other signaling pathways through the production of metabolic intermediates has been increasingly noted. In this review, we provide an overview of the cardiac metabolic network and highlight alterations observed in cardiac pathologies as well as strategies used as metabolic therapies in heart failure. Lastly, the ability of metabolic derivatives to intersect growth and survival are also discussed.

Nutrition intervention to decrease symptoms in patients with advanced heart failure.

For a majority of patients with advanced heart failure, there is a need for complementary, non-pharmacologic interventions that could be easily implemented by health care providers to provide palliative care. Three major pathologic pathways underlying heart failure symptoms have been identified: fluid overload, inflammation, and oxidative stress. Prior research has demonstrated that three nutrients-sodium, omega-3 fatty acids, and lycopene-can alter these pathologic pathways. Therefore, the purposes of this study are to test the effects of a 6-month nutrition intervention of dietary sodium reduction combined with supplementation of lycopene and omega-3 fatty acids on heart failure symptoms, health-related quality of life, and time to heart failure rehospitalization or all-cause death. The aims of this double blind-placebo controlled study are (1) to determine the effects of a 6-month nutrition intervention on symptom burden (edema, shortness of air, and fatigue) and health-related quality of life at 3 and 6 months, and time to heart failure rehospitalization or all-cause death over 12 months from baseline; (2) compare dietary sodium intake, inflammation, and markers of oxidative stress between the nutrition intervention group and a placebo group at 3 and 6 months; and (3) compare body weight, serum lycopene, and erythrocyte omega-3 index between the nutrition intervention group and a placebo group at 3 and 6 months. A total of 175 patients with advanced heart failure will be randomized to either the nutrition intervention or placebo group.

Low-sodium diet self-management intervention in heart failure: pilot study results.

BACKGROUND: Self-care management of a low-sodium diet is a critical component of comprehensive heart failure (HF) treatment. AIMS: The primary purpose of this study was to examine the effectiveness of an educational intervention on reducing the dietary sodium intake of patients with HF. Secondary purposes were to examine the effects of the intervention on attitudes, subjective norm, and perceived behavioural control towards following a low-sodium diet. METHODS: This was a randomized clinical trial of an educational intervention based on The Theory of Planned Behavior. Patients were randomized to either a usual care (n=25) or intervention group (n=27) with data collection at baseline, 6 weeks, and 6 months. The intervention group received low-sodium diet instructions and the usual care group received no dietary instructions. Nutrition Data Systems-Research software was used to identify the sodium content of foods on food diaries. Attitudes, subjective norm, and perceived behavioural control were measured using the Dietary Sodium Restriction Questionnaire. RESULTS: Analysis of covariance (between-subjects effects) revealed that dietary sodium intake did not differ between usual care and intervention groups at 6 weeks; however, dietary sodium intake was lower in the intervention group (F=7.3, df=1,29, p=0.01) at 6 months. Attitudes subscale scores were higher in the intervention group at 6 weeks (F=7.6, df=1, 38, p<0.01). CONCLUSION: Carefully designed educational programmes have the potential to produce desired patient outcomes such as low-sodium diet adherence in patients with heart failure.

[Role of nutrition in heart failure patients]. / Ruolo dell'alimentazione nel paziente scompensato.

Heart failure is the leading cause of death and hospitalization in industrialized countries and a major cause of healthcare costs. It is associated with severe symptoms and its prognosis remains poor. Further improvement is needed beyond the results of pharmacological treatment and devices. The role of nutrition has therefore been studied both in the early stages of heart failure, as a tool for the reduction of cardiovascular risk factors and in symptomatic heart failure, for the prevention and treatment of congestion and fluid overload. In addition, dietary supplements, such as n-3 polyunsaturated fatty acids and amino acids, may contribute to the improvement of prognosis and cardiac function, respectively. Finally, in advanced heart failure, nutrition may counteract the effects of muscle wasting and cardiac cachexia through an increase in caloric and protein intake and amino acid supplementation.