Omega-3 supplementation and outcomes of heart failure: A systematic review of clinical trials.

BACKGROUNDS: Omega-3 supplements are endorsed for heart failure (HF) patients to reduce hospitalizations and mortality, offering anti-inflammatory and cardioprotective benefits. METHODS: A comprehensive search was conducted in various databases until November 2022. Eligible studies included clinical trials on patients with HF. Data extraction covered study details, omega-3 specifics, outcomes, and limitations. The JADAD scale was used to assess the risk of bias in randomized controlled trials. RESULTS: The review process involved 572 records from database searches, resulting in 19 studies after eliminating duplicates and screening. These studies assessed the impact of omega-3 on various clinical outcomes, such as mortality, hospitalization, cardiac function, and quality of life. Studied duration varied from weeks to years. Omega-3 supplementation demonstrated potential benefits such as improved heart function, reduced inflammation, and decreased risk of cardiovascular events. CONCLUSION: Omega-3 supplementation could benefit heart disease treatment, potentially reducing therapy duration and improving outcomes. Starting omega-3 supplementation for HF patients seems favorable.

Prescription, Compliance, and Burden Associated with Salt-Restricted Diets in Heart Failure Patients: Results from the French National OFICSel Observatory.

(1) Background: There is much debate about the use of salt-restricted diet for managing heart failure (HF). Dietary guidelines are inconsistent and lack evidence. (2) Method: The OFICSel observatory collected data about adults hospitalised for HF. The data, collected using study-specific surveys, were used to describe HF management, including diets, from the cardiologists' and patients' perspectives. Cardiologists provided the patients' clinical, biological, echocardiography, and treatment data, while the patients provided dietary, medical history, sociodemographic, morphometric, quality of life, and burden data (burden scale in restricted diets (BIRD) questionnaire). The differences between the diet recommended by the cardiologist, understood by the patient, and the estimated salt intake (by the patient) and diet burden were assessed. (3) Results: Between March and June 2017, 300 cardiologists enrolled 2822 patients. Most patients (90%) were recommended diets with <6 g of salt/day. Mean daily salt consumption was 4.7 g (standard deviation (SD): 2.4). Only 33% of patients complied with their recommended diet, 34% over-complied, and 19% under-complied (14% unknown). Dietary restrictions in HF patients were associated with increased burden (mean BIRD score of 8.1/48 [SD: 8.8]). (4) Conclusion: Healthcare professionals do not always follow dietary recommendations, and their patients do not always understand and comply with diets recommended. Restrictive diets in HF patients are associated with increased burden. An evidence-based approach to developing and recommending HF-specific diets is required.

Promising Nutritional Fruits Against Cardiovascular Diseases: An Overview of Experimental Evidence and Understanding Their Mechanisms of Action.

Cardiovascular diseases (CVDs) are one of the leading causes of morbidity and mortality in both developed and developing countries, affecting millions of individuals each year. Despite the fact that successful therapeutic drugs for the management and treatment of CVDs are available on the market, nutritional fruits appear to offer the greatest benefits to the heart and have been proved to alleviate CVDs. Experimental studies have also demonstrated that nutritional fruits have potential protective effects against CVDs. The aim of the review was to provide a comprehensive summary of scientific evidence on the effect of 10 of the most commonly available nutritional fruits reported against CVDs and describe the associated mechanisms of action. Relevant literatures were searched and collected from several scientific databases including PubMed, ScienceDirect, Google Scholar and Scopus. In the context of CVDs, 10 commonly consumed nutritious fruits including apple, avocado, grapes, mango, orange, kiwi, pomegranate, papaya, pineapple, and watermelon were analysed and addressed. The cardioprotective mechanisms of the 10 nutritional fruits were also compiled and highlighted. Overall, the present review found that the nutritious fruits and their constituents have significant benefits for the management and treatment of CVDs such as myocardial infarction, hypertension, peripheral artery disease, coronary artery disease, cardiomyopathies, dyslipidemias, ischemic stroke, aortic aneurysm, atherosclerosis, cardiac hypertrophy and heart failure, diabetic cardiovascular complications, drug-induced cardiotoxicity and cardiomyopathy. Among the 10 nutritional fruits, pomegranate and grapes have been well explored, and the mechanisms of action are well documented against CVDs. All of the nutritional fruits mentioned are edible and readily accessible on the market. Consuming these fruits, which may contain varying amounts of active constituents depending on the food source and season, the development of nutritious fruits-based health supplements would be more realistic for consistent CVD protection.

Dietary Management of Heart Failure: DASH Diet and Precision Nutrition Perspectives.

Heart failure (HF) is a major health care burden increasing in prevalence over time. Effective, evidence-based interventions for HF prevention and management are needed to improve patient longevity, symptom control, and quality of life. Dietary Approaches to Stop Hypertension (DASH) diet interventions can have a positive impact for HF patients. However, the absence of a consensus for comprehensive dietary guidelines and for pragmatic evidence limits the ability of health care providers to implement clinical recommendations. The refinement of medical nutrition therapy through precision nutrition approaches has the potential to reduce the burden of HF, improve clinical care, and meet the needs of diverse patients. The aim of this review is to summarize current evidence related to HF dietary recommendations including DASH diet nutritional interventions and to develop initial recommendations for DASH diet implementation in outpatient HF management. Articles involving human studies were obtained using the following search terms: Dietary Approaches to Stop Hypertension (DASH diet), diet pattern, diet, metabolism, and heart failure. Only full-text articles written in English were included in this review. As DASH nutritional interventions have been proposed, limitations of these studies are the small sample size and non-randomization of interventions, leading to less reliable evidence. Randomized controlled interventions are needed to offer definitive evidence related to the use of the DASH diet in HF management.

Caloric restriction reduces sympathetic activity similar to beta-blockers but conveys additional mitochondrio-protective effects in aged myocardium.

Increased activation of sympathetic nervous system contributes to congestive heart failure (CHF) progression, and inhibition of sympathetic overactivation by beta-blockers is successful in CHF patients. Similarly, caloric restriction (CR) reduces sympathetic activity but mediates additional effects. Here, we compared the cardiac effects of CR (- 40% kcal, 3 months) with beta-blocker therapy (BB), diuretic medication (DF) or control diet in 18-months-old Wistar rats. We continuously recorded blood pressure, heart rate, body temperature and activity with telemetric devices and analysed cardiac function, activated signalling cascades and markers of apoptosis and mitochondrial biogenesis. During our study, left ventricular (LV) systolic function improved markedly (CR), mildly (BB) or even deteriorated (DF; control). Diastolic function was preserved by CR and BB but impaired by DF. CR reduced blood pressure identical to DF and BB and heart rate identical to BB. Plasma noradrenaline was decreased by CR and BB but increased by DF. Only CR reduced LV oxidative damage and apoptosis, induced AMPK and Akt phosphorylation and increased mitochondrial biogenesis. Thus, additive to the reduction of sympathetic activity, CR achieves protective effects on mitochondria and improves LV function and ROS damage in aged hearts. CR mechanisms may provide additional therapeutic targets compared to traditional CHF therapy.

Simultaneous Pharmacokinetic Analysis of Nitrate and its Reduced Metabolite, Nitrite, Following Ingestion of Inorganic Nitrate in a Mixed Patient Population.

PURPOSE: The pharmacokinetic properties of plasma NO3- and its reduced metabolite, NO2-, have been separately described, but there has been no reported attempt to simultaneously model their pharmacokinetics following NO3- ingestion. This report describes development of such a model from retrospective analyses of concentrations largely obtained from primary endpoint efficacy trials. METHODS: Linear and non-linear mixed effects analyses were used to statistically define concentration dependency on time, dose, as well as patient and study variables, and to integrate NO3- and NO2- concentrations from studies conducted at different times, locations, patient groups, and several studies in which sample range was limited to a few hours. Published pharmacokinetic studies for both substances were used to supplement model development. RESULTS: A population pharmacokinetic model relating NO3- and NO2- concentrations was developed. The model incorporated endogenous levels of the two entities, and determined these were not influenced by exogenous NO3- delivery. Covariate analysis revealed intersubject variability in NO3- exposure was partially described by body weight differences influencing volume of distribution. The model was applied to visualize exposure versus response (muscle contraction performance) in individual patients. CONCLUSIONS: Extension of the present first-generation model, to ultimately optimize NO3- dose versus pharmacological effects, is warranted.

Comparison of probiotic yogurt and ordinary yogurt consumption on serum Pentraxin3, NT-proBNP, oxLDL, and ApoB100 in patients with chronic heart failure: a randomized, triple-blind, controlled trial.

BACKGROUND AND AIMS: Nowadays, the potential beneficial effects of probiotic yogurt as a functional food has raised much interest. Thus, the aim of this study was to compare the probiotic yogurt and ordinary yogurt consumption on some indices in patients with chronic heart failure (CHF). METHODS AND RESULTS: In this randomized, triple-blind clinical trial, 90 patients with CHF were randomly allocated into two groups to take either probiotic yogurt or ordinary yogurt for 10 weeks. The serum levels of pentraxin3 (PTX3), N-terminal pro-brain natriuretic peptide (NT-proBNP), oxidized low density lipoprotein (oxLDL), and apolipoprotein B100 (ApoB100) were measured at the baseline and at the end of week 10. P-Value <0.05 was defined as statistically significant. Final analyses were performed on 78 patients. The levels of PTX3 and oxLDL in both the groups decreased significantly after 10 weeks, and these reductions were greater in the probiotic group, where the difference between the groups was statistically significant for oxLDL (P-value: 0.051, adjusted P-value: 0.010) but not significant for PTX3 (P-value: 0.956, adjusted P-value: 0.236). The changes in the serum NT-proBNP levels were not statistically significant between the groups (P-value: 0.948, adjusted P-value: 0.306). ApoB100 significantly decreased in the control group compared to the probiotic group and the difference between the groups was significant at first but was not significant after adjusting for the confounders (P-value: 0.004, adjusted P-value: 0.280). CONCLUSION: The serum oxLDL significantly reduced due to probiotic yogurt consumption after 10 weeks compared to ordinary yogurt; thus, it may be useful for improving the oxidative status of CHF patients. The clinical trial registry number is IRCT20091114002709N48 (https://www.irct.ir/IRCT20091114002709N48, registered 12 March 2018).

The role of diet and nutrition in heart failure: A state-of-the-art narrative review.

Heart Failure (HF) incidence is increasing steadily worldwide, while prognosis remains poor. Though nutrition is a lifestyle factor implicated in prevention of HF, little is known about the effects of macro- and micronutrients as well as dietary patterns on the progression and treatment of HF. This is reflected in a lack of nutrition recommendations in all major HF scientific guidelines. In this state-of-the-art review, we examine and discuss the implications of evidence contained in existing randomized control trials as well as observational studies covering the topics of sodium restriction, dietary patterns and caloric restriction as well as supplementation of dietary fats and fatty acids, protein and amino acids and micronutrients in the setting of pre-existing HF. Finally, we explore future directions and discuss knowledge gaps regarding nutrition therapies for the treatment of HF.

Dietary Sodium Restriction for Heart Failure: A Systematic Review of Intervention Outcomes and Behavioral Determinants.

The 1500 mg/d dietary sodium restriction commonly recommended for patients with heart failure has recently been questioned. Poor adherence to sodium-restricted diets makes assessing the efficacy of sodium restriction challenging. Therefore, successful behavioral interventions are needed. We reviewed sodium restriction trials and descriptive studies of sodium restriction to: 1) determine if sodium restriction was achieved in interventions among heart failure patients; and 2) characterize predictors of successful dietary sodium restriction. Among 638 identified studies, 10 intervention trials, and 25 descriptive studies met inclusion criteria. We used content analysis to extract information about sodium restriction and behavioral determinants of sodium restriction. Dietary sodium was reduced in 7 trials; none achieved 1500 mg/d (range 1938-4564 mg/d). The interventions implemented in the interventional trials emphasized knowledge, skills, and self-regulation strategies, but few addressed the determinants correlated with successful sodium restriction in the descriptive studies (eg, social/cultural norms, social support, taste preferences, food access, self-efficacy). Findings suggest that incorporating determinants predictive of successful dietary sodium restriction may improve the success of interventional trials. Without effective interventions to deploy in trials, the safety and efficacy of sodium restriction remains unknown.

Evidence related to sodium restriction in patients with heart failure.

OBJECTIVES: to analyze the scientific production about sodium restriction in patients with heart failure. METHODS: integrative literature review from articles published from 2007 to 2017, located in the CINAHL and Scopus databases. RESULTS: thirteen studies were analyzed. Sodium intake restriction was associated with lower unfavorable clinical outcomes in patients with marked symptomatology. The 24-hour urine sodium dosage was the main tool to assess adherence to the low sodium diet. CONCLUSIONS: based on the studies included in this review, in symptomatic patients, dietary sodium restriction should be encouraged in clinical practice as a protective measure for health. However, in asymptomatic patients, it should be well studied.

Implications of Altered Ketone Metabolism and Therapeutic Ketosis in Heart Failure.

Despite existing therapy, patients with heart failure (HF) experience substantial morbidity and mortality, highlighting the urgent need to identify novel pathophysiological mechanisms and therapies, as well. Traditional models for pharmacological intervention have targeted neurohormonal axes and hemodynamic disturbances in HF. However, several studies have now highlighted the potential for ketone metabolic modulation as a promising treatment paradigm. During the pathophysiological progression of HF, the failing heart reduces fatty acid and glucose oxidation, with associated increases in ketone metabolism. Recent studies indicate that enhanced myocardial ketone use is adaptive in HF, and limited data demonstrate beneficial effects of exogenous ketone therapy in studies of animal models and humans with HF. This review will summarize current evidence supporting a salutary role for ketones in HF including (1) normal myocardial ketone use, (2) alterations in ketone metabolism in the failing heart, (3) effects of therapeutic ketosis in animals and humans with HF, and (4) the potential significance of ketosis associated with sodium-glucose cotransporter 2 inhibitors. Although a number of important questions remain regarding the use of therapeutic ketosis and mechanism of action in HF, current evidence suggests potential benefit, in particular, in HF with reduced ejection fraction, with theoretical rationale for its use in HF with preserved ejection fraction. Although it is early in its study and development, therapeutic ketosis across the spectrum of HF holds significant promise.

Effect of Prebiotic Complex on Gut Microbiota and Endotoxemia in Female Rats with Modeled Heart Failure.

We studied the levels endotoxin and microbial markers in the blood of female rats with experimental heart failure and the effects of preliminary treatment with a prebiotic complex based on fermented wheat bran and inactivated Saccharomyces cerevisiae culture on these parameters. The concentrations of endotoxin, markers of lactobacilli, and opportunistic microorganisms were found to increase in rats with experimental heart failure and significantly decreased against the background of treatment with prebiotic complex. The dynamics of markers of bifidobacteria, eubacteria, and propionibacteria were reciprocal. The observed effect of the prebiotic complex effect on gut microbiota in rats with experimental heart failure suggests that this complex can be used for the correction of intestinal dysbiosis and endotoxemia in this clinical condition.

Why a d-ß-hydroxybutyrate monoester?

Much of the world's prominent and burdensome chronic diseases, such as diabetes, Alzheimer's, and heart disease, are caused by impaired metabolism. By acting as both an efficient fuel and a powerful signalling molecule, the natural ketone body, d-ß-hydroxybutyrate (ßHB), may help circumvent the metabolic malfunctions that aggravate some diseases. Historically, dietary interventions that elevate ßHB production by the liver, such as high-fat diets and partial starvation, have been used to treat chronic disease with varying degrees of success, owing to the potential downsides of such diets. The recent development of an ingestible ßHB monoester provides a new tool to quickly and accurately raise blood ketone concentration, opening a myriad of potential health applications. The ßHB monoester is a salt-free ßHB precursor that yields only the biologically active d-isoform of the metabolite, the pharmacokinetics of which have been studied, as has safety for human consumption in athletes and healthy volunteers. This review describes fundamental concepts of endogenous and exogenous ketone body metabolism, the differences between the ßHB monoester and other exogenous ketones and summarises the disease-specific biochemical and physiological rationales behind its clinical use in diabetes, neurodegenerative diseases, heart failure, sepsis related muscle atrophy, migraine, and epilepsy. We also address the limitations of using the ßHB monoester as an adjunctive nutritional therapy and areas of uncertainty that could guide future research.

Safety and efficacy of salt substitution with a low sodium-potassium enriched dietary salt in patients with heart failure with reduced ejection fraction: A pilot study.

BACKGROUND AND AIMS: Increased sodium intake is associated with increased risk of decompensation in patients with heart failure. This non-randomized, open-label, controlled study aimed to examine the feasibility, preliminary safety and efficacy of a low sodium-potassium enriched salt substitute compared to regular table salt in patients with heart failure with reduced ejection fraction (HFREF). METHODS: Fifty patients (68% male, NYHA I/II/III 6%/68%/26%, mean age 70 ± 9 years, LVEF 31 ± 5%, median BNP 112 pg/ml) were included. Of these, 30 patients received the salt substitute (maximum consumption of 2 g daily), who were prospectively compared to a control group of 20 age/sex/NYHA class-matched HFREF patients who consumed regular salt (maximum consumption of 2 g daily). Consumption of regular salt was prohibited in the salt substitution group. All patients were followed for 12 weeks. RESULTS: Patient groups did not differ by sex, age, LVEF, NYHA class, 6MWD, and BNP at baseline. In primary safety analysis, no significant differences were detected between groups regarding SBP (p = 0.052), DBP (p = 0.159), HR (p = 0.246), serum potassium (p = 0.579), serum sodium (p = 0.125), and eGFR (p = 0.710) throughout the 12 weeks. Secondary efficacy analysis revealed a statistically significant difference in 6MWD at 12 weeks between the salt substitute and regular salt groups after adjustment for baseline 6MWD (mean difference±SEM, 4.7 ± 2.1 m, F = 4.92, p = 0.031). CONCLUSIONS: In this pilot study, a low sodium-potassium enriched salt substitute was found to be safe compared to regular salt in HFREF patients, while it resulted in a small albeit significant improvement in exercise capacity, possibly justifying further investigation with randomized clinical studies.

Zinc Deficiency and Heart Failure: A Systematic Review of the Current Literature.

Zinc is an essential micronutrient that impacts the cardiovascular system through modulation of oxidative stress. It is unknown whether zinc levels are affected in heart failure (HF), and whether the association, if present, is causal. A systematic search for publications that report coexisting zinc deficiency in patients with HF was performed to provide an overview of the pathophysiological and epidemiological aspects of this association (last search April 2019). Review of the literature suggests multiple potential pathophysiologic causes for zinc deficiency in HF as a result of impaired micronutrient consumption, hyper-inflammatory state, upregulation of the renin-angiotensin-aldosterone axis, diminished absorption, and hyperzincuria from HF medications. In a longitudinal study of patients with HF in the setting of intestinal malabsorption, there was partial cardiomyocyte and left ventricular ejection fraction recovery with intravenous selenium and zinc supplementation. Two randomized double-blind control trials evaluating micronutrient and macronutrient supplementation including zinc in patients with HF found improvement in echocardiographic findings compared with placebo. Two recently completed studies evaluated the role for zinc supplementation in 2 different HF populations: a trial of zinc supplementation in patients with non-ischemic HF, and a trial of micronutrient supplementation (including B vitamins, vitamin D, and zinc) in veterans with systolic dysfunction; the results of which are still pending. Several pathobiological pathways to link zinc deficiency with the development and deterioration of HF are presented. Preliminary clinical data are supportive of such an association and future studies should further investigate the effects of zinc supplementation on outcomes in patients with HF.

The Mediterranean Diet Benefit on Cardiovascular Hemodynamics and Erectile Function in Chronic Heart Failure Male Patients by Decoding Central and Peripheral Vessel Rheology.

BACKGROUND: Mediterranean diet was evaluated on erectile performance and cardiovascular hemodynamics, in chronic heart failure patients. METHODS: 150 male stable heart failure patients were enrolled in the study (62 ± 10 years, New York Heart Association (NYHA) classes I-II, ejection fraction ≤40%). A detailed echocardiographic evaluation including estimation of the global longitudinal strain of the left ventricle and the systolic tissue doppler velocity of the tricuspid annulus was performed. Erectile dysfunction severity was assessed by the Sexual Health Inventory for Men-5 (SHIM-5) score. Adherence to the Mediterranean diet was evaluated by the MedDietScore. RESULTS: The SHIM-5 score was positively correlated with the MedDietScore (p = 0.006) and augmentation index (p = 0.031) and inversely correlated with age (p = 0.002). MedDietScore was negatively associated with intima-media-thickness (p < 0.001) and serum prolactin levels (p = 0.05). Multi-adjusted analysis revealed that the inverse relation of SHIM-5 and prolactin levels remained significant only among patients with low adherence to the Mediterranean diet (p = 0.012). CONCLUSION: Consumption of Mediterranean diet benefits cardiovascular hemodynamics, while suppressing serum prolactin levels. Such physiology may enhance erectile ability independently of the of the left ventricle ejection fraction.

Influence of nutrition support therapy on readmission among patients with acute heart failure in the intensive care unit: A single-center observational study.

BACKGROUND & AIMS: The effect of nutrition support therapy on prevention of readmission among patients with acute heart failure (HF) in an intensive care unit (ICU) setting remains unclear. We hypothesized that nutrition support therapy might decrease the readmission rate among these patients. Thus, we conducted a single-center prospective observational study to verify this hypothesis. METHODS: Patients diagnosed with acute HF admitted to the ICU for more than 14 days between April 2016 and March 2017 were included in the analysis. The primary outcome was the relationship between nutritional intake and HF-related hospital readmission due to HF at 180 days after discharge. We divided the participants into 2 groups: patients who were not readmitted to hospital within 180 days after discharge (non-readmission group) and patients who were readmitted within this timeframe (HF-related readmission group). Data were expressed as median (interquartile range). RESULTS: Sixty patients required readmission due to HF-related events (HF-related readmission group). On the other hand, 127 patients did not require readmission (non-readmission group). The calorie and protein intake on day 3 after ICU admission in the HF-related readmission group was significantly higher than that in the non-readmission group [20.5 (14.2, 27.8) vs. 27.7 (22.5, 31.2) kcal/kg/day, p < 0.001; 0.7 (0.5, 0.9) vs. 0.9 (0.7, 1.2) g/kg/day, p < 0.001, respectively]. Similarly, the protein intake values on day 7 were also significantly higher in the HF-related readmission group [0.8 (0.6, 1.0) vs. 0.9 (0.7, 1.2) g/kg/day, p = 0.04]. Multivariate analysis indicated that total caloric intake on day 3 was an independent factor affecting readmission (odds ratio = 1.05, 95% confidence interval = 1.01-1.09, p = 0.006). In addition, when the cut off value of calorie intake was set to 18 kcal/kg/day, the group ingesting ≥18 kcal/kg/day on day 3 had a significantly higher readmission rate within 180 days after discharge. CONCLUSIONS: Our data showed that total calorie intake ≥18 kcal/kg/day on day 3 might increase the readmission rate among patients with acute HF.

Salt, No Salt, or Less Salt for Patients With Heart Failure?

Restricting dietary sodium is a common recommendation given by clinicians to patients with heart failure and is one supported by current guidelines. However, the quality of evidence for this recommendation is suboptimal, and there is no consensus on the optimal level of sodium intake. Though excessive sodium intake is associated with left ventricular hypertrophy and hypertension, recent data have suggested that very low sodium intake is paradoxically associated with worse outcomes for patients with heart failure. This is possibly explained by the association between low sodium intake and activation of the sympathetic and renin-angiotensin-aldosterone systems. Nevertheless, sodium restriction is routinely recommended and remains a cornerstone of heart failure and blood pressure therapy. In this review we discuss the pros and cons of sodium restriction for patients with heart failure from the current literature.